Screening DNA Stool Test for Colorectal Cancer

February 29, 2008

Steve E. Phurrough, MD, MPA
Director, Coverage and Analysis Group
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Mail Stop C1-09-06
Baltimore, MD 21244

RE: CAG-00144N; Medicare Program; Proposed Decision Memo for Screening DNA Stool Test for Colorectal Cancer

Dear Dr. Phurrough:

The American Cancer Society Cancer Action Network (ACS CAN), the sister advocacy organization of the American Cancer Society, respectfully submits the following comments for your consideration regarding the Centers for Medicare & Medicaid Services’ (CMS’) proposed decision for Screening DNA Stool Test for Colorectal Cancer.

We are committed to ensuring that our nation’s seniors have access to high quality cancer prevention, early detection, and treatment tools through the Medicare program. As you may know, colorectal cancer is a disease that disproportionately affects the elderly—according to the Society’s 2007 Facts & Figures, more than 70 percent of new colorectal cancer diagnoses occur among the 65-year-old and over, Medicare-eligible population. Given the importance of early detection and prevention of cancer, ACS CAN appreciates the opportunity to provide comments on the proposed decision and looks forward to working with CMS to strengthen the Medicare program.

Comment on Screening DNA Stool Test for Colorectal Cancer

It is critical that Medicare beneficiaries have access to the best and newest screening tools that are recommended by the U.S. Preventive Services Task Force (USPSTF), the American Cancer Society and other appropriate organizations. The American Cancer Society is in the process of finalizing their colorectal cancer screening guidelines and expects to release these in March of this year. With respect to the CMS coverage decision, we understand that the DNA stool test requires FDA approval and any coverage is contingent on that approval. ACS CAN proposes that Medicare re-evaluate the evidence if the test is recommended by widely accepted guidelines and approved by the FDA. This recommendation is in line with our efforts to give the Secretary of Health and Human Services the authority to consider evidence-based recommendations by the USPSTF and other appropriate organizations, like the American Cancer Society, to add screenings to Medicare once they have been appropriately tested and approved.

We want to stress that due to variability in access, patient choice, and physician options, it will be very important to cover all recommended colorectal cancer screening options as acceptable choices. Colorectal cancer screening is already underutilized among Medicare beneficiaries and ensuring coverage for all screening tests is an integral part of access to early detection and prevention, we would not want to jeopardize the availability of these services for beneficiaries.

Conclusion

This proposed decision has the potential to affect millions of Medicare beneficiaries. We appreciate the hard work that you and your agency have put into evaluating the evidence on the DNA Stool Test. ACS CAN stands ready to work with you to improve the cancer screening rates and reduce the cancer burden among Medicare beneficiaries.

Respectfully,

Daniel E. Smith
President

cc: William Larson, Lead Analyst

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February 29, 2008

Steve Phurrough, MD, MPA
Director, Coverage and Analysis Group
Centers for Medicare and Medicaid Services
Mail Stop C1-09-06
7500 Security Boulevard
Baltimore, MD 21244-1850

Dear Dr. Phurrough:

Thank you for the opportunity to comment on the Centers for Medicare and Medicaid Services’ (CMS’s) proposed national coverage decision (NCD), Screening DNA Stoll Test for Colorectal Cancer (CAG-00144N). America’s Health Insurance Plans (AHIP) is the national association representing nearly 1,300 health insurance plans providing coverage to more than 200 million Americans. We are pleased to submit these comments on behalf of our members.

AHIP concurs with CMS’s proposed decision to not expand the colorectal cancer screening benefit to include coverage of the Screening DNA Stool Test. Health plans consider both premarket review and approval by the FDA as minimum pre-requisites for consideration of coverage. Given the FDA has determined that the only commercially available screening DNA stool test, PreGen-Plus™, requires premarket review, our community believes that coverage of this test is premature.

Thank you for the opportunity to comment on this important issue.

Sincerely,
Carmella Bocchino
Executive Vice President, Clinical Affairs and Strategic Planning

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How many people have to die of colorectal cancer before the beaurocrats allow the public access to this life-saving screening test?!?!?! It has been proven more effective than the currently approved fecal occult blood tests that can''t be relied on, it poses no possible harm to the patient (unlike virtual colonoscopies and CT scans tests), and it would save taxpayers many millions of dollars by catching cancer while it is still curable in medicare/medicaid patients.

Is the hold-up due to financial pressure from certain lobby groups who financially benefit from sick & dying Americans?

Does the FDA need years to study this test to make sure no one gets hurt by pooping into a bag to donate the required stool sample?

Would certain types of doctors make more money if this test was not used?

Please do your moral duty and approve this test.

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While i understand that CMS wants the stool based DNA test to be covered from a regulatory standpoint, The comment from Richard Justman of United Healthcare regarding a pending study funded by the "NCI" regarding 4000 average risk patients and comparing fDNA to FOBT was competed four years ago. Thus; his negative comments regarding fDNA should be considered moot.

