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Completion and Publication Rates of Randomized Controlled Trials in Surgery: An Empirical Study

Rosenthal, Rachel MD, MSc*; Kasenda, Benjamin MD†,‡; Dell-Kuster, Salome MD, MSc*,†; von Elm, Erik MD, MSc§; You, John MD, MSc¶,‖; Blümle, Anette PhD**; Tomonaga, Yuki MSc††; Saccilotto, Ramon MD*,†; Amstutz, Alain BSc; Bengough, Theresa MA§; Meerpohl, Joerg J. MD**; Stegert, Mihaela MD; Tikkinen, Kari A. O. MD, PhD¶,‡‡,§§; Neumann, Ignacio MD, MSc¶,¶¶; Carrasco-Labra, Alonso DDS, MSc¶,‖‖; Faulhaber, Markus MD, MSc¶,***; Mulla, Sohail MSc; Mertz, Dominik MD, MSc¶,†††; Akl, Elie A. MD, PhD, MPH¶,‡‡‡,§§§; Bassler, Dirk MD, MSc¶¶¶; Busse, Jason W. DC, PhD¶,‖‖‖,****; Ferreira-González, Ignacio MD, PhD††††; Lamontagne, Francois MD, MSc‡‡‡‡; Nordmann, Alain MD, MSc; Gloy, Viktoria PhD†,§§§§; Olu, Kelechi K. MD, MSc; Raatz, Heike MD, MSc; Moja, Lorenzo MD, MSc¶¶¶¶; Ebrahim, Shanil PhD¶,‖‖‖,‖‖‖‖,*****; Schandelmaier, Stefan MD†,†††††; Sun, Xin PhD¶,‡‡‡‡‡; Vandvik, Per O. MD, PhD§§§§§; Johnston, Bradley C. PhD¶,‖‖‖‖; Walter, Martin A. MD§§§§; Burnand, Bernard MD, MPH§; Schwenkglenks, Matthias PhD, MPH††; Hemkens, Lars G. MD, MPH; Bucher, Heiner C. MD, MPH; Guyatt, Gordon H. MD, MSc; Briel, Matthias MD, MSc†,¶

doi: 10.1097/SLA.0000000000000810
Original Articles

Objective: To investigate the prevalence of discontinuation and nonpublication of surgical versus medical randomized controlled trials (RCTs) and to explore risk factors for discontinuation and nonpublication of surgical RCTs.

Background: Trial discontinuation has significant scientific, ethical, and economic implications. To date, the prevalence of discontinuation of surgical RCTs is unknown.

Methods: All RCT protocols approved between 2000 and 2003 by 6 ethics committees in Canada, Germany, and Switzerland were screened. Baseline characteristics were collected and, if published, full reports retrieved. Risk factors for early discontinuation for slow recruitment and nonpublication were explored using multivariable logistic regression analyses.

Results: In total, 863 RCT protocols involving adult patients were identified, 127 in surgery (15%) and 736 in medicine (85%). Surgical trials were discontinued for any reason more often than medical trials [43% vs 27%, risk difference 16% (95% confidence interval [CI]: 5%–26%); P = 0.001] and more often discontinued for slow recruitment [18% vs 11%, risk difference 8% (95% CI: 0.1%–16%); P = 0.020]. The percentage of trials not published as full journal article was similar in surgical and medical trials (44% vs 40%, risk difference 4% (95% CI: −5% to 14%); P = 0.373). Discontinuation of surgical trials was a strong risk factor for nonpublication (odds ratio = 4.18, 95% CI: 1.45–12.06; P = 0.008).

Conclusions: Discontinuation and nonpublication rates were substantial in surgical RCTs and trial discontinuation was strongly associated with nonpublication. These findings need to be taken into account when interpreting surgical literature. Surgical trialists should consider feasibility studies before embarking on full-scale trials.

We evaluated early discontinuation and nonpublication of surgical trials approved in Canada, Germany, and Switzerland. Forty-three percent were stopped early, 18% for slow recruitment. Trial discontinuation was strongly associated with nonpublication. These findings are relevant when interpreting surgical literature, and surgical trialists should consider feasibility studies before starting full-scale trials.

*Department of Surgery, University Hospital Basel, Spitalstrasse, Basel, Switzerland

Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Hebelstrasse, Basel, Switzerland

Department of Oncology, Basel University Hospital, Basel, Switzerland

§Cochrane Switzerland, Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Lausanne, Switzerland

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

Department of Medicine, McMaster University, Hamilton, Ontario, Canada

**German Cochrane Centre, Department of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Freiburg, Germany

††Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland

‡‡Department of Public Health, University of Helsinki, Helsinki, Finland

§§Department of Urology, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland

¶¶Department of Internal Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile

‖‖Evidence-Based Dentistry Unit, Faculty of Dentistry, Universidad de Chile, Santiago, Chile

***Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada

†††Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, Ontario, Canada

‡‡‡Department of Internal Medicine, American University of Beirut, Riad-El-Solh, Beirut, Lebanon

§§§Department of Medicine, State University of New York at Buffalo, Buffalo, NY

¶¶¶Center for Pediatric Clinical Studies, Department of Neonatology, University Children's Hospital, Tuebingen, Germany and Division of Neonatology, University Hospital Zurich, Zurich, Switzerland

‖‖‖Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada

****Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada

††††Epidemiology Unit, Department of Cardiology, Vall d'Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain

‡‡‡‡Centre de Recherche Clinique Étienne-Le Bel and Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada

§§§§Institute of Nuclear Medicine and Department of Clinical Research, University Hospital Bern, Bern, Switzerland

¶¶¶¶IRCCS Orthopedic Institute Galeazzi, Milano, Italy

‖‖‖‖Department of Anesthesia and Pain Medicine Hospital for Sick Children and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada

*****Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, CA

†††††Academy of Swiss Insurance Medicine, University Hospital of Basel, Basel, Switzerland

‡‡‡‡‡Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China; and

§§§§§Department of Medicine, Innlandet Hospital Trust-Division Gjovik, Oppland, and Norwegian Knowledge Centre for the Health Services, Oslo, Norway.

Reprints: Rachel Rosenthal, MD, MSc, Department of Surgery, Spitalstrasse 26, CH-4031 Basel, Switzerland. E-mail: rachel.rosenthal@unibas.ch.

Disclosure: This study was funded by the Swiss National Science Foundation (grant 320030-133540/1) and the German Research Foundation (grant EL 544/1-2). M.B., A.N., V.G., H.R., S.D.K., L.G.H., and H.C.B. are supported by Santésuisse and the Gottfried and Julia Bangerter-Rhyner-Foundation. During study preparation, E.v.E. was supported by the Brocher Foundation. K.A.O.T. is supported by unrestricted grants from the Finnish Cultural Foundation and the Finnish Medical Foundation. J.W.B. is funded by a New Investigator Award from the Canadian Institutes of Health Research and Canadian Chiropractic Research Foundation. D.M. is a recipient of a Research Early Career Award from Hamilton Health Sciences Foundation (Jack Hirsh Fellowship). S.E. is supported by MITACS Elevate and Sickkids Restracomp Fellowship Awards. S.M. is supported by an Ontario Graduate Scholarship. There are no conflicts of interest to declare.

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