Response to Comments: Skin Substitute Grafts/Cellular and/or Tissue-Based Products for the Treatment of Diabetic Foot Ulcers and Venous Leg Ulcers

Comments received from the Wound Healing Society (WHS), the Alliance of Wound Care Stakeholders (Alliance), and the Coalition of Wound Care Manufacturers (the Coalition) recommend the adoption of the term “Cellular and/or tissue-based products for wounds” (CTPs) which accurately describes these products inclusive of both current and future technology. This terminology has been adopted and accepted by the wound care community, contractors, and other government agencies. The American Society for Testing and Materials (ASTM) updated its standard guide to define CTP nomenclature and they have also included synthetic products within the definition of a CTP. The Alliance cited one reference with their comment.

Thank you for the comments. The term CTPs has been incorporated into the finalized LCD and associated article. Even though we believe that the existing terminology of ‘‘skin substitutes’’ is problematic as it is an overly broad misnomer, the contractor will not eliminate the use of this term, since ‘‘skin substitutes’’ is used within the Current Procedural Terminology (CPT^®) code series 15271–15278 as maintained by the American Medical Association (AMA).

A comment from a wound care specialist physician indicates that even though venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) are the most commonly seen, limiting the use of a skin substitute to only these categories would be tragic. In the early days when he only had Apligraf and Dermagraft approved for DFUs and VLUs so many conditions were excluded. When new products became available, and he was able to treat patients with them he saw the light. Surgical wounds, ulcers due to pyoderma gangrenosum, degloving injuries, etc. could not be healed much faster.

A second commenter indicates the proposed LCD limits are unclear but perceived to be only DFU and VLU as medically necessary – If this is the case, all other wound types will no longer be covered; example burns, or pressure ulcers/injury.

A third commenter implies that the proposed LCD uses terminology for acute wounds (e.g., surgical and trauma wounds). Inclusion of these terms creates confusion as to the scope of the policy. The commenter recommends streamlining the language to be specific to DFUs and VLUs.

A fourth commenter confirms agreement with the proposed LCD only pertaining to VLU and DFU. However, the policy should clearly state all wounds-acute and chronic should follow the FDA package insert and clinician determined medical necessity.

A fifth comment from the WHS, the Alliance, and the Coalition requests that the LCD not refer to other types of ulcers or wounds throughout the policy since this policy applies to only DFUs and VLUs. Specifically, this policy refers to pressure ulcers, decubitus ulcers, burns and trauma wounds. None of these are the subject of this policy and any reference to these terms is inappropriate and needs to be removed from the policy. The Alliance indicates that based on Medicare claims data, DFUs affect 0.7% of Medicare beneficiaries and VLUs 0.9%. In point of fact, dehisced surgical ulcers are the most prevalent wound/ulcer type suffered by Medicare beneficiaries, based on claims data, with traumatic wounds and "generic" chronic ulcers following after that. One reference was cited with this comment.

A sixth comment from Peripheral Vascular Associates expresses concern that the proposed LCD only addresses skin substitute indications for DFUs and VLUs, eliminating patients with other wound types such as arterial, pressure, surgical, burns, trauma, vasculitis, and mixed arterial-venous disease. This excludes a population of patients whose lives are significantly impaired by wounds that would benefit from a skin substitute placement. The commenter recommends allowing skin substitute placement for all wound types.

A seventh comment from Vohra Wound Physicians references the sentence under the ‘History/Background and/or General Information’ section: “Application of skin substitute grafts for wound care indications other than for DFU or VLU are not addressed by this LCD.” The commenter asks if other indications and etiologies are limited in anyway by a separate policy or coverage determinations or if they have no applicable LCD and only NCD guidance applies. In their experience, when a detailed LCD is published specific to wound care and such an LCD is silent on coverage of certain wound conditions not listed in the LCD, a de facto ghost medical necessity policy is created, and these ghost policies result in denial of appropriate patient care. The commenter encourages the publication of clear and distinct guidance on the coverage and medical necessity guidelines for all chronic wound etiologies not just DFU and VLU etiologies.

Thank you for the comments. As noted in the second paragraph of the ‘History/Background and/or General Information’ section of the proposed LCD: “Application of skin substitute grafts for wound care indications other than for DFU or VLU are not addressed by this LCD. Use of skin substitute grafts must meet the medically reasonable and necessary threshold for coverage and these devices must be used in accordance with their approved United States (U.S.) Food and Drug Administration (FDA) intended use.” This language has been revised in the finalized LCD to: “Application of skin substitute grafts/CTPs for wound/ulcer care indications other than for DFU or VLU are not addressed by this LCD. Use of skin substitute grafts/CTPs must meet the medically reasonable and necessary threshold for coverage and must be used in accordance with their intended use as approved/regulated by the United States (U.S.) Food and Drug Administration (FDA).” In addition, the third paragraph in the proposed LCD has been removed which states: “Chronic wounds of the lower extremities, including venous stasis ulcers, DFUs and pressure sores, are a major public health problem. While lower extremity ulcers have numerous causes such as burns, trauma, mixed venous-arterial disease, immobility, and vasculitis, nutritional or other neuropathy, over 90% of the lesions in the U.S. are related to venous stasis disease and diabetic neuropathy.”

Comments were received regarding the following language in the ‘History/Background and/or General Information’ section of the proposed LCD: “Although skin substitutes have attributes of both biologicals and devices, the current position is that these products are best characterized as surgical supplies or devices because of their required surgical application and their similarity to other surgical supplies.”

One commenter specifies that skin substitutes/CTPs are not surgical supplies and should not be referred to as surgical supplies; this reference is clinically incorrect. Unlike traditional wound dressings, a CTP interacts, directly or indirectly, with the patient’s body tissues. A CTP is an adjunctive therapy, which is why it is billed separately. The AMA crafted application codes for them in the surgical section of the CPT book because they require specific wound bed preparation. These codes apply to the surgical application regardless of whether it is done in a physician’s office or a provider-based department, and they apply to all CTPs. They must be applied by a physician or other qualified health professional, not by a nurse or physical therapist, and they must be fixated (i.e., sutured or otherwise secured into place). Redefining CTPs as surgical supplies is a substantive departure from accepted terminology that could have reimbursement implications for CTPs beyond the scope of the proposed LCD at issue. The finalized LCD must utilize the appropriate, accepted terminology for CTPs as adjunctive therapies.

A second commenter signifies that this language is inconsistent with CMS’ characterization of these products. As discussed in the CY 2014 OPPS/ASC final rule, CMS has previously acknowledged the distinction between skin substitutes and surgical dressings. Skin substitutes are applied surgically to wounds to enhance wound management through various mechanisms of action that stimulate the host to replace lost tissue and should be defined as such. The commenter requests that the finalized LCD align its definition of skin substitutes to conform with CMS’ characterization. Skin substitutes include extracellular matrices, biologicals, and synthetic products.

A third commenter declares that this is not an accurate description of these products, as surgical supplies are adjuncts meant to support a main procedure. Skin substitutes represented by Q4XXX and A2XXX represent an advanced treatment product that is an integral component (both clinically and from a coding perspective) with the application codes 15271-15278. Additionally, “supplies” has connotations from a reimbursement perspective. Supplies do not typically elicit separate reimbursement, and those that do (under “surgical dressings” for example) fall to the realm of DME.

A fourth commenter asks why skin substitutes/CTPs are categorized as surgical supplies and requests further definition of products as well as more clarity surrounding the appropriate categorization of skin subs/CTPs.

A fifth commenter indicates that surgical supplies are items that are utilized to prevent infection and provide a physical barrier to protect the ulcer (wound) surface. Graft products are fixated on the wound bed by a physician or nurse practitioner following appropriate wound bed preparation, as a method of aiding in the promotion of wound healing. The reference to surgical dressings should either be removed, or the language should be amended to more appropriately describe the products and their use by physicians and nurse practitioners.

A sixth comment from the WHS, the Alliance, and the Coalition signifies that CTPs are not surgical supplies and should not be referred to as surgical supplies. The role of CTPs is not to cover and protect wounds like a surgical dressing but rather to stimulate endogenous healing. CTPs are distinct from surgical dressings in that: 1) The AMA crafted application codes for them in the surgical section of the CPT book because they require specific wound bed preparation. These codes apply to the surgical application no matter whether done in the physician office, provider-based departments and apply to all CTPs, 2) They must be applied by a physician or nurse practitioner not by a nurse or physical therapist, and 3) They must be fixated. The Alliance and the Coalition specify that CMS has acknowledged the distinction between skin substitutes and surgical dressings in the CY 2014 OPPS/ASC final rule. While skin substitutes may be considered supplies used in a surgical procedure, similar to an implantable biological, this is not their sole purpose or use, unlike surgical dressings. Skin substitutes are applied to wounds to aid healing through various mechanisms of action that stimulate the host to regenerate lost tissue and should be defined as such. One reference was cited with this comment.

A seventh commenter indicates surgical supplies or dressings are typically removed as the ulcer or chronic wound heals. They are used as a protective covering and can be applied by an individual other than a clinician, including the patient or patient’s caregiver. Skin substitutes are applied by a licensed provider and are integrated into the wound bed through the healing process and are not removed. Surgical dressings or supplies are categorized as “Durable Medical Equipment” and can be purchased “over the counter” in contrast to skin substitutes which require a prescription or physician order. Surgical dressings are used to cover or protect the skin substitute as it is incorporated into the wound bed.

An eighth comment from a wound care physician recommends this statement be removed from the policy as he cannot understand how anyone could categorize an HCT/P as a supply or device. Certainly, there must be a better way to categorize these for they are not dressings, they are not instruments or implants and they are certainly not devices. As well, some of these are biological.

Thank you for the comments. The language referred to in the comments has been removed in the finalized LCD. The Contractor acknowledges that unlike traditional wound dressings, which are typically removed as the ulcer or chronic wound heals and are utilized to prevent infection and provide a physical barrier to protect the ulcer (wound) surface, a true skin substitute graft/CTP is applied surgically to ulcers to enhance wound management as they form a sheet scaffolding for skin growth.

Regarding the comments from the coding perspective, the LCD addresses skin replacement surgery and the application of skin substitute grafts/CTPs. The definition in the AMA CPT^® book states in part, "Skin substitute grafts include non-autologous human skin (dermal or epidermal, cellular and acellular) grafts (e.g., homograft, allograft), non-human skin substitute grafts (i.e., xenograft), and biological products that form a sheet scaffolding for skin growth. These codes are not to be reported for application of non-graft wound dressings (e.g., gel, powder, ointment, foam, liquid) or injected skin substitutes.”

A comment received from a physician indicates that oxygen therapy is listed as a preliminary procedure and asked if that is meant to be hyperbaric oxygen therapy.

Thank you for the comment. It appears this comment is referring to the sixth paragraph in the ‘History/Background and/or General Information’ section of the proposed LCD that states: “Standard treatment of lower extremity ulcers (e.g., DFUs and/or VLUs) may include mechanical offloading, infection control, mechanical compression, limb elevation, debridement of necrotic tissue, management of systemic disease and medications, nutrition assessment, tissue perfusion and oxygenation, and counseling on the risk of continued tobacco use.”

Regarding this language, we refer to the article cited for Lavery (2016) which provides diabetic foot ulcer treatment guidelines. These guidelines include the following recommendation: “Examination of the patient as a whole is important to evaluate and correct causes of tissue damage. This includes factors such as: (A) systemic diseases and medications, (B) nutrition, and (C) tissue perfusion and oxygenation.”

A comment received from the WHS and the Coalition indicates there are several places within this policy in which the application of CTPs is described as an adjunct therapy. This is not a correct description. It is widely known and supported in the literature that after a wound fails to heal after 30 days or four weeks of standard of care the application of advanced therapies such as CTPs is warranted. The commenters recommend removal of the reference to CTPs as adjunct therapy and instead refer to them as an advanced therapy.

A second comment from a wound care physician denotes that skin substitutes should not be classified as an ‘adjunct’, but instead a normal progression of caring for these wounds when they are not healing after four weeks.

A third comment from the Alliance and the Coalition references the language in the seventh paragraph in the ‘History/Background and/or General Information’ section of the proposed LCD: “Despite advancements in various synthetic occlusive dressings some ulcers fail to heal. The development of skin substitutes has been employed as an adjunct to established wound care methods to increase the chances of healing.”

The Alliance believes this statement was intended to describe a surgical dressing. If so, then this statement can be fixed by changing "synthetic occlusive" to " surgical" which would make the statement correct. However, if the statement was issued in reference to synthetic CTPs, then this statement is not correct. Synthetics are not considered dressings. Synthetic CTPs are a class of CTP and have not only been added into the definition of what is a CTP by CMS they are part of the ASTM standard for CTPs. Therefore, reference to synthetics as dressings needs to be eliminated. One reference was cited with this comment.

The Alliance also indicates that the use of CTPs is not considered adjunct to established wound care methods as stated. Rather after four weeks of standard of care, advanced therapy such as the use of CTPs is warranted if the ulcer has not healed. The policy incorrectly uses the term adjunct in this statement but correctly identifies CTPs as an advanced therapy in other portions of the policy. They recommend revising this language to: “The development of CTPs have been employed as an advanced therapy to established ulcer management methods which failed and increase the chances of healing." One reference is cited with this comment.

Thank you for the comments. The language referred to in the comments has been revised in the finalized LCD to: “Despite advancements in various surgical dressings, which maintain a moist healing environment, some ulcers fail to heal. Skin substitute grafts/CTPs have been employed after an ulcer fails to heal, as an ulcer management method intended to increase the chances of healing.”

The remainder of the finalized LCD has been revised to remove the reference to skin substitutes/CTPs as adjunct therapy.

A comment received from the WHS, the Alliance, and the Coalition denotes that the proposed LCD refers to conservative treatment when in fact the treatment being referred to is standard of care. The commenters would like to better understand why the standard of care is being referred to as conservative treatment. The Alliance suggests the following language: “The CTP is applied to an ulcer that has failed to respond to documented standard of care.”

Thank you for the comment. Some of the literature referenced in the proposed LCD use the term ‘conservative care’, for example, Zelen (2017). However, to avoid confusion, the term ‘conservative treatment’ has been replaced with ‘standard of care’ in the finalized LCD.

A comment received from a physician, twenty-one podiatrists, and a nurse practitioner recommends a noted reference for defining a chronic wound.

A second commenter implies there is confusion with the language in the proposed LCD ‘History and Background’ section that states: “A wound that has not healed within one to three months may be considered chronic and the application of a skin substitute, an advanced treatment modality, may be considered medically reasonable and necessary.” This range creates confusion as clinicians will not know if the application will be covered for a patient after one month or three months. Defining a chronic non-healing ulcer as a wound that does not respond to standard wound treatment for four weeks is more consistent with the literature, and with all other LCDs and NCDs related to wound products, therapies, and devices. The LCD should clearly define a chronic non-healing wound based on non-response after four weeks, which is consistent with the literature. Two references were cited with these comments.

A third comment from a physician indicates it is imperative that we settle on a clinically accepted definition of a “chronic wound” and that we stay consistent. The Draft fails in this regard, and we believe that the first step in developing an effective policy is to have a consistent reference or definition of a “chronic wound.” Please consider clarifying a clinically accepted definition or reference for “chronic wound.”

A fourth comment from the WHS, Peripheral Vascular Associates, the Alliance, and the Coalition indicates concern regarding the lack of a consistent and accurate definition of a chronic non healing wound, which should be a wound that fails to heal after 30 days or four weeks. In some places the LCD defines this as a wound that has not healed in one to three months; in other places it says greater than four weeks. None of the measurements provided in this proposed LCD are based on evidence. Defining a chronic non healing wound as a wound that does not respond to standard wound treatment for four weeks or 30 days is more consistent with the literature, and with all other LCDs and NCDs related to wound products, therapies, and devices. The commenters recommend removal of the one to three month measure of a chronic non-healing wound and use the 30 day or four week timeframe in the policy. The Alliance cited two references with their comment.

A fifth comment from a wound care physician indicates that the definition of a chronic ulcer has been determined to be 30 days or four weeks and recommends that the policy be revised accordingly. This definition has been documented in other LCDs, used by CMS, and noted in clinical guidelines.

Thank you for the comments. The language in the finalized LCD has been revised to remove reference to ‘one to three months’ and will state: “A DFU or VLU that has failed to respond to standard of care treatment after four weeks (defined as 30 days) may be considered chronic, and the application of a skin substitute graft/CTP may be considered medically reasonable and necessary for certain patients.”

Please note that the ‘Covered Indications’ section of the finalized LCD has been revised as follows: “All of the following criteria must be met for the application of a skin substitute graft/CTP for lower extremity DFU or VLU to be considered medically reasonable and necessary: The presence of a chronic, non-infected DFU or chronic, non-infected VLU having failed to respond to documented standard of care treatment (outlined below) for a minimum of four weeks (defined as 30 days) with documented compliance to prescribed treatment.”

A comment received from a podiatrist indicates many of their patients have significant comorbidity, diabetes being one of the many factors. Often times patients have undergone months of medical optimization with significant reductions in HbA1c. The commenter believes the biggest predictor is not just the current A1c value of the patient but rather the trend of reduction of A1c in preparation for grafting. A value of 7 or lower is ideal for their diabetic patients but sometimes not attainable in the setting these patients are in with respect to the time frame in which they utilize these products. A delay in time to grafting again leaves opportunity for delay in healing, infection, amputation, etc. The commenter believes a set marker or target of HbA1c of 7 is inappropriate for these reasons.

A second comment from a physician, twenty-one podiatrists, and a nurse practitioner asserts that dictating specific lab or diagnostic values could inadvertently exclude patients who would benefit from this type of advanced treatment. Individual patient wound assessments in conjunction with past and present laboratory and diagnostic values should be the basis for determining the most appropriate clinical care.

A third commenter expresses agreement with the language regarding Hgb A1c in the proposed LCD, however compliance, culture, educational and social economic status all get in the middle of this simple lab report and ability for a patient to keep it at a normal range. The commenter points out that he has healed smokers and uncontrolled diabetics with grafting, avoiding amputations. It is harder to heal but depriving them from advanced therapy would be unfair to a human being.

A fourth comment from a podiatrist and a wound care physician indicates that a restriction to care is being proposed on caregivers for a more stringent A1c criteria (<7%) for graft replacement. The wound care physician recommends revising the LCD to indicate that the diabetes and glycemic control are addressed by the provider.

A fifth comment from a physician indicates that while he appreciates the importance of having standardized care for applying skin substitutes, referencing specific diagnostic services and lab values, such as glucose controls (HbA1c < 7%) and vascular assessment (ABIs as noted in the Evidence-based guidelines), should not be specific targets. Rather improving trends of those comorbid conditions and other complications should be the focus. For example, a diabetic with a Hgb A1c <7 would exclude most of our wound care patients from receiving this essential treatment option.

A sixth comment from two physicians indicates that with the proposed A1c restriction, patients will be excluded that would benefit most from the skin substitutes.

A seventh comment from the WHS, Peripheral Vascular Associates, and the Alliance indicates the draft LCD reads that “adequate glycemic control of hemoglobin A1c defined by this policy as <7% is recommended to reduce the incidence of DFUs and infections.” The commenters disagree with this statement clinically for chronic wound care patients as these patients can die when their A1c goes below 7%. Among diabetics, controlling Hgb A1c may reduce long term complications if implemented early. However, among Medicare beneficiaries with diabetes, Hgb A1c should be interpreted with care. The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes the ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. For older adults with complex/intermediate conditions (multiple coexisting chronic illnesses or 21 instrumental ADL impairments or mild-to-moderate cognitive impairment), a reasonable A1c goal is <8%. However, for older adults with very complex conditions or who are in poor health (LTC or end stage chronic illnesses or moderate cognitive impairment or 21 ADL impairments), the ADA cautions clinicians to avoid reliance on A1c and states that glucose control decisions should be based on avoiding hypoglycemia and symptomatic hyperglycemia. (Some prospective studies have shown an increased death rate among older adults whose Hgb A1c was less than 7.4%). Of note, the one study that reported on the relationship between Hgb A1c levels and diabetic foot ulcer healing after application of a CTP found that the baseline Hgb A1c level at the time of initial CTP application did not matter in healing of the DFU. What mattered was whether the Hgb A1c level improved or worsened over the 12-week study time frame. The implication is that baseline A1c levels are less important than control of glucose levels during the time of treatment with the CTP and other therapy to heal the DFU (Marston et al, Ostomy Wound Mgmt 2006;52:26-32). The commenters recommend that this section of the LCD be revised to comport with clinical evidence as well as with clinical practice recommendations by the ADA and the National Committee on Quality Assurance. The Alliance cited four references with their comment.

An eighth commenter asserts the proposed utilization guidelines and limitations make no mention of A1c or ABI thresholds and limits. In addition to use of toe pressures in lieu of ABI nor compression levels in secondary dressings. If the policy intends to enforce certain limits in clinical documentation reviews, then those limitations should be published in the LCD clearly under utilization guidelines. Currently there is some mention in the AHRQ and clinical documentation review cited in the policy but it is unclear if those limits will be enforced by the policy.

A ninth comment from a certified wound specialist signifies there is ample evidence to show that there is no difference in wound healing with a tightly controlled hemoglobin A1c, and sufficient evidence that healing actually took longer in those with a tightly controlled hemoglobin A1c. Also, a meta-analysis from John Hopkins in 2020 showed the glycemic control in DFUs is not associated with wound healing. 1) Fesseha, Betiel K., et al. “Association of hemoglobin A1c and wound healing in diabetic foot ulcers.” Diabetes Care 41.7(2018): 1478-1485 2) Markuson, Melanie, et al. “The relationship between hemoglobin A1 values and healing time for lower extremity ulcers in individuals with diabetes.” Advances in Skin and wound care 22.8 (2009): 365-372. 3). “Glycemic control and diabetic foot ulcer outcomes. A systematic review and meta-analysis of observational studies.” Journal of Diabetes and its Complications 34.10(2020): 107638. Hemoglobin A1c is only reimbursable every 90 days, adding cost to the patients for a lab draw that is not a significant factor in improving or delaying outcomes in the interim. The ADA recommends a hemoglobin A1c goal of 8-8.5% for older patients with complex medical issues. Tightly controlled hemoglobin A1c in elderly patients with multiple comorbidities increases the chance of life-threatening hypoglycemia and subsequent cardiac and neurological events. 1) Qaseem, Amir, et al. “Hemoglobin A1c targets glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians.” Annals of internal medicine 168.8(2018): 569-576. 2) Cho, Nam Han, et al. “Managing older people with type 2 diabetes.” (2013). 3) Frier, Brian M. “Hypoglycemia in diabetes mellitus; epidemiology and clinical implications.” Nature Reviews Endocrinology 10.12 (2014): 711-722. 4) American Diabetes Association; Older Adults; Standards of Medical Care in Diabetes-2021. Diabetes Care January 2021; 44 (Supplement_1): S168-S179. Nine references were cited with this comment.

A tenth commenter signifies they do not observe any hard requirements regarding Hemoglobin A1c within the Indications, Limitations, Utilization Management, or Documentation. However, the section Evidence-Based Guidelines for Standard of Care references “Adequate glycemic control of hemoglobin A1c (HbA1c < 7%).” We are aware of providers who are worried this represents a predicate for initiation of advanced treatment with skin substitutes. Provider confusion can translate into reduced services to patients. As well, if providers are reading this as a limitation, future readers such as Medicare auditors may form the same impression and apply criteria that does not exist in actuality. Many of the well-designed RCTs for skin substitutes (as recognized by the 2020 AHRQ Technology Assessment) included patients with HbA1c as high as 12% (and sometimes above). While lower A1c levels are better for the patient overall, there is no research indicating skin substitutes will not work in these populations. A 2015 paper published in the Undersea and Hyperbaric Medicine Journal reviewed the available literature to determine if there was any direct correlation between the HbA1c level and healing of a diabetic ulcer. After reviewing 25 studies, it concluded that no direct correlation existed between the level of the HbA1c and the ability of a diabetic ulcer to heal. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the ADA. There was no RCT data demonstrating that HbA1c ≤ 7% improves diabetic wound healing. These findings support the clinical experience of practicing wound care physicians. The commenter requests that the LCD provide clarification that diabetes should be managed and HbA1c levels addressed, but that there is no threshold prior to skin substitute application. If a hard number is preferred, many policies offer HbA1c <12% based on research inclusion/exclusion protocols.

An eleventh commenter noted appreciation that the proposed LCD avoids the use of discrete values for tests as cutoffs for limitations as they recognize the presence of warranted clinical variability in individual patients and the requirement to individualize care to optimize patients. For instance, the commenter supports the absence of a hemoglobin A1c cutoff in the proposed LCD. It is recognized that tight glycemic control in the elderly diabetic population can lead to hypoglycemia, which in turn has known consequences of increased mortality.

A twelfth comment from the Pennsylvania Podiatric Medical Association indicates that glycemic control criteria will markedly increase the amount of time that it will take to get a patient approved for a graft.

A thirteenth comment from a wound care physician indicates that patients with elevated A1cs have a very difficult time resolving wounds; grafts are one of the only ways to give them a chance at healing while they are attempting to bring down their A1c.

A fourteenth comment from a podiatrist states: “Stringent A1c criteria of less than 7%, some patients despite care by endocrinologists can’t get that A1c down below a 7, this is also a three month average so to delay care of a wound for three months with the use of advance tissue products would increase morbidity and mortality.”

A fifteenth comment from a podiatric surgeon indicates the requirement of hemoglobin A1c lower than 7 is a moot point because the non-healing diabetic foot wounds they see are rarely going to have an Hgb a1c under 7. Two references were cited with this comment.

A sixteenth commenter does not agree that patients with a hemoglobin A1C greater than 7% should be denied access to advanced wound care. Diabetic patients in the wound community rarely have an HbA1C at that level due to high levels of noncompliance; therefore, placing a skin substitute that does not require patients to adhere to dressing changes daily gives them the highest chance of healing.

A seventeenth comment from the Alliance indicates that among diabetics, controlling HbA1c may reduce long term complications if implemented early. However, among Medicare beneficiaries with diabetes, HbA1c should be interpreted with care.

An eighteenth comment from a podiatrist indicates the proposed restrictions on A1c may also prove to be very difficult for many diabetic patients who are rendered partially or completely immobile due to their foot wounds, thereby making it virtually impossible to achieve an A1c <7%. Perhaps an A1c <8% would be a more realistic criteria as this is used in the scheduling of elective procedures.

Thank you for the comments. The ‘Covered Indications’ section of the proposed LCD, in the 2nd open bullet under bullet #2, provides various standard of care treatment measures (not an all-inclusive list) that includes a review of current blood glucose levels/hemoglobin A1c (HbA1c). The term ‘conservative wound care’ noted in the proposed LCD has been revised to ‘standard of care treatment’ in the finalized LCD. Standard of care treatment measures should be documented in the medical record. In the proposed LCD, the sixth paragraph in the ‘Evidence-Based Guidelines for Standard of Care’ section under the ‘Summary of Evidence’ references an article by Hingorani et al (2016) that includes recommendations such as those for adequate glycemic control. The recommendation in this article states: “We suggest adequate glycemic control (hemoglobin A1c < 7% with strategies to minimize hypoglycemia) to reduce the incidence of diabetic foot ulcers (DFUs) and infections, with subsequent risk of amputation (Grade 2B).”

The finalized LCD will be revised to remove the reference to “HbA1c <7” to avoid any confusion. The intent is to emphasize the importance of adequate glycemic control of hemoglobin A1c to reduce the incidence of diabetic foot ulcers and infections.

For comments and responses referring to ABI language in the proposed LCD, please see comment #9.

Comments were received regarding the language in the ‘Covered Indications’ section of the proposed LCD under bullet #2 which states: “For purposes of this LCD, conservative wound care measures include, but are not limited to: For patients with a VLU - assessment of clinical history (prior ulcers, thrombosis risks), physical exam (edema, skin changes), ABI, diagnostic testing to verify superficial or deep venous reflux, perforator incompetence, and chronic (or acute) venous thrombosis. In this regard, venous duplex ultrasound is recommended to confirm the Clinical class, Etiology, Anatomy, and Pathophysiology (CEAP) classification and categorize the patient’s chronic venous disorder to guide the analysis of management alternatives. The Venous Clinical Severity Score (VCSS) is used to assess changes in response to therapy.”

A comment from the WHS denotes this language indicates ‘recommended’ but asks if a provider does not perform these assessments and documents the results in the file would the CTP be denied. They request clarification and indicate that all patients with a venous ulcer are a CEAP-6. The VCSS is not needed to assess response to the treatment of an active venous ulcer.

The WHS also comments regarding a sentence in the third paragraph of the ‘Evidence-Based Guidelines for Standard of Care’ section under the ‘Summary of Evidence’ in the proposed LCD that states: “The patient is considered to have impaired arterial perfusion when the ABI is below 0.9.” The commenter indicates there is a level of uncertainty as to where this number came from since no evidence or literature is provided to support this number. The WHS requests clarification as to how this number was reached and the evidence to support it. The majority of clinical trials of CTPs included patients with ABIs lower than 0.9, typically with an exclusion at < 0.7 or <0.8.

A second comment from a wound care physician indicates if a patient has palpable pulses, and your LCD mandates an ABI study prior to use of the product, delaying care is needless and increases cost.

A third comment from a podiatrist indicates that while diagnostic services and lab values are important to monitor and track while treating DFUs or VLUs, specifically ABI studies, there may be nothing that can be done to improve this and many patients who have poor blood flow need all the advanced care that they can get in order for them to heal difficult wounds. Patients with poor circulation do not require much trauma to create a wound, but once they have a wound, at times it is exceedingly difficult to heal and requires all the tools that are available.

A fourth comment from the Alliance specifies that it is appropriate for a patient with a DFU to have appropriate assessments. However, it does not matter whether a patient has Type 1 or Type 2 or any other form of diabetes in order to conduct the assessment. Rather diabetic management assessment is appropriate. Furthermore, the policy states that a review of ABI is required but does not provide what the cut off is and evidence to support that number. Since 2014, CMS has approved a quality measure requiring arterial assessment of all wounds and ulcers of the lower extremity and, per this CMS approved measure, acceptable assessments include ‘ABI, TBI, skin perfusion pressure, and transcutaneous oximetry’ (https://uswoundregistry.com/quality-measures/). While the standard of care is arterial screening, no one non-invasive method has been proven to be superior and the method may have to be adapted based on clinical/patient factors.

The commenter suggests the following language: “For patients with a DFU - diabetic management assessment and management history with attention to certain comorbidities (e.g., vascular disease, neuropathy, osteomyelitis), review of current blood glucose levels/hemoglobin A1c (HbA1c), diet and nutritional status, activity level, physical exam that includes non-invasive arterial assessment with methods such as ABI, TBI, skin perfusion pressure or transcutaneous oximetry." One reference/link was cited with this comment.

The Alliance also indicates the proposed LCD appropriately identifies that VLUs by definition are ulcers which have an underlying problem with venous return and that evaluation and treatment of this venous disease should be addressed in addition to the topical treatment of the ulcer. However, the language provided in the draft is confusing in its discussion of the CEAP classification system and lacks necessary details in regard to the venous ultrasound study which is required for the assessment of patients with VLUs. A common error is to obtain a “rule out DVT” ultrasound which does not provide information on reflux. Since there is clear evidence that treatment of superficial venous reflux hastens healing of VLUs, in suitable candidates (EVRA trial), we support the requirement for early venous testing. However as there is likely additive benefit to venous interventions and application of CTPs, and certainly no data to guide sequencing of these therapies, the use of CTPs should not be predicated on prior correction of venous disease. We hope that the proposed revision will encourage the appropriate evaluation and treatment of venous disease while at the same time allow for appropriate access to CTPs for the benefit of VLU patients. Also, all patients with a venous ulcer are a CEAP 6. The VCSS is not needed to assess response to the treatment of an active venous ulcer. Usually, healing is the way VLUs area is assessed. Classic venous duplex ultrasound will assess for deep venous thrombosis. Special techniques need to be employed to assess for venous insufficiency and reflux. This is an entirely different test with a different order to the hospital vascular lab. The Alliance does not believe that the language provided provides clarity and as written there are access ramifications for patients in rural areas as well as low-income neighborhoods where some of these assessment tools are not available. One reference was cited with this comment.

The Alliance suggests the following language: “For patients with a VLU - assessment of clinical history (prior ulcers, thrombosis risks), physical exam (edema, skin changes), ABI (to assess for a peripheral arterial component), and venous testing to identify superficial or deep venous reflux, perforator incompetence, and chronic (or acute) venous thrombosis. In this regard, venous duplex ultrasound with provocative maneuvers to examine reflux (compression and rapid release, standing or in reverse Trendelenburg position) is indicated. These history, physical examination, and testing results allow for classification according to the CEAP Classification system (Clinical class, Etiology, Anatomy, and Pathophysiology) which guides the analysis of management alternatives. The Venous Clinical Severity Score (VCSS) is used to assess changes in response to therapy.”

A fifth comment from Vohra Wound Physicians indicates the proposed LCD lists but fails to define what ABI value(s) are acceptable, what alternatives to ABI are acceptable, and does not specify the time frame in which a study should be obtained in temporal relation to the application of a skin substitute graft. Vague guidelines such as these do not provide adequate guidance to clinicians and create the scenario where different constituents may interpret the application of these criteria differently. A variety of methods should be published to assess and document arterial sufficiency and leave the medical interpretation and diagnosis of adequate arterial supply to the clinical decision making of the provider (ABI, toe pressures, duplex ultrasound, history of successful revascularization or intervention, etc.). Similarly, to an ABI, the LCD lists a specific criterion related to VLU. Specifically, the draft lists “diagnostic testing to verify superficial perforator incompetence and chronic (or) acute venous thrombosis” and “venous duplex ultrasound is recommended.” Does this requirement mean only patients with active saphenous vein reflux, perforator incompetence or deep vein thrombosis meet medical reasonable and necessary criteria? Fully treated incompetence, reflux, or thrombosis? No incompetence, reflux, or thrombosis? Do patients without duplex ultrasound documentation meet the “criteria”? What other “diagnostic testing” are contemplated to meet these coverage criteria? Providers should be given the ability to choose when and what assessment of potentially contributing venous disease, in their medical opinion, is required. Providers should also be allowed to determine to what extent these assessments would preclude the wound from healing and be allowed to determine which findings of an assessment would contraindicate wound treatment with a skin substitute graft.

Thank you for the comments. The sentence referenced in the comments is from an article by Frykberg (2015) (cited in the proposed LCD) which states: “…when the ABI is below 0.9, the patient should be considered to have impaired arterial perfusion.” The finalized LCD will be revised to remove this sentence to avoid any confusion.

The ‘Covered Indications’ section of the LCD provides a bulleted list of conservative wound care measures. The finalized LCD has revised this language to: ‘standard of care treatment’. This list of recommendations includes an ABI, etc. for assessment of a VLU. This paragraph has been revised to delete the following language: “In this regard, venous duplex ultrasound is recommended to confirm the Clinical class, Etiology, Anatomy, and Pathophysiology (CEAP) classification and categorize the patient’s chronic venous disorder to guide the analysis of management alternatives. The Venous Clinical Severity Score (VCSS) is used to assess changes in response to therapy.”

The intent is to emphasize the importance of a vascular examination to ensure adequate circulation/oxygenation to support tissue growth/wound healing. These are recommendations, not requirements and this is not an all-inclusive list as noted in the LCD. It is expected that the provider will perform the necessary examinations and/or diagnostic tests appropriate for the patient’s condition.

A comment from the American Vein and Lymphatic Society underscores the importance of early assessment of conditions contributing to VLU that is essential to make decisions regarding appropriate care. They note the New England Journal of Medicine article of 2018, A Randomized Trial of Early Endovenous Ablation in Venous Ulceration. This landmark article underscores that VLUs will heal faster and more durably with prompt venous intervention versus conservative therapy alone. Unfortunately, some patients who are diagnosed with VLU do not undergo objective testing to determine the presence or severity of venous disease that might be treatable. The commenter recommends revision of the LCD to require early venous color duplex ultrasound evaluation of the affected limb(s) with Doppler reflux testing with the patient standing whenever feasible and, otherwise, with the limb(s) in a dependent position. The commenter suggests that the venous evaluation should be performed no later than four weeks after presentation to a wound center unless extenuating circumstances exist.

Thank you for the comment. As noted in the response for comment #9 regarding standard of care, the intent is to emphasize the importance of a vascular examination to ensure adequate circulation/oxygenation to support tissue growth/wound healing. These are recommendations, not requirements and this is not an all-inclusive list as noted in the LCD. It is expected that the provider will perform the necessary examinations and/or diagnostic tests appropriate for the patient’s condition. Therefore, the finalized LCD will not be revised as suggested.

Comments were received regarding the ‘Covered Indications’ section of the proposed LCD for the fifth closed bullet under bullet #3: “If the patient meets all of the criteria as outlined in this LCD, application of a skin substitute graft for lower extremity DFU or VLU is considered medically reasonable and necessary for the following: An implemented treatment plan demonstrating the following: Patient is a nonsmoker or has refrained from smoking for at least 6 weeks prior to planned skin replacement surgery or has received counseling on the effects of smoking on surgical outcomes and treatment for smoking cessation.”

A comment from a physician indicates that as a cardiovascular specialist with experience in managing patients with peripheral arterial disease, including percutaneous interventions, he is concerned that patients with failed revascularization and continued smoking will not benefit from skin grafts for non-healing ulcers. The literature doesn't specifically address this subset in a statistically significant fashion.

A second commenter expresses that smoking cessation is a sensitive subject that he brings up on a daily basis to his patients. However, it’s almost impossible to get them to listen and comply. Do we abandon the patient for doing something that is known as legal? These are adults and although smoking cessation is something he advocates for, it is not a reason to treat the patients with substandard care. Imagine if we just fired them and stopped their care altogether. How many legs would be amputated and how much would it end up costing the system.

A third comment from a podiatrist indicates that a restriction to care is being proposed on caregivers for smoking cessation of six weeks prior to graft placement.

A fourth commenter indicates that the proposed LCD suggests that smokers should not receive skin substitutes.

A fifth comment from a wound care physician indicates that although most patients are able to cut back on their smoking, it is unrealistic for them to quit smoking all together. She has had numerous patients who go on to heal with graft applications regardless of their smoking status. She does not believe that it is medically ethical to deny a patient a limb or lifesaving treatment because of this.

A sixth comment from a podiatrist states: “Smoking cessation at least 6 weeks prior to use, again the delay of care for these wounds will increase morbidity and mortality.“

A seventh comment from the Pennsylvania Podiatric Medical Association denotes that implementation of tobacco use restrictions will markedly increase the amount of time that it will take to get a patient approved for a graft.

An eighth comment from the WHS indicates that the increase in the smoking cessation timeframe prior to the use of a CTP to six weeks is not only problematic it is not based on any evidence cited in the LCD.

A ninth comment from a wound care physician expresses concern that this recommendation will turn into a mandate to stop smoking, which can take months and years which would most certainly be an unrealistic demand as to when to start using wound care products on a patient. He agrees that the discussion should happen, and that will continue to be the case in his practice. He has never liked the idea of anyone withholding care due to smoking, except when the procedures are purely elective.

A tenth comment from the Alliance and the Coalition indicates that although it is very well documented that smoking impairs wound healing, the actual time required for smoking cessation to reverse the effects on wound healing is not known. Unless evidence can be cited to support this language it needs to be removed. The Alliance agrees and supports counseling patients on the effects of smoking on surgical outcomes. The following language is suggested: Patient is a nonsmoker or has received counseling on the effects of smoking on surgical outcomes and treatment for smoking cessation. Five references were cited with this comment.