Here is what the "NCI" concluded

"As the NCI has recognized, recent publications also offer evidence for the superiority for the new stool-based DNA tests over the FOBT test."

While the cost of the fDNA test is likely to come down in the near term, the technology and clinical evidence supporting fDNA compared with FOBT/FIT is clear and transparent.

While many self serving interest groups are nervous about new novel technologies taking market share, they have a civic duty to the American People to increase the poor CRC screening rates. The "status quo" as they like to keep is not working. sDNA is a technology that will be preferred by the average risk individual over FOBT as prior studies have shown. This alone will increase screening rates and, by default, lower the cost to Medicare.

I look forward to you revisiting a national coverage decision when FDA approval is granted.

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Conclusion and Recommendation: We agree with the proposed non-coverage decision for stool DNA testing for colorectal cancer. We believe that this decision should extend to both average-risk and persons at high-risk for colorectal cancer. We base our conclusion not on the current level of FDA review and approval, but the quality of clinical evidence supporting the use of stool DNA testing for colorectal cancer screening.

About UnitedHealth Group: UnitedHealth Group is a diversified health services delivery company which promotes the health and well-being of our enrollees through all stage of life. Through its six business segments, UnitedHealth Group touches the lives of 70 million Americans.

Rationale for Stool DNA Testing: Colorectal cancer is the third-leading cause of cancer deaths in the United States. 55,000 Americans die of colorectal cancer each year. Many deaths from colorectal cancer could be prevented by widespread screening since prognosis improves dramatically with early detection of localized disease. Existing screening methods include the noninvasive fecal occult blood test (FOBT), flexible sigmoidoscopy, barium enema, and colonoscopy. Patient compliance with recommendations for colon cancer screening is generally poor, particularly for use of invasive techniques. Although the FOBT is noninvasive and therefore compliance may be better, it has the disadvantage that false positive results can be caused by certain drugs and foods, and it fails to detect lesions that do not bleed, giving false negative results.

A test that detects mutated DNA in stool attempts to remedy the shortcomings of other available tests has been developed. The PreGen-Plus™ test is a multitarget fecal DNA test, which has been proposed as a screening test for colorectal cancer in asymptomatic adults. This test assesses stool samples for 21 point mutations in the adenomatous polyposis coli (APC), K-ras, and p53 genes in addition to detecting alterations in DNA fragment length and mutations in the BAT-26 microsatellite instability marker. A test involving only the BAT-26 marker, the PreGen-26™ test, has been proposed as a means to detect colorectal cancer in patients with known or suspected hereditary nonpolyposis colorectal cancer (HNPCC).

UnitedHealthcare’s conclusion: Clinical evidence does not support fecal DNA testing for screening of colorectal cancer in individuals of low or average-risk in the general population.

Clinical evidence does not support fecal DNA testing for screening and monitoring of colorectal cancer in high-risk patients with known or suspected hereditary colorectal cancer syndromes.

While current published clinical studies indicate that stool DNA testing can detect precancerous and cancerous lesions with moderate-to-high accuracy, there is insufficient evidence to conclude that stool DNA testing improves patient management or decreases mortality from colon cancer. None of the studies published to date evaluated the use of either single target or multitarget DNA testing in average-risk individuals eligible for colon cancer screening, and none evaluated the use of single marker (BAT-26) testing for detection of colorectal cancer in individuals with known or suspected hereditary nonpolyposis colorectal cancer (HNPCC).

A randomized, multicenter trial to determine the efficacy and feasibility of stool DNA screening for colorectal cancer funded by the National Cancer Institute (NCI) is currently being conducted. This trial is ongoing and is scheduled to enroll 4000 average-risk patients at least 50 years old who will be tested with both the FOBT and the multitarget stool DNA assay. We believe that a decision on the medically necessary and appropriate use of stool DNA testing should await the result of this trial.

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ADDENDUM:
The signifcance of the false negative DNA Stool Test can be highlighted by the November 15, 2007, press release by the manufacturer EXACT Science.

Using Version 2 technology, 82 colonoscopy proven colorectal cancers were tested. The results showed an 83% sensitivity. This means that 68 of the 82 colorectal cancers were correctly diagnosed by the DNA Stool Test. However, this also means that 14 of the colorectal cancers were missed by the DNA Stool Test.

The initial interim results showed a slightly higher sensitivity rate of 88% of the 40 colorectal cancers. This would correlate with finding 35 and missing 5 colorectal cancers, using the DNA Stool Test. Consequently, the second half of the study found 33 and missed 9 colorectal cancersa sensitivity of only 79%. Based upon the small study results, the DNA Stool Test may miss one out of every 5 to 8 actual colorectal cancers.

