Response to Comments: Platelet Rich Plasma

Comments were received from the American Association of Oral and Maxillofacial Surgeons (AAOMS). They submitted an additional study to provide evidence of benefit on the use of  platelet rich plasma (PRP) in oral and maxillofacial surgery, specifically with major bone graft procedures.

The commentor further indicates that PRP use in dental and oral surgery has increased in utilization due to the use of platelet rich fibrin (PRF) and bone marrow aspirate concentrate (BMAC), which are different services from PRP, but do not have their own CPT code. Therefore, usage is likely being reported as PRP.

Thank you for the submission of additional literature. This article has been added to the review in the LCD. While this article suggests potential promise, the small numbers, prospective study design, lack of comparator, and lack of long-term outcome data do not provide robust evidence to demonstrate the efficacy of PRP in this population. If additional studies are published that support this indication, they can be reviewed through the LCD reconsideration process.

The use of PRF and BMAC in these procedures and reporting these services as PRP would be incorrect. When a service does not have a CPT code that adequately describes the service, it should be reported with a Not Otherwise Classified (NOC) code.

The AAOMS also submitted a comment stating “Use of PRP is vital as a bioactive material in certain types of bone grafting scenarios. PRP is essential in cases of osteoradionecrosis; the treatment of failed bone grafts; and grafting in the presence of infection. It has been documented that PRP has been helpful with soft tissue repair and revascularization of the operative site.”

The literature reviewed and included in the LCD Summary of Evidence does not support the use of PRP for these scenarios. Literature was not submitted with the comment to support the role of PRP in these conditions. If additional studies are published that support these indications, they can be submitted once the LCD is finalized and reviewed through the LCD reconsideration process.

A comment was submitted from a blood component, therapeutic apheresis, cellular and autologous biologic technologies company requesting medical necessity for PRP. The company provided additional clinical studies to support the use of PRP for a variety of chronic and degenerative diseases to repair tissue and organ damage.

Thank you for your comment. Several of the submitted studies were already included in the LCD; the others were reviewed and added to the LCD if appropriate. Non-English studies were excluded. Park et al provides a Level I study for the use of PRP in osteoarthritis of the knee. While this study is high-quality, its sample size was too small to extrapolate to a larger population. It alone cannot address the lack of standardization across the body of literature on this subject. Efforts to achieve this were attempted with several meta-analyses, which were included in the list. However, meta-analysis is ineffective when there is a lack of high-quality data and does not address the fundamental issues as multiple confounders such as the source of stem cells, most effective delivery method, the role of surgery, and type and amount of PRP used. As more high-quality literature is produced, answers to these questions may be found. In that case, the role of PRP for the treatment of osteoarthritis of the knee can be re-evaluated through the LCD reconsideration process once the LCD is finalized.

A comment was submitted from Zimmer Biomet, a manufacturer of devices for preparation for PRP. The company acknowledged that the efficacy/medical necessity of PRP is not clearly proven for all musculoskeletal soft tissue injuries. However, they requested coverage of PRP for Chronic Lateral Epicondylitis (Tennis Elbow), Chronic Plantar Fasciitis, Chronic Achilles Tendinopathy, and Chronic Patellar Tendinopathy (Jumper’s Knee) because they feel treatment with PRP is well supported in clinical literature for these conditions. Additional literature to support use was submitted. These studies with comments included:

1. Mishra et al study, while there was a lack of improvement in global pain scores at 12 weeks, the authors did report improvement at 24 weeks which was not included in the LCD evidence analysis.
2. Watt et al 2018 was submitted which reviewed a study comparing leukocyte-rich platelet-rich plasma injections with a surgical intervention for the management of refractory tennis elbow.
3. The commenters state that they did not feel that the review of the 2014 Cochrane database review by Moraes et al was a full assessment of the reported outcomes and pointed out that the authors did report evidence to support the use of PRP to treat lateral epicondylitis through improved function (PRTEE, Liverpool Elbow scores) vs. control at both 3 and 6 months (p=0.044, p=0.00074).
4. The commentator notes the Fitzpatrick et al (2017) study differentiates between leukocyte-rich and leukocyte-poor PRPs for treatment of tendinopathies. It concludes that Leukocyte-rich PRP improves outcomes in tendinopathies. They state, "the authors concluded that the analysis found strong evidence that LR-PRP improves outcomes in tendinopathy and that the type of PRP and the techniques used affect the outcomes and should always be included in any future meta-analysis."

