Reporting Bias in Drug Trials Submitted to the Food and Drug Administration:
Review of Publication and Presentation
Background:
Previous studies of drug trials submitted to regulatory authorities have documented
selective reporting of both entire trials and favorable results. The objective of this
study is to determine the publication rate of efficacy trials submitted to the Food and
Drug Administration (FDA) in approved New Drug Applications (NDAs) and to compare the
trial characteristics as reported by the FDA with those reported in publications.
Methods and Findings:
This is an observational study of all efficacy trials found in approved NDAs for New
Molecular Entities (NMEs) from 2001 to 2002 inclusive and all published clinical trials
corresponding to the trials within the NDAs. For each trial included in the NDA, we
assessed its publication status, primary outcome(s) reported and their statistical
significance, and conclusions. Seventy-eight percent (128/164) of efficacy trials
contained in FDA reviews of NDAs were published. In a multivariate model, trials with
favorable primary outcomes (OR = 4.7, 95% confidence interval
[CI] 1.
33–17.1, p = 0.018) and
active controls (OR = 3.4, 95% CI 1.02–11.2,
p = 0.047) were more likely to be published. Forty-one
primary outcomes from the NDAs were omitted from the papers. Papers included 155
outcomes that were in the NDAs, 15 additional outcomes that favored the test drug, and
two other neutral or unknown additional outcomes. Excluding outcomes with unknown
significance, there were 43 outcomes in the NDAs that did not favor the NDA drug. Of
these, 20 (47%) were not included in the papers. The statistical significance
of five of the remaining 23 outcomes (22%) changed between the NDA and the
paper, with four changing to favor the test drug in the paper (p
= 0.
38). Excluding unknowns, 99 conclusions were provided in both NDAs and
papers, nine conclusions (9%) changed from the FDA review of the NDA to the
paper, and all nine did so to favor the test drug (100%, 95% CI
72%–100%, p = 0.0039).
Conclusions:
Many trials were still not published 5 y after FDA approval. Discrepancies between the
trial information reviewed by the FDA and information found in published trials tended
to lead to more favorable presentations of the NDA drugs in the publications. Thus, the
information that is readily available in the scientific literature to health care
professionals is incomplete and potentially biased.
Vyšlo v časopise:
Reporting Bias in Drug Trials Submitted to the Food and Drug Administration:
Review of Publication and Presentation. PLoS Med 5(11): e217. doi:10.1371/journal.pmed.0050217
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.0050217
Souhrn
Background:
Previous studies of drug trials submitted to regulatory authorities have documented
selective reporting of both entire trials and favorable results. The objective of this
study is to determine the publication rate of efficacy trials submitted to the Food and
Drug Administration (FDA) in approved New Drug Applications (NDAs) and to compare the
trial characteristics as reported by the FDA with those reported in publications.
Methods and Findings:
This is an observational study of all efficacy trials found in approved NDAs for New
Molecular Entities (NMEs) from 2001 to 2002 inclusive and all published clinical trials
corresponding to the trials within the NDAs. For each trial included in the NDA, we
assessed its publication status, primary outcome(s) reported and their statistical
significance, and conclusions. Seventy-eight percent (128/164) of efficacy trials
contained in FDA reviews of NDAs were published. In a multivariate model, trials with
favorable primary outcomes (OR = 4.7, 95% confidence interval
[CI] 1.
33–17.1, p = 0.018) and
active controls (OR = 3.4, 95% CI 1.02–11.2,
p = 0.047) were more likely to be published. Forty-one
primary outcomes from the NDAs were omitted from the papers. Papers included 155
outcomes that were in the NDAs, 15 additional outcomes that favored the test drug, and
two other neutral or unknown additional outcomes. Excluding outcomes with unknown
significance, there were 43 outcomes in the NDAs that did not favor the NDA drug. Of
these, 20 (47%) were not included in the papers. The statistical significance
of five of the remaining 23 outcomes (22%) changed between the NDA and the
paper, with four changing to favor the test drug in the paper (p
= 0.
38). Excluding unknowns, 99 conclusions were provided in both NDAs and
papers, nine conclusions (9%) changed from the FDA review of the NDA to the
paper, and all nine did so to favor the test drug (100%, 95% CI
72%–100%, p = 0.0039).
Conclusions:
Many trials were still not published 5 y after FDA approval. Discrepancies between the
trial information reviewed by the FDA and information found in published trials tended
to lead to more favorable presentations of the NDA drugs in the publications. Thus, the
information that is readily available in the scientific literature to health care
professionals is incomplete and potentially biased.
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