An eleventh comment from a podiatrist indicates the smoking cessation requirement is a fair and clinically valid restriction.

Thank you for the comments. To avoid confusion, this bullet has been revised in the finalized LCD to: “Documentation of smoking history, and that the patient has received counseling on the effect of smoking on surgical outcomes and treatment for smoking cessation (if applicable) as well as outcome of counselling (if applicable).”

Comments were received regarding language in the ‘Covered Indications’ section of the proposed LCD for bullet #7: “The patient is under the care of a qualified physician/NPP for their underlying chronic condition.”

A comment from the WHS and the Alliance inquires if this means that the patient must be seen by an endocrinologist for the DM or a vascular surgeon for their venous disease, can the patient see internal medicine or a family doctor or if the wound center does the vascular studies and there is nothing to do surgically to optimize from a venous structural standpoint, does the patient have to see a vascular surgeon to confirm or can they just read the studies.

A second comment from a wound care physician indicates that he has many patients who come to their center who have no provider before they see them. He signifies that he does not want to withhold care from them while they are in the process of getting established with someone that they would refer them to. They do get these patients to the specialists that they need for their comorbidities (Vascular surgery, Endocrinology, Internist, Cardiology), but it can take weeks and/or months to get an appointment to see these providers.

Thank you for the comments. This covered indication has been revised in the finalized LCD for clarification to: “The patient is under the care of a qualified physician/NPP for the treatment of the systemic disease process(es) etiologic for the condition (e.g., venous insufficiency, diabetes, neuropathy).”

Many comments were received regarding the ‘Limitations’ section of the proposed LCD, for bullet #1: “Greater than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care (defined as 12 weeks from the first application of a skin substitute graft) are not medically reasonable and necessary:”

One commenter asks why only two applications would be allowed during a 12-week period. Previously, 10 applications, applied weekly during a period of 12 weeks from the first application of the skin substitute graft was allowed.

A second comment from a wound care physician indicates it has already been well-established through clinical trials that advanced wound care interventions improve outcomes and reduce overall costs as compared to standard of care. Used appropriately, skin substitutes should be applied weekly to change the wound healing trajectory. Several applications (>2) are often necessary to achieve the desired outcome. It is not unusual to see a significant lag in positive wound change after application of a tissue product. Expecting all wounds to achieve the expected outcome from tissue application after two weeks (two applications) is unrealistic. Applying only two tissue products to a wound across a 12-week period is clinically and economically unsound and wasteful.

A third comment from a physician indicates that the proposed new LCD requirement limiting the use of skin substitutes to only two applications is not based in any scientific principle. No wound heals with only two applications. If that were the criteria, this becomes a useless option for complicated wounds, and will result in the need for more wound care, more wound products, more time to treat, and additional costs.

A fourth comment from a podiatrist indicates he manages diabetic foot ulcers and has extensive experience with various wound care products and grafts. He signifies limiting graft applications to just two would eliminate the whole point of doing them because in most instances, it takes four to five serial applications before any improvement is noted.

A fifth comment from a wound, ostomy, continence nurse practitioner denotes her objection to the proposed LCD/LCA that would limit the number of skin substitute applications to DFU/VLU to two. There is a large body of evidence to support skin substitution applications up to 10 times over the course of 12 weeks. Chronic wound care patients often require weekly visits to heal their wounds. Even standard of care when followed strictly will only heal wounds less than half the time. Additionally, these patients are often admitted to inpatient for infection, amputations, and sepsis.

A sixth commenter indicates it is about time reimbursement is limited for skin substitutes. Far too many non-expert wound providers use these products as a money-making tool to cover for the fact that they don't know Woundology therefore they can't heal wounds or determine whether or not a wound is in fact palliative in nature. There are far too many times a CTP is used on a palliative wound which is a complete waste of insurance/government dollars. Skin subs/CTPs are essentially an expensive collagen (some with growth factors which may assist in some ways). Collagen is far too often a sacrificial element of a wound dressing to mitigate the inflammation associated with elevated MMP's. Thousands of dollars don’t need to be paid for CTPs when there are less costly and equally effective products available and when wound science has evolved to the point of understanding how to control these elevated MMP's in the first place.

A seventh comment from a podiatrist indicates that to restrict the application amount to two applications per patient is a disservice to both the patient and the products we use. Research has shown many of these wounds, which have already failed standard of care therapy, require multiples of repeat application to show a change in quality and size of wounds, moreover many of which require 10+ to close. This is over months of therapy. To truncate the treatment window would open opportunity for further delays in healing rates, thus increase infection rate, hospitalization, amputation etc. as well as cost. The current guidelines regarding application amount support the literature and the commenter believes it should remain the standard.

An eighth comment from a podiatric surgeon indicates he has been doing advanced wound care for over 15 years and utilization of skin substitutes has been an indispensable tool in his treatment. These advanced tissue products heal wounds and also reduce hospitalization time and morbidity. The current proposed LCD will greatly limit the ability to treat these patients by restricting it to two applications. Most of these products require multiple applications to achieve closure of wounds. It is important to understand that these patients are very complicated and have not been able to heal with traditional methods. Limiting applications to only two may lead to prolonged hospitalization and possible amputation of the lower extremity. The cost of these products is high and utilization needs oversight. However, it should be noted that the cost of prolonged hospitalization with amputation of limb and prolonged subacute rehab stays, prosthesis costs and home health dwarf the cost of these products. The commenter strongly opposes the restriction of utilization of these products to help heal the wounds of our most vulnerable patients.

A ninth commenter indicates some non-healing wounds can achieve complete closure with one or two applications of a skin substitute, each chronic wound and patient have unique characteristics that require individualized treatment. In published clinical trials, the average time to healing for wounds treated with various skin substitutes was four to six weeks. In the majority of trials, skin substitutes were applied weekly or bi-weekly. The average number of grafts to achieve complete closure in skin substitute treatment arms ranged between 2-12, with most trials reporting an average of four to six grafts applied. Therefore, the limitation of two graft applications is inconsistent with clinical trial evidence and clinical experience. One reference was cited with this comment.

A tenth comment from a podiatrist indicates he has applied a number of different skin substitute grafts over the years with moderate success rates. In the right situation, there is nothing else comparable and indicates that we absolutely need to keep using them. The cost is high and he tries to be prudent with his use. In his experience, the average patient needs about five applications and indicates this is true for the successful patients, but also, if the graft is not going to work, it often takes three or four grafts over four weeks to determine that decision. The commenter supports setting the limit of grafts at six or eight, but not limiting it to two.

An eleventh comment from a podiatrist indicates limiting skin substitutes to only two applications would be a gross disservice to patients. Additionally, it would render these products worthless to patient care. The diabetic patient population is already underserved. Limiting access to care-altering wound care products sends a simple message that you don’t care. Anybody who utilizes skin substitutes regularly knows it takes several applications before you see significant wound contraction. The commenter indicates that progress is not seen until the third or fourth application, and then relatively rapid improvement/contraction is seen. By utilizing these products amputations are prevented.

A twelfth comment from a podiatrist indicates he has used a variety of skin substitute products on very high-risk patients, many who are not candidates to go to the OR for split thickness skin grafts or similar. After using hundreds of these grafts, on many challenging patients over several years, the commenter indicates that never once has a patient had a lower extremity wound, even in ideal conditions (young, healthy trauma patient with clean wound bed and no arterial insufficiency) heal with two skin substitute applications. It does not matter which product. Two applications of these grafts usually do not even bring a wound down in size 50%. At a bare minimum, four or five applications are needed of these grafts before they start making a major difference on the wound bed (and they do). Generally, after seven or so applications the wound is either healed or close enough to discontinue treatment. Limiting these grafts to two applications would cause a huge injustice to patients, many at which are high risk, and increase limb loss. Furthermore, it will increase OR costs, as now surgeons will be forced to take patients to the OR for either STSG or for biologics. The commenter highly recommends that at a bare minimum, five to seven grafts be allowed.

A thirteenth comment from a podiatrist indicates the proposed changes to treatment of DFU and VLU will only lead to increased cost to CMS and increased morbidity for patients and will do nothing to enhance care. He has been treating wounds for 25 years and there is no doubt that use of advanced wound products have helped him close wounds which otherwise would have gone on to amputation. Limiting skin substitutes to two per 12-week period would be a waste of product. This limitation does not take into account the size of the wound and the need for continued use of skin subs to aid in wound closure. There are no medical studies cited in the proposed LCD to justify this change.

A fourteenth comment from a wound care specialist physician indicates that in his experience, weekly applications of skin substitute are necessary in most cases. The delivery of growth factors to a wound or ulcer needs to be ongoing as with chronic ulcerations the healing mechanisms are impaired, and the use of skin substitutes provide the biological help these ulcers need to heal. Patients that for some reason could not receive weekly applications because they lived far away from the clinic or due to other reasons tend to heal less than those that receive weekly treatments. The commenter is convinced that limiting to only two applications will harm wound care patients leading to more delayed healing times, exposing the wounds/ulcers to a higher risk of infection. Also, he agrees, not all wounds will require the maximum number of applications. He can tell from experience that several patients will not need more than five out of ten but there are some that show sustained improvement but due to the size of the wound they will require a lengthier treatment.

A fifteenth comment from three wound care physicians and four wound care nurses indicates two applications would greatly limit the healing capacity in these patients. Skin substitutes work wonders and go a long way in helping the patient heal an open wound and prevent limb loss and hospital admissions. The commenters are aware skin substitutes can be expensive however in the long run they absolutely save the healthcare dollars by preventing below the knee amputations (BKAs) and hospital admissions by closing an open wound quickly to prevent infection. They indicate two applications is not even close to achieving this goal.

A sixteenth comment from a podiatrist indicates she treats diabetic foot wounds and has read the peer reviewed studies on use of the various wound grafting materials. She has not seen in the literature or in her experience proof that two grafts are successful in healing the vast majority of diabetic foot ulcerations. Arbitrary limitations on the use of these materials would likely just lead to failure, which means that the two grafts used would be a complete waste of resources. Restricting these grafts will ultimately lead to more limb loss, hospitalizations, need for prosthetics and shorter life spans.

A seventeenth comment from a podiatrist indicates the use of skin substitutes has greatly enhanced our ability to heal diabetic foot ulcerations. He recommends that the same policy of allowing 10 be continued given that most diabetic ulcers take greater than two months to heal.

An eighteenth comment from a certified wound care physician indicates he treats patients with complex, challenging, difficult to heal ulcers and wounds in a busy outpatient wound care clinic. They frequently utilize skin substitutes on patients when traditional wound care has failed with great success. While limiting the application of skin substitutes to a quantity of two will likely save money initially, it will almost certainly cost Medicare and our patients more over time. The longer that an ulcer or wound remains open, the more likely that patients are to get infection and progression of the ulcer or wound. This often results in hospitalization, extensive treatments including imaging, IV antibiotics, surgery, more morbidity, and occasionally even death. The commenter requests that skin substitutes not be limited to a quantity of two.

A nineteenth comment from a wound care provider asserts that limiting the application of skin substitutes to two will be like limiting the chemotherapy to two treatments to a cancer patient. He has had patients with chronic wounds for years that have benefited from the skin substitute and rarely two applications were enough. He agrees that the clinician should apply the minimum necessary to get the ulcer to a manageable state where we can use less expensive material but disagrees with the proposal to limit the application of skin substitutes to two.

A twentieth comment from a physician indicates the limitation for more than two applications is not supported by either the literature or his clinical experience. The articles referenced in the summary of evidence do not support the proposed application limitation, since more than two applications were needed to achieve closure in all the articles that were discussed. Barbul needed an average of 2.9 applications, Lavery required an average of six applications for closure, Sanders needed either four or nine applications depending on treatment type, and Zelen necessitated an average of 4.7 applications for wound closure. In addition to the articles in the proposed LCD, David Armstrong recently published a retrospective review of the Medicare Database, which found that an average of 4.9 applications were required for wound closure. The numbers presented in the articles all align to his clinical experience, with the majority of his chronic wound patients requiring between five and seven applications of an advanced skin substitute to achieve closure. He has had some patients with wounds that heal in fewer applications and other patients with wounds that take up to 10 applications to achieve wound closure. He indicates the LCD should continue to allow up to 10 applications provided that the wound is progressing towards closure. A similar comment was received and indicated that the skin substitute literature supports that more than two applications may be required to achieve the clinically meaningful outcome and they believe the number and frequency of applications should remain at the discretion of the clinician, understanding indication requirements, as well as utilization review. This comment cited eight references.

A twenty-first comment from a wound care physician indicates that in patients with underlying co-morbidities and old age, they often have a very hard time to heal and hence these skin substitutes come in very handy to help as an adjunctive treatment to all the advanced wound care provided in their wound care center. It takes up to 10 applications and sometimes many more to help heal these chronic wounds. Limiting the applications to two is going to be insufficient to help heal these wounds. Four articles were included with this comment.

A twenty-second commenter indicates the number of applications within a period of weeks should consider the progression of a wound’s closure which in turn depends on the wound type and initial size as well as the patient’s medical case to be evaluated by the clinician using the instructions for use as an aid. A fixed number of allowable applications with 12-weeks risks replacing sound clinical practices as it goes against existing clinical evidence. Wound healing outcomes were assessed in large propensity-matched cohorts in patients receiving advanced treatment (AT) with skin substitutes for lower extremity diabetic ulcers obtained from The Medicare Limited Dataset (1 October 2015 through 2 October 2018). The average number of applications was found to be 3.7 if followed according to instructions for use.

Level 1 (multiple randomized controlled trials and systematic reviews) and real-world evidence demonstrate that repeated application can result in improved probability of wound closure or reduction in wound size, significant reductions in major and minor amputation, ED use, hospital readmission, cost of care, ulcer recurrence and mortality. Following instructions for use parameters to achieve these results and not restricting number of applications against clinical judgement or existing practice is essential to achieve these results. However, repeat or alternative applications of skin substitute grafts should not be considered medically reasonable and necessary when a previous full course of applications was unsuccessful. Unsuccessful treatment is defined as increase in size or depth of an ulcer or no change in baseline size or depth and no sign of improvement or indication that improvement is likely (such as granulation, epithelialization, or progress towards closing) for a period of four weeks past start of therapy. Retreatment of healed ulcers, those showing greater than 75% size reduction and smaller than 0.5 square cm, is also not considered medically reasonable and necessary. Four references were cited with this comment.

A twenty-third comment from a physician, twenty-one podiatrists, and a nurse practitioner indicates concern regarding a limit of two applications as this proposed limit would likely exclude patients who are most often in need of more advanced wound treatment and would meet the criteria for additional applications. In as much, this limit would also negate or disregard clinical judgement and decision making from providers that treat patients with chronic wounds.

A twenty-fourth comment from a podiatrist affirms she has been treating patients with diabetic foot wounds and venous leg wounds during her career and has seen great results with graft applications. On average, she has been applying five to six grafts per patient. The proposed 2 applications in 12 weeks is unreasonable as this barely scratches the surface of putting these patients on the right path. The commenter strongly disagrees with this proposition.

A twenty-fifth commenter asserted that despite aggressive therapy with debridements, revascularization, offloading and compression, depending on the case of the diabetic and venous insufficiency, patients don’t always heal with one or two grafts. Although most do, limiting the number of grafts could represent the difference between a healed wound or a patient in the clinic for months. Not to mention the fact that these products were approved based on the data submitted after their studies and all of them were done with once weekly applications. This could lead to non-healing due to lack of appropriate dosing based in their prescribing recommendations.

A twenty-sixth comment from eight wound care physicians, five wound care nurses and two stakeholders indicates that placing a cap of two skin sub applications on this advanced wound healing modality is overly restrictive and limits access to care. It appears that the LCD has taken a narrow view of the number of applications in articles cited when the majority of literature shows that utilizing more applications in their treatment have positive results compared to standard care. The number and frequency of applications should remain at the discretion of the clinician, understanding indication requirements as well as critical utilization review. As clinicians seeing and caring for these patients with challenging wounds and comorbidities, every tool is necessary to achieve positive outcomes. Limiting skin subs to two applications is upsetting since it sometimes takes multiple to heal wound. This will delay wound healing more.

A twenty-seventh commenter indicates that although there are published RCTs referenced in the draft LCD that support the two-application limitation for wounds treated in outpatient sites of service, those trials have limitations when applied to real-world settings, including: (1) none of these studies report the closure of 100% of study patients’ wounds; and (2) none of the studies include larger and deeper chronic wounds that providers treat regularly. These trials, by their nature, are carefully controlled and exclude many patients (e.g., those with uncontrolled co-morbidities and/or associated wound sizes and depths), who are routinely seen in a typical outpatient site of service. Thus, results may not be generalizable to the Medicare population. Finally, some skin substitutes explicitly require more than two applications per their FDA labeling.

Given the lack of generalizability of the clinical data relied on in the draft LCD, the number of applications should not be limited to two across the board. Otherwise, providers may not continue treating patients with more complex wounds for the fear of being audited. More robust products perform well with biweekly applications. Thus, provided the wound has reduced in size after each of the first two applications, additional applications of up to a total of six over the 12-week course of treatment should be deemed medically reasonable and necessary, so long as the patients’ charts document that the wound is reduced in size between each additional application, up to six applications. If the LCD is finalized with a lower limitation than six, an exceptions process is requested for patients with a documented need for a higher number of applications.

A twenty-eighth commenter signifies proposing to limit CTP utilization to only two applications may create too may patient outliers and denials that may adversely affect patient care, particularly in wounds that are either large in size (i.e., > 25 sq cm) and/or more difficult to heal due to patient comorbidities. They anticipate that about 70% of lower extremity DFU and VLU wounds that are < 25 sq cm will heal with three to four applications when a clinically proven and effective product is first utilized. Meanwhile, there could be up to 30% of patients that require additional applications, or more than 12 weeks of care beyond the overarching policy utilization parameters. They suggest extending the application limit of CTP coverage to three to four applications per wound and suggest the use of the KX modifier to identify that wound(s) treated meet all documentation and support medical necessity for resource-intensive care, or services will be denied (e.g., patient required greater than three to four applications or greater than 12 weeks of care).

A twenty-ninth comment from six podiatrists indicates chronic wounds require time, dedicated treatment, consistent follow up and evaluation and in many cases several applications of skin substitutes to complete the healing process and prevent regression of a wound. In their experience, it is not only medically reasonable and necessary, but extremely common for chronic wounds to require more than the two applications provided for in the proposed LCD. The evaluation, assessment and treatment of the wound should remain the purview of the clinician treating the wound. Although it may be medically appropriate to treat a very small wound with two applications, more than two applications are often necessary when treating larger and irregular shaped wounds. It is their experience that these types of wounds consistently necessitate the application of more than two grafts based on the size, location and extent of the wound. Limiting applications to two grafts poses a threat to the patients’ ability to properly heal and regain function and exponentially increases the possibility of limb or tissue loss, particularly in larger and irregular wounds. As cited by the proposed LCD, diabetic foot ulcer wounds are associated with a high risk of limb amputation, with about 20 percent of moderate to severe diabetic foot ulcer infections leading to amputation. Mortality after amputation exceeds 70 percent at five years. As written, the proposed LCD would restrict access to a treatment that has proven to be highly effective and more cost effective than having a patient require multiple hospitalizations, multiple surgeries, antibiotic treatments and an increase in the costs of multispecialty care that arises when dealing with chronic non-healing wounds.

