Publication of Clinical Trials Supporting Successful New Drug Applications: A
Literature Analysis
Background:
The United States (US) Food and Drug Administration (FDA) approves new drugs based on
sponsor-submitted clinical trials. The publication status of these trials in the medical
literature and factors associated with publication have not been evaluated. We sought to
determine the proportion of trials submitted to the FDA in support of newly approved
drugs that are published in biomedical journals that a typical clinician, consumer, or
policy maker living in the US would reasonably search.
Methods and Findings:
We conducted a cohort study of trials supporting new drugs approved between 1998 and
2000, as described in FDA medical and statistical review documents and the FDA approved
drug label. We determined publication status and time from approval to full publication
in the medical literature at 2 and 5 y by searching PubMed and other databases through
01 August 2006. We then evaluated trial characteristics associated with publication. We
identified 909 trials supporting 90 approved drugs in the FDA reviews, of which
43% (394/909) were published. Among the subset of trials described in the
FDA-approved drug label and classified as “pivotal trials” for our
analysis, 76% (257/340) were published. In multivariable logistic regression
for all trials 5 y postapproval, likelihood of publication correlated with statistically
significant results (odds ratio [OR] 3.03, 95% confidence
interval [CI] 1.78–5.17); larger sample sizes (OR 1.33 per
2-fold increase in sample size, 95% CI 1.17–1.52); and pivotal
status (OR 5.31, 95% CI 3.30–8.55). In multivariable logistic
regression for only the pivotal trials 5 y postapproval, likelihood of publication
correlated with statistically significant results (OR 2.96, 95% CI
1. 24–7.06) and larger sample sizes (OR 1.47 per 2-fold increase in sample
size, 95% CI 1.15–1.88). Statistically significant results and
larger sample sizes were also predictive of publication at 2 y postapproval and in
multivariable Cox proportional models for all trials and the subset of pivotal
trials.
Conclusions:
Over half of all supporting trials for FDA-approved drugs remained unpublished ≥
5 y after approval. Pivotal trials and trials with statistically significant results and
larger sample sizes are more likely to be published. Selective reporting of trial
results exists for commonly marketed drugs. Our data provide a baseline for evaluating
publication bias as the new FDA Amendments Act comes into force mandating basic results
reporting of clinical trials.
Vyšlo v časopise:
Publication of Clinical Trials Supporting Successful New Drug Applications: A
Literature Analysis. PLoS Med 5(9): e191. doi:10.1371/journal.pmed.0050191
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.0050191
Souhrn
Background:
The United States (US) Food and Drug Administration (FDA) approves new drugs based on
sponsor-submitted clinical trials. The publication status of these trials in the medical
literature and factors associated with publication have not been evaluated. We sought to
determine the proportion of trials submitted to the FDA in support of newly approved
drugs that are published in biomedical journals that a typical clinician, consumer, or
policy maker living in the US would reasonably search.
Methods and Findings:
We conducted a cohort study of trials supporting new drugs approved between 1998 and
2000, as described in FDA medical and statistical review documents and the FDA approved
drug label. We determined publication status and time from approval to full publication
in the medical literature at 2 and 5 y by searching PubMed and other databases through
01 August 2006. We then evaluated trial characteristics associated with publication. We
identified 909 trials supporting 90 approved drugs in the FDA reviews, of which
43% (394/909) were published. Among the subset of trials described in the
FDA-approved drug label and classified as “pivotal trials” for our
analysis, 76% (257/340) were published. In multivariable logistic regression
for all trials 5 y postapproval, likelihood of publication correlated with statistically
significant results (odds ratio [OR] 3.03, 95% confidence
interval [CI] 1.78–5.17); larger sample sizes (OR 1.33 per
2-fold increase in sample size, 95% CI 1.17–1.52); and pivotal
status (OR 5.31, 95% CI 3.30–8.55). In multivariable logistic
regression for only the pivotal trials 5 y postapproval, likelihood of publication
correlated with statistically significant results (OR 2.96, 95% CI
1. 24–7.06) and larger sample sizes (OR 1.47 per 2-fold increase in sample
size, 95% CI 1.15–1.88). Statistically significant results and
larger sample sizes were also predictive of publication at 2 y postapproval and in
multivariable Cox proportional models for all trials and the subset of pivotal
trials.
Conclusions:
Over half of all supporting trials for FDA-approved drugs remained unpublished ≥
5 y after approval. Pivotal trials and trials with statistically significant results and
larger sample sizes are more likely to be published. Selective reporting of trial
results exists for commonly marketed drugs. Our data provide a baseline for evaluating
publication bias as the new FDA Amendments Act comes into force mandating basic results
reporting of clinical trials.
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