title: Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis.
abstract: BACKGROUND
  It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did ("insiders") and did not ("outsiders") enter RCTs, without regard to the specific therapies received for their respective diagnoses.
  
  
  METHODS
  By searching the MEDLINE (1966-2010), Embase (1980-2010), CENTRAL (1960-2010) and PsycINFO (1880-2010) databases, we identified 147 studies that reported the health outcomes of "insiders" and a group of parallel or consecutive "outsiders" within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients' outcomes.
  
  
  RESULTS
  We found no clinically or statistically significant differences in outcomes between "insiders" and "outsiders" in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes -0.03, 95% confidence interval [CI] -0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both "insiders" and "outsiders" (mean difference 0.04, 95% CI -0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by "insiders," the "outsiders" experienced significantly worse health outcomes (mean difference -0.36, 95% CI -0.61 to -0.12).
  
  
  CONCLUSIONS
  We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont. natasha.fernandes31@gmail.com.
authors.forename: Natasha
authors.initials: N
authors.lastname: Fernandes
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Dianne
authors.initials: D
authors.lastname: Bryant
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Lauren
authors.initials: L
authors.lastname: Griffith
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Rabbany
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Nisha M
authors.initials: NM
authors.lastname: Fernandes
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Crystal
authors.initials: C
authors.lastname: Kean
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Marsh
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Siddhi
authors.initials: S
authors.lastname: Mathur
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Moyer
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Clare J
authors.initials: CJ
authors.lastname: Reade
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: John J
authors.initials: JJ
authors.lastname: Riva
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Lyndsay
authors.initials: L
authors.lastname: Somerville
authors.affiliation: Faculty of Medicine (Natasha Fernandes, Mathur), University of Ottawa, Ottawa, Ont.; Faculty of Health Sciences (Bryant, Marsh, Moyer) and Schulich School of Medicine and Dentistry (Bryant), The University of Western Ontario, London, Ont.; Department of Clinical Epidemiology and Biostatistics (Bryant, Griffith), Department of Medicine (Nisha Fernandes), Health Sciences Library (Bhatnagar), Department of Family Medicine (Riva) and Division of Gynecologic Oncology (Reade), McMaster University, Hamilton, Ont.; Faculty of Dentistry (El-Rabbany), University of Toronto, Toronto, Ont.; School of Medical and Applied Sciences (Kean), Central Queensland University, Rockhampton, Australia; Department of Orthopaedic Surgery (Somerville), London Health Sciences Centre, London, Ont.
authors.forename: Neera
authors.initials: N
authors.lastname: Bhatnagar
mesh_terms: D006801:Humans; D017063:Outcome Assessment, Health Care; D010358:Patient Participation; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D035842:Research Subjects; D012306:Risk