A thirtieth commenter signifies ten applications or treatments within a 12-week period is consistent with most other LCDs. The specific number of applications needed are not contained on any skin substitute product labeling and will vary significantly based on the patient’s clinical condition. Additionally, the proposed LCD does not cite evidence for this reduction in applications, and in many cases limiting applications to only two will significantly limit the ability for skin substitutes to be fully effective for patients. If the limitation remains at a maximum of two applications, there must be a process in place for providers to be able to obtain authorization prior to subsequent applications when medically necessary. There will always be outliers that fall outside these parameters. The decisions must be timely as providers will need to provide an advanced beneficiary notice (ABN) to beneficiaries for services that may not be covered by Medicare. The commenter recommends that the finalized LCD allow for up to ten applications in a 12-week period. A process should be created for providers to be able to obtain approval for additional applications regardless of whether the limit is two or ten.

A thirty first comment from a physician denotes a limit of two applications per wound would negatively impact needed patient care. This proposed limit of two appears to be random and unsupported in the referenced literature. This proposed limit excludes patients who are in need of more advanced wound treatment and meet the criteria for additional applications. In as much, this limit would also negate or disregard clinical judgement and decision making from providers that treat patients with chronic wounds. Individual patient wound assessments should be the basis for determining the most appropriate clinical care, particularly for consideration of advanced treatment options such as skin substitutes. While we agree there is a need for standardized coverage, each patient’s case is different, requiring a variation of treatments.

A thirty second commenter indicates there is no clinical basis for the proposed limitation of two applications. The clinical guidelines from the WHS on the treatment of VLU and DFU and the joint guidelines from the Society of Vascular Surgery (SVS), American Podiatric Medical Association (APMA), and Society for Vascular Medicine (SVM) on the treatment of DFU do not specify a recommended number of applications. The societies provide guidance about when wounds should be evaluated and changes in therapy considered but do not identify a maximum number of applications of skin substitutes. Depending on the assessment of the wound’s status (i.e., degree of improvement), three or more applications of skin substitutes are consistent with the guidelines.

All pre-market approval (PMA) skin substitutes have labeling that is consistent with more than two uses. Further, a limit of two applications is in conflict with data used to support each PMA approval for DFU and VLU products. For most skin substitute products, the FDA authorization is silent on the number or frequency of administrations, particularly products that are authorized as HCT/Ps and as 510(k) devices. For those products for which the FDA label does address the number of applications, primarily products that are authorized by FDA as PMA devices, there is a considerable range in the number of applications cited and data from the large RCTs supporting FDA approval of PMA products do not support limiting the use of skin substitutes to two applications. For example, data from the FDA approved labelling from the DFU pivotal trial for a bilayered living cellular construct, (Apligraf^®) show that 81 percent (91/112) of Apligraf- treated patients received between three and five applications of the skin substitute. The mean number of applications was 3.9, and the percent healed for the patients who received >2 applications was 41%. These RCT data showed that over 80% of the DFU patient population were not healed with one or two applications of a skin substitute and that three, four or five treatment applications were medically necessary to achieve complete wound closure. Data from comparative effectiveness research (CER) studies using real world data have demonstrated similar findings showing that use of >2 applications of skin substitutes (means ranged from 2.2 –5.0) are warranted.

A source that supports the proposed limitation to two applications is not identified and we are not aware of any study or guideline that recommends this restriction. Inclusion of such a limitation would arbitrarily restrict access to an important therapy and could impede appropriate care. This restriction could have significant negative consequences. Patients who are responding to skin substitute therapy but still have open wounds would have that therapeutic option eliminated, potentially halting the wound’s progress or causing it to regress. The longer wounds are open, the more likely a patient is to incur an infection, be hospitalized, or require an amputation. Not only could this restriction lead to dire clinical outcomes for patients, but it would also negate the benefit of the skin substitute applications that Medicare and the beneficiary have already paid for.

The proposed limitation to two applications is not supported by analysis of Medicare claims data. The Moran Company reviewed data for Medicare patients treated in the physician office in 2020. Most patients received one or two applications. A diminishing number of patients received between three to nine applications with an uptick in the number who receive the current maximum of 10 applications. The commenter indicates that any concerns about the appropriateness of a particularly high number of applications (e.g., more than ten) could best be addressed through medical review rather than applying an across-the-board limitation for all patients that will impose restrictions on medically necessary care. Twelve references were cited with this comment.

A thirty-third comment from a physician indicates it has been his experience that in the best of circumstances, it takes at least five or six applications for the skin substitute to be effective, and in most patients, it takes ten applications. There is already a restriction of a thirty day wait and less than 30% improvement of the wound before skin substitutes are applied and making this more restrictive will only adversely affect the outcome of wound healing even more. Failure of wound healing can have detrimental results on patients who already have complicated wounds which could possibly lead to more complications including amputations.

A thirty-fourth comment from a nurse practitioner indicates she has witnessed positive results using skin substitutes to treat wounds and studies have shown that it reduces amputations and costs. Studies have shown that once a diabetic has an amputation, they have a 50% chance of death in a five year period. The commenter requests reconsideration for the limit of two applications of skin substitutes.

A thirty-fifth comment from a physician indicates she typically sees some improvement in the first two applications, but the majority of the progress happens with repeated applications. She believes stopping applications prematurely can have a detrimental effect on the patients as well.

A thirty-sixth comment from the Texas Podiatric Medical Association (TPMA), the APMA, the Maryland Podiatric Medical Association (MPMA), the American Society of Plastic Surgeons (ASPS), the American Society for Surgery of the Hand (ASSH), and the New Mexico Podiatric Medical Association (NMPMA) strongly disagrees with this limitation that is not rooted in science and not supported by peer-reviewed literature and would certainly lead to poor outcomes for their patients. Evidence supporting more than two applications:

A paper published in the International Wound Journal in 2016 evaluated the clinical outcomes at 12 weeks in 100 patients with diabetic foot ulcers. The patients received weekly applications of popular skin substitutes (Apligraf versus Epifix) versus a collagen-alginate dressing (control group). More people in the skin substitute group achieved full healing at 12 weeks compared to the collagen-alginate group (73% healing at 12 weeks for Apligraf, 93% for Epifix and 51% for collagen-alginate). The median number of grafts used to achieve healing was six for Apligraf and 2.5 for Epifix, but graft applications ranged anywhere from one application up to 12 applications of skin substitutes before healing. This peer-reviewed literature supports the need for more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care. The following peer-reviewed literature supports the need for more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care.

• Raspovic et al performed a retrospective review of 350 people with diabetic foot ulcers with an average wound size of 5.1cm² who were treated with a skin substitute graft (cryopreserved placental membrane). Almost 60% of the wounds healed by a median of 42 days but required four graft applications to do so. The authors predicted that the likelihood of healing at 12 weeks was 71% with the treatment.
• DiDomenico et al also reported an improved healing rate for people treated with skin substitute grafts compared to standard-of-care treatment (85% versus 25%). In this randomized controlled trial, the average number of grafts used to achieve this outcome was 3.8.
• Similar results are echoed by other clinical trials which report successful and faster closure of wounds with the use of skin substitutes but note an average of 6.8 grafts to achieve this.
• Several other articles report greater than two graft applications being necessary to achieve healing, ranging from three to nine applications of skin substitute grafts.

The Society of Vascular Surgery and American Venous Forum’s clinical practice guidelines for management of VLUs suggest that reapplication of cellular therapy should continue “as long as the venous leg ulcer continues to respond on the basis of wound documentation.” These multi-society clinical practice guidelines refute the proposal that more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care is never medically reasonable or necessary. These guidelines also suggest the frequency of application of cellular therapy “remains at the discretion of the clinician.” These multi-society clinical practice guidelines refute the proposal that more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care is never medically reasonable or necessary.

The following peer-reviewed papers referenced in the proposed LCD evaluated the number of applications of different cell based wound dressings needed to achieve closure of chronic wounds and literature support the need for more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care:

The average numbers of applications needed to achieve wound closure included 2.15, 4.3, 1.68, 3.43, 1.24, 2.03, 3.23, and 3 (Pourmoussa, 2016). The average numbers of applications needed to achieve wound closure included 2.7, 3.1, 2.9, and 2.5 (Barbul, 2020). The average number of applications needed to achieve wound closure was 8.92 (Sanders, 2014). The average number of applications needed to achieve wound closure was 4.7 (Zelen, 2017).

In general, the findings detailed above generally reflect the mean or median number of applications required to achieve wound healing. However, these numbers reveal that a meaningful subset of patients required an even greater number of applications to achieve full wound closure. A limit of two applications would therefore significantly constrain practitioners treating patients with the most severe wounds from providing the care needed to support complete healing.

The draft LCD specifies that products are expected to be used per their labeling. However, the prohibition on the use of more than two applications places practitioners at risk of furnishing care inconsistent with product labeling. While the commenters agree that not every ulcer will require the maximum number of applications, they believe that products should be used in the manner and frequency specified by the manufacturer.

The robust body of evidence presented here supports the need for more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care and refutes the proposal that more than two applications of a specific skin substitute graft product within the episode of skin replacement surgery for wound care is never medically reasonable or necessary. Therefore, TPMA and APMA request that this proposed limitation be removed when this policy is finalized. Twelve references were cited with these comments.

A thirty-seventh comment from the Pennsylvania Podiatric Medical Association signifies that reducing the number of available skin substitute/allografts to only two applications will markedly hamper wound healing and lead to poorer outcomes and potential increase in amputation rates and the attendant cost of amputation. As a result, this will ultimately translate to higher treatment and system costs. Numerous studies prove the efficacy of applying allografts and reducing healing times in both diabetic and venous leg ulcers. When comparing various allografts in the treatment of venous leg ulcers:

• Serena et al concluded the average mean number of grafts to achieve complete healing was four applications and concluded a significant difference in healing rate when comparing weekly application of allograft versus every other week application. Healing rates were markedly slower when applying graft every other week (Zelen, CM; Serena, TE; Snyder, RJ). A prospective, randomized comparative study of weekly vs. biweekly application of dehydrated human amnion/chorion membrane allograft in management of diabetic foot ulcers. (International Wound Journal, 2014).
• Zelen et al concluded that after six weeks, there was an 8% healing rate with patients utilizing standard of care treatment versus 92% healing rate utilizing allograft tissue when treating diabetic foot ulcers (Zelen, CM; Serena, TE; Snyder, RJ). A Multi-center randomized controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts multi-layer compression therapy vs multi-layer compression therapy alone in the treatment of venous leg ulcers (Wound Repair Regeneration, 2014).
• When comparing the use of allograft versus collagen alginate dressing, Lulove et al, concluded a 67% healing rate of diabetic foot ulcers after 12 weeks compared to 32% utilizing collagen and alginate dressing (Evaluating the Effect of Omega 3 rich Fish Skin in the Treatment of Chronic Nonresponsive Diabetic Foot Ulcers; Penultimate Analysis of a Multicenter Prospective Randomized Controlled Trial) (Lulove et al, Wounds, April 2022).

A thirty-eighth comment from two wound care nurses indicates they have used various skin substitutes which have proven very beneficial for healing of diabetic ulcers. For optimal healing results after four weeks of unsuccessful attempts of closing wound with other modalities, skin substitutes have shown marked improvement with their wounds up to the point of total closure of the wound with at least 10 applications. Some wounds that did not reach full closure but had marked improvement could have benefited from even more than 10 applications. With closure of these wounds the patient is less likely to develop infection which in turn means less chance of amputation.

A thirty-ninth comment from a podiatrist indicates that the following statements in the proposed LCD provide guidelines to justify reapplication, support an argument that limitation of two applications in a 12-week episode may contradict the approved FDA intended use, and indicate the guidance on application but do not state or justify a reason for a maximum of two within 12 weeks:

• Repeat application of a skin substitute graft within the 12-week episode of skin replacement surgery for wound care may be appropriate per the package insert based on wound re-assessment and must be supported in the medical record documentation for that encounter.
• Skin substitute grafts utilized per the approved FDA intended use.
• The expectation is treatment will consist of the fewest repeat applications and amount of product to heal the wound. It is expected that products are used per the labeling. It is not expected that every ulcer, in every patient will require the maximum number of applications listed on the product label. This utilization pattern may be subject to focused medical review.

This commenter indicates that the following statement in the proposed LCD provides a mechanism to address abuse/overutilization: “This utilization pattern may be subject to focused medical review.” This commenter also noted that the studies cited in the proposed LCD by Driver, Lavery, Sanders, Zelen, Cazzell, and Harding do not appear to indicate limitations on maximum applications of skin substitutes.

A fortieth commenter asserts that while they agree that not all wounds require the current allotted amount of 10 grafts in a 12-week episode, most wounds require more than two applications. In Kerecis clinical studies, the average number of applications until complete wound closure is 4.5 grafts. In fact, many wounds regress and begin to get larger once grafting has stopped. In these instances, not only does the patient’s quality of life suffer with a wound that has begun to regress, but they also no longer have treatment options besides conservative care (which has already failed leading to the current grafting episode of care). Most patients will not heal with two graft applications. This in turn will cost Medicare more money treating patients for weekly debridement and dressing changes (sometimes for years), in addition open unhealed wounds lead to further expensive complications such as infection, hospital admissions/readmissions, and amputations. Grafting should be allowed until wound closure.

A forty-first comment from a certified wound specialist recommends allowing clinicians to use their medical judgement to determine the number of skin substitute applications, if the wound is progressing towards closure, retaining the current max of 10 applications over 12 weeks. Not every wound requires all 10 applications to heal. By sheer size alone, some wounds require larger products, or more applications to achieve the wound healing based on the rate of contraction being directly proportional to the size of the wound. Larger wounds are at a greater risk for complication, to include but not limited to infection, sepsis, hospitalization, and possible amputation if the wound is on a limb, and ultimately the patient is at risk for death if not treated proactively and aggressively. We know risk for mortality increases with amputation, and subsequently puts the patient at risk for contralateral amputation, increasing risk for death. Limiting the number of skin sub applications to two is not sufficient for adequate treatment of a chronic or nonhealing wound. The expectation is that the fewest number of applications will be applied, with improved healing rates and outcomes. It is not expected that every patient and every wound will require the max number of applications. Some products are manufactured in limited sizes and require multiple pieces to cover the wound area, depending on the size of the ulcer and the approved product. Trials have showed the effectiveness of 12 applications of skin substitutes: 1) Bianchi, C., Cazzell, S., Vayser, D., Reyzelman, A. M., Dosluoglu, H., Tovmassian, G., and EpiFix VLU Study Group (2017). A multicenter randomized controlled trial evaluating the efficacy of dehydrated human amnion/chorion membrane (EpiFix) allograft for the treatment of venous leg ulcers. International Wound Journal, 114–122. https://doi.org/10.1111/iwj.12843 2) Dehghani, M., Azarpira, N., Mohammadkarimi, V., Mossayebi, H., and Esfandiari, E. (2017). Grafting with cryopreserved amniotic membrane versus conservative wound care in treatment of pressure ulcers: A randomized clinical trial. Bulletin of Emergency and Trauma, 5(4), 249–258.

A forty-second comment from MIMEDX Group Inc. indicates that no clinical source can be located to support this limit and such a limit would inflict profound consequences on a vulnerable population that is at risk for infection, hospitalization, amputation and death. Recently published Health Economics data, based on a five year analysis of Medicare outpatient claims data (2015-2019), demonstrated that patients with chronic lower extremity diabetic ulcers benefit most when 1) advanced therapy with a skin substitute is started within 30-45 days of the initial diabetic ulcer diagnosis, 2) with clinically proven products, while 3) routinely applying within a range of every 7 to 14 days once the first application is initiated. However, the same Medicare data also revealed that in terms of real clinical practices, the average time to the first application of a skin substitute is approximately 80 days from the initial diabetic ulcer diagnosis. The clinical reality is that wound care providers are waiting too long before starting an advanced treatment with a skin substitute. Within the algorithm suggested by the recent Health Economics publications, reapplications can be guided by signs of improvement with the ulcer bed, as assessed through 30-day reevaluations (evaluations should assess reduced surface area, reduced depth, increased granulation tissue in the ulcer base, or reduced drainage). Continued applications falling within the range of every 7 to 14 days should be predicated on evidence of improvement. Two articles discussed in this comment were included with the comment: Observed impact of skin substitutes in lower extremity diabetic ulcers: lessons from the Medicare Database (2015–2018) and Cost-effectiveness of dehydrated human amnion/chorion membrane allografts in lower extremity diabetic ulcer treatment.

A forty-third comment from a physician and a physician’s assistant opposes the proposed rule of two applications in 12 weeks as this limit may put patients at increased risk of hospitalization, infection, amputation, and death. The best results, when dealing with chronic ulcers, have come from weekly applications of skin substitute and the current system of 10 applications in 12 weeks has been beneficial.

A forty-fourth comment from three physicians requests a reconsideration of this limit as it is unnecessarily restrictive and will result in longer treatment times.

A forty-fifth comment from a program director for a wound center indicates she has seen the benefit of skin substitute applications. Very rare is it needed for the full usual and customary ten applications. That being said, most instances, because these wounds are chronic with underlying issues, you may not see a change in measurements up to four weeks post initial application. Limiting the use of skin substitute applications to two is prohibitive to wound healing and ultimate closure.

A forty-sixth commenter indicates surprise by the limitation of two applications of skin substitute/CTP as most of the quoted articles in the proposed LCD describe more than two applications being required to achieve the intended benefit.

A forty-seventh commenter notes that treatment for each patient is carefully tailored according to the size, location and extent of the wound. Many wounds treated with skin substitutes require more than the proposed two applications outlined in this proposed policy. Treatment would thus become extremely challenging in cases of large and irregular wounds. In several articles published in recent years, the median number of grafts applied per healed wound has been between five and six. Limiting applications to two grafts poses a threat to the patients’ ability to properly heal and regain function and exponentially increases the possibility of limb or tissue loss, particularly in larger and irregular wounds.

A forty-eighth comment from a podiatrist indicates skin substitutes help reduce bioburden and provide a scaffold to healing for a three month period that is an integral part of limb salvage. A vast majority of the time these patients require 12 applications to get them 100% healed or very close to it. Limiting the number of applications to only two in a 12-week period is going to undo all of the progress we have already made.

A forty-ninth comment from a podiatrist and a wound care nurse indicates that more than two applications is often necessary when treating larger and irregular shaped wounds based on the size, location and extent of the wound. As written, the proposed LCD would restrict access to a treatment that has proven to be highly effective and more cost effective than having a patient require multiple hospitalizations, multiple surgeries, antibiotic treatments, and an increase in the costs of multispecialty care that arises when dealing with chronic non-healing wounds.

A fiftieth comment from a plastic surgeon indicates this proposed LCD establishes arbitrary, medically inappropriate, and unnecessary limitations on the number of applications of a skin substitute to a wound that is not supported by clinical evidence.

A fifty-first comment from two physicians and a nurse indicates limiting the amount of skin substitutes will result in: increasing the time to heal chronic DFUs and VLUs, increasing the overall treatment cost for chronic DFUs and VLUs, unnecessarily increasing the patient morbidity for either partial foot amputation or below the knee amputation, worsening the patient’s quality of life, and potentially worsening the patient’s co-morbidities.

A fifty-second comment from a wound care physician indicates that most, if not all patients benefit from significantly more applications than two within the 12-week episode of care. Two applications are not nearly an acceptable amount to allow the patient the proper healing time and opportunity for prevention.

A fifty-third comment from a podiatrist indicates limiting the use of two grafts per 12-week period is not sufficient as the wound dressing is changed every third day at least weekly. This limit is not reasonable for the proper care of the patient’s wound.

