A third of new drugs had a safety problem found after approval; psychiatric drugs at nearly four times the rate
Of 222 drugs approved 2001 to 2010, 32 percent later had a withdrawal, a new boxed warning or an FDA safety communication, the first a median 4.2 years after approval. For psychiatric drugs the rate ratio was 3.78.
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: A composite outcome that treats a safety communication and a withdrawal alike. A higher event rate can reflect closer surveillance and wider, longer use as much as greater hazard. Covers approvals through 2010; the newest psychiatric brands are not in it.
Approval is the start of what is known about a drug's safety, not the end. This study counted how often something important turned up afterwards.
Significant findings
Downing and colleagues (JAMA, 2017) followed "all novel therapeutics approved by the FDA between January 1, 2001, and December 31, 2010" through February 2017. The outcome was a composite of "(1) withdrawals due to safety concerns, (2) FDA issuance of incremental boxed warnings added in the postmarket period, and (3) FDA issuance of safety communications."
"There were 123 new postmarket safety events (3 withdrawals, 61 boxed warnings, and 59 safety communications) during a median follow-up period of 11.7 years", "affecting 71 (32.0%) of the novel therapeutics. The median time from approval to first postmarket safety event was 4.2 years".
Events "were statistically significantly more frequent among biologics (incidence rate ratio [IRR] = 1.93", "therapeutics indicated for the treatment of psychiatric disease (IRR = 3.78; 95% CI, 1.77-8.06; P < .001), those receiving accelerated approval (IRR = 2.20" and "those with near-regulatory deadline approval (IRR = 1.90".
Worth asking
Psychiatric drugs had the highest rate ratio in the study. One reading is that they are riskier than their trials showed. Another is that they are watched more closely and taken by more people for longer, so problems are found. Both fit the data. Either way, the typical gap between approval and the first new warning was about four years, and the drugs with the largest marketing budgets are the ones in their first few years on the market. A new warning is also the system working. The question for a newly launched drug is what is not yet known, and that is a fair thing to ask a prescriber.
Source
Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010 — Downing NS, Shah ND, Aminawung JA, Pease AM, Zeitoun JD, Krumholz HM, Ross JS (2017)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1001/jama.2017.5150
DOI: 10.1001/jama.2017.5150
How this was scored
- Study design
- Cohort study
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 222
- 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 64 out of 100 on our published rubric. One caveat travels with that badge: A composite outcome that treats a safety communication and a withdrawal alike. A higher event rate can reflect closer surveillance and wider, longer use as much as greater hazard. Covers approvals through 2010; the newest psychiatric brands are not in it. 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?
Postmarket Safety Events Among Novel Therapeutics Approved by the US Food and Drug Administration Between 2001 and 2010 — Downing NS, Shah ND, Aminawung JA, Pease AM, Zeitoun JD, Krumholz HM, Ross JS (2017). Published in: Top-tier peer-reviewed journal. DOI: 10.1001/jama.2017.5150. 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: Cohort study. 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.