1. While the Mishra study (2013) did report improvement in the PRP group at 24 weeks compared to the control group, the results were not statically significant (P= 0.037).
2. Watt et al was not included in the proposed LCD. In this study, patients with chronic tennis elbow were randomized to surgery vs. PRP. They reported that surgical patients have lower pain scores at 12 months and that 70% of PRP patients avoided surgery. However, there was not a conservative arm, so the outcomes without either intervention are unknown. Additionally, the number of patients who received PRP who eventually proceeded with surgical management after 12 months is unknown. Due to the nature of the study, blinding was not feasible but still introduces the risk of bias.
3. While the Cochrane review did report that three elbow epicondylitis trials showed a statistically significant difference in favor of PRP, the author also acknowledges the clinical significance of this finding is uncertain. The available evidence was deemed insufficient to conclude if the effect of PRP will “differ importantly in individual conditions.”
4. The investigation of leukocyte poor vs leukocyte rich plasma is a useful step in providing evidence towards more standardization of the PRP preparations. Clinical trials must use standardizations to gain the evidence needed to fully understand and evaluate the role of PRP. While this study is a step towards providing evidence to support one factor, it has not been reproduced or confirmed. The authors are accurate in stating that future meta-analysis should clarify platelet rich or platelet poor PRP but unfortunately many of the studies that would be included in analysis do not specify this information as that has not been a subject of investigation in many of the PRP studies.

Zimmer Biomet also provided an evidence table of twenty articles published on the safety and performance of the Zimmer Biomet devices used to treat tendinosis, which were summarized in an evidence table.

Thank you for the evidence summary. The performance of specific devices for the preparation of PRP is beyond the scope of the LCD. The evidence table provided represented studies in a population notably younger than the average Medicare population. Only one of the submitted studies includes patients over 65; therefore, extrapolation to the Medicare population is uncertain.

Nonetheless, we agree that there is clinical literature that favors the safety of PRP. However, this does not address the fundamental problem of lack of standardized protocols and wide variations in procedural technique. As stated in the LCD, for a treatment to be considered medically reasonable and necessary per 1862(a)(1)(A) of The Act the treatment must be appropriate, including duration and frequency furnished following accepted standards of medical practice for the condition. The lack of accepted standards of medical practice and, therefore, a lack of consistency in these studies has resulted in a heterogeneous body of literature that does not answer the fundamental questions of safety and efficacy nor provide standard practices for use. Once PRP preparations, injection volumes, and techniques are more standardized, the literature may provide these answers and appropriate patient selection criteria, which is currently lacking. New literature and societal guidelines that address these concerns may be submitted for reconsideration of the non-coverage policy.

A comment was received from Mayo Clinic indicating non-support of the proposed PRP LCD. They state, "higher quality level 1 research for knee osteoarthritis has amassed in recent years" and draws attention to the conclusions on pages 12 and 13 of the LCD regarding PRP in the treatment of knee osteoarthritis. The commentor feels the "conclusions do not accurately reflect the current efficacy of the literature on PRP for knee osteoarthritis." While the commentor does "acknowledge the heterogeneity of PRP preparation and follow-up duration in these studies as a potential factor that can make interpreting the results difficult", the commentor believes that "despite this heterogeneity, the literature demonstrates either effectiveness, better effect or non-inferiority" compared to standard treatments for mild or moderate knee osteoarthritis. The commentor referenced 28 sources, but did not include any full-text articles to support the use of PRP.

Thank you for your comments. While we agree there is emerging evidence for PRP therapy, this does not address the fundamental problem of lack of standardized protocols and wide variations in procedural technique. As stated in the LCD, for a treatment to be considered medically reasonable and necessary per 1862(a)(1)(A) of The Act the treatment must be appropriate, including duration and frequency following accepted standards of medical practice for the condition. The lack of accepted standards of medical practice and, therefore, a lack of consistency in the studies has resulted in a heterogenous body of literature that does not answer the fundamental questions of safety and efficacy nor provide standard practices for use. As more high-quality literature is produced, answers to these questions may be found. In that case, any new literature and societal guidelines that address these concerns may be submitted once the LCD is finalized for reconsideration of the non-coverage policy.