Abstract
BackgroundThe 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 FindingsWe 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trials and the subset of pivotal trials.ConclusionsOver half of all supporting trials for FDA-approved drugs remained unpublished ≥ 5 y after approval.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.
Highlights
In the United States, the Food and Drug Administration (FDA) approves new drug products for sale and marketing based on results from clinical investigations that demonstrate the safety and efficacy of a drug for a proposed indication
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 United States (US) would reasonably search
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
Summary
In the United States, the Food and Drug Administration (FDA) approves new drug products for sale and marketing based on results from clinical investigations that demonstrate the safety and efficacy of a drug for a proposed indication. In the most important of these trials—so-called ‘‘pivotal’’ clinical trials—the efficacy and safety of the new drug and of a standard treatment are compared by giving groups of patients the different treatments and measuring several predefined ‘‘outcomes.’’ These outcomes indicate whether the new drug is more effective than the standard treatment and whether it has any other effects on the patients’ health and daily life All this information is submitted by the sponsor of the new drug (usually a pharmaceutical company) to the government body responsible for drug approval—in the US, this is the Food and Drug Administration (FDA). The researchers investigate whether selective trial reporting is common by evaluating the publication status of trials submitted to the FDA for a wide variety of approved drugs They ask which factors affect a trial’s chances of publication
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