Behind the ASCO Review

Behind the ASCO Panel Findings

We have noted in an editorial discussion appearing on the “Controversy and Validation” section of the Weisenthal Cancer Group website that an ASCO review panel sought to impose criteria which never have been applied to any laboratory test. However, there is more to consider when weighing the position of ASCO based upon its “technology review.”

First, much relevant data were ignored by the review panel. ASCO’s recommendations were based upon a review of 12 previously-published clinical studies which focused only on outmoded cell-growth assay methods. Drug induced cell-death as a surrogate for apoptosis is the most relevant biological measure and must not be confused with growth-based (Cell Proliferation) testing. The panel made no attempt to distinguish cell death from cell growth techniques and yet there have been dozens of studies of Cell Death assays, producing the overwhelming majority of functional tumor cell profiling data published in the past decade.

Not only did the ASCO panel fail to discriminate studies of Cell Death assays from studies of Cell Proliferation assays, the ASCO panel pointedly cast aside all evidence of assay accuracy, stating, “We excluded reports that only reported correlations between assay results and clinical outcomes.” In other words, the ASCO panel deliberately ignored the only standard which ever has applied to medical laboratory tests.

Another troubling aspect of the review relates to the composition of the ASCO panel and specifically to the qualifications and potential conflicts of interest of the reviewers. No investigator actively working with Cell Death-based Functional Tumor Cell Profiling technologies endpoints was included in the panel. Further no such expert was even consulted. This would have been very easily accomplished because the Cell Death endpoint is used by nearly every published investigator in the field. Neither was a single oncologist consulted from among the many who are ASCO’s own members who use Functional Tumor Cell Profiling routinely to assist in therapy selection.

One such user of functional tumor cell profiling is a well-respected medical oncologist, ASCO member, and former President of his state's medical oncology society. His statement appears in the written record of a CMS/Medicare hearing: “My experience with cell death CSRAs [Cell Culture Drug Resistance Tests – the term used in the ASCO review to describe Functional Tumor Cell Profiling] is that they have accuracy in predicting clinical outcomes and defining novel chemotherapeutic synergies. They also have frequent curative value in treating many adult malignancies which the current medical literature has deemed incurable…I believe that it would be unethical for me not to use such CSRAs in my practice.”

Rather than consulting published experts and ASCO members who are users of functional tumor cell profiling, the three ASCO panelists relied upon their own knowledge, which derives from having worked several years ago with an assay technology which is based not upon Cell Death but rather upon Cell Proliferation. That particular assay technology was criticized in a 1983 editorial published in the New England Journal of Medicine and the method has been almost universally ignored for over 20 years. The lead ASCO panelist had devoted much of his early career to promoting the cell proliferation method for financial profit. The second and third ASCO panelists had collaborated in the past with the lead panelist using this same, now-abandoned technology.

We believe that the composition of the panel, along with ASCO’s failure to seek comment from respected experts in the field or even from oncologists who use the tests, coupled with the deliberate exclusion of the entire body of the most highly relevant data created a bias which is not consistent with a balanced and credible technology assessment.

Contrast the ACSO approach with that of Medicare Administrator, National Heritage Insurance Company (NHIC) which conducted its own technology assessment in 2006. NHIC reviewed the full body of data, seeking also the advice of unbiased users of Functional Tumor Cell Profiling, and issued a Local Coverage Determination in which functional tumor cell profiling became a fully-approved service for Medicare beneficiaries.

Finally, there is the issue of conflict of interest. ASCO, the American Society of Clinical Oncology, exists to advance the professional interests of its members. Such interests include, among many others, those which are financial. In an era in which physicians’ incomes are threatened in many ways, ASCO functions as a political action organization, working closely with Medicare and often lobbying legislators to protect the livelihoods of medical oncologists. We think this is entirely reasonable. However, an area of concern for oncologists and therefore for ASCO has been the issue of what is called the “drug concession,” a phrase which describes oncologist revenues deriving from the sale of chemotherapy drugs.

Traditionally, physicians have been able to buy chemotherapy drugs at wholesale prices and then mark-up the drugs to patients when they administer them at their offices or in free-standing chemotherapy infusion centers. Separate stories have appeared in The New York Times¹, on the NBC Nightly News², and elsewhere examining the practice of oncology drug mark-up. Further, at least one academic study³, involving 9,357 cancer patients and conducted jointly by the University of Michigan and Harvard University, concluded that physicians take into account the amount of “margin” afforded by one drug over another when choosing from otherwise equally-acceptable drug regimens. (An ASCO spokesperson later disputed but did not disprove these findings.) Clearly, a test which helps to guide therapy selection might potentially erode to some degree the wide latitude currently enjoyed by oncologists in prescribing drugs on the basis of “physician’s best judgment.” This does not, by itself, taint the opinions expressed in the ASCO functional tumor cell profiling review but, in fairness, the issue probably should have been disclosed as a potential conflict of interest.

References

Abelson R. Pay Method Said to Sway Drug Choices of Oncologists, New York Times, March 8, 2006.

Ellis, R. Cancer Docs Profit from Chemotherapy Drugs. NBC Nightly News, September 21, 2006.

Jacobson, M., O'Malley, A.J., Earle, C.C., et al. Does Reimbursement Influence Chemotherapy Treatment For Cancer Patients?, Health Affairs 25(2):437-443, 2006.