One in three FDA approvals from 2005 to 2012 had a six-month pivotal trial; one in three rested on a single trial
448 pivotal trials behind 188 new drugs: "74 indications (36.8%) were approved on the basis of a single pivotal trial"; a trial "of 6 months or greater supported the approval of 68 indications (33.8%)". Median 760 patients.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: All therapeutic areas pooled; the psychiatric subset is not reported in the abstract. Trial duration was measured as any pivotal trial of six months or more supporting an indication, not the median length of all trials.
The trials that get a drug approved are shorter and smaller than most people assume. This is the audit across every new drug the FDA approved in eight years.
Significant findings
Downing and colleagues (JAMA, 2014) analysed public FDA documents for all novel therapeutic agents approved from 2005 to 2012: "Between 2005 and 2012, the FDA approved 188 novel therapeutic agents for 206 indications on the basis of 448 pivotal efficacy trials. The median number of pivotal trials per indication was 2 (interquartile range, 1-2.5), although 74 indications (36.8%) were approved on the basis of a single pivotal trial."
The trials were mostly well designed: "Nearly all trials were randomized (89.3%), double-blinded (79.5%), and used either an active or placebo comparator (87.1%)." Size and length: "The median number of patients enrolled per indication among all pivotal trials was 760 (interquartile range, 270-1550). At least 1 pivotal trial with a duration of 6 months or greater supported the approval of 68 indications (33.8% [95% CI, 27.2%-40.4%])."
What they measured: "Pivotal trials using surrogate end points as their primary outcome formed the exclusive basis of approval for 91 indications (45.3%), clinical outcomes for 67 (33.3%), and clinical scales for 36 (17.9%)." The authors: "The quality of clinical trial evidence used by the FDA as the basis for recent approvals of novel therapeutic agents varied widely across indications."
Worth asking
Psychiatric drugs are approved on clinical scales, the 17.9 percent, and their trials are among the short ones; the library's own count of trial horizons and the page on the longest trial behind each approval give the psychiatric figures. This audit is the backdrop: two in three new drugs had no pivotal trial that lasted six months, and one in three had one trial. Neither is a scandal. Both are what "FDA approved" means, and both belong next to the phrase when someone uses it as a guarantee.
Source
Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005-2012 — Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS (2014)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jama.2013.282034
DOI: 10.1001/jama.2013.282034
How this was scored
- Study design
- Cross-sectional study / survey
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 448
- Preregistered
- not recorded
- Conflicts disclosed
- Yes
- Independent of proponent
- not recorded
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published September 21, 2026.
Questions
How strong is the evidence behind this?
veisund rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 62 out of 100 on our published rubric. One caveat travels with that badge: All therapeutic areas pooled; the psychiatric subset is not reported in the abstract. Trial duration was measured as any pivotal trial of six months or more supporting an indication, not the median length of all trials. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005-2012 — Downing NS, Aminawung JA, Shah ND, Krumholz HM, Ross JS (2014). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jama.2013.282034. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Cross-sectional study / survey. Funding: Independently funded. Independence from the proponent is not recorded. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.