Prevalence, characteristics, and publication of discontinued randomized trials

Benjamin Kasenda, Erik Von Elm, John You, Anette Blümle, Yuki Tomonaga, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Joerg J. Meerpohl, Mihaela Stegert, Kari A O Tikkinen, Ignacio Neumann, Alonso Carrasco-Labra, Markus Faulhaber, Sohail M. Mulla, Dominik Mertz, Elie A. Akl, Dirk Bassler, Jason W. Busse, Ignacio Ferreira-González & 18 others Francois Lamontagne, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Stefan Schandelmaier, Sun Xin, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Heiner C. Bucher, Gordon H. Guyatt, Matthias Briel

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003.We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95%CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95%CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9%[95%CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95%CI, 0.15-0.43]; P <.001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95%CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95%CI, 2.29-4.43]; P <.001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalJournal of the American Medical Association
Volume311
Issue number10
DOIs
Publication statusPublished - 2014

Fingerprint

Publications
Randomized Controlled Trials
Research Ethics Committees
Odds Ratio
Clinical Protocols
Research Personnel
Ethics Committees
Switzerland
Sample Size
Canada
Germany
Industry
Epidemiology
Outcome Assessment (Health Care)
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kasenda, B., Von Elm, E., You, J., Blümle, A., Tomonaga, Y., Saccilotto, R., ... Briel, M. (2014). Prevalence, characteristics, and publication of discontinued randomized trials. Journal of the American Medical Association, 311(10), 1045-1051. https://doi.org/10.1001/jama.2014.1361

Prevalence, characteristics, and publication of discontinued randomized trials. / Kasenda, Benjamin; Von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Bassler, Dirk; Busse, Jason W.; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Schandelmaier, Stefan; Xin, Sun; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G.; Bucher, Heiner C.; Guyatt, Gordon H.; Briel, Matthias.

In: Journal of the American Medical Association, Vol. 311, No. 10, 2014, p. 1045-1051.

