For drugs approved on limited evidence, a third of indications had no controlled study published afterwards
Drugs the FDA approved 2005 to 2012 on a single trial or a surrogate marker: "no postapproval studies were identified for 43 of the 123 (35.0%) approved indications."
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: Counts published studies only; unpublished or ongoing postapproval work is invisible to it. All therapeutic areas; the abstract gives no psychiatry breakdown.
When a drug is approved on thin evidence, the promise is that better evidence will follow. This review went looking for it.
Significant findings
Pease and colleagues (BMJ, 2017) took every novel drug approved by the FDA "between 2005 and 2012 on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease as primary endpoints, or both": "117 novel drugs for 123 indications". They searched for every prospective controlled study published afterwards, "over a median of 5.5 years".
"Overall, no postapproval studies were identified for 43 of the 123 (35.0%) approved indications."
Where studies did exist, most measured surrogate markers again. The share of indications with at least one randomized, double blind study "using a clinical outcome for the primary endpoint that was published after approval and showed superior efficacy was 18.2% (6 of 33), 2.0% (1 of 49), and 4.9% (2 of 41)" across the three approval groups.
The authors' conclusion: "few controlled studies published after approval that confirmed efficacy using clinical outcomes for the original FDA approved indication."
Worth asking
This covers all of medicine, not psychiatry alone, and most psychiatric drugs are approved on two short trials, not one. But the pattern is the one that matters for anyone on a drug for years: once a product is on the market, nobody is obliged to find out whether it works over the long run, and the company has little reason to pay for a study that could only hurt sales. The evidence you have on approval day is often the evidence you will have a decade later.
Source
Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review — Pease AM, Krumholz HM, Downing NS, Aminawung JA, Shah ND, Ross JS (2017)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1136/bmj.j1680
DOI: 10.1136/bmj.j1680
How this was scored
- Study design
- Systematic review of observational studies
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 123
- Preregistered
- not recorded
- Conflicts disclosed
- not recorded
- 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 68 out of 100 on our published rubric. One caveat travels with that badge: Counts published studies only; unpublished or ongoing postapproval work is invisible to it. All therapeutic areas; the abstract gives no psychiatry breakdown. 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?
Postapproval studies of drugs initially approved by the FDA on the basis of limited evidence: systematic review — Pease AM, Krumholz HM, Downing NS, Aminawung JA, Shah ND, Ross JS (2017). Published in: Top-tier peer-reviewed journal. DOI: 10.1136/bmj.j1680. 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: Systematic review of observational studies. 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.