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Systematic review to determine whether participation in a trial influences outcome

BMJ 2005; 330 doi: (Published 19 May 2005) Cite this as: BMJ 2005;330:1175
  1. Gunn Elisabeth Vist, senior researcher (gev{at},
  2. Kâre Birger Hagen, senior researcher2,
  3. P J Devereaux, senior researcher3,
  4. Dianne Bryant, senior researcher3,
  5. Doris Tove Kristoffersen, statistician1,
  6. Andrew David Oxman, researcher1
  1. 1Norwegian Health Services Research Centre, PO Box 7004, 0130 Oslo, Norway
  2. 2National Research Centre for Rehabilitation in Rheumatology, Diakonhjemmet Hospital, Oslo
  3. 3Clinical Epidemiology and Biostatistics, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada
  1. Correspondence to: G E Vist
  • Accepted 31 March 2005


Objective To systematically compare the outcomes of participants in randomised controlled trials (RCTs) with those in comparable non-participants who received the same or similar treatment.

Table 1

Summary of studies included in sensitivity analysis

View this table:

Data sources Bibliographic databases, reference lists from eligible articles, medical journals, and study authors.

Review methods RCTs and cohort studies that evaluated the clinical outcomes of participants in RCTs and comparable non-participants who received the same or similar treatment.

Results Five RCTs (six comparisons) and 50 cohort studies (85 comparisons) provided data on 31 140 patients treated in RCTs and 20 380 comparable patients treated outside RCTs. In the five RCTs, in which patients were given the option of participating or not, the comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions considered. 73 dichotomous outcomes were compared, of which 59 reported no statistically significant differences. For patients treated within RCTs, 10 comparisons reported significantly better outcomes and four reported significantly worse outcomes. Significantly heterogeneity was found (I2 = 89%) among the comparisons of 73 dichotomous outcomes; