Harms reporting was frequently incomplete or discordant in biomedical randomized trials published: a...

To characterize harms specification, harms reporting, concordance between specified and reported harms, transparency about harms reporting criteria, and equity-related harms reporting in randomized controlled trials (RCTs) of biomedical interventions.

We conducted a meta-epidemiological study of 200 randomly sampled biomedical RCTs indexed in PubMed in 2023. Using publicly available protocols, trial registries, and publications, we assessed harms specification, harms reporting, concordance between specified and reported harms, transparency about harms reporting criteria, and whether trials had considered PROGRESS-Plus equity-related factors when reporting harms.

Sixty-four percent (128/200) of the trials were registered, and 15.5% (31/200) had an accessible protocol. Harms were specified in 64.0% (128/200) across publicly available protocols, registry study details, or method section and reported in 69.5% (139/200). Across the 200 RCTs, 120 trials (60.0%) both specified and reported harms, 8 (4.0%) specified harms but reported none, 19 (9.5%) reported harms without prior specification, and 53 (26.5%) neither specified nor reported harms. Among the 120 trials that both specified and reported harms, concordance was complete in 87 trials (72.5%), partial in 29 trials (24.2%), and absent in 4 trials (3.3%). Only 1.0% (2/200) clearly specified harms reporting criteria, and 7.0% (14/200) indicated using criteria when reporting. Trials with a registry listing or an identified protocol had higher odds of specifying harms compared with trials without (OR = 2.1 [1.2, 3.8] and OR = 5.6 [1.8, 18.1], respectively). Compared with behavioral or physical therapy interventions, pharmacological trials had higher odds of harms specification (OR = 3.5 [1.9, 6.5]) and harms reporting (OR = 3.3 [1.7, 6.2]). No trials reported harms stratified by PROGRESS-Plus equity-related factors.

In a contemporary sample of biomedical RCTs, harms were frequently specified and reported, but concordance between planned and reported harms and transparency about reporting criteria remain deficient. Trialists should prespecify harms outcomes in protocols/registrations and report harms comprehensively and consistently across all public sources; when counts and collected participant characteristics support it, descriptive harms summaries by key equity-related factors may help identify potential vulnerability, with cautious interpretation for rare harms.

Randomized trials are often used to understand how biomedical interventions work, but they should also be used to identify potential harms. In this study of 200 randomized trials published in 2023, most trials specified or reported at least one harm, but the harms planned in protocols, registries, or methods sections often did not fully match those reported in the results. Trials that were registered or had a study protocol were more likely to specify potential harms than trials without them. Drug, surgery, and medical device trials were also more likely than behavioral or physical therapy trials to both specify and report harms. Very few trials explained the criteria used to decide which harms were reported, and none reported harms by equity-related participant characteristics. Better planning for and more complete reporting of harms would help clinicians, patients, reviewers, and policymakers better judge the balance between the benefits and harms of a health intervention.