A fifty-fourth comment from the WHS, Peripheral Vascular Associates, and the Coalition denotes that the limitation of two applications in an episode (defined as 12 weeks) being not medically reasonable and necessary is an arbitrary application limitation that is not only contradictory to other statements in the draft policy (that products should be used based on their labeling instructions), but also not supported in the literature cited or in any evidence that they have reviewed. In fact, the evidence cited in this policy either shows the number of applications to be higher than the two permitted under this draft policy or is very clear that the number of applications should be based on the labeling instructions for the specific product being used. More specifically, the number of applications cited in the evidence ranges from 1 – 8.9 applications and is based on individual product studies as the number of applications is not located on product labels. If the clinician does follow the product labels – one of two things will happen based on the language in this policy -the clinician will be over the number of applications under this policy while following the labeling instructions for the CTP being used to treat their patient OR they will be required to stop treatment midstream, prior to the wound being healed to comply with the requirements of this LCD. This seems counter intuitive and is clinically detrimental to patient care. Moreover, if the LCD limits treatment to 12 weeks, some of these products will not be able to be used since some of them, according to their FDA labeling, require multiple treatments in a span of time that would exceed 12 weeks. This is problematic and troubling in that the two application limitation is not founded on any evidence in literature. The commenters recommend that the LCD simply include a statement that the products should be applied in accordance with their FDA labeling of the product which places the responsibility on the physician/clinician to apply the product correctly and documentation in their files should be sufficient to show that the physician/clinician was following guidelines for the product being utilized.

A fifty-fifth commenter signifies physicians and advanced practice providers (nurse practitioners and physician assistants) should be permitted to use their medical judgement to determine the number of applications a particular wound requires to progress towards closure. No research studies prove that a maximum of two skin substitute applications provide optimal healing outcomes, including those referenced in the proposed LCD. The instructions for use (IFU) provided by the manufacturers of skin substitute products do not prescribe a quantity of applications. Clinical impairments that impede healing are individual to each patient and each wound. The commenter recommends a maximum of 10 applications with added criteria to continue applications beyond 10. For example, if a wound continues to show a reduction in area after the 10th application, skin substitute treatments may continue based on this as a determination of medical necessity.

A fifty-sixth comment from a wound care physician indicates that one paragraph in the proposed LCD states the following, “Repeat application of a skin substitute graft within the 12-week episode of skin replacement surgery for wound care may be appropriate per the package insert based on wound re-assessment and must be supported in the medical record documentation for that encounter.” But Limitation #1 appears to be a contradiction to this statement. One statement allows what the product package insert allows and the other appears to allow only two.

A fifty-seventh comment from a podiatric surgeon indicates skin substitutes have always been an effective option for stagnant wounds but the wound is never resolved with two applications. The grafts provide a lattice for healing not a onetime quick fix. Skin substitute grafts decrease time to healing compared to standard of care, but literature supports it can still take 6-12 weeks of this form of treatment. A two graft limit would provide no leeway in a lapse of treatment. One reference was cited with this comment.

A fifty-eighth comment from a podiatrist indicates that numerous peer reviewed studies have shown the advantage of using skin substitutes through the course of treating a wound particularly in the case of wounds that are difficult to heal and those that have failed the standard of care for at least one month. Limiting application to two applications would significantly affect patient outcomes and lead to longer healing times which in turn will increase rates of amputation as well as infection.

A fifty-ninth commenter notes that on average, the patients at their wound care center take seven applications. To their knowledge, there is no science to support that two applications of any skin substitute is sufficient to heal DFUs or VLUs.

A sixtieth comment from the Alliance specifies that the evidence does not support the two application limitation. Repeat application of a CTP to a DFU or VLU is clinically and medically appropriate at intervals of one to two weeks, based on ulcer re-assessment and best medical judgement of provider. There is no known research that defines the exact length of treatment or number of applications but must be suited to the best needs and circumstances of the individual patient (thus following an individual plan of care). As such, they recommend that no limitation is placed but rather language which supports clinical decision making and following package inserts for the product chosen to treat the patient. Furthermore, it is questionable how retreatment of a successfully healed ulcer will be covered or how retreatment of an ulcer following an unsuccessful course of treatment would be covered. Due to mechanical issues often not resolvable, patients can later develop another ulcer in the same location OR can have further breakdown OR can be switched to another type of product after an unsuccessful course of treatment on one type of product. The commenter recommends repeat application of a CTP should be based on the product label as well as clinician discretion based on patient need. Documentation must be part of the medical record. Four references were cited with this comment.

A sixty-first commenter indicates disagreement with this limitation as this seems to be arbitrary as data from numerous RCTs do not suggest this as being a reasonable number to heal a DFU or VLU over a 12-week period of care. For example, Veves et al (2001) in their Graftskin (Apligraf) study had an average of 3.9 Graftskin applications to heal a DFU with a limitation of no greater than five device applications as per their package insert precautions; Marston et al (2003) in their Dermagraft study’s treatment group after their first application, received up to seven additional weekly applications to heal a DFU with a limitation of no greater than eight device applications as per their package insert precautions; Lavery et al (2014) in their study of Grafix required on average six applications over a 12-week period to heal a DFU; and Zelen et al (2015) study of Epifix required on average 3.4 applications over a 12-week period to heal a DFU. To that end, and based upon the referenced studies, the commenter supports a utilization of four initial applications with additional applications of up to a maximum of eight for the 12-week period of care when there is evidence of wound healing (e.g., signs of epithelization and reduction in ulcer size) based upon the beneficiary’s medical record and progress notes.

A sixty-second comment from a wound care physician indicates he is uncertain if this limitation is indicating that no more than two applications of a skin substitute for the entire treatment period as some of the limitations don’t seem to support that conclusion. For example, changing products if you only have two applications doesn't seem to support that conclusion. There is not a concern if the intent is to limit the number of skin substitutes to a single wound in a single visit. The commenter has concern if the intent is to limit the number that can be applied to a wound to two applications for the entire treatment of the wound. The criteria by which a skin substitute can be applied implies the difficult wound has not responded to traditional treatment and it would be entirely reasonable that this wound could require more than two applications of a skin substitute. Many of the products manipulate the biochemical milieu of the wound to affect healing. It can take more than two applications to effectively change this milieu.

A sixty-third comment from a podiatrist indicates that too often patients present with wounds that are excessive in size and despite standard treatment, the wounds stall out and can continue for years on end with multiple hospitalizations, amputations, sepsis and death. Often these wounds have been treated for several months with standard of care treatment options only to find them stalled and growth factor deficient. It is these very wounds that can often benefit from a series of applications within a 12-week time period. Consideration should be given based upon the size of the wound, i.e., wound sizes greater than 10cm² often require up to 10 applications. The vendor sponsored literature that is available typically excluded patients with wounds that are larger than 25cm² and too often the less complicated patients are chosen for these studies. There needs to be time-based studies conducted on patients receiving skin substitutes that are wound size specific to identify the average healing rate and wound improvement over time. There is also a disparity among ethnicity groups when it comes to the prevalence of amputations. According to Goodman, et al. African Americans are four times more likely to end up with an amputation than White Americans. We should be good stewards of the resources available and work together in resolving these issues. Three references were cited with this comment.

A sixty-fourth comment from a podiatrist indicates the use of skin substitutes saves lives and limbs. If the LCD is changed to restrict the number of skin substitute applications to two, this will have a devastating outcome for many patients. This commenter has extensive experience with these products, which are some of the most powerful and successful methods of treating diabetic foot ulcers. The vast majority of these ulcers treated with skin substitutes do not require the current maximum of 10 applications, but seldom do they go on to heal after only two applications. These are some of the most medically vulnerable patients in our population, and if the proposed LCD change is enacted, these patients will likely go on to have higher rates of hospitalization and major amputation. Although skin substitutes may be costly, a wound that fails to heal can certainly be far more burdensome on the healthcare system due to the high cost of hospital admission, surgery, and the long-term care of patients who are debilitated by major amputations.

A sixty-fifth comment from a podiatrist asserts that if the application limit is reduced to two, 95% of the wounds seen will not be healed and the cost of the two applications will have been wasted.

A sixty-sixth comment from two wound care nurses requests that 12 or more skin substitute applications be allowed per episode of care.

A sixty-seventh comment from a podiatrist indicates he has extensive experience in applications of skin substitutes and affirms that two applications in a 12-week period is inadequate and inferior treatment. Weekly applications of skin substitutes are necessary to stimulate the wound, maintain the granular wound bed, and promote epithelialization. He would like to see the current LCD continue and not undergo any changes.

A sixty-eighth comment from Vohra Wound Physicians indicates their experience shows wounds commonly require three to six applications to achieve closure. The limit of only two applications is not based on any scientific principal or supported by the literature referenced. In fact, the LCD does not indicate the rationale or support for this restriction. The medical literature supports application on a weekly basis for six to twelve weeks and this results in a 2.75 times higher likelihood of wound healing as published in one high quality meta-analysis by Haughs et al (Haugh, AM, Witt, JG, Hauch, A, Darden, M, Parker, G, Ellsworth, WA, & Buell, JF [2017]. Amnion Membrane in Diabetic Foot Wounds: A Meta-analysis. Plastic and reconstructive surgery. Global open, 5(4), e1302. https://doi.org/10.1097/GOX.0000000000001302). It should be noted that the wording of your draft LCD suggests that repeated applications (beyond two applications) are in fact supported “The expectation is treatment will consist of the fewest repeat applications and amount of product to heal the wound.” The commenter recommends coverage of up to 10 applications per episode of skin replacement surgery.

We appreciate these comments. The limitation of two applications was based on published RCTs referenced in the proposed LCD. After a review of the comments and the associated evidence related to this limitation, we agree that a revision to the LCD is warranted. The Contractor recognizes that there is a paucity of evidence addressing frequency of application. In general, the current quality of the evidence for these products is moderate to low with high likelihood of publication bias and study limitations. Using real world evidence derived from sources other than RCTs was emphasized in the 21st Century Cures Act.

As indicated in one of the comments, Armstrong (2021) evaluated large propensity-matched cohorts to assess outcomes in patients receiving AT with skin substitutes for lower extremity diabetic ulcers (LEDUs) versus no AT (NAT) for the management of LEDUs. This study used the Medicare Limited Dataset (1 October 2015 through 2 October 2018) to provide a retrospective analysis. The average number of applications used was found to be 3.7. Based on the available data, the limitation language will be revised in the finalized LCD to indicate that “greater than four applications of a skin substitute graft/CTP within the episode of skin replacement surgery (defined as 12 weeks from the first application of a skin substitute graft/CTP) will not be considered medically reasonable and necessary. Product change within the episode of skin replacement surgery is allowed but in situations where more than one specific product is used, it is expected that the number of applications or treatments will still not exceed four.”

Regarding the articles submitted with comments, some of the products being investigated were used as dressings and did not meet the medically reasonable and necessary threshold for coverage of skin replacement surgery as a skin substitute graft/CTP. These products were not applied surgically to ulcers to enhance wound management and they lacked evidence of forming a sheet scaffolding for skin growth.

Several comments were received for Limitation #2 in the proposed LCD: “Switching skin substitute graft products in a 12-week episode of skin replacement surgery for wound care is not considered medically reasonable and necessary. Exceptions should be rare and may be considered on appeal when the medical necessity of the change is clearly documented in the medical record.”

A comment from a wound care specialist physician indicates switching products is sometimes necessary due to a variety of factors that could include availability, clinical response, intolerance by the patient, etc. Requesting an appeal will impose another burden to practitioners and delay treatment.

A second comment from a physician indicates different products have different indications and just like any other medication different patients respond differently to different products. Limiting the change of product would make clinicians use a product that is not effective when the clinicians could be changing it if there are no significant improvements to help the patients.

A third comment from a physician indicates the restriction on changing products during treatment challenges his ability to assess and treat his patients as medically necessary. Patients with chronic wounds tend to be less healthy and have more comorbidities than other patients. Wound healing in chronic wound patients typically ebbs and flows and may require changes in treatment throughout the episode of care. Any restriction on his ability to match the best product to his patient’s needs will lead to worsened patient outcomes. The LCD should allow clinicians to use their medical judgment to change products during an episode to best treat patients.

A fourth comment from two podiatrists indicates there are cases when one product is used to clean the biofilm and then a switch is made to another product for quick healing. This proposed limitation will dampen this ability and seems counterproductive.

A fifth commenter indicates switching of skin substitutes should be encouraged if needed as the wound progresses. As the wound heals, it may have different contour and may need different biological support provided by different substitutes. Therefore, assessing the need of the wound and switching to a different substitute as the wound progresses to closure may help in closing the wound faster and require less number of skin substitutes in total.

A sixth commenter indicates this limitation does not take into account that all wounds are different and respond differently to certain grafts. There are a variety of grafts that have different properties that can affect the wound. If they cannot switch and are stuck with one type of graft, then the patient may not heal.

A seventh commenter expresses that if he had a biopsy of the wound telling him what the wound was missing wound care would be much easier. As of now, treatment is based on what he thinks the wound is missing. Some of these products are cell based, others scaffold, others have antimicrobial therapy. Infected or heavily colonized wounds need to be treated with an antimicrobial graft first, then you can use a scaffold or a cell-based therapy to accelerate healing and close the wound.

An eighth commenter implies that this limitation fails to account for scenarios (e.g., with larger and deeper wounds), where wound healing stops progressing with a single product. In such cases, use of a different CTP may be the better clinical decision and more clinically effective treatment to heal the wound. Should a wound stop progressing, medically, it makes sense to change clinical direction and apply a different product. To be limited to the same course of treatment when wound healing stalls is a disservice to patients and will ultimately drive-up health care costs. As such, if the provider documents that the wound healing has stalled, then the provider should have the option to utilize different CTPs.

A ninth comment from a podiatrist indicates it is important to stress that wounds require consistent evaluation and documentation of healing progression. It should remain the clinician’s purview to determine if a patient would be best served by the use of another skin substitute when progress hasn’t been noted while using another within a 12-week episode. Wound treatment should be tailored to each individual patient’s medical necessity.

A tenth commenter signifies this limitation is not consistent with good wound care practice and would hamper the ability of clinicians to provide appropriate therapy for individual wounds. A patient’s response or lack of response to one product may require switching to another product, especially to a product that is technologically different. For example, if the depth or characteristics of a wound changes, it may be appropriate to utilize a different type of skin substitute that better addresses the current nature of the wound. In such a case, switching may result in fewer overall skin substitute applications. Prohibiting switching could incentivize continued use of products that are no longer the most appropriate therapeutic option. There is no clinical evidence supporting the limitation on switching products. Switching is not addressed in the medical practice guidelines and there is no clinical evidence indicating that it is inappropriate. Real-world claims data have been consistent with estimates that approximately 15%-25% of DFU and VLU patients have been treated with more than one skin substitute (CMS; WoundExpert^® de-identified patient claims data). This same pattern is seen in Medicare claims data. For example, analysis of 2020 professional provider fee-for-service claims data shows that patients with six applications received an average of 1.32 products. Three references were cited with this comment.

An eleventh commenter indicates that the proposed policy states several different times that the provider should not continue to graft the patient if the wound is not progressing. Not all skin substitutes are the same as evidenced in the literature reviews cited in the draft policy. If the wound is not responding to the current skin substitute, it should be clinically reasonable that the provider stops grafting, reassesses the wound, addresses any issues and then be able to re-graft again with a different graft that the wound may respond to. However, the commenter does agree that when a graft is chosen, it should be continued for at least four weeks (30 days) before determining its efficacy. The grafts should not be interchanged weekly determined by whatever the provider has on hand.

A twelfth comment from a certified wound specialist recommends allowing clinicians to use their medical judgement to switch skin substitutes based upon the patient’s needs. Wound healing is often delayed for a multitude of factors. What the wound “needs” can change during the course of treatment. She feels strongly that the selection of product should be determined by a qualified wound specialist, one who is well versed in the impediments to a specific wound’s healing, such as growth factor deficiencies, as well as the compilation of the product, extracellular matrices, or antimicrobial products for chronically colonized or wounds at risk for contamination or critical colonization.

A thirteenth commenter signifies that there are very legitimate clinical reasons to switch products. Sometimes a patient may not respond to the first product. Switching to an alternative skin substitute product within a 12-week episode of care to find the most effective treatment is not an uncommon tactic when providing care to the chronic wound population. This happens frequently enough that an automatic appeal process represents an obstacle to care and an administrative burden.

A fourteenth commenter expresses that as therapeutic agents, the individual skin substitutes have different mechanisms of action and, therefore, there should not be a limitation that restricts switching products. In medicine, clinicians are frequently required to change a therapeutic agent when a desired response is not achieved. A different mechanism of action may be required to achieve a response. This decision should remain at the discretion of the clinician based on medical judgement. The commenter supports the need for the documentation to support the justification for switching the CTP and using multiple products.

A fifteenth comment from eight podiatrists and two stakeholders stresses that wounds require consistent evaluation and documentation of healing progression. It should remain the clinician’s purview to determine if a patient would be best served by the use of another skin substitute when progress hasn’t been noted within a 12-week episode. Wound treatment should be tailored to each individual patient’s medical necessity.

A sixteenth comment from a plastic surgeon declares this proposed LCD arbitrarily prohibits switching from one skin substitute to another during an episode of care.

A seventeenth comment from a wound care physician indicates that within the 12-week episode of care, a wound has the potential to change drastically because of the benefits of the graft. If a wound should experience a remarkable change, often this would change the graft which would be most appropriate. By limiting the ability to change grafts, the payer is both incurring more costs by using a product that is not the best fit and preventing patients from receiving the best possible care.

An eighteenth comment from a podiatrist indicates the inability to switch products within the 12-week episode of care does not make sense. As physicians we must respond to the state of the wound and not be hindered.

A nineteenth commenter indicates what the wound needs for optimal healing often changes during the healing process. Wound healing is individual to each patient for each wound and recommends this limitation be removed from the policy.

A twentieth comment from a wound care physician indicates this limitation will likely create issues with his patient. Hospital owned clinics may change suppliers, creating an issue with the availability of the product a provider is currently using. Patient’s insurance may change, prompting a change in products that are covered under their benefit design. This statement needs to be deleted from the LCD.

A twenty-first comment from Peripheral Vascular Associates indicates the policy is contradictory by stating reapplication is denied if the wound is not progressing. But stopping to readdress the wound and change therapy is not allowed. Not being able to change products during the episode of care will not allow a patient to fully benefit from the placement of a skin substitute graft.

A twenty-second commenter indicates that a great deal of success has been shown when the physician at their wound care center switches skin substitute products within the 12-week period. They have found that less skin substitutes are used time and time again whenever the providers switch.

A twenty-third comment from the Alliance and the Coalition indicates this limitation is not only limiting treatment options for the clinician but is also inhibiting a patient from receiving the best optimal treatment to address their ulcer. Sometimes a treatment option chosen is not successful. This limitation prevents the ability to change course, when treating patients, upon the realization that the product chosen is not successfully working on that patient. Often one CTP is used to achieve a certain goal, such as to initiate granulation. Then, depending on the presentation of the ulcer and the patient’s current health status, they may switch to another product to close the ulcer. To afford all clinicians the type of autonomy needed to customize their treatment plan for individual patients – they recommend allowing treatment according to the FDA label and placing the burden on the clinicians to document the need for multiple products. Additionally, if the practitioner is required not to switch to a different CTP, as the ulcer gets smaller, a CTP that comes in only one size may become "too large" based on the arbitrary criteria, and the clinician would have to pick an entirely different product to use a smaller one. You cannot prohibit a change in product brand as well as require the product size be matched to the wound size. If you wish the smallest product possible to be used, then the provider must be permitted to switch CTP brands throughout the management of a DFU and VLU. Furthermore, Covid has created unpredictable shortages and issues with shipping and receiving products. Thus, a provider may have to change product brand when the ulcer requires another application of a brand that is not available when needed. If a provider determines that the initial brand of CTP must be switched to a different brand, documentation should be provided in the medical record to justify the use of a different brand. The Coalition suggests the following language: If a clinician determines that the original CTP being utilized needs to be switched, documentation must be provided in the medical record to justify the use of multiple products.

A twenty-fourth comment from a podiatrist indicates products may need to be switched due to product availability or as the wound sizes change it may be more appropriate to switch to a product that is available in a smaller size. Also, the patient’s wound status could change warranting a different type of skin substitute (i.e., cryopreserved versus dehydrated versus collagen-based scaffold). The commenter is unsure of the advantage to CMS by not allowing for products to be changed out during the 12-week window based upon patient’s clinical presentation.