Research output: Contribution to journalArticle

Kasenda, B, Von Elm, E, You, J, Blümle, A, Tomonaga, Y, Saccilotto, R, Amstutz, A, Bengough, T, Meerpohl, JJ, Stegert, M, Tikkinen, KAO, Neumann, I, Carrasco-Labra, A, Faulhaber, M, Mulla, SM, Mertz, D, Akl, EA, Bassler, D, Busse, JW, Ferreira-González, I, Lamontagne, F, Nordmann, A, Gloy, V, Raatz, H, Moja, L, Rosenthal, R, Ebrahim, S, Schandelmaier, S, Xin, S, Vandvik, PO, Johnston, BC, Walter, MA, Burnand, B, Schwenkglenks, M, Hemkens, LG, Bucher, HC, Guyatt, GH & Briel, M 2014, 'Prevalence, characteristics, and publication of discontinued randomized trials', Journal of the American Medical Association, vol. 311, no. 10, pp. 1045-1051. https://doi.org/10.1001/jama.2014.1361
Kasenda, Benjamin ; Von Elm, Erik ; You, John ; Blümle, Anette ; Tomonaga, Yuki ; Saccilotto, Ramon ; Amstutz, Alain ; Bengough, Theresa ; Meerpohl, Joerg J. ; Stegert, Mihaela ; Tikkinen, Kari A O ; Neumann, Ignacio ; Carrasco-Labra, Alonso ; Faulhaber, Markus ; Mulla, Sohail M. ; Mertz, Dominik ; Akl, Elie A. ; Bassler, Dirk ; Busse, Jason W. ; Ferreira-González, Ignacio ; Lamontagne, Francois ; Nordmann, Alain ; Gloy, Viktoria ; Raatz, Heike ; Moja, Lorenzo ; Rosenthal, Rachel ; Ebrahim, Shanil ; Schandelmaier, Stefan ; Xin, Sun ; Vandvik, Per O. ; Johnston, Bradley C. ; Walter, Martin A. ; Burnand, Bernard ; Schwenkglenks, Matthias ; Hemkens, Lars G. ; Bucher, Heiner C. ; Guyatt, Gordon H. ; Briel, Matthias. / Prevalence, characteristics, and publication of discontinued randomized trials. In: Journal of the American Medical Association. 2014 ; Vol. 311, No. 10. pp. 1045-1051.
@article{d64b0df08b5f4266b5c6cec61bf5f70c,
title = "Prevalence, characteristics, and publication of discontinued randomized trials",
abstract = "IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003.We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9{\%} [95{\%}CI, 22.3{\%}-27.6{\%}]). Only 96 of 253 discontinuations (37.9{\%} [95{\%}CI, 32.0{\%}-44.3{\%}]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9{\%}[95{\%}CI, 8.2{\%}-12.0{\%}]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4{\%} vs 26.5{\%}; odds ratio [OR], 0.25 [95{\%}CI, 0.15-0.43]; P <.001) and a larger planned sample size in increments of 100 (-0.7{\%}; OR, 0.96 [95{\%}CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1{\%} vs 33.6{\%}; OR, 3.19 [95{\%}CI, 2.29-4.43]; P <.001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.",
author = "Benjamin Kasenda and {Von Elm}, Erik and John You and Anette Bl{\"u}mle and Yuki Tomonaga and Ramon Saccilotto and Alain Amstutz and Theresa Bengough and Meerpohl, {Joerg J.} and Mihaela Stegert and Tikkinen, {Kari A O} and Ignacio Neumann and Alonso Carrasco-Labra and Markus Faulhaber and Mulla, {Sohail M.} and Dominik Mertz and Akl, {Elie A.} and Dirk Bassler and Busse, {Jason W.} and Ignacio Ferreira-Gonz{\'a}lez and Francois Lamontagne and Alain Nordmann and Viktoria Gloy and Heike Raatz and Lorenzo Moja and Rachel Rosenthal and Shanil Ebrahim and Stefan Schandelmaier and Sun Xin and Vandvik, {Per O.} and Johnston, {Bradley C.} and Walter, {Martin A.} and Bernard Burnand and Matthias Schwenkglenks and Hemkens, {Lars G.} and Bucher, {Heiner C.} and Guyatt, {Gordon H.} and Matthias Briel",
year = "2014",
doi = "10.1001/jama.2014.1361",
language = "English",
volume = "311",
pages = "1045--1051",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "10",

}

TY - JOUR

T1 - Prevalence, characteristics, and publication of discontinued randomized trials

AU - Kasenda, Benjamin

AU - Von Elm, Erik

AU - You, John

AU - Blümle, Anette

AU - Tomonaga, Yuki

AU - Saccilotto, Ramon

AU - Amstutz, Alain

AU - Bengough, Theresa

AU - Meerpohl, Joerg J.

AU - Stegert, Mihaela

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 - Bassler, Dirk

AU - Busse, Jason W.

AU - Ferreira-González, Ignacio

AU - Lamontagne, Francois

AU - Nordmann, Alain

AU - Gloy, Viktoria

AU - Raatz, Heike

AU - Moja, Lorenzo

AU - Rosenthal, Rachel

AU - Ebrahim, Shanil

AU - Schandelmaier, Stefan

AU - Xin, Sun

AU - Vandvik, Per O.

AU - Johnston, Bradley C.

AU - Walter, Martin A.

AU - Burnand, Bernard

AU - Schwenkglenks, Matthias

AU - Hemkens, Lars G.

AU - Bucher, Heiner C.

AU - Guyatt, Gordon H.

AU - Briel, Matthias

PY - 2014

Y1 - 2014

N2 - IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003.We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95%CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95%CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9%[95%CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95%CI, 0.15-0.43]; P <.001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95%CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95%CI, 2.29-4.43]; P <.001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

AB - IMPORTANCE: The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING: Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003.We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES: Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS: After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95%CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95%CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9%[95%CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95%CI, 0.15-0.43]; P <.001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95%CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95%CI, 2.29-4.43]; P <.001). CONCLUSIONS AND RELEVANCE: In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

UR - http://www.scopus.com/inward/record.url?scp=84896800584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896800584&partnerID=8YFLogxK

U2 - 10.1001/jama.2014.1361

DO - 10.1001/jama.2014.1361

M3 - Article

VL - 311

SP - 1045

EP - 1051

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 10

ER -