Comparative Efficacy Data and Drug Approval in the United States

The 2009 American Recovery and Reinvestment Act included an allocation of $1.1 billion for comparative effectiveness research (CER). The Institute of Medicine defines CER as the “generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition or to improve the delivery of care.” Information gathered via CER is used not only to inform evidence-based decisions on treatment made by prescribers and patients; it is crucial for formulary and coverage decisions as well. The gold standard for comparing the efficacy of drugs and treatments has been large-scale, randomized, head-to-head comparisons; however, such comparisons are costly and time-consuming. According to researchers, observational studies of comparative effectiveness are becoming increasingly common because “they allow for simultaneous comparisons of multiple medical products, represent care in routine practice, and can be completed at a fraction of the cost of most clinical trials.” Formulary and coverage decision makers require information on drugs shortly after marketing approval, when observational data are not yet available, raising a question about the extent to which pre-approval data might inform comparative effectiveness decisions in the early marketing phase of a new medication. The researchers recently conducted a study to determine the proportion of recently approved drugs that had comparative efficacy data available at the time of market authorization in the United States and to examine trends in availability of this information over time and by therapeutic indication. They reported study results in the Journal of the American Medical Association [2011;305(17):1786-1789]. Using data from approval packages publicly available through the online database of drug products approved by the US Food and Drug Administration (FDA), the researchers identified all new molecular entities (NMEs) approved from 2000 through 2010, excluding diagnostic agents, hyaluronidase, and sunscreens. For each eligible NME, they accessed the drug approval package and determined whether any of the efficacy studies that supported the approved indication used active comparators. The active comparator must have been approved by the FDA by the time the NME was approved. The researchers determined whether eligible studies were head-to-head active controlled trials and whether the results of such studies were available in the approval packages. They determined whether the NME of interest was compared with a specific alternative treatment option (drug A vs drug B) or standard care alone, whether the drug was an orphan product, the review classification, the approved indications, and whether the approval decision was based primarily on placebo-controlled or active drug–controlled trial data. In all, 197 of the identified NMEs met eligibility criteria. Of those, 51% (n=100) met criteria for having comparative efficacy data available at the time of market authorization. The proportion increased to 70% (95% confidence interval [CI], 62%-77%) after orphan products (n=37) and products approved for indications for which there was no other existing treatment (n=17) were excluded. Availability of comparative efficacy data was more common for specific therapeutic indications, including diabetes mellitus (89%; 95% CI, 56%-99%) and infectious diseases (73%; 95% CI, 54%-87%) compared with hormones and contraceptives (33%; 95% CI, 9%-67%), cancer (35%; 95% CI, 18%-54%), and genitourinary tract conditions (38%; 95% CI, 16%-66%). In conclusion, the researchers noted that “publicly available FDA approval packages contain comparative efficacy data for about half of NMEs recently approved in the United States and for more than two thirds of NMEs for which alternative treatment options exist. We did not investigate the extent to which available comparative efficacy information is useful for clinical guidance.”