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Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration: A Secondary Analysis of Pooled Trial Data.

Publication ,  Journal Article
Meyerson, WU; Pieper, CF; Hoyle, RH
Published in: JAMA Netw Open
June 1, 2023

IMPORTANCE: Major depressive disorder (MDD) is a leading cause of global distress and disability. Earlier studies have indicated that antidepressant therapy confers a modest reduction in depressive symptoms on average, but the distribution of this reduction requires more research. OBJECTIVE: To estimate the distribution of antidepressant response by depression severity. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of pooled trial data, quantile treatment effect (QTE) analysis was conducted from the US Food and Drug Administration (FDA) database of antidepressant monotherapy for patients with MDD, encompassing 232 positive and negative trials submitted to the FDA between 1979 and 2016. Analysis was restricted to participants with severe MDD (17-item Hamilton Rating Scale for Depression [HAMD-17] score ≥20). Data analysis was conducted from August 16, 2022, to April 16, 2023. INTERVENTION: Antidepressant monotherapy compared with placebo. MAIN OUTCOMES AND MEASURES: The distribution of percentage depression response was compared between the pooled treatment arm and pooled placebo arm. Percentage depression response was defined as 1 minus the ratio of final depression severity to baseline depression severity, expressed as a percentage. Depression severity was reported in HAMD-17-equivalent units. RESULTS: A total of 57 313 participants with severe depression were included in the analysis. There was no significant imbalance in baseline depression severity between the pooled treatment arm and pooled placebo arm, with a mean HAMD-17 difference of 0.037 points (P = .11 by Wilcoxon rank sum test). An interaction term test for rank similarity did not reject the rank similarity governing percentage depression response (P > .99). The entire distribution of depression response was more favorable in the pooled treatment arm than in the pooled placebo arm. The maximum separation between treatment and placebo occurred at the 55th quantile and corresponded to an absolute improvement in depression due to active drug of 13.5% (95% CI, 12.4%-14.4%). The separation between treatment and placebo diminished near the tails of the distribution. CONCLUSIONS AND RELEVANCE: In this QTE analysis of pooled clinical trial data from the FDA, antidepressants were found to confer a small reduction in depression severity that was broadly distributed across participants with severe depression. Alternatively, if the assumptions behind the QTE analysis are not met, then the data are also compatible with antidepressants eliciting more complete response in a smaller subset of participants than is suggested by this QTE analysis.

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Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

June 1, 2023

Volume

6

Issue

6

Start / End Page

e2317714

Location

United States

Related Subject Headings

  • United States Food and Drug Administration
  • United States
  • Remission Induction
  • Randomized Controlled Trials as Topic
  • Humans
  • Depressive Disorder, Major
  • Antidepressive Agents
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Meyerson, W. U., Pieper, C. F., & Hoyle, R. H. (2023). Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration: A Secondary Analysis of Pooled Trial Data. JAMA Netw Open, 6(6), e2317714. https://doi.org/10.1001/jamanetworkopen.2023.17714
Meyerson, William U., Carl F. Pieper, and Rick H. Hoyle. “Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration: A Secondary Analysis of Pooled Trial Data.JAMA Netw Open 6, no. 6 (June 1, 2023): e2317714. https://doi.org/10.1001/jamanetworkopen.2023.17714.
Meyerson, William U., et al. “Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration: A Secondary Analysis of Pooled Trial Data.JAMA Netw Open, vol. 6, no. 6, June 2023, p. e2317714. Pubmed, doi:10.1001/jamanetworkopen.2023.17714.

Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

June 1, 2023

Volume

6

Issue

6

Start / End Page

e2317714

Location

United States

Related Subject Headings

  • United States Food and Drug Administration
  • United States
  • Remission Induction
  • Randomized Controlled Trials as Topic
  • Humans
  • Depressive Disorder, Major
  • Antidepressive Agents
  • 42 Health sciences
  • 32 Biomedical and clinical sciences