Thank you for the comments. After a review of the limitation referred to in the comments and the associated evidence related to this limitation, we agree that a revision to the LCD is warranted. The limitation will be revised in the finalized LCD. Product change within the episode of skin replacement surgery will be allowed. Please refer to the response for Comment #13 for additional information.

Comments have been received regarding Limitation #3 in the proposed LCD: “Application of a skin substitute graft product beyond 12-weeks is not considered medically reasonable and necessary.”

A comment from a wound care specialist physician asserts that not all patients are created equal. He sees this rule as a harmful one as patients, especially those with chronic wounds, frequently have other issues going on that may require special care. For example, a patient gets started on a skin substitute and is doing well but needs to interrupt treatment because of hospitalization. By this rule the possibility to continue with the use of the skin substitute is taken away. Just today, one of his patients in need of a skin substitute will be starting radiation for lung cancer. The skin substitute will need to be interrupted and by the time she returns, she may not qualify for any further applications.

A second commenter indicates that this does not take into account the obstacles which these patients with chronic wounds face on a daily basis. Immunosuppression and open wounds lead to increased risk of infections. If healing process is delayed to outside the 12-week window, then they are punished and cannot receive a wound graft. This is unreasonable and puts the patient at risk.

A third commenter indicates that many wounds do not heal within 12 weeks. Kerecis has numerous case studies demonstrating wound closure, over the course of 6-12 months, utilizing grafts as needed rather than squeezing as many in as possible in the short time frame allowed. Most of these case studies utilized only five or less grafts over a longer period of time. This short episode of care causes providers to over utilize grafts weekly to try to heal the wound quickly since grafting is prohibited after the 12 weeks. In addition, many patients are progressing toward closure at week 12 or 13 and only need one or two additional grafts, without this treatment the wounds can regress, and all progress made while grafting could be lost with a hard stop at week 12 irrelevant of clinical progression of treatment of the wound. There should not be a time frame limit for grafting. Clinical progression should determine grafting time as all wounds and patients heal differently. Medicare is likely spending more money on more grafts as providers have strict limitations and try to use grafts weekly in 12 weeks because they have run out of options after the episode of care. If Medicare would eliminate the 12-week limitation and let providers graft as clinically appropriate (or put in a limit such as 10 but without 12-week limit), significant cost savings would most likely be recognized as well as better clinical outcomes.

Margolis and Sheehan have published widely used prognostic indicators in wound healing. The basic rule of thumb has been four weeks, 40% (VLU)/50% (DFU). Meaning if the wound closed by 40%/50% in four weeks then what the provider is doing is working and the treatment should be continued. This stands true in the four weeks leading up to grafting during the conservative therapy period as well as the grafting period. If during the conservative care treatment period, through debridement, exudate management, and dressing changes the provider can achieve a 40%/50% reduction in wound size, then the wound has a 91% chance of closing without additional therapy. If the wound does not close by 40% or 50% depending on etiology, the chance of it closing with current therapy is 9%. Continuing standard of care at this point would cost Medicare if they did not allow a skin substitute to be initiated. Therefore, at this point, a skin substitute should be allowed. Treatment with a skin substitute should be allowed as long as the wound shows progression every 30 days.

A fourth comment from the APMA confirms support for this limitation which is consistent with guidance APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

A fifth comment from a wound care physician indicates that a skin substitute is needed > than a 12-week period. He has many examples of wounds which were initially responding within the first three months of caring for them only to need a growth stimulating skin substitute. Not only does that present an issue but limiting the use of these within a 12-week window will not allow for their use if the wound stalls again.

A sixth comment from a podiatrist asks what if the size of the wound is greater than 200 cm² and continues to show marked improvement week over week and at week 12 the wound has reduced in size by 80% and is now 40 cm² and then stalls and fails to continue reduction in size despite standard of care/treatment once the skin substitute stops. Consideration needs to be made even if it requires a focused medical review to allow these patients to go on to full closure of the wound when appropriate.

A seventh comment from a wound care physician suggests not to limit the length of treatment to a 12-week period if there is evidence of progressive improvement if the wound continues to be open. He recently treated a patient with bilateral circumferential venous leg ulcers who achieved about 75% reduction in ulcer size, but they had to stop the applications because he was out of the 12-week period and had received only seven. Since the stop of his applications the healing process has stalled again. He indicates that the faster we get a wound to close the less likely it will be for the patient to develop skin and soft tissue infections as well as osteomyelitis, sepsis and possible limb loss.

An eighth comment from the Alliance questions why the proposed LCD refers to an episode of care. There are no "episode-based, bundled payment" models for CTPs. They are concerned that the use of the term "episode" implies a bundled payment model which does not exist. We would like to know what evidence has been used to create this "episode of care" and why treatment is 12 weeks from the first application of a CTP. Based on the 21st Century Cures Act evidence needs to be provided to support this position. There is no evidence to support this statement. Furthermore, there is no way an episode can be tied to DFUs or VLUs in the CPT code manual. Patients can have multiple ulcers in different anatomic sites and as such the coding will not allow for - nor would it be appropriate - to tie care to an episode with the current coding framework. They recommend this language be deleted.

Thank you for the comments. The 12-week episode of care is predicated on existing research protocols. Therefore, a revision to the finalized LCD will not be made as requested by some of the commenters. The support of the APMA for this criterion is appreciated. As noted above in the comment from APMA, this criterion is consistent with guidance they have provided to their members.

Comments were received regarding Limitation #4 in the proposed LCD: “Repeat applications of skin substitute grafts when a previous application was unsuccessful are considered not medically reasonable and necessary. Unsuccessful treatment is defined as increase in size or depth of an ulcer, or no change in baseline size or depth and no sign of improvement or indication that improvement is likely (such as granulation, epithelialization, or progress towards closing).”

A comment from a wound care specialist physician indicates he agrees with the fact that if a skin substitute is not working it should not be continued however room should be provided for some exceptions that could be documented in the chart indicating the reason which could include a recent infection that led to worsening of the wound/ulcer.

A second comment from the APMA confirms support for this limitation which is consistent with guidance APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

A third comment from a wound care physician indicates he can understand not putting another graft on the week after seeing a worsening wound with the graft, but there are multiple times that we place a graft and see no improvement clinically after one week. It can take two to three applications to simply get things started in these very chronic, non-healing wounds. In fact, if one skin sub does not work, another should be tried to escalate our efforts to get this wound healed. Simply saying that when a graft is unsuccessful, do not try again, is certainly limiting many other treatments which may eventually help.

A fourth comment from Vohra Wound Physicians asserts this limitation fails to define “indication that improvement is likely”. The commenter suggests that the clinical factors and objective points of an unsuccessful treatment versus what objective data shows successful treatment should be clearly specified.

Thank you for the comments. A revision to the finalized LCD will not be made as requested by some of the commenters. The support of the APMA for this criterion is appreciated. As noted in the comment from APMA, this criterion is consistent with guidance they have provided to their members.

Comments were received regarding Limitation #5 in the proposed LCD: “Application of skin substitute grafts in patients with inadequate control of underlying conditions or exacerbating factors, or other contraindications (e.g., uncontrolled diabetes, active infection, active Charcot arthropathy of the ulcer extremity, active vasculitis) are considered not medically reasonable and necessary.”

A comment from a wound care specialist indicates this is reasonable but suggests we think clearly about how to define for example uncontrolled diabetes. “Is there a maximal Hgb A1c allowed?”

A second commenter notes this language is extremely broad and does not identify how the MAC would determine that an underlying condition or exacerbating factor is inadequately controlled. The commenter shares the belief that comprehensive wound care should address underlying conditions and comorbidities and that some factors, such as active infection, may contradict use of skin substitutes. In the covered indications section, it is noted that skin substitutes are limited to substitutes for “chronic, non-infected” DFU or VLU and the commenter believes that this language appropriately identifies wounds that are not candidates for skin substitutes.

A third comment from the APMA confirms support for this limitation which is consistent with guidance APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

A fourth comment from the WHS requests a definition for uncontrolled diabetes and evidence to support the definition.

Thank you for the comments. The medical record must address any underlying conditions or exacerbating factors, or other contraindications (e.g., uncontrolled diabetes, active infection, active Charcot arthropathy of the ulcer extremity, active vasculitis).

As noted in the ‘Summary of Evidence’ section of the proposed LCD in the ‘Evidence-Based Guidelines for Standard of Care’: “A comprehensive assessment of patients and their wounds will also facilitate appropriate care by identifying and correcting systemic causes of impaired healing. The presence of a severe illness or systemic disease and drug treatments such as immunosuppressive drugs and systemic steroids may inhibit wound healing by changes in immune functioning, metabolism, inflammation, nutrition, and tissue perfusion. Therefore, this information in conjunction with a detailed history of the wound itself is essential.”^3,9 Also, please see the response to comment #8 regarding Hbg A1c.

Comments were received regarding Limitation #6 in the proposed LCD: “Use of surgical preparation services (for example, debridement), in conjunction with routine, simple and/or repeat skin replacement surgery with a skin substitute graft is considered not medically reasonable and necessary.”

A comment from a wound care specialist physician indicates he agrees that there is no absolute need for debridement of all ulcers every time but the option to debride should be left up to the treating physician. Typically, if he is not mistaken, the debridement is not reimbursed if done on the same day of the application of the skin substitute.

A second comment from the APMA confirms support for this limitation which is consistent with guidance APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

A third comment from a podiatrist asks if this is specific to CPT 15000 series (wound bed prep) and not 11000 or 97597 and 97598 series or 97610. It is imperative to continue “debridement” principals to clean the wound versus mechanical debridement only. Where is the evidence that indicates that debridement is not warranted when skin substitute grafts are applied? This position of not providing for reimbursement of the debridement that was done in conjunction with the skin substitute application can be taken; however, do not deny the skin substitute application because the provider documented that they performed a “debridement” with today’s application of a skin substitute because this is best practices.

Thank you for your comments. A revision to the finalized LCD will not be made as requested by some of the commenters. The support of the APMA for this criterion is appreciated. As noted in the comment from APMA, this criterion is consistent with guidance they have provided to their members.

Regarding the comment on coding, the skin substitute graft/CTP application procedure codes include the surgical preparation services for the skin substitute graft/CTP. Therefore, reporting additional services in this regard would not be appropriate billing.

Comments were received regarding Limitation #7 in the proposed LCD: “Excessive wastage is not considered medically reasonable and necessary (discarded amount). The skin substitute graft or CTP must be used in an efficient manner utilizing the smallest package size available for purchase from the manufacturer that could provide the appropriate amount for the patient.”

A comment from a wound care specialist physician expresses agreement with this limitation and acknowledges that we should limit wastage as much as possible however there are some skin substitutes that don’t come in smaller sizes.

A second commenter indicates that the guidance to use the smallest size should not be inadvertently translated into using the smallest size to fit any wound size. Rather, the meaning of “smallest” should be clarified to be in proportion of the size of a wound to achieve the maximum increment of closure in between applications, and following a final application for complete closure, to be determined by the sound judgement of a clinician for the interest of his/her patient’s wound closure.

A third comment from the APMA confirms support for this limitation, which is consistent with guidance APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

A fourth commenter greatly respects limitations that control overutilization that can occur when too large a size is chosen on any given date of service. However, for both hospitals and physician offices, some of these variables stem from supply chain decisions throughout the health systems that order them. For example, the IDN (Integrated Delivery Network, or hospital system) may have contracted to purchase specific sizes (It is important to note that the ability for IDNs to negotiate preserves cost savings to healthcare overall). In any place of service, specific sizes may not be on the shelf when the provider goes to treat. In the private office, providers purchase these products in advance, and it is often not feasible from a cost perspective for a practice to stock the entire array of available sizes. However, the most pertinent variable is clinical. Ulcer size and shape is variable week-to-week. When ordering for the next reapplication, providers cannot always anticipate the size ordered will still be the smallest size possible when the patient presents at the next appointment. The commenter recommends using strong language that represents the reasonableness of both the amount chosen for application and the amount wasted.

A fifth comment from the Alliance indicates that based on the physician’s/NPP’s individualized plan of care, one should try to match the CTP to the needs of the patient and to the size of the ulcer. But this may not always be possible given different sizes produced by various manufacturers, hospital purchasing agreements, and current COVID related supply chain issues. Furthermore, in the hospital owned outpatient wound/ulcer management provider-based department, CTPs are reimbursed under OPPS packaged pricing based on the size of the ulcer, not based on the size of the CTP purchased. Hospitals contract for a small number of products through their purchasing intermediaries and physicians/NPPs may have no choice in the size of product available, nor will the size impact the payment rate. Products come in a limited number of sizes and even a private practitioner may not be able to match the size of the product to the size of the ulcer and/or it may not be economically feasible. The following language is suggested: “The CTP must be used in an efficient manner with the most accurate size product available to the physician/other qualified healthcare professional at the time of treatment in circumstances where it is economically feasible. The physician/other qualified healthcare professional should document in the patient's medical record the size of the ulcer(s), the size of the product opened for that patient, the number of square centimeters applied, and the number of square centimeters wasted.”

A sixth comment from the Coalition signifies recognition that this limitation is proposed to ensure that clinicians use the most appropriate size product available to them at the time of treatment. However, the requirement that clinicians utilize the smallest package size available for purchase from the manufacturer is not appropriate. Clinicians often do not control what products are purchased or on formulary thus on hand at their facilities. They simply use the best product to treat the patient that is either on the hospital formulary or on the shelf at their clinic. There are different types of CTPs in the marketplace which come in different sizes and not all come in multiple sizes. In the hospital-based outpatient setting, these products are packaged into payment for the procedure and not paid separately based on the amount of product furnished. Hospitals contract for a small number of products through purchasing intermediaries and clinicians may have no choice in the size of product available, nor will the size impact the payment rate. Products come in a limited number of sizes and even a private practitioner may not be able to match the size of the product to the size of the wound. The commenter suggests revising this limitation to read: “CTPs must be used in an efficient manner utilizing the most accurate size product available to the provider at the time of treatment. The provider must document in the patient file the size of the wound, the product used and how the product was used (i.e., if a large CTP was used on multiple wounds for the same patient) and the amount of product wasted. Should the wound begin to heal, and a smaller size CTP is necessary, the provider may switch products in order to have the least amount of product wastage.”

A seventh comment from a podiatrist asserts this limitation contradicts Limitation #2 in the proposed LCD for switching products. If the wound would benefit from a product that comes in a smaller size, then it could be prudent to switch in attempt to minimize wastage. Otherwise, most providers would agree that the smallest package size available for purchase from the manufacturer should be utilized to match the size of the wound.

Thank you for the comments. The language has been revised in the finalized LCD to clarify this limitation: “The skin substitute graft/CTP must be used in an efficient manner utilizing the most appropriate size product available at the time of treatment. It is expected that where multiple sizes of a specific product are available, the size that best fits the ulcer with the least amount of wastage will be utilized.”

A comment from the WHS, the Alliance, and the Coalition conveys concern that the proposed LCD is conflating the terms ‘wound’ and ‘ulcer’. Per ICD-10 coding rules, "wounds" are acute and are caused by surgical misadventure or trauma, whereas "ulcers" such as DFUs and VLUs are chronic and are linked to underlying comorbid diseases. CMS audits have threatened repayment for clinicians who use the term "wound" when referring to an "ulcer”. Since this policy is for the application of CTPs for diabetic foot ulcers and venous leg ulcers, the commenters request that the term wound is not used in the policy when referring to chronic non-healing ulcers such as DFUs or VLUs. The Alliance cited two references with their comment.

A second commenter requests that the following sentence be removed from the eighth paragraph of the proposed LCD: “Chronic wounds and frequently recurring wounds related to DFUs and VLUs are a challenge to treat effectively.” The Alliance also comments that this sentence could be revised to: “DFUs and VLUs are a challenge to treat.”

Thank you for the comments. The finalized LCD has been revised to provide clarity regarding an ulcer versus a wound. Also, the following sentence has been deleted as requested: “Chronic wounds and frequently recurring wounds related to DFUs and VLUs are a challenge to treat effectively.”

Comments were received regarding bullet #4 in the ‘Covered Indications’ section of the proposed LCD: “The skin substitute graft is applied to an ulcer that has failed to respond to documented conservative wound care measures. “Failed response” is defined as an ulcer that has increased in size or depth, or no change in baseline size or depth, or no sign of improvement or indication that improvement is likely (such as granulation, epithelialization, or progress towards closing). Documentation of response requires measurements of the initial ulcer, measurements at the completion of at least four weeks of conservative wound care measures, and measurements immediately prior to placement of the skin substitute graft for a DFU. For VLUs, conservative wound care measures must continue for no less than four weeks and include on-going compression therapy.”

A comment from Vohra Wound Physicians indicates that it would seem from this guideline that a wound that has minimal granulation or has made little movement toward closure would support skin substitute application regardless of change in size. This vague guidance does not define under what specific objective criteria a practitioner can consider a wound unlikely to improve or likely to improve and this needs clarification and further definition.

A second commenter indicates they have observed this language to be a common source of substantial confusion for providers. The use of the absolutes: “no change in baseline size or depth” and “no sign of improvement” leads providers to believe that they cannot apply a skin substitute if the ulcer has progressed even as little as a millimeter. For chronic ulcers, the AHRQ notes the industry guideline, which is backed by research exploring healing markers for DFUs and VLUs: “Four weeks of standard of care without achieving a 50 percent reduction in wound size may signal the need for a change or additional therapies.” The commenter requests that the definition of failed response to conservative measures be updated to this industry-accepted benchmark.

Thank you for the comments. The LCD emphasizes the documentation supporting failure of standard of care treatment. The medical record must clearly document that the criteria listed in the LCD has been met. Of note, the literature does not universally support that an ulcer that has not achieved at least a 50% reduction in size after four weeks of treatment would benefit from a skin substitute/CTP.

A comment from the Alliance indicates the evidence does not support the measurement of greater than four weeks. Rather the standard which has been placed in other LCDs and used by CMS is 30 days or four weeks of standard of care. The literature supports this time frame and not greater than four weeks. They recommend revising the language to: “The presence of a chronic, non-infected DFU having failed to respond to documented standard of care for 30 days or four weeks with documented compliance.” Three references were cited with this comment.

Thank you for the comment. The language in the ‘Covered Indications’ section of the finalized LCD has been revised to indicate “for a minimum of four weeks (defined as 30 days).” The ‘Evidence-Based Guidelines for Skin Substitutes’ in the ‘Summary of Evidence’ section of the proposed LCD has been revised in the finalized LCD to: “Skin substitute grafts/CTPs are recommended for DFUs that have failed to demonstrate more than 50% wound area reduction after a minimum of four weeks of standard therapy. For VLUs, if substantial improvement of the ulcer is not demonstrated after a minimum of four weeks of standard therapy, skin substitute grafts/CTPs are recommended in addition to compression therapy.”

A comment from the Alliance expresses agreement that compression should be utilized however, Medicare does not currently cover it when provided at the same encounter as the application of a CTP. In order to correct this problem, NCCI procedure-to-procedure edits must be eliminated. The Alliance has worked with NCCI and are awaiting a response. NCCI changed the manual so that compression can be provided to the patient at the same encounter as the application of a CTP. However, the NCCI procedure-to-procedure edits have not been removed. If the MAC is going to strongly recommend compression after the application of a CTP, the MAC should first ensure that the NCCI procedure-to-procedure edits are removed.

Thank you for the comment. As stated in the proposed LCD, for VLUs, if substantial improvement of the ulcer is not demonstrated after a minimum of four weeks of standard therapy, skin substitute grafts/CTPs are recommended in addition to compression therapy. This statement is supported by the Society for Vascular Surgery and the American Venous Forum Joint Clinical Practice Guidelines.

Regarding the comment on the National Correct Coding Initiative (NCCI) procedure-to-procedure edits, the Contractor will defer to the NCCI process. The CMS developed the NCCI program to promote national correct coding methodologies and to control improper coding that leads to inappropriate payment of Part B claims. The coding policies are based on coding conventions defined in the AMA CPT^® Manual, national and local Medicare policies and edits, coding guidelines developed by national societies, standard medical and surgical practice, or current coding practice. The NCCI program is responsible for developing, revising, and maintaining NCCI edits, responding to inquiries regarding the NCCI program, and promoting program integrity and compliance. Changes in the NCCI program are the result of comments submitted to the CMS. Prior to implementing new edits, the CMS generally provides a review and comment period to representative national organizations that may be impacted by the edits.

A comment from the WHS signifies the reference to synthetic occlusive dressings throughout the policy is confusing. A synthetic CTP is not a dressing. Synthetic products should be treated like all other CTPs and not singled out as CMS has included them in the definition of what is a skin substitute in recent rulemaking.

Thank you for the comment. The language in the finalized LCD has been revised to: “Despite advancements in various surgical dressings, which maintain a moist healing environment, some ulcers fail to heal.”

A comment from the TPMA conveys support for the covered indications section of the proposed LCD for indications #1-3.

A second comment from the APMA, the MPMA, the ASPS, and the ASSH conveys support for the covered indications section of the proposed LCD for indications #1-7 and for the limitations #3-7. The APMA indicates these indications and limitations are consistent with guidance the APMA has provided to its members and will continue to provide should these be included in the finalized LCD.

Thank you for the comments.

A comment from a wound care specialist physician indicates that the minimum size of the ulcer should be changed. He considers it arbitrary to limit the application of a skin substitute to an ulcer or wound smaller than one square centimeter. There are occasionally scenarios where there is a small opening but significant undermining or tunneling or small ulcers that just won't heal with conservative measures such in the case of a condition called Atrophie Blanche or Livedo Vasculitis; this condition is associated with venous insufficiency, but the ulcers tend to be chronic, extremely painful and debilitating and very small. Tunneling wounds with a small opening are not infrequent and they could respond to this treatment modality.

Thank you for the comment. The proposed LCD does not have criteria and/or a limitation in place regarding the size of the ulcer. However, it is noted that the majority of the studies reviewed in the development of the proposed LCD only included wounds with a minimum size of 1 cm².

A comment from a wound care specialist physician requests to eliminate the language regarding “the presence of exposed bone”. He indicates exposed bone will not interfere with the healing process. A wound with exposed bone is the one that needs advanced therapeutics the most.

Thank you for the comment. The proposed LCD does not include language referring to “the presence of exposed bone”. However, the associated billing and coding article includes ICD-10 codes to reflect the depth of wounds which do not include ulcers that extend to the bone. The majority of studies reviewed in the development of the proposed LCD excluded wounds that extended down to the bone.

A commenter declares hope that this ridiculous proposal is shut down.

Four commenters indicate they vote “no” for this proposed LCD.

Thank you for the comments. We have reviewed all comments received to make appropriate revisions to the finalized LCD and associated article. The Contractor will be finalizing this LCD in accordance with the LCD development process.

A comment from the Coalition signifies disappointment that stakeholders were not engaged in the development of this proposed LCD; including convening a meeting of its CAC to answer questions and discuss the evidence. Many of the clinical errors in this policy as well as the incorrect use of the evidence could have been caught prior to this draft being released.

Thank you for the comment. The Contractor is working to improve CAC member engagement. Stakeholder involvement is assured through their participation in the open meeting and through the public comment process.

Comments were received regarding the sixth paragraph in the ‘Analysis of Evidence’ section of the proposed LCD: “Amniotic/chorionic-based products that are HCT/Ps as defined in 21 CFR 1271.3(d) must meet criteria in 21 CFR 1271 and 361 of the PHS Act. Manufacturers of HCT/Ps should consult with the FDA Tissue Reference Group (TRG) or obtain a determination through a Request for Designation (RFD) on whether their HCT/Ps are appropriately regulated solely under section 361 of the PHS Act and the regulations in 21 CFR Part 1271 (85 FR 86058). The HCT/Ps that are drugs are defined under section 201(g) of the Federal FD&C Act [21 U.S.C. 321(g)] and biological products are defined in section 351(i) of the PHS Act [42 U.S.C. 262(i)]. To lawfully market a drug that is also a biological product, a valid biologics license must be in effect [42 U.S.C. 262(a)]. Such licenses are issued only after a showing of safety and efficacy for the product's intended use. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug (IND) application in effect as specified by FDA regulations [21 U.S.C. 355(i); 42 U.S.C. 262(a)(3); 21 CFR Part 312].”

One commenter signifies that the first sentence makes a statement about amniotic/chorionic based products must meet criteria in 21 CFR 1271 and 361 of the PHS Act. The second sentence states: “Manufacturers of HCT/Ps should consult with the FDA Tissue Reference Group (TRG) or obtain a determination through a Request for Designation (RFD) on whether their HCT/Ps are appropriately regulated solely under section 361 of the PHS Act and the regulations in 21 CFR Part 1271 (85 FR 86058).” It is unclear if the second sentence is making a statement specific to amniotic/chorionic based products, or all HCT/Ps should consult with the TRG or obtain an RFD.

A second comment from the WHS indicates the TRG is used for coding not coverage and a provider should not be required to provide a TRG letter in order to use any given product. Providers will not have those letters and not all CTPs require a TRG to obtain a code. In fact, manufacturers who obtain a 510K, PMA or BLA do not obtain TRG letters, nor are they required to do so. When a manufacturer does obtain a letter from the TRG, approval or clearance from the FDA, this information is not provided to providers and as such providers should not be required to provide this type of documentation in their records to provide a particular product to their patients. Rather, this information should be provided to the MAC in order for the product to be vetted and then ultimately covered in the policy.

A third comment from the Alliance and the Coalition indicates this language as written means that any product regulated under the PHS as an HCT/P is not considered medically necessary and reasonable despite the fact that this contractor indicated that a letter from the Tissue Reference Group for these products would be sufficient to provide coverage. This contradicts the contractor’s statements, and this language should be deleted from the policy.

Thank you for the comments. Regarding human cells, tissues, and cellular and tissue-based products (HCT/Ps), in the Physician Fee Schedule final rule for 2022, the CMS states: “We clarify that the availability of a HCPCS code for a particular HCT/P does not mean that the product is appropriately regulated solely under section 361 of the PHS Act and the FDA regulations in 21 CFR part 1271. Manufacturers of HCT/Ps should consult with the FDA Tissue Reference Group (TRG) or obtain a determination through a Request for Designation (RFD) on whether their HCT/Ps are appropriately regulated solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271 (85 FR 86058).” Therefore, Manufacturers of products that are considered HCT/Ps should consult with the FDA TRG or obtain a determination through a RFD on whether their HCT/Ps are appropriately regulated solely under section 361 of the PHS Act and the regulations in 21 CFR Part 1271 (85 FR 86058). Once this information (the TRG letter) has been received by the MAC, along with available evidence-based literature, the product will be reconsidered for coverage and moved into the appropriate Group in the associated article. The ‘Analysis of Evidence’ section has been revised in the finalized LCD to add the following sentence: “It is recommended that the manufacturer of the particular skin substitute graft/CTP obtain the appropriate evidence of FDA regulatory compliance (at least one of the items listed above that indicates the skin substitute graft/CTP provides scaffolding for skin growth, and is intended to remain on the recipient, and allows the recipient’s skin to grow into the implanted graft material) and send it to the MAC along WITH available peer reviewed evidence-based literature to support the medically reasonable and necessary criteria for the product(s). Once this information has been received by the MAC, the product will be considered for coverage.”

A comment was received regarding the second sentence in the eighth paragraph in the ‘Analysis of Evidence’ section of the proposed LCD: “To establish compliance with the FDA requires a letter from the FDA indicating that the HCT/P has met regulatory compliance under section 361 of the Public Health Service Act and/or the Federal Food, Drug, & Cosmetic Act.”

The commenter indicates this is not an accurate statement.

Thank you for the comment. Please refer to comment response number #30 and to the ‘Bibliography’ section of the LCD for references 4-6 which provide FDA guidance.

Several comments were received regarding the ‘Documentation Requirements’ in the associated article for bullets #8 and #9.

A commenter indicates these requirements are not able to be entered in the patient’s electronic medical record (EMR), resulting in manual documentation, which would create a significant administrative burden for providers. The documentation requirement to submit an FDA approval letter, listing and package insert for each bill submitted represents a redundant documentation requirement as CMS has this information included with all HCPCS applications for skin substitutes. This requirement should be deleted as it would be expected that CMS has reviewed this information in order to provide coverage for any skin substitute on the market. The commenter recommends that these documentation requirements be removed from the finalized article.

A second commenter indicates these documentation requirements (#8 and #9) appear to require providers to do extensive vetting of regulatory requirements, and upkeep requiring these in each patient chart. This type of vetting is beyond the scope of what is expected of a provider; moreover, it requires a level of library-keeping that represents an undue administrative burden and recommends that these bullets be removed.

A third commenter indicates that a letter from the FDA indicating that the HCT/P has met regulatory guidance under 361 is not provided by the FDA when the product is registered and is not an FDA condition to market a product. The only way for a letter to be obtained from the FDA by a manufacturer is by submitting a request for a recommendation with the TRG or submitting a RFD with the Office of Combination Products (OCP). The FDA states that the goal of the TRG and the RFD process is to respond within 60 days. Based on this being a documentation requirement, the commenter has concerns about the time frame to acquire a letter after requesting a recommendation from the TRG or submitting an RFD, will now exceed 60 days given the number of products that will now need to be reviewed by these FDA departments. Will there be a grace period provided to allow manufacturers time to make the request and receive a response back from the FDA? Will facilities/providers now need to maintain a copy of this letter in patient’s medical records?

A fourth commenter signifies providers would not have immediate access to this information. It is not clear why this is being requested from the providers, which is clerical in nature and is an undue administrative burden.

A fifth comment from a plastic surgeon indicates these requirements inappropriately require providers to obtain and curate documents related to regulation of products as human cells, tissues, and cellular and tissue-based products (HCT/Ps) and include these documents in patient records.

A sixth comment from the Alliance and the Coalition denotes these requirements present an undue administrative burden for providers. Because the language appears under Documentation Requirements, it gives the impression that physicians/other qualified healthcare professionals are responsible for heavily vetting and proving the FDA status of a CTP within each patient 's medical record and at each encounter. This requires a lot of work for the provider that is at odds with administrative simplification and this information should not be in patients' medical records. Rather it is the responsibility of this MAC to obtain the FDA information to ensure that the CTPs meet requirements for coverage. Specifically, the LCD states that coverage for Group 2 products “will be provided…in the associated billing and coding guideline meeting the necessary FDA regulatory requirements as of publication. Each product has specific designated approved usage.” Therefore, Group 2 and Group 3 products have already been vetted by the MAC, especially within a policy that has the prescribed scope of DFU/VLU only, and documentation in the patients' medical records should not be required. This language should be eliminated from this policy given the MAC has already vetted these products and providers do not have access to this information.

Thank you for the comments. The finalized associated article has been revised to remove bullets #8 and #9 under ‘Documentation Requirements’ and this information has been placed into a separate paragraph. This information is intended as a notice to the manufacturers of the products that this information should be sent to the MAC for the product to be considered for coverage. Providers would not be expected to send this information in with the claim or to maintain this documentation in the medical records. It is also important to note that the provision of a CPT/HCPCS code for a product or service does not equate to coverage of the product or service.

Comments were received regarding the following statement in the ‘Coding Guidance’ section of the associated article: “Application codes billed must use the appropriate modifier (e.g., RT, LT) to identify the location where the skin substitute was applied, or the service will be denied.”

One commenter indicates right (RT) and left (LT) modifiers are inappropriate for skin substitutes as this requirement conflicts with how skin substitutes are measured and coded. The correct CPT code to identify the service is determined by the depth of the wound. The appropriate code for a patient that has multiple wounds is determined by the sum of all the patients’ wounds by depth and site. The AMA CPT manual states “for multiple wounds, sum the surface area of all wounds from all anatomic sites that are grouped together in the same code descriptor.” Thus, mandating right and left modifiers could create confusion if the patient has multiple wounds on both the left and right side of the body. Moreover, granularity of ICD 10 CM diagnosis codes will in most cases provide information on which side(s) of the body the ulcers occur. The commenter recommends that the requirement to use RT and LT modifiers be removed to avoid potential confusion and better align with CPT guidelines and proper coding of these services.

A second comment from the TPMA, the APMA, the MPMA, the ASPS, the ASSH, and the NMPMA signifies this guidance is contrary to current CPT guidance. If two different contralateral ulcers from the same CPT code anatomic group receive application of a skin substitute graft, using a RT or LT modifier would contradict CPT guidance regarding appropriate use of its codes and modifiers. Page 112 of the 2022 CPT Professional book provides direction regarding appropriate utilization of these skin substitute graft application CPT codes. It states: “Select the appropriate code from 15271-15278 based upon location and size of the defect. For multiple wounds, sum the surface area of all wounds from all anatomic sites that are grouped together into the same code descriptor.” Therefore, if a skin substitute graft was applied to both a 4 sq cm ulcer on the left foot and a 2 sq cm ulcer on the right foot at the same session, the appropriate CPT coding to represent this service would be one unit of CPT 15275 (Application of skin substitute graft to face, scalp, eyelids, mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits, total wound surface area up to 100 sq cm; first 25 sq cm or less wound surface area). It would be inappropriate to apply either a RT or LT modifier in this instance since both the right and left limbs were addressed. Generally, RT and LT modifiers are not appended to CPT codes that quantify the work performed. Often that guideline applies for the situation in which summed work may have been performed contralaterally, which is often the case with skin substitute applications, and is modeled in the example provided above. The Health Insurance Portability and Accountability Act [HIPAA] of 1996, Pub. L. No. 104-191 requires that all health plans use the most recent version of the medical data code set. To remain consistent with CPT guidance, the TPMA and the APMA request that this sentence be removed for referencing required use of RT or LT modifier from the LCA when it is finalized. This will help to avoid confusion in coding and ensure compliance with HIPAA.

A third comment from a podiatrist declares this must be an error. The CPT codes address size and have appropriate codes available. Assigning RT/LT would add confusion and inappropriate adjudication of claims. The current CPT codes are assigned based on the total amount of area regardless of RT or LT.

A fourth commenter confirms support for utilizing the RT and LT modifier in the coding process.

A fifth commenter signifies the left/right modifier requirement for 15271-15278 is unnecessary and goes against the intention of these codes, which is to sum like anatomical parts (for example, all foot ulcers) regardless of laterality. The commenter suggests removing the LT/RT modifier requirement and relying on the ICD-10 codes for data related to laterality.

A sixth commenter recommends this requirement be deleted as the ICD-10 codes include the designation of right or left when reporting the diagnoses on a claim form. There is no need for the RT or LT modifier to correspond with the CPT coding series 15271-15278.

A seventh comment from the Alliance signifies that while they are aware of some payers that request these informational modifiers when reporting 15271-15278, it is not a CPT requirement and has the potential to create confusion. RT and LT modifiers are unnecessary because it is literally already captured within the ICD-10 diagnoses codes. Moreover, it is illogical in the context of these procedure codes: 1) the skin is a contiguous organ without a left or right, and 2) 15271-15278 sums the area of like anatomical sites (For example, on the same date of service and same patient, a CTP applied to both left and right feet will only generate one code based on the sum of all foot ulcers receiving the product). Furthermore, the AMA CPT manual states “for multiple wounds, sum the surface area of all wounds from all anatomic sites that are grouped together in the same code descriptor.” Thus, mandating right and left modifiers could create confusion if the patient has multiple wounds on both the left and right side of the body. The MAC should remove the LT/RT modifier requirement and rely on ICD-10 codes to avoid potential confusion and better align with CPT guidelines and proper coding of these services.

Thank you for the comments. Following additional review of the CPT guidance and consideration of the comments received, this requirement has been removed from the finalized associated article.

A comment from a physician indicates concern regarding the proposal to designate certain products as ‘covered’ and other products as ‘non-covered' for the treatment of diabetic foot ulcers and venous leg ulcers. His concerns arise from a lack of clarity as to how products would be assigned to one of the two categories as well as how much reimbursement confusion this proposal would create. If this LCD becomes active, he would be able to say that he has used ‘covered’ and ‘non-covered’ products that have achieved good results for the closure of wounds. Under the proposed LCD, he could initiate a patient’s treatment with a ‘covered’ product and even though the wound could be progressing towards healing, the product could suddenly become ‘non-covered’ mid-treatment. He would then need to either convert the patient to a different product, which could also be prohibited by the proposed LCD, or have the patient assume the cost of the skin substitute that is actively moving their wound towards healing. The proposed LCD should either remove the categorization of ‘covered’ or ‘non-covered’ products altogether or it should provide a more detailed definition of the criteria to be assigned to the different categories.

A second commenter expresses there is omitted coverage of products in the associated article including many sheet products despite meeting the requirements provided in the LCD. Additionally, there is no transparency or reasons provided as to why products that are currently covered have been moved to the non-covered grouping. Justification or rationale for moving these products in the noncovered list in the draft was not provided and therefore the requirements for the decrease in coverage has not been met.

A third comment from a physician, twenty-one podiatrists, and a nurse practitioner indicates certain product exclusions should also be re-reviewed with consideration to their approved FDA packaging information or instructions for use.

A fourth commenter signifies the LCD does not list the criteria or rationale for its grouping decisions, the distinction between Groups 2 and 3 seems to be the presence or absence of a biologics license application (BLA) or, in the case of 361 HCT/Ps, a letter from FDA’s TRG. Rather than focus on particular paperwork from the FDA, the MAC should list all sheet products (i.e., those with a Q code that are reimbursed on a “per sq cm” basis) to the covered list (i.e., Group 2) and list all non-sheet products (i.e., those with a Q code that are reimbursed on a “per cc”) as non-covered in Group 3. The terminology “per sq cm” and “per cc” easily distinguishes whether the product is a sheet product or non-sheet product (i.e., the latter being a more than minimally manipulated HCT/P requiring a BLA). Alternatively, the MAC could provide Group 3 “per sq cm” products with a grace period of 12 months to be covered in Group 2 on an interim basis to allow manufacturers sufficient time to obtain a TRG letter. Such a period would account for the current backlogs at the TRG. If, at the conclusion of the grace period, the product remains without a TRG letter, it could then be moved to Group 3.

A fifth commenter agrees with the language on HCTP injectable and particulate products as this aligns with the FDA guidance document enforced in 2021.

A sixth commenter confirms agreement with listing covered and non-covered codes in Groups 2 and 3 respectively.

A seventh commenter asserts it should be the responsibility of the MAC to have on file the regulatory information for each skin substitute Q or A code. The provider should not be obligated to scan in the same regulatory approval information into each patient chart and date of service. This is redundant and takes time away from patient care. The group 2 and 3 code lists should reflect whether a product is covered and if the MAC has the appropriate paperwork on file.

An eighth comment from a certified wound specialist recommends allowing clinicians to use their medical judgement to continue to select skin substitutes that are currently approved and reimbursed. The proposition of “Grouping” products by covered and non-covered is not clearly justified or defined. Many of the grafts moved to Group 3 have been clinically efficacious in their practice. Wound healing is often delayed for a multitude of factors. What the wound “needs” can change during the course of treatment. She feels strongly that the selection of product should be determined by a qualified, wound specialist, one who is well versed in the impediments to a specific wound’s healing, as well as the compilation of the product, such as growth factor deficiencies, extracellular matrices, or antimicrobial products for chronically colonized or wounds at risk for contamination or critical colonization. Specific medical justification is not listed in the proposed changes. Please share these details if there is a reason why these products have been moved to an unapproved or non-covered list for a medical reason.

