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 language | English |
|---|---|
| Pages (from-to) | 130-137 |
| Number of pages | 8 |
| Journal | Critical Care Medicine |
| Volume | 44 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2016 |
Fingerprint
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
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 journal › Article
}
TY - JOUR
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
PY - 2016/1/1
Y1 - 2016/1/1
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
UR - http://www.scopus.com/inward/record.url?scp=84951201707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951201707&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000001369
DO - 10.1097/CCM.0000000000001369
M3 - Article
C2 - 26468895
AN - SCOPUS:84951201707
VL - 44
SP - 130
EP - 137
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 1
ER -