When it comes to laboratory developed tests (LDTs), the FDA has generally taken what it calls a “discretionary” stance: it elected not to exercise its enforcement powers under the Federal Food, Drug, and Cosmetic Act and FDA regulations. However, according to a new report from the FDA, it turns out this type of discretion was not the wisest of paths. The FDA has indicated there are many problems associated with LDTs that clearly warrant a much greater level of oversight to protect the public.
In this month’s issue of Oncology Business Management
, we bring you a panel debate on exactly what role the FDA should take on this issue. The panel, held at the American Journal of Managed Care 4th Annual Patient-Centered Oncology Care conference in Baltimore in late November, included Scott Gottlieb, MD, a former FDA commissioner for medical and scientific affairs. There was clear agreement that greater FDA oversight is necessary. What form that oversight should take was one of the question marks left hovering over the discussion. As far as the FDA is concerned, LDTs are neither drugs nor food. Currently, laboratories that offer LDTs follow the regulatory requirements of Clinical Laboratory Improvement Amendments (CLIAs). However, CLIA guidelines were followed in all 20 examples of problematic tests examined by the FDA for its report, which illustrates that there are shortcomings to the current standards for marketing of these tests.
Below are two examples of the failures of these tests.
In June 2008, OvaSure, a test designed to screen for ovarian cancer in high-risk women, was brought to market. However, the stated positive predictive value of the test was incorrectly derived, and it would have dropped from 99.3% to 6.5% if the true population prevalence of disease had been used. This meant that only 1 in 15 patients who tested positive actually had the disease. Under intense pressure from physicians and the FDA, the manufacturer of the test pulled it from market in October 2008, nearly half a year later. The cost to women in terms of unnecessary surgery? The FDA estimated a minimum of $12,578 per ovary removal after a false-positive test.
The cost to women patients was far greater, however, with the Oncotype Dx HER2 RT-PCR breast cancer test. This test incorrectly correlated high or low amounts of RNA with high or low amounts of human epidermal growth factor receptor 2 (HER2), which, the FDA said, is overexpressed in 20% to 25% of breast cancer cases. In one study, it was determined in 2014 that the LDT had overlooked HER2-positive patients, diagnosing 2 as negative and 1 as equivocal. Each of those women would potentially have received trastuzumab and, consequently, 3 additional quality years of life, valued at $775,278, or over $2.3 million for all three patients. “Tests that are inaccurate, unreliable, or have unproven or disproven claims expose patients to a range of harms. These include patients told incorrectly that they have life-threatening diseases and others whose life-threatening diseases have gone undetected,” the FDA wrote in its conclusion, making the case for greater FDA oversight of LDTs.
We hope you find the debate on this issue illuminating, along with all of the other fascinating stories this month in Oncology Business Management