Intended for healthcare professionals


Quality of evidence behind FDA approvals varies widely

BMJ 2014; 348 doi: (Published 27 January 2014) Cite this as: BMJ 2014;348:g1075
  1. Michael McCarthy, editor,
  1. 1Seattle, Washington
  1. mxmc{at}

The approval processes of the US Food and Drug Administration have been scrutinized by several studies. Michael McCarthy explains

Three studies appearing in JAMA, the journal of the American Medical Association, take a peek under the hood of the often recondite approval processes of the US Food and Drug Administration (FDA).

Study 1: FDA approval of new drugs

The first of these studies looked at recent FDA drug approvals and found that the quality of the clinical trial evidence used by the agency to approve new drugs varies considerably depending on the proposed drug’s indications.1

In this study, Nicholas S Downing of Yale University School of Medicine, New Haven, Connecticut, and colleagues reviewed pivotal efficacy trials used to support FDA approval decisions for novel therapeutic agents between 2005 and 2012, looking at such factors as trial size, design, duration, and endpoints.

Gathering records through Drugs@FDA, a publicly accessible database, Downing and his coworkers found that during this period the FDA approved 188 novel therapeutic drugs.

Of these, 31 (16.5%) had been granted orphan status because they targeted a rare disease for which effective treatments are lacking and 22 (11.7%) were approved by the agency’s accelerated approval pathway, which is reserved for drugs for serious conditions that fill an unmet medical need.

All told, these 188 drugs were approved for 206 indications. “Three therapeutic areas accounted for nearly half of indications: 41 agents (19.9%) were used to treat cancer, 29 (14.1%) to treat infectious disease, and 23 (11.2%) to treat cardiovascular disease, diabetes mellitus, or hyperlipidemia,” the researchers write.

The approvals were based on 448 clinical trials. The median number of pivotal trials per indication was two (interquartile range, 1 to 2.5). But 74 indications (36.8%) were approved on the basis of a single pivotal trial.

“Nearly all trials were randomized ([proportion of trials] 89.3%, 95% …

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