Despite the continued drive toward companion diagnostic development, as witnessed by the increasing number of diagnostic-pharmaceutical company partnerships, new research raises doubts as to whether biomarker testing recommendations are ready to be included in drug labels, given a lack of associated clinical utility data. “Our analysis revealed deficiencies in the evidence provided in drug labels that supports the use of many pharmacogenomics biomarkers,” write the authors of an Oct. 13 JAMA Internal Medicine study. “It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.” Biomarkers are increasingly being relied upon to predict a drug’s efficacy and the likelihood of toxicity in individual patients. But the researchers say that while more than half of drug labels make clinical recommendations based on biomarker test results, less than one-sixth of drug labels contained or referenced convincing evidence of the clinical utility of biomarker testing. The researchers utilized publicly available U.S. Food and Drug Administration databases to evaluate the evidence supporting pharmacogenomic biomarker testing in drug labels (both clinical validity and clinical utility). They examined the first available drug label that contained mention of a drug’s associated biomarker. The researchers […]
Despite the continued drive toward companion diagnostic development, as witnessed by the increasing number of diagnostic-pharmaceutical company partnerships, new research raises doubts as to whether biomarker testing recommendations are ready to be included in drug labels, given a lack of associated clinical utility data.
“Our analysis revealed deficiencies in the evidence provided in drug labels that supports the use of many pharmacogenomics biomarkers,” write the authors of an Oct. 13 JAMA Internal Medicine study. “It may be premature to include biomarker testing recommendations in drug labels when convincing data that link testing to patient outcomes do not exist.”
Biomarkers are increasingly being relied upon to predict a drug’s efficacy and the likelihood of toxicity in individual patients. But the researchers say that while more than half of drug labels make clinical recommendations based on biomarker test results, less than one-sixth of drug labels contained or referenced convincing evidence of the clinical utility of biomarker testing.
The researchers utilized publicly available U.S. Food and Drug Administration databases to evaluate the evidence supporting pharmacogenomic biomarker testing in drug labels (both clinical validity and clinical utility). They examined the first available drug label that contained mention of a drug’s associated biomarker.
The researchers identified 119 drug-biomarker combinations (107 drugs and 39 unique biomarkers) and found that most of these combinations (63 percent) are intended to reduce the occurrence of adverse drug events, while 37 percent related to the drugs’ efficacy. Just over one-third of the labels (36.1 percent) provided convincing evidence of clinical validity, the association between the pharmacogenetic variant and drug response, while only 15.1 percent of the labels (n = 18) provided convincing evidence of clinical utility, improved clinical outcomes associated with test use. Oncology drug labels were significantly more likely to demonstrate convincing evidence of clinical utility, compared with all other biomarker-drug combinations (14 of 37 cancer drugs versus four of 82 other drugs).
More than half of all of the labels (51.3 percent) made recommendations about how test results should impact clinical decisions, but of these labels providing recommendations, less than one-third (30.3 percent) contained convincing clinical utility data. And among the 76 labels with neither convincing clinical utility nor validity data, nearly one-third (31.6 percent) still contained clinical decision recommendations.
While acknowledging that evidence of benefit may exist but may not be adequately captured in all drug labels, Wylie Burke, M.D., Ph.D., from the University of Washington, Seattle, in an accompanying editorial called the study a “sobering” demonstration of the “limitations” of the current state of knowledge about pharmacogenetics.
“Because only one in 10 U.S. physicians reports being adequately informed about the appropriate use of pharmacogenomic biomarkers, the information and recommendations included in labels should be not only evidence based but also directly relevant to clinical decision making,” write the authors, led by Bo Wang, Pharm.D., from Brigham and Women’s Hospital in Boston. “We believe that testing recommendations supported by clinical validity alone adds confusion, not clarity, to the clinical decision-making process, especially if the evidence is not clearly explicated or cited alongside the guidance.”
Both the study and editorial authors suggest standardization of the pharmacogenomics section for all drug labels, including a list of available pharmacogenomic tests, summaries of the associated evidence, and relevant practice guidelines, including acknowledgement if no pharmacogenetic tests meet these standards. To make the labels consistent, consensus definitions of the evidence required to establish clinical validity and utility will be needed.
Takeaway: Despite the promise of pharmacogenomic testing to support personalized medicine, there is some doubt as to whether there is currently enough widespread, high-quality evidence to support biomarker labeling on many drugs.