What would you tell the 14 patients in this study who had colorectal cancer but were given results saying that their test results were negative for colorectal cancer? Would these patients incorrectly assume that they were safe from colorectal cancer? How many of these 14 patients would have had their colorectal cancers progress to metastatic disease and ultimate death? Fortunately, in this study they all had a colonoscopy performed, and they should have been treated appropriately.

These 14 patients that had a false negative result are only the tip of the iceberg if thousands upon thousands are screened by a test with a low sensitivity. What would you tell your patient when there is no cure; but if you had screened properly his disease would have been cured? What will you tell the grieving spouse, child, or parents? What will you tell your malpractice carrier or even worse, the jury?

The DNA Stool Test may have value in the effort to identify more colorectal cancers, but a full disclaimer must be made for the cases that would also be missed. The FDA equivalent of a BLACK BOX WARNING.

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Using the Screening DNA Stool Test with a sensitivity of only 88%,then 1 out of every 8 patients with colorectal cancer will get a false negative test. This should be unacceptable because these patients will falsely assume that they are cancer free and should not need another test for 5 years as recommended by the manufacturer. During this time, the progression of the cancer would result in several fatalities that could have been prevented by the current colonoscopy recommendations.

The recent literature suggests that the survival rates of colorectal cancer is correlated with the earlier use of colonoscopy.

If the screening DNA Stool Test is used and the result is a false negative (ie. missed cancer),and the patient subsequently dies of metastatic colon cancer, who would be responsible for this potential malpractice case. The primary care physician ordering the test should be held liable if he did not fully disclose the limitations of this test. If the manufacturer promoted the test without fully explaining the pitfalls of the 12% false negatives, then the manufacturer and promoter of this test should be held liable. Physicians are bombarded by new information and many will not understand the implications of the sensitivity and specificity of this test. Yet many physicians would order this test as a alternative to colonoscopy especially if approved by Medicare or the FDA. Like the Vioxx case, how many patients would have to die from the false security of a test result, when they could have been diagnosed correctly by a colonoscopy?

The proposed handling of the stool specimenhome collection and mailing, has many potential pitfalls. The collection at home and the addition of the preservative may improve sensitivty of this test, but if the patient performs this wrong then the sensivitity would go down. The placement of the human feces sample in the mail has potential problems of spreading disease. This biohazard should be clearly marked and not placed in the mail.

A good screening test needs very high sensitivity and should be relatively inexpensive. For example, the testing for HIV is very sensitive and needs a comfirmatory test. Likewise, the Screening DNA Stool Test should have sensitivity close to colonoscopy. Unfortunately, the DNA Stool Test does not fulfill the sensitivity needs of a good screening test.

While the DNA Stool Test is more sensitive than the fecal occult blood test, it is much more expensive and not recommended yearly which may or may not have additional benefits of cancer detection. The fecal occult blood test is used in conjunction with colonoscopy screening guidelines.

Improved colorectal screening rates requires the education of both the general public and primary care physicians.

As an informed physician, I would not recommend DNA Stool Test because of the sensitivity issues.

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As a prime candidate for colorectal cancer I would very much like to see this type of screening offered. As of now I have a colonscopy every five years...however, in between 5 years..that is long time for a polyp to grow...if this testing were offered it would be affordable even if my insurance company did not cover it...and it would be something I would have done in between the colonoscopies...

The ease alone, will encourage those that do not want to go through the discomfiture and the time (2 days - one prep, one procedure) needed for a colonoscopy...also this test can be recommended by the family Dr. or internist as a specialist would not be needed.

Does it not make sense to catch the signs of cancer in its early stage rather than spend the thousands of dollars treating cancer in it''s more advanced stages? This type of testing is not only convenient but will help to save thousands of lives.

Please consider carefully as this too may save the life of someone you know..including yourself.

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As a taxpayer, and as a son with parents enrolled under Medicare, I am very disappointed with the CMS decision to decline national coverage for DNA Stool testing for Colorectal Cancer. To decline this simple, cost effective, and non-invasive test procedure because it lacks official FDA approval is an absurd and purely political decision that borders on criminal negligence. It is also a decision to waste thousands of future of taxpayer dollars and displays a gross lack of concern for medicare recipients. After reading the background to this decision it is obvious that the major detractors are organizations representing Doctors (the Gastroenterologists) who anticipate a decline in scheduled colonoscopy procedures if DNA testing is approved. Did they forget their medical ethics? It is plain to see that the CMS is making this decision based on political pressure from lobbying groups. Does the CMS not have any concern about the thousands of Medicare recipients who will suffer from the complications of advanced colon cancer because they resist having an uncomfortable and invasive procedure such as a colonoscopy performed? Please also consider the cost to this country associated with treating late stage colon cancer. Much of this cost and suffering could easily be avoided through early cancer detection using this non-invasive DNA stool test. Please reconsider and grant national coverage approval for this test with no further delay. Thank you.

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