Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study

Stefan Schandelmaier¹, Yuki Tomonaga², Dirk Bassler³, Joerg J Meerpohl⁴, Erik von Elm⁵, John J You⁶, Anette Bluemle⁷, Francois Lamontagne⁸, Ramon Saccilotto⁹, Alain Amstutz⁹, Theresa Bengough¹⁰, Mihaela Stegert⁹, Kelechi K Olu⁹, Kari A O Tikkinen¹¹, Ignacio Neumann¹², Alonso Carrasco-Labra¹³, Markus Faulhaber¹⁴, Sohail M Mulla¹⁴, Dominik Mertz¹⁵, Elie A Akl¹⁶, Xin Sun¹⁷, Jason W Busse¹⁸, Ignacio Ferreira-González¹⁹, Alain Nordmann⁹, Viktoria Gloy²⁰, Heike Raatz⁹, Lorenzo Moja²¹, Rachel Rosenthal²², Shanil Ebrahim²³, Per O Vandvik²⁴, Bradley C Johnston²⁵, Martin A Walter²⁶, Bernard Burnand⁵, Matthias Schwenkglenks², Lars G Hemkens⁹, Gordon Guyatt¹⁴, Heiner C Bucher⁹, Benjamin Kasenda²⁷, Matthias Briel²⁸

Affiliations

¹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland. Electronic address: s.schandelmaier@gmail.com.
² Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
³ Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ German Cochrane Centre, Medical Center, University of Freiburg, Freiburg, Germany; Center of Research in Epidemiology and Statistics Sorbonne Paris Cité-U1153, INSERM/Université Paris Descartes, Cochrane France, Hôpital Hôtel-Dieu, Paris Cedex 04, France.
⁵ Cochrane Switzerland, Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁷ German Cochrane Centre, Medical Center, University of Freiburg, Freiburg, Germany.
⁸ Centre de Recherche Clinique du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁰ Department of Health and Society, Austrian Federal Institute for Health Care, Vienna, Austria.
¹¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Departments of Urology and Public Health, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
¹³ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
¹⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁵ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
¹⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
¹⁷ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
¹⁸ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
¹⁹ Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain.
²⁰ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
²¹ IRCCS Orthopedic Institute Galeazzi, Milano, Italy.
²² Department of Surgery, University Hospital Basel, Basel, Switzerland.
²³ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Stanford Prevention Research Center, Stanford University, Stanford, CA.
²⁴ Department of Medicine, Innlandet Hospital Trust-Division Gjøvik, Oppland, Norway.
²⁵ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
²⁶ Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
²⁷ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Haematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
²⁸ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Clinical Research, University of Basel, Basel, Switzerland.

PMID: 28410086
DOI: 10.1016/j.jpeds.2017.01.071

Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study

Stefan Schandelmaier et al. J Pediatr. 2017 May.

. 2017 May:184:209-214.e1.

doi: 10.1016/j.jpeds.2017.01.071. Epub 2017 Mar 3.

Authors

Affiliations

¹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland. Electronic address: s.schandelmaier@gmail.com.
² Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
³ Department of Neonatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁴ German Cochrane Centre, Medical Center, University of Freiburg, Freiburg, Germany; Center of Research in Epidemiology and Statistics Sorbonne Paris Cité-U1153, INSERM/Université Paris Descartes, Cochrane France, Hôpital Hôtel-Dieu, Paris Cedex 04, France.
⁵ Cochrane Switzerland, Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
⁷ German Cochrane Centre, Medical Center, University of Freiburg, Freiburg, Germany.
⁸ Centre de Recherche Clinique du Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁰ Department of Health and Society, Austrian Federal Institute for Health Care, Vienna, Austria.
¹¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Departments of Urology and Public Health, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
¹² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
¹³ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, Chile.
¹⁴ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁵ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada.
¹⁶ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
¹⁷ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University, Chengdu, China.
¹⁸ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, ON, Canada.
¹⁹ Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain.
²⁰ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
²¹ IRCCS Orthopedic Institute Galeazzi, Milano, Italy.
²² Department of Surgery, University Hospital Basel, Basel, Switzerland.
²³ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia, McMaster University, Hamilton, ON, Canada; Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Stanford Prevention Research Center, Stanford University, Stanford, CA.
²⁴ Department of Medicine, Innlandet Hospital Trust-Division Gjøvik, Oppland, Norway.
²⁵ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
²⁶ Institute of Nuclear Medicine, University Hospital Bern, Bern, Switzerland.
²⁷ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Haematology/Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany.
²⁸ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; Department of Clinical Research, University of Basel, Basel, Switzerland.

PMID: 28410086
DOI: 10.1016/j.jpeds.2017.01.071

Abstract

Objectives: To determine the proportion of pediatric randomized controlled trials (RCTs) that are prematurely discontinued, examine the reasons for discontinuation, and compare the risk for recruitment failure in pediatric and adult RCTs.

Study design: A retrospective cohort study of RCTs approved by 1 of 6 Research Ethics Committees (RECs) in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics, trial discontinuation, and reasons for discontinuation from protocols, corresponding publications, REC files, and a survey of trialists.

Results: We included 894 RCTs, of which 86 enrolled children and 808 enrolled adults. Forty percent of the pediatric RCTs and 29% of the adult RCTs were discontinued. Slow recruitment accounted for 56% of pediatric RCT discontinuations and 43% of adult RCT discontinuations. Multivariable logistic regression analyses suggested that pediatric RCT was not an independent risk factor for recruitment failure after adjustment for other potential risk factors (aOR, 1.22; 95% CI, 0.57-2.63). Independent risk factors were acute care setting (aOR, 4.00; 95% CI, 1.72-9.31), nonindustry sponsorship (aOR, 4.45; 95% CI, 2.59-7.65), and smaller planned sample size (aOR, 1.05; 95% CI 1.01-1.09, in decrements of 100 participants).

Conclusion: Forty percent of pediatric RCTs were discontinued prematurely, owing predominately to slow recruitment. Enrollment of children was not an independent risk factor for recruitment failure.

Keywords: early termination of clinical trials (MeSH); pediatrics (MeSH); randomized controlled trials as a topic (MeSH); risk factors (MeSH).

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Pediatric clinical trials-number needed to recruit.
Goodman DM. Goodman DM. J Pediatr. 2017 May;184:1-2. doi: 10.1016/j.jpeds.2017.03.011. J Pediatr. 2017. PMID: 28434563 No abstract available.

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Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study

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Premature Discontinuation of Pediatric Randomized Controlled Trials: A Retrospective Cohort Study

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