Pharma Strategy Blog

An interesting decision by the CMS was announced last Thursday on the Government HHS website, declaring that:

Predictably, radiologists are up in arms and apparently shocked that the recent publication last September in the New England Medical Journal and other journals was deemed insufficient.  However, a quick look at the demographic data show that the average age of the Johnson study participants was 52-62, as were the Pickhart, Kim and Imperiale studies, whereas Medicare is for patients aged 65 and older.  It might be predictable, therefore, that a broad conclusion cannot be reached for Medicare eligible patients without sufficient data. 

In the same way, drug trials in the metastatic setting do not necessarily translate to the adjuvant setting without conclusive data, so you can see where the CMS is coming from.  Clearly, the CMS views CTC as a promising technology, but believes that questions on its use need to be answered with well-designed clinical studies that focus on the Medicare population. Physicians and beneficiaries should choose among several other colorectal cancer screening tests currently covered under Medicare until sufficient evidence to support CTC becomes available.

Fletcher, in an editorial in the NEJM where the two studies were published highlighted weaknesses in the approach of the two studies.  Firstly, he noted of the Imperiale trial that:

Secondly, in the Johnson study:

Extracolonic findings were common in the studies with CT colonoscopies, but as both Fletcher and the CMS pointed out, it is unclear what the clinical significance of these is and there are other considerations, such as the stress and worry the findings will inevitably induce as well as the burden of extra tests on the healthcare system for x-rays, biopsies etc without any clear idea of what the risk-benefits might be for the investigation of such polyps.

The American Cancer Society (ACS) and other organizations recommend more intensive surveillance for individuals at higher risk for CRC.  These risk factors were defined as:

1. Individuals with a history of adenomatous polyps
2. Individuals with a personal history of curative-intent resection of CRC
3. Individuals with a family history of either CRC or colorectal adenomas diagnosed in a first-degree relative before age 60 years
4. Individuals at significantly higher risk due to a history of inflammatory bowel disease of significant duration
5. Individuals at significantly higher risk due to the known or suspected presence of 1 of 2 hereditary syndromes, specifically, hereditary nonpolyposis colon cancer (HNPCC) or familial adenomatous polyposis (FAP)

These criteria make much sense but note that age alone is not a risk factor for colorectal cancer adenocarcinomas.

Predicatbly, the American Gastroenterology Association managed to sit on the fence and see both sides, which was amusing given that gastroenterologists have most to gain from existing invasive colonoscopies, whereas CT colonoscopies would be performed by qualified radiologists:

"The AGA agrees that the limitations of CTC cannot be ignored and must be taken under advisement in the development of a coverage policy for CTC. Concerns related to test sensitivity, specificity, reporting, training and technology requirements, radiation exposure, and appropriate surveillance intervals are well documented.

While the AGA supports optical colonoscopy as the definitive screening test for colon cancer, we also support CTC and other screening tests if patients and their physicians believe that test is the appropriate one for them."

Fletcher's editorial also noted some of the potential downsides of CT colonoscopies more specifically:

So, not only are the CMS likely looking for some studies specifically looking at the accuracy of CT colonoscopies in the Medicare population, but the long term effects of the radiation exposure should also be considered, especially as an aging population is more susceptible to mutational changes and cancer in general.

My own view is that the value of CT colonoscopies in younger (<65yo), high risk patients
as a screening tool for early colorectal cancer has clearly been
demonstrated, but in the Medicare eligible (>65yo) group, the
evidence is much less clear and questions remain.  I can see why the CMS is therefore requesting public comments on the decision before a final one is made.  This can be accessed at the HHS website.

Sources:

Health of Human Sciences CMS website

C. Daniel Johnson, Mei-Hsiu Chen, Alicia Y. Toledano, Jay P. Heiken, Abraham Dachman, Mark D. Kuo, Christine O. Menias, Betina Siewert, Jugesh I. Cheema, Richard G. Obregon, Jeff L. Fidler, Peter Zimmerman, Karen M. Horton, Kevin Coakley, Revathy B. Iyer, Amy K. Hara, Robert A. Halvorsen, Jr., Giovanna Casola, Judy Yee, Benjamin A. Herman, Lawrence J. Burgart, Paul J. Limburg (2008). Accuracy of CT Colonography for Detection of Large Adenomas and Cancers New England Journal of Medicine, 359 (12), 1207-1217


Fletcher, R.H (2008). Colorectal Cancer Screening on Stronger Footing New England Journal of Medicine, 359 (12), 1285-1287


David H. Kim, Perry J. Pickhardt, Andrew J. Taylor, Winifred K. Leung, Thomas C. Winter, J. Louis Hinshaw, Deepak V. Gopal, Mark Reichelderfer, Richard H. Hsu, Patrick R. Pfau (2007). CT Colonography versus Colonoscopy for the Detection of Advanced Neoplasia New England Journal of Medicine, 357 (14), 1403-1412


Perry J. Pickhardt, J. Richard Choi, Inku Hwang, James A. Butler, Michael L. Puckett, Hans A. Hildebrandt, Roy K. Wong, Pamela A. Nugent, Pauline A. Mysliwiec, William R. Schindler (2003). Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in Asymptomatic Adults New England Journal of Medicine, 349 (23), 2191-2200

R. A. Smith, V. Cokkinides, O. W. Brawley (2009). Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening CA: A Cancer Journal for Clinicians, 59 (1), 27-41 DOI: 10.3322/caac.20008