Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design

Gabriela J. Prutsky, Juan P. Domecq, Patricia J. Erwin, Matthias Briel, Victor M. Montori, Elie A. Akl, Joerg J. Meerpohl, Dirk Bassler, Stefan Schandelmaier, Stephen D. Walter, Qi Zhou, Pablo A. Coello, Lorenzo Moja, Martin Walter, Kristian Thorlund, Paul Glasziou, Regina Kunz, Ignacio Ferreira-Gonzalez, Jason Busse, Xin Sun & 8 others Annette Kristiansen, Benjamin Kasenda, Osama Qasim-Agha, Gennaro Pagano, Hector Pardo-Hernandez, Gerard Urrutia, Mohammad H. Murad, Gordon Guyatt

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Abstract

Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.Methods/design: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.Discussion: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

Original languageEnglish
Article number335
JournalTrials
Volume14
Issue number1
DOIs
Publication statusPublished - 16 Oct 2013
Externally publishedYes

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Prutsky, Gabriela J. ; Domecq, Juan P. ; Erwin, Patricia J. ; Briel, Matthias ; Montori, Victor M. ; Akl, Elie A. ; Meerpohl, Joerg J. ; Bassler, Dirk ; Schandelmaier, Stefan ; Walter, Stephen D. ; Zhou, Qi ; Coello, Pablo A. ; Moja, Lorenzo ; Walter, Martin ; Thorlund, Kristian ; Glasziou, Paul ; Kunz, Regina ; Ferreira-Gonzalez, Ignacio ; Busse, Jason ; Sun, Xin ; Kristiansen, Annette ; Kasenda, Benjamin ; Qasim-Agha, Osama ; Pagano, Gennaro ; Pardo-Hernandez, Hector ; Urrutia, Gerard ; Murad, Mohammad H. ; Guyatt, Gordon. / Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question : STOPIT-3 study design. In: Trials. 2013 ; Vol. 14, No. 1.
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title = "Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design",
abstract = "Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30{\%}. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.Methods/design: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.Discussion: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.",
author = "Prutsky, {Gabriela J.} and Domecq, {Juan P.} and Erwin, {Patricia J.} and Matthias Briel and Montori, {Victor M.} and Akl, {Elie A.} and Meerpohl, {Joerg J.} and Dirk Bassler and Stefan Schandelmaier and Walter, {Stephen D.} and Qi Zhou and Coello, {Pablo A.} and Lorenzo Moja and Martin Walter and Kristian Thorlund and Paul Glasziou and Regina Kunz and Ignacio Ferreira-Gonzalez and Jason Busse and Xin Sun and Annette Kristiansen and Benjamin Kasenda and Osama Qasim-Agha and Gennaro Pagano and Hector Pardo-Hernandez and Gerard Urrutia and Murad, {Mohammad H.} and Gordon Guyatt",
year = "2013",
month = "10",
day = "16",
doi = "10.1186/1745-6215-14-335",
language = "English",
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journal = "Current Controlled Trials in Cardiovascular Medicine",
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Prutsky, GJ, Domecq, JP, Erwin, PJ, Briel, M, Montori, VM, Akl, EA, Meerpohl, JJ, Bassler, D, Schandelmaier, S, Walter, SD, Zhou, Q, Coello, PA, Moja, L, Walter, M, Thorlund, K, Glasziou, P, Kunz, R, Ferreira-Gonzalez, I, Busse, J, Sun, X, Kristiansen, A, Kasenda, B, Qasim-Agha, O, Pagano, G, Pardo-Hernandez, H, Urrutia, G, Murad, MH & Guyatt, G 2013, 'Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design' Trials, vol. 14, no. 1, 335. https://doi.org/10.1186/1745-6215-14-335

Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question : STOPIT-3 study design. / Prutsky, Gabriela J.; Domecq, Juan P.; Erwin, Patricia J.; Briel, Matthias; Montori, Victor M.; Akl, Elie A.; Meerpohl, Joerg J.; Bassler, Dirk; Schandelmaier, Stefan; Walter, Stephen D.; Zhou, Qi; Coello, Pablo A.; Moja, Lorenzo; Walter, Martin; Thorlund, Kristian; Glasziou, Paul; Kunz, Regina; Ferreira-Gonzalez, Ignacio; Busse, Jason; Sun, Xin; Kristiansen, Annette; Kasenda, Benjamin; Qasim-Agha, Osama; Pagano, Gennaro; Pardo-Hernandez, Hector; Urrutia, Gerard; Murad, Mohammad H.; Guyatt, Gordon.

In: Trials, Vol. 14, No. 1, 335, 16.10.2013.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question

T2 - STOPIT-3 study design

AU - Prutsky, Gabriela J.

AU - Domecq, Juan P.

AU - Erwin, Patricia J.

AU - Briel, Matthias

AU - Montori, Victor M.

AU - Akl, Elie A.

AU - Meerpohl, Joerg J.

AU - Bassler, Dirk

AU - Schandelmaier, Stefan

AU - Walter, Stephen D.

AU - Zhou, Qi

AU - Coello, Pablo A.

AU - Moja, Lorenzo

AU - Walter, Martin

AU - Thorlund, Kristian

AU - Glasziou, Paul

AU - Kunz, Regina

AU - Ferreira-Gonzalez, Ignacio

AU - Busse, Jason

AU - Sun, Xin

AU - Kristiansen, Annette

AU - Kasenda, Benjamin

AU - Qasim-Agha, Osama

AU - Pagano, Gennaro

AU - Pardo-Hernandez, Hector

AU - Urrutia, Gerard

AU - Murad, Mohammad H.

AU - Guyatt, Gordon

PY - 2013/10/16

Y1 - 2013/10/16

N2 - Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.Methods/design: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.Discussion: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

AB - Background: Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.Methods/design: We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs'). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.Discussion: To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

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U2 - 10.1186/1745-6215-14-335

DO - 10.1186/1745-6215-14-335

M3 - Article

VL - 14

JO - Current Controlled Trials in Cardiovascular Medicine

JF - Current Controlled Trials in Cardiovascular Medicine

SN - 1745-6215

IS - 1

M1 - 335

ER -