October 22, 2014
How Valuable Is Current Biomarker Information
in Drug Labels?

Boston—Pharmacotherapy is becoming increasingly personalized, with information about genetic biomarkers in the labels of many prescription drugs.

How much evidence exists for pharmacogenomic biomarker testing in drug labels and does that help the clinical decision-making process or just add to the confusion?

Those are questions examined in a review led by researchers from Brigham and Women’s Hospital and Harvard Medical School. The results were published online recently in JAMA Internal Medicine.

Using publicly available FDA databases, the researchers identified drug labels that described the use of a biomarker and evaluated whether the label contained or referenced convincing evidence of its clinical validity (i.e., the ability to predict phenotype) and clinical utility (i.e., the ability to improve clinical outcomes), using guidelines published by the Evaluation of Genomic Applications in Practice and Prevention Working Group.

The completeness of the citation of supporting studies was graded, and the investigators determined whether the label recommended incorporation of biomarker test results in therapeutic decision making.

Of the 119 drug-biomarker combinations, only 43 (36.1%) had labels that provided convincing clinical validity evidence, whereas 18 (15.1%) provided convincing evidence of clinical utility, according to study results.

Making recommendations about how clinical decisions should be based on the results of a biomarker test were 61 labels (51.3%), with 36 (30.3%) of those containing convincing clinical utility data. Just 13 labels (10.9%) incorporated a full description of supporting studies.

“Fewer than one-sixth of drug labels contained or referenced convincing evidence of clinical utility of biomarker testing, whereas more than half made recommendations based on biomarker test results,” the authors conclude. “It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.”

An invited commentary from Wylie Burke, MD, PhD and Kenneth Thummel, PhD, both of the University of Washington in Seattle, called the results “sobering,” pointing out that “the paucity of evidence about most genetic tests is well documented, suggesting that the limitations in drug label information reflect in significant part our current state of knowledge about pharmacogenetics.”

Noting that the study finds that “current drug labels are an unreliable source for what is known about pharmacogenetic tests,” the commentators suggest a remedy for the problem.

“To accomplish this goal, the FDA should provide clear and specific direction, extending beyond its current guidance, to establish a standardized pharmacogenomics section for all drug labels,” Burke and Thummel write. “This section should inform health care professionals about pharmacogenetic tests with established clinical validity and clinical utility. When such tests are available, summaries of the evidence and relevant practice guidelines should be provided, with appropriate citations. If there is no pharmacogenetic test that meets these standards, the label should say so.

“A black box label should be reserved for the few drug-test combinations with convincing evidence that test use prevents serious patient harm, making it easy for health care professionals to discern the tests with highest effect.”

U.S. Pharmacist Social Connect