Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders

A report of 2 meta-analyses

Annelieke M. Roest, Peter De Jonge, Craig D. Williams, Ymkje Anna De Vries, Robert A. Schoevers, Erick Turner

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

IMPORTANCE: Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered. OBJECTIVE: To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases inflate estimates of drug efficacy. DATA SOURCES AND STUDY SELECTION: We included reviews obtained from the US Food and Drug Administration (FDA) for premarketing trials of 9 second-generation antidepressants in the treatment of anxiety disorders. A systematic search for matching publications (until December 19, 2012) was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. DATA EXTRACTION AND SYNTHESIS: Double data extraction was performed for the FDA reviews and the journal articles. The Hedges g value was calculated as the measure of effect size. MAIN OUTCOMES AND MEASURES: Reporting bias was examined and classified as study publication bias, outcome reporting bias, or spin (abstract conclusion not consistent with published results on primary end point). Separate meta-analyses were conducted for the 2 sources, and the effect of publication status on the effect estimates was examined using meta-regression. RESULTS: The findings of 41 of the 57 trials (72%) were positive according to the FDA, but 43 of the 45 published article conclusions (96%) were positive (P < .001). Trials that the FDA determined as positive were 5 times more likely to be published in agreement with that determination compared with trials determined as not positive (risk ratio, 5.20; 95% CI, 1.87 to 14.45; P < .001). We found evidence for study publication bias (P < .001), outcome reporting bias (P = .02), and spin (P = .02). The pooled effect size based on the published literature (Hedges g, 0.38; 95% CI, 0.33 to 0.42; P < .001) was 15% higher than the effect size based on the FDA data (Hedges g, 0.33; 95% CI, 0.29 to 0.38; P < .001), but this difference was not statistically significant (β = 0.04; 95% CI, -0.02 to 0.10; P = .18). CONCLUSIONS AND RELEVANCE: Various reporting biases were present for trials on the efficacy of FDA-approved second-generation antidepressants for anxiety disorders. Although these biases did not significantly inflate estimates of drug efficacy, reporting biases led to significant increases in the number of positive findings in the literature.

Original languageEnglish (US)
Pages (from-to)500-510
Number of pages11
JournalJAMA Psychiatry
Volume72
Issue number5
DOIs
StatePublished - May 1 2015

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United States Food and Drug Administration
Anxiety Disorders
Antidepressive Agents
Meta-Analysis
Clinical Trials
Publication Bias
Publications
Therapeutics
Pharmaceutical Preparations
Literature
Information Storage and Retrieval
PubMed
Efficacy
Antidepressants
Odds Ratio
Placebos
Depression
Food and Drug Administration

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health
  • Medicine(all)

Cite this

Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders : A report of 2 meta-analyses. / Roest, Annelieke M.; De Jonge, Peter; Williams, Craig D.; De Vries, Ymkje Anna; Schoevers, Robert A.; Turner, Erick.

In: JAMA Psychiatry, Vol. 72, No. 5, 01.05.2015, p. 500-510.

Research output: Contribution to journalArticle

Roest, Annelieke M. ; De Jonge, Peter ; Williams, Craig D. ; De Vries, Ymkje Anna ; Schoevers, Robert A. ; Turner, Erick. / Reporting bias in clinical trials investigating the efficacy of second-generation antidepressants in the treatment of anxiety disorders : A report of 2 meta-analyses. In: JAMA Psychiatry. 2015 ; Vol. 72, No. 5. pp. 500-510.
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abstract = "IMPORTANCE: Studies have shown that the scientific literature has overestimated the efficacy of antidepressants for depression, but other indications for these drugs have not been considered. OBJECTIVE: To examine reporting biases in double-blind, placebo-controlled trials on the pharmacologic treatment of anxiety disorders and quantify the extent to which these biases inflate estimates of drug efficacy. DATA SOURCES AND STUDY SELECTION: We included reviews obtained from the US Food and Drug Administration (FDA) for premarketing trials of 9 second-generation antidepressants in the treatment of anxiety disorders. A systematic search for matching publications (until December 19, 2012) was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. DATA EXTRACTION AND SYNTHESIS: Double data extraction was performed for the FDA reviews and the journal articles. The Hedges g value was calculated as the measure of effect size. MAIN OUTCOMES AND MEASURES: Reporting bias was examined and classified as study publication bias, outcome reporting bias, or spin (abstract conclusion not consistent with published results on primary end point). Separate meta-analyses were conducted for the 2 sources, and the effect of publication status on the effect estimates was examined using meta-regression. RESULTS: The findings of 41 of the 57 trials (72{\%}) were positive according to the FDA, but 43 of the 45 published article conclusions (96{\%}) were positive (P < .001). Trials that the FDA determined as positive were 5 times more likely to be published in agreement with that determination compared with trials determined as not positive (risk ratio, 5.20; 95{\%} CI, 1.87 to 14.45; P < .001). We found evidence for study publication bias (P < .001), outcome reporting bias (P = .02), and spin (P = .02). The pooled effect size based on the published literature (Hedges g, 0.38; 95{\%} CI, 0.33 to 0.42; P < .001) was 15{\%} higher than the effect size based on the FDA data (Hedges g, 0.33; 95{\%} CI, 0.29 to 0.38; P < .001), but this difference was not statistically significant (β = 0.04; 95{\%} CI, -0.02 to 0.10; P = .18). CONCLUSIONS AND RELEVANCE: Various reporting biases were present for trials on the efficacy of FDA-approved second-generation antidepressants for anxiety disorders. Although these biases did not significantly inflate estimates of drug efficacy, reporting biases led to significant increases in the number of positive findings in the literature.",
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