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Subgroup Analysis of Trials Is Rarely Easy (SATIRE): a study protocol for a systematic review to characterize the analysis, reporting, and claim of subgroup effects in randomized trials

Xin Sun12, Matthias Briel13, Jason W Busse14, Elie A Akl5, John J You16, Filip Mejza7, Malgorzata Bala8, Natalia Diaz-Granados1, Dirk Bassler9, Dominik Mertz110, Sadeesh K Srinathan111, Per Olav Vandvik12, German Malaga13, Mohamed Alshurafa1, Philipp Dahm14, Pablo Alonso-Coello1516, Diane M Heels-Ansdell1, Neera Bhatnagar17, Bradley C Johnston1, Li Wang2, Stephen D Walter1, Douglas G Altman18 and Gordon H Guyatt16*

Author Affiliations

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

2 Center for Clinical Epidemiology and Evidence-Based Medicine, West China Hospital, Sichuan University, Chengdu, PR China

3 Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland

4 The Institute for Work & Health, Toronto, Ontario, Canada

5 Departments of Medicine and Family Medicine, State University of New York at Buffalo, NY, USA

6 Department of Medicine, McMaster University, Hamilton, Canada

7 Department of Pulmonary Diseases, Jagiellonian University School of Medicine, Krakow, Poland

8 Department of Internal Medicine, Jagiellonian University School of Medicine, Krakow, Poland

9 University Children's Hospital Tuebingen, Department of Neonatology, Tuebingen, Germany

10 Division of Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Switzerland

11 Section of Thoracic Surgery, Department of Surgery, University of Manitoba, Winnipeg, Manitoba, Canada

12 Norwegian Knowledge Centre for the Health Services, Oslo, Norway

13 Universidad Peruana Cayetano Heredia, Lima, Peru

14 Department of Urology, University of Florida, College of Medicine, Gainesville, Florida, USA

15 Iberoamerican Cochrane Center. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

16 CIBER de Epidemiología y Salud Pública (CIBERESP), Spain

17 Health Sciences Library, McMaster University, Hamilton, Canada

18 Centre for Statistics in Medicine, University of Oxford, Oxford, UK

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Trials 2009, 10:101  doi:10.1186/1745-6215-10-101

Published: 9 November 2009

Abstract

Background

Subgroup analyses in randomized trials examine whether effects of interventions differ between subgroups of study populations according to characteristics of patients or interventions. However, findings from subgroup analyses may be misleading, potentially resulting in suboptimal clinical and health decision making. Few studies have investigated the reporting and conduct of subgroup analyses and a number of important questions remain unanswered. The objectives of this study are: 1) to describe the reporting of subgroup analyses and claims of subgroup effects in randomized controlled trials, 2) to assess study characteristics associated with reporting of subgroup analyses and with claims of subgroup effects, and 3) to examine the analysis, and interpretation of subgroup effects for each study's primary outcome.

Methods

We will conduct a systematic review of 464 randomized controlled human trials published in 2007 in the 118 Core Clinical Journals defined by the National Library of Medicine. We will randomly select journal articles, stratified in a 1:1 ratio by higher impact versus lower impact journals. According to 2007 ISI total citations, we consider the New England Journal of Medicine, JAMA, Lancet, Annals of Internal Medicine, and BMJ as higher impact journals. Teams of two reviewers will independently screen full texts of reports for eligibility, and abstract data, using standardized, pilot-tested extraction forms. We will conduct univariable and multivariable logistic regression analyses to examine the association of pre-specified study characteristics with reporting of subgroup analyses and with claims of subgroup effects for the primary and any other outcomes.

Discussion

A clear understanding of subgroup analyses, as currently conducted and reported in published randomized controlled trials, will reveal both strengths and weaknesses of this practice. Our findings will contribute to a set of recommendations to optimize the conduct and reporting of subgroup analyses, and claim and interpretation of subgroup effects in randomized trials.