Premature discontinuation of randomized trials in critical and emergency care: A retrospective cohort study

Stefan Schandelmaier, Erik Von Elm, John J. You, Anette Blümle, Yuki Tomonaga, Francois Lamontagne, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Joerg J. Meerpohl, Mihaela Stegert, Kelechi K. Olu, Kari A O Tikkinen, Ignacio Neumann, Alonso Carrasco-Labra, Markus Faulhaber, Sohail M. Mulla, Dominik Mertz, Elie A. Akl, Xin SunDirk Bassler, Jason W. Busse, Ignacio Ferreira-González, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Deborah J. Cook, Maureen O. Meade, Heiner C. Bucher, Benjamin Kasenda, Matthias Briel

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objectives: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. Design: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. Setting: Randomized clinical trials involving patients in an acute or nonacute care setting. Subjects and Interventions: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. Measurements and Main Results: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. Conclusions: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

Original languageEnglish
Pages (from-to)130-137
Number of pages8
JournalCritical Care Medicine
Volume44
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Emergency Medical Services
Critical Care
Cohort Studies
Randomized Controlled Trials
Retrospective Studies
Research Ethics Committees
Informed Consent
Switzerland
Sample Size
Patient Selection
Canada
Germany
Publications
Logistic Models

Keywords

  • critical care
  • early termination of clinical trials
  • emergency medicine
  • ethics committees
  • randomized controlled trials

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Schandelmaier, S., Von Elm, E., You, J. J., Blümle, A., Tomonaga, Y., Lamontagne, F., ... Briel, M. (2016). Premature discontinuation of randomized trials in critical and emergency care: A retrospective cohort study. Critical Care Medicine, 44(1), 130-137. https://doi.org/10.1097/CCM.0000000000001369

Premature discontinuation of randomized trials in critical and emergency care : A retrospective cohort study. / Schandelmaier, Stefan; Von Elm, Erik; You, John J.; Blümle, Anette; Tomonaga, Yuki; Lamontagne, Francois; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Olu, Kelechi K.; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Sun, Xin; Bassler, Dirk; Busse, Jason W.; Ferreira-González, Ignacio; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G.; Cook, Deborah J.; Meade, Maureen O.; Bucher, Heiner C.; Kasenda, Benjamin; Briel, Matthias.

In: Critical Care Medicine, Vol. 44, No. 1, 01.01.2016, p. 130-137.

Research output: Contribution to journalArticle

Schandelmaier, S, Von Elm, E, You, JJ, Blümle, A, Tomonaga, Y, Lamontagne, F, Saccilotto, R, Amstutz, A, Bengough, T, Meerpohl, JJ, Stegert, M, Olu, KK, Tikkinen, KAO, Neumann, I, Carrasco-Labra, A, Faulhaber, M, Mulla, SM, Mertz, D, Akl, EA, Sun, X, Bassler, D, Busse, JW, Ferreira-González, I, Nordmann, A, Gloy, V, Raatz, H, Moja, L, Rosenthal, R, Ebrahim, S, Vandvik, PO, Johnston, BC, Walter, MA, Burnand, B, Schwenkglenks, M, Hemkens, LG, Cook, DJ, Meade, MO, Bucher, HC, Kasenda, B & Briel, M 2016, 'Premature discontinuation of randomized trials in critical and emergency care: A retrospective cohort study', Critical Care Medicine, vol. 44, no. 1, pp. 130-137. https://doi.org/10.1097/CCM.0000000000001369
Schandelmaier, Stefan ; Von Elm, Erik ; You, John J. ; Blümle, Anette ; Tomonaga, Yuki ; Lamontagne, Francois ; Saccilotto, Ramon ; Amstutz, Alain ; Bengough, Theresa ; Meerpohl, Joerg J. ; Stegert, Mihaela ; Olu, Kelechi K. ; Tikkinen, Kari A O ; Neumann, Ignacio ; Carrasco-Labra, Alonso ; Faulhaber, Markus ; Mulla, Sohail M. ; Mertz, Dominik ; Akl, Elie A. ; Sun, Xin ; Bassler, Dirk ; Busse, Jason W. ; Ferreira-González, Ignacio ; Nordmann, Alain ; Gloy, Viktoria ; Raatz, Heike ; Moja, Lorenzo ; Rosenthal, Rachel ; Ebrahim, Shanil ; Vandvik, Per O. ; Johnston, Bradley C. ; Walter, Martin A. ; Burnand, Bernard ; Schwenkglenks, Matthias ; Hemkens, Lars G. ; Cook, Deborah J. ; Meade, Maureen O. ; Bucher, Heiner C. ; Kasenda, Benjamin ; Briel, Matthias. / Premature discontinuation of randomized trials in critical and emergency care : A retrospective cohort study. In: Critical Care Medicine. 2016 ; Vol. 44, No. 1. pp. 130-137.
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abstract = "Objectives: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. Design: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. Setting: Randomized clinical trials involving patients in an acute or nonacute care setting. Subjects and Interventions: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. Measurements and Main Results: Of 894 randomized clinical trials, 64 (7{\%}) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44{\%} vs 221 of 830, 27{\%}; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20{\%}) and in nonacute care randomized clinical trials (7 of 64, 11{\%}). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95{\%} CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. Conclusions: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.",
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T1 - Premature discontinuation of randomized trials in critical and emergency care

T2 - A retrospective cohort study

AU - Schandelmaier, Stefan

AU - Von Elm, Erik

AU - You, John J.

AU - Blümle, Anette

AU - Tomonaga, Yuki

AU - Lamontagne, Francois

AU - Saccilotto, Ramon

AU - Amstutz, Alain

AU - Bengough, Theresa

AU - Meerpohl, Joerg J.

AU - Stegert, Mihaela

AU - Olu, Kelechi K.

AU - Tikkinen, Kari A O

AU - Neumann, Ignacio

AU - Carrasco-Labra, Alonso

AU - Faulhaber, Markus

AU - Mulla, Sohail M.

AU - Mertz, Dominik

AU - Akl, Elie A.

AU - Sun, Xin

AU - Bassler, Dirk

AU - Busse, Jason W.

AU - Ferreira-González, Ignacio

AU - Nordmann, Alain

AU - Gloy, Viktoria

AU - Raatz, Heike

AU - Moja, Lorenzo

AU - Rosenthal, Rachel

AU - Ebrahim, Shanil

AU - Vandvik, Per O.

AU - Johnston, Bradley C.

AU - Walter, Martin A.

AU - Burnand, Bernard

AU - Schwenkglenks, Matthias

AU - Hemkens, Lars G.

AU - Cook, Deborah J.

AU - Meade, Maureen O.

AU - Bucher, Heiner C.

AU - Kasenda, Benjamin

AU - Briel, Matthias

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N2 - Objectives: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. Design: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. Setting: Randomized clinical trials involving patients in an acute or nonacute care setting. Subjects and Interventions: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. Measurements and Main Results: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. Conclusions: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

AB - Objectives: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. Design: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. Setting: Randomized clinical trials involving patients in an acute or nonacute care setting. Subjects and Interventions: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. Measurements and Main Results: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. Conclusions: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

KW - critical care

KW - early termination of clinical trials

KW - emergency medicine

KW - ethics committees

KW - randomized controlled trials

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