A ninth commenter denotes that the existing body of high quality, Level 1 Evidence was disregarded for several skin substitutes and instead proposes coverage solely on FDA registration. FDA regulation across 510K or HCT/P 361 exempted products does not confer evidence of clinical efficacy. Rather these regulatory classifications only represent a substantial equivalence (510 K) or safety with homologous use (HCT/P 361). Government and commercial payers can and should look to cover products and services backed by research. The commenter disagrees with the conclusion drawn from the 2012 and 2020 AHRQ Technology Assessment, Skin Substitutes for Treating Chronic Wounds. The statement, “Studies are lacking for many wound care products (e.g., skin substitutes) which are essential to evaluate effectiveness and the impact that the product has on health outcomes” is correct for most skin substitutes but not all. In fact, the latest AHRQ report identified 22 RCTs that met comprehensive inclusion/exclusion criteria for the assessment. To ignore the statistically significant Level 1 RCTs that do exist, (thus allowing coverage for any product regardless of evidence) contradicts the rationale that more evidence is needed. How will more studies be completed if all products are covered? If coverage is maintained solely through correct filing with the FDA, there is no incentive for a manufacturer or any other sponsor to spend the time and expense to conduct randomized controlled trials. Using HCPCS codes as a metric, there are approximately 150 skin substitutes commercially available and a finite number of well-designed RCTs identified throughout the 2012 and 2020 AHRQ Technology Assessments. To cover any product that files correctly with the FDA contradicts the 21st Century Cures Act that explicitly states the LCD development must summarize clinical evidence supporting LCD development and MAC coverage determination rationale. We recommend that skin substitutes are considered for coverage that have published, peer reviewed RCTs. Other products are eligible to submit for coverage through the reconsideration process as evidence emerges and possibly consider Level 2 evidence or other research such as Real World Evidence in coverage decisions. However, relying on no research in determining coverage is contradictory to most payer coverage policies as well as the 21st Century Cures Act.

A tenth commenter denotes provider choice and provider preference are extremely important in the treatment of DFUs and VLUs and providers use and trust different products for different ulcers in varying circumstances. Limiting product choice would limit patient care.

An eleventh commenter requests that the timeline be delayed for all Group 3 products in the associated coding and billing article to comply with the requirements to be approved for reimbursement.

A twelfth comment from a wound care physician conveys the proposed LCD indicates that the skin substitute products are to be in accordance with their approved FDA intended use. He points out that not all products are FDA approved and wants to ensure that those products will also be allowed in the LCD.

A thirteenth comment from the Alliance specifies that not all products under this policy require FDA approval as indicated. The pathway in which products are brought to market varies and thus the evidence required varies depending on the pathway. For example, products designated under 361 of the PHS do not obtain FDA approval nor do products under the 510K process as they are not approved but rather receive clearance. The commenter recommends revising the language to: FDA approval/clearance and/or coverage for devices is determined by the evidence required for the applicable pathway. The appropriate use of a device and accepted medical practice are often different from the FDA approval/clearance since additional and better research and evidence often come to light after said approval. Thus, the process of FDA clearance/approval should not be confused with the process of determining coverage policy. The use of a CTP must meet the medically reasonable and necessary threshold for coverage.

A fourteenth commenter indicates the list of covered codes notes they meet the guidelines in the proposed LCD, leading us to believe the ones that are listed as not covered do not. However, there are a number of codes on the not covered list that do meet that criteria and are either cleared via the 510K process or 361 HCT/P route. Please provide info as to why they are listed as not covered so they can properly respond.

A fifteenth comment from a podiatrist maintains many providers (hospitals and physician practices) have purchased and stocked items that are now being moved to Group 3 non-covered items despite having proven clinical efficacy. This creates a great financial risk and burden on providers who have stocked these items and risk losing them due to the proposed LCD changes. They request that the necessary time is given to either allow manufacturers to comply with regulations allowing them to enter Group 2 covered items and/or allow providers ample time to utilize their already purchased items i.e., 12-18 months before moving into agreements with Group 2 manufacturers.

Thank you for the comments. As noted in the ‘Analysis of Evidence’ section of the finalized LCD: “Coverage will be provided for products which meet the necessary FDA regulatory requirements as of publication, and that act as a skin substitute graft/CTP providing scaffolding for skin growth, and are intended to remain on the recipient, and allow the recipient’s skin to grow into the implanted graft material. Products that require regular replacement (e.g., weekly) which do not act as a skin substitute graft/CTP are non-covered. These products act as coverings/dressings, are part of standard wound care, and do not provide active ulcer treatment by providing scaffolding and stimulating cell growth. In conclusion, there is no separate payment for the application of wound coverings or wound dressings, which are utilized to provide a physical barrier to protect the ulcer (wound) surface, prevent infection, and allow healing underneath, and are typically removed as the ulcer or chronic wound heals. Wound coverings are not anchored or applied surgically to ulcers to form scaffolding for skin growth and are therefore not skin substitute grafts/CTPs.”

“Each skin substitute graft/CTP has a specific designated approved usage. New products will be considered for coverage if meeting the regulatory requirements and criteria. Satisfactory evidence of compliance with FDA regulatory requirements includes: 1) A copy of the FDA’s letter to the drug’s manufacturer approving the new drug application (NDA), 2) A listing of the drug or biological in the FDA’s “Approved Drug Products” or “FDA Drug and Device Product Approvals”, 3) A copy of the manufacturer’s package insert approved by the FDA as part of the labeling of the drug, containing its recommended uses and dosage, as well as possible adverse reactions and recommended precautions in using it, 4) A TRG letter from the FDA, or 5) Information from the FDA’s Website regarding intended use of the product as approved/regulated by the FDA. For skin substitute grafts/CTPs classified as HCT/Ps, a letter from the FDA indicating that the HCT/P has met regulatory guidance is acceptable evidence of the FDA regulatory compliance for HCT/Ps regulated under section 361 of the PHS Act and/or the FFDCA. It is recommended that the manufacturer of the particular skin substitute graft/CTP obtain the appropriate evidence of FDA regulatory compliance (at least one of the items listed above that indicates the skin substitute graft/CTP provides scaffolding for skin growth, and is intended to remain on the recipient, and allows the recipient’s skin to grow into the implanted graft material) and send it to the MAC along WITH available peer-reviewed evidence-based literature to support the medically reasonable and necessary criteria for the product(s). Once this information has been received by the MAC, the product will be considered for coverage.”

This information is also listed in the associated article. In this regard, please see the Contractor response to Comment #32.

The CMS provision of a CPT/HCPCS code does not equate to coverage of the service. As stated in the proposed LCD: “Use of skin substitute grafts or CTPs must meet the medically reasonable and necessary threshold for coverage and these devices must be used in accordance with their approved United States (U.S.) Food and Drug Administration (FDA) intended use.” This sentence has been revised in the finalized LCD to: “Use of skin substitute grafts/CTPs must meet the medically reasonable and necessary threshold for coverage and must be used in accordance with their intended use as approved/regulated by the United States (U.S.) Food and Drug Administration (FDA).”

A comment from a podiatrist expresses concern that ICD-10 L97.5- codes will not be allowed for use of biologic skin grafts. Most of his diabetic patients (probably around 95%) have the majority of their ulcers on forefoot and toes. Since using biologics in his practice amputation rates have significantly decreased. Without the use of grafts on forefoot and toes, he is afraid the amputation rate will significantly increase. Once amputations have begun, these patients can eventually end up with leg amputation. This in turn increases mortality of the patient to a level of 50% within five years once a leg has been amputated. Six articles were included with this comment.

A second comment from the TPMA, the APMA, the MPMA, the ASPS, and the ASSH requests the addition of ICD-10 L97.5- codes to the ‘ICD-10 codes that Support Medical Necessity’ section. These codes are used, in part, to identify DFUs of the forefoot (the area of the foot distal to the midfoot). The TPMA, the APMA, and the NMPMA request that the following ICD-10 codes be added to the associated article for coverage: I83.011, I83.012, I83.013, I83.014, I83.015, I83.018, I83.021, I83.022, I83.023, I83.024, I83.025, I83.028, I83.211, I83.212, I83.213, I83.214, I83.215, I83.218, I83.221, I83.222, I83.223, I83.224, I83.225, I83.228, I87.011, I87.012, I87.013, I87.031, I87.032, I87.033, L97.111, L97.121, L97.211, L97.221, L97.311, L97.321, L97.411, L97.421, L97.511, L97.512, L97.521, L97.522, L97.811 and L97.821.

A third comment from the Alliance and the Coalition requests most of the codes requested above in the ‘second comment’ in addition to I83.019, I83.029, I83.219, I83.229, I87.019, I87.039, I87.311, I87.319, I87.339, L97.113, L97.114, L97.115, L97.116, L97.118, L97.119, L97.123, L97.124, L97.125, L97.126, L97.128, L97.129, L97.202, L97.203, L97.204, L97.205, L97.206, L97.208, L97.209, L97.213, L97.214, L97.215, L97.216, L97.218, L97.219, L97.223, L97.224, L97.225, L97.226, L97.228, L97.229, L97.313, L97.314, L97.315, L97.316, L97.318, L97.319, L97.323, L97.324, L97.325, L97.326, L97.328, L97.329, L97.413, L97.414, L97.415, L97.416, L97.418, L97.419, L97.423, L97.424, L97.425, L97.426, L97.428, L97.429, L97.513, L97.514, L97.515, L97.516, L97.518, L97.519, L97.523, L97.524, L97.525, L97.526, L97.528, L97.529, L97.813, L97.814, L97.815, L97.816, L97.818, L97.819, L97.823, L97.824, L97.825, L97.826, L97.828, L97.829, L97.912, L97.913, L97.914, L97.915, L97.916, L97.918, L97.919, L97.922, L97.923, L97.924, L97.925, L97.926, L97.928, L97.929, E08.621, E08.622, E09.621, E09.622, E10.621, E10.622, E11.621, E11.622, E13.621, E13.622, I87.312, I87.313, I87.331, I87.332, I87.333, L97.112, L97.122, L97.212, L97.222, L97.312, L97.322, l97.412, L97.422, L97.812, and L97.822 (for I83-I87, use an additional code to specify site and severity of ulcer).

A fourth commenter denotes that the venous insufficiency codes are incomplete and do not capture varicose veins with ulcer, varicose veins with ulcer or inflammation or postthrombotic syndrome with ulcer. L97.5XX is omitted, which captures ulcers on other parts of feet including toes. The instructions reference “standalone” L97 codes, which is not possible if the LCD pertains to DFU/VLU only (ulcers with these etiologies must have an accompanying E or I code, per ICD-10 coding guidelines). The L97 codes listed are for one depth of ulcer (fat layer exposed). Patients with other depths of ulcers (both shallower and deeper) also require skin substitutes, and many product IFUs allow for this. Deeper ulcers in particular may require a combination of sequential advanced therapies (e.g., negative pressure wound therapy followed by a skin substitute) as part of a limb salvage plan. Amputation is a potential consequence of not allowing skin substitutes outside of codes represented by fat layer exposed. Both major and minor amputations are in turn associated with a five year mortality rate comparable to many forms of cancer. Perhaps most importantly, the listed diabetes codes only contain those with the EXX.621 suffix. Providers will be unable to treat diabetic ulcers even at the ankle level (L97.3XX) as they map to EXX.622. The commenter recommends that the ICD-10 list be eliminated from the associated article.

A fifth comment from Peripheral Vascular Associates requests the addition of diagnosis codes for partial and full thickness ulcers to the associated article.

A sixth comment from the Coalition notes several issues/examples within the associated article related to ICD-10 (Group 1) coding including but not limited to:

• The diabetes codes (EXX.621) contain only those codes with the .621 suffix. They submit that the proposed LCD focuses on DFUs. However, although industry uses “DFU” most policies actually mean to include diabetic lower extremity ulcers.
• The code list as written allows diabetic foot only and precludes any diabetic ulcer even as low as the ankle. (Per coding instructions, EXX.621 uses additional code L97.4XX and L97.5XX to identify site of ulcer. These are heel and midfoot, and other part of foot respectively. Anything ankle or above is not included).
• The article does not allow for the necessary EXX codes that are captured with the .622 suffix.
• The included L97 codes capture only “fat layer exposed.” No other depth of ulcer is included in this list (such as breakdown of skin, muscle involvement without evidence of necrosis, bone involvement without evidence of necrosis). While some product Instructions for Use (IFUs) or FDA labelling may prohibit application over muscle, joint capsule, tendon, or bone, this is not true for all of them.
• Moreover, these patients with deeper ulcers are the ones at highest risk for infection, hospitalization, amputation, and death. As written, this administrative list creates a reality where the patients who need advanced care most, these codes are “not covered” by their local MAC.
• The list omits L97 codes that capture other part of the foot (L97.5XX). L97.5XX are not unspecified codes, but rather very specific codes that capture anything on the foot that is not on the heel or midfoot. Toes are included in L97.5XX. The current list implies that diabetic ulcers on the toes or other parts of the foot cannot meet medical necessity for skin substitutes.
• The below instruction is contradictory and confusing: For example: As noted above, the EXX codes listed within the article do not allow for the .622 suffix. This means that the ankle codes L97.3X2 that are listed do have the correct mapping available.
• As well, the instruction states, “the L97 codes are standalone codes if they are listed in the table above.” This does not fit with the expressed purpose of the draft LCD, which is to address DFU/VLU only. To capture (accurately) DFUs or VLUs, two codes are needed: one to identify the underlying etiology and basic location, and one to identify the exact site and depth. L97 codes by themselves do not capture diabetes or venous insufficiency. There are no possible standalone L97 codes if the LCD and article are devoted to these two etiologies.
• The list of covered venous insufficiency codes does not capture patients’ needs. Omitted codes include those that represent varicose veins with ulcer, or post thrombotic syndrome with ulcer.

A seventh comment from a podiatrist affirms that L97.5 is not included in the proposed ICD-10 list. He indicates that omission of this code would leave a void by not addressing forefoot ulcers.

Thank you for the comments. After reviewing the comments and the coverage verbiage in the revised LCD, the Contractor agrees with the inclusion of the following diagnoses in the finalized associated article that fall under the revised indications and limitations of the LCD: I83.011, I83.012, I83.013, I83.014, I83.015, I83.018, I83.021, I83.022, I83.023, I83.024, I83.025, I83.028, I83.211, I83.212, I83.213, I83.214, I83.215, I83.218, I83.221, I83.222, I83.223, I83.224, I83.225, I83.228, I87.011, I87.012, I87.013, I87.031, I87.032, I87.033, L97.111, L97.121, L97.211, L97.221, L97.311, L97.321, L97.411, L97.421, L97.511, L97.512, L97.521, L97.522, L97.811 and L97.821.

A commenter indicates many Medicaid and commercial payers look to Medicare LCDs for guidance and utilize revenue codes for their payment models. Only a handful of skin substitute products have NDC codes. The rest utilize UDIs, GTINs, or another numbering system. Some EMR systems require an NDC number when revenue code 636 (drugs requiring detailed coding) is used. This is the most common revenue code used when utilizing skin substitutes in an HOPD setting however, it causes numerous billing and reimbursement errors if the product does not have an NDC. Several other revenue codes can be used such as 270 (med/surgical supplies), 271 (non-sterile supplies), 272 (sterile supplies), 623 (surgical dressings). These would also be applicable in the description of a skin substitute product. The commenter recommends that the billing article list all possible revenue codes that can be used when billing a skin substitute product in the HOPD setting so hospitals and providers have clearer guidance.

Thank you for the comment. Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report a service. In most instances Revenue Codes are purely advisory. Unless specified in the billing and coding article, services reported under other Revenue Codes are equally subject to the local coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Codes and the associated article should be assumed to apply equally to all Revenue Codes.

A commenter indicates many patients cannot afford or obtain transportation to a hospital outpatient facility or physician office to receive treatment. The COVID pandemic has shown us that the use of telemedicine and home visits has been successful in the treatment of patients. Medicare should not discriminate toward patients living in assisted living, nursing home or other various sites of care that are paid under Part B. If the physician provides face to face services at their current location and that location is payable to physician under the NF rate (non-facility) then the skin substitute treatment should be covered. Currently some MACs limit coverage to only a physician office (POS 11) or HOPD (22). This leads to reduced patient care and increased costs to Medicare for transportation or not seeking treatment at all resulting in expensive complications (amputation, hospital admissions/readmissions, infections etc.). The LCD Billing Article should list out each place of service paid for under Part B at NF rate so providers understand where they can treat the patient.

A second commenter asks if the use of skin substitutes for treatment of DFUs and VLUs can be conducted in the Office setting (Place of Service-11). And if so, will the payment for skin substitute products in the office setting follow the same payment packaging assignment as OPPS payment? For example, the Ambulatory Surgical Center (ASC) Payment says, do not separately bill for packaged skin substitutes (ASC PI=N1) since packaged codes are not reportable under the ASC payment system. Which means those HCPCS codes for skin substitutes products are classified by “High” or “Low” and depending on the classification either CPT codes 15271-15278 (used for High) or C5271-C5278 (used for Low) will be billed, and the skin substitutes products will be considered bundled with procedure. Also, please provide information if the Office setting will follow the same payment principle as ASC. Or at least provide where I can find answers.

Thank you for the comments. Services provided within the LCD coverage indications will be considered medically reasonable and necessary when all aspects of care are within the scope of practice of the provider’s professional licensure; and when all procedures are performed by appropriately trained providers in an appropriate setting. For payment information, please reference the CMS website https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/FeeScheduleGenInfo.

A comment was received requesting that documentation requirements should include a photo of the wound. The commenter indicated that photo documentation is part of the medical record which physicians rely on for wound assessment and treatment evaluations such as medical necessity and appropriate use of skin substitutes for the treatment of DFUs and VLUs.

Thank you for the comment. Photographic evidence is not required by the Contractor. Photographs may be a part of the documentation supporting that the criteria listed in the LCD has been met. All documentation supportive of the reasonable and necessary criteria listed in the LCD must be maintained in the patient’s medical record and made available to the Contractor upon request.

Comments were received requesting the rationale for moving products into the Group 3 non-covered list when article was re-posted.

Thank you for the comments. Products moved into the Group 3 Codes section in the re-posted article included products which the Contractor had no evidence of FDA regulatory compliance and products with FDA designation or approval as a dressing or wound covering that the Contractor lacked evidence that they improve health outcomes or provide benefits relative to established alternatives or standard of care when used as an ulcer treatment by forming a sheet scaffolding for skin growth.

Several comments were received requesting specific skin substitute products/CTPs in the Group 3 Codes section of the associated billing and coding article be moved into the Group 2 Codes section.

Thank you for your comments. Despite the paucity of-quality studies, the moderate to low quality of current research and the likelihood of bias, coverage has been provided to increase the chances of improved health outcomes of interest which include patient quality of life and function. Coverage will be provided for products which meet the necessary FDA regulatory requirements as of publication and that act as a skin substitute graft/CTP providing scaffolding for skin growth and are intended to remain on the recipient and allow the recipient’s skin to grow into the implanted graft material. Products that require regular replacement (e.g., weekly) which do not act as a skin substitute graft/CTP are non-covered. These products act as coverings/dressings, are part of standard wound care, and do not provide active ulcer treatment by providing scaffolding and stimulating cell growth. In conclusion, there is no separate payment for the application of wound coverings or wound dressings, which are utilized to provide a physical barrier to protect the ulcer (wound) surface, prevent infection, and allow healing underneath, and are typically removed as the ulcer or chronic wound heals. Wound coverings are not anchored or applied surgically to ulcers to form scaffolding for skin growth and are therefore not skin substitute grafts/CTPs.

Comments were received requesting that this LCD be postponed to align this policy with the CMS 2023 physician proposed rule, which contemplates that any change for skin substitutes occur by January 2024 or within one to five years of this date to eliminate any provider confusion in clinical treatment considerations.

Thank you for your comments. The LCD will be finalized as stipulated in the LCD development process. This LCD addresses coverage criteria which are not affected by the proposed CMS payment rules.