Initiation and continuation of randomized trials after the publication of a trial stopped early for benefit asking the same study question: STOPIT-3 study design

Trials

Gordon Guyatt^1,15  Mohammad Hassan Murad⁶  Gerard Urrutia^1,13  Hector Pardo-Hernandez¹  Gennaro Pagano⁸  Osama Qasim-Agha^2,20  Benjamin Kasenda^1,19  Annette Kristiansen^1,17  Xin Sun⁴  Jason Busse^1,15  Ignacio Ferreira-Gonzalez^1,16  Regina Kunz^1,11  Paul Glasziou²  Kristian Thorlund^1,15  Martin Walter⁹  Lorenzo Moja^1,12  Pablo Alonso Coello^1,13  Qi Zhou^1,15  Stephen D Walter^1,15  Stefan Schandelmaier^1,11  Dirk Bassler⁷  Joerg J Meerpohl³  Elie A Akl⁵  Victor M Montori^1,14  Matthias Briel^1,15  Patricia J Erwin^2,20  Juan Pablo Domecq^1,18  Gabriela J Prutsky^1,10 

[1] Iberoamerican Cochrane Center, CIBER de Epidemiología y Salud Pública, IIB, Sant Pau, 08041, Barcelona, Spain;Centre for Evidence-Based Medicine, University of Oxford, Oxford, UK;German Cochrane Centre, Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Berliner Allee 29, 79110, Freiburg, Germany;Center for Health Research, Kaiser Permanente Northwest, Portland OR 97227, USA;Department of Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA;Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN 55905, USA;Department of Neonatology, University Children’s Hospital Tuebingen, Tuebingen, Germany;Department of Translational Medical Sciences, Federico II University of Naples, Via Pansini 5, 80131, Naples, Italy;Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland;Department of Pediatrics, Children’s Hospital of Michigan, Wayne State University School of Medicine/Detroit Medical Center, Detroit, MI 48201, USA;Academy of Swiss Insurance Medicine, University Hospital Basel, Basel, Switzerland;IRCCS Galeazzi Orthopedic Institute, Milan, Italy;Epidemiology and Public Health CIBER (CIBERESP), Hospital de la Sant Pau Creu i, Sant Pau, 08041, Barcelona, Spain;Division of Endocrinology, Diabetes, Metabolism, Nutrition, Mayo Clinic, Rochester, MN 55905, USA;Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON L8S 4L8, Canada;Epidemiology Unit, Department of Cardiology, Vall d’Hebron Hospital and CIBER de Epidemiología y Salud Publica (CIBERESP), Barcelona, Spain;Norwegian Knowledge Centre for the Health Services, Central Invoicing DFO, PO 4104, Hamar, 2307, Norway;Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA;Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland;Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA

关键词: Protocol;    Systematic review;    RCT;    Randomized controlled trials stopped early for benefit;   

Others  :  1092895
DOI  :  10.1186/1745-6215-14-335

 received in 2013-06-03, accepted in 2013-09-27,  发布年份 2013

【 摘 要 】

Background

Randomized control trials (RCTs) stopped early for benefit (truncated RCTs) are increasingly common and, on average, overestimate the relative magnitude of benefit by approximately 30%. Investigators stop trials early when they consider it is no longer ethical to enroll patients in a control group. The goal of this systematic review is to determine how investigators of ongoing or planned RCTs respond to the publication of a truncated RCT addressing a similar question.

Methods/design

We will conduct systematic reviews to update the searches of 210 truncated RCTs to identify similar trials ongoing at the time of publication, or started subsequently, to the truncated trials ('subsequent RCTs’). Reviewers will determine in duplicate the similarity between the truncated and subsequent trials. We will analyze the epidemiology, distribution, and predictors of subsequent RCTs. We will also contact authors of subsequent trials to determine reasons for beginning, continuing, or prematurely discontinuing their own trials, and the extent to which they rely on the estimates from truncated trials.

Discussion

To the extent that investigators begin or continue subsequent trials they implicitly disagree with the decision to stop the truncated RCT because of an ethical mandate to administer the experimental treatment. The results of this study will help guide future decisions about when to stop RCTs early for benefit.

【 授权许可】

   
2013 Prutsky et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Pocock SJ: When to stop a clinical trial. BMJ 1992, 305:235-240.
• [2]Zannad F, GattisStough W, McMurray JJ, Remme WJ, Pitt B, Borer JS, Geller NL, Pocock SJ: When to stop a clinical trial early for benefit: lessons learned and future approaches. Circ Heart Fail 2012, 5:294-302.
• [3]DAMOCLES Study Group: NHS Health Technology Assessment Programme: A proposed charter for clinical trial data monitoring committees: helping them to do their job well. Lancet 2005, 365:711-722.
• [4]Mueller PS, Montori VM, Bassler D, Koenig BA, Guyatt GH: Ethical issues in stopping randomized trials early because of apparent benefit. Ann Intern Med 2007, 146:878-881.
• [5]Montori VM, Devereaux PJ, Adhikari NK, Burns KE, Eggert CH, Briel M, Lacchetti C, Leung TW, Darling E, Bryant DM, Bucher HC, Schünemann HJ, Meade MO, Cook DJ, Erwin PJ, Sood A, Sood R, Lo B, Thompson CA, Zhou Q, Mills E, Guyatt GH: Randomized trials stopped early for benefit: a systematic review. JAMA 2005, 294:2203-2209.
• [6]Bassler D, Briel M, Montori VM, Lane M, Glasziou P, Zhou Q, Heels-Ansdell D, Walter SD, Guyatt GH, STOPIT-2 Study Group , Flynn DN, Elamin MB, Murad MH, Abu Elnour NO, Lampropulos JF, Sood A, Mullan RJ, Erwin PJ, Bankhead CR, Perera R, Ruiz Culebro C, You JJ, Mulla SM, Kaur J, Nerenberg KA, Schünemann H, Cook DJ, Lutz K, Ribic CM, Vale N, et al.: Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis. Jama 2010, 303:1180-1187.
• [7]Ioannidis JP: Why most published research findings are false. PLoS Med 2005, 2:e124.
• [8]Cochrane Handbook for Systematic Reviews of Interventions: Book Cochrane Handbook for Systematic Reviews of Interventions. Oxford: The Cochrane Collaboration: Higgins J, Green S; 2011.
• [9]Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D: The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 2009, 62:e1-34.
• [10]Hoaglin DC, Hawkins N, Jansen JP, Scott DA, Itzler R, Cappelleri JC, Boersma C, Thompson D, Larholt KM, Diaz M, Barrett A: Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices: part 2. Value Health 2011, 14:429-437.
• [11]Sydes MR, Altman DG, Babiker AB, Parmar MK, Spiegelhalter DJ: DAMOCLES Group: Reported use of data monitoring committees in the main published reports of randomized controlled trials: a cross-sectional study. Clin Trials 2004, 1:48-59.
• [12]Bassler D, Montori VM, Briel M, Glasziou P, Walter SD, Ramsay T, Guyatt G: Reflections on meta-analyses involving trials stopped early for benefit: Is there a problem and if so, what is it? Stat Methods Med Res 2013, 22:159-168.