Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit

Mohammad H Murad, Gordon H. Guyatt, Juan Pablo Domecq, Robin W M Vernooij, Patricia J. Erwin, Joerg J. Meerpohl, Gabriela J. Prutsky, Elie A. Akl, Katharina Mueller, Dirk Bassler, Stefan Schandelmaier, Stephen D. Walter, Jason W. Busse, Benjamin Kasenda, Gennaro Pagano, Hector Pardo-Hernandez, Victor Manuel Montori, Zhen Wang, Matthias Briel

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

Original languageEnglish (US)
Pages (from-to)12-19
Number of pages8
JournalJournal of Clinical Epidemiology
Volume82
DOIs
StatePublished - Feb 1 2017

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Keywords

  • Early termination of trials
  • Methodology
  • Randomized controlled trials
  • Systematic review
  • Trial design
  • Trials stopped early for benefit

ASJC Scopus subject areas

  • Epidemiology

Cite this

Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit. / Murad, Mohammad H; Guyatt, Gordon H.; Domecq, Juan Pablo; Vernooij, Robin W M; Erwin, Patricia J.; Meerpohl, Joerg J.; Prutsky, Gabriela J.; Akl, Elie A.; Mueller, Katharina; Bassler, Dirk; Schandelmaier, Stefan; Walter, Stephen D.; Busse, Jason W.; Kasenda, Benjamin; Pagano, Gennaro; Pardo-Hernandez, Hector; Montori, Victor Manuel; Wang, Zhen; Briel, Matthias.

In: Journal of Clinical Epidemiology, Vol. 82, 01.02.2017, p. 12-19.

Research output: Contribution to journalReview article

Murad, MH, Guyatt, GH, Domecq, JP, Vernooij, RWM, Erwin, PJ, Meerpohl, JJ, Prutsky, GJ, Akl, EA, Mueller, K, Bassler, D, Schandelmaier, S, Walter, SD, Busse, JW, Kasenda, B, Pagano, G, Pardo-Hernandez, H, Montori, VM, Wang, Z & Briel, M 2017, 'Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit', Journal of Clinical Epidemiology, vol. 82, pp. 12-19. https://doi.org/10.1016/j.jclinepi.2016.10.006
Murad, Mohammad H ; Guyatt, Gordon H. ; Domecq, Juan Pablo ; Vernooij, Robin W M ; Erwin, Patricia J. ; Meerpohl, Joerg J. ; Prutsky, Gabriela J. ; Akl, Elie A. ; Mueller, Katharina ; Bassler, Dirk ; Schandelmaier, Stefan ; Walter, Stephen D. ; Busse, Jason W. ; Kasenda, Benjamin ; Pagano, Gennaro ; Pardo-Hernandez, Hector ; Montori, Victor Manuel ; Wang, Zhen ; Briel, Matthias. / Randomized trials addressing a similar question are commonly published after a trial stopped early for benefit. In: Journal of Clinical Epidemiology. 2017 ; Vol. 82. pp. 12-19.
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abstract = "Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49{\%}) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38{\%}) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33{\%}), skepticism of truncated trials findings because of small sample size (12{\%}), inconsistency with other evidence (11{\%}), or increased risk of bias (7{\%}). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.",
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AU - Murad, Mohammad H

AU - Guyatt, Gordon H.

AU - Domecq, Juan Pablo

AU - Vernooij, Robin W M

AU - Erwin, Patricia J.

AU - Meerpohl, Joerg J.

AU - Prutsky, Gabriela J.

AU - Akl, Elie A.

AU - Mueller, Katharina

AU - Bassler, Dirk

AU - Schandelmaier, Stefan

AU - Walter, Stephen D.

AU - Busse, Jason W.

AU - Kasenda, Benjamin

AU - Pagano, Gennaro

AU - Pardo-Hernandez, Hector

AU - Montori, Victor Manuel

AU - Wang, Zhen

AU - Briel, Matthias

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N2 - Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

AB - Objective We explored how investigators of ongoing or planned trials respond to the publication of a trial stopped early for benefit addressing a similar question. Study Design and Setting We searched multiple databases from the date of publication of the truncated trial through August, 2015. Independent reviewers selected trials and extracted data. Results We identified 207 trials truncated for early benefit; of which 102 (49%) were followed by subsequent trials (262 subsequent trials, median 2 per truncated trial, range 1–13). Only 99 (38%) provided a rationale justifying conducting a trial despite prior stopping. The top reasons were to address different population or setting (33%), skepticism of truncated trials findings because of small sample size (12%), inconsistency with other evidence (11%), or increased risk of bias (7%). We did not identify significant associations between subsequent trials and characteristics of truncated ones (risk of bias, precision, funding, or rigor of stopping decision). Conclusion About half of the trials stopped early for benefit were followed by subsequent trials addressing a similar question. This suggests that future trialists may have been skeptic about the decision to stop prior trials. A more rigorous threshold for stopping early for benefit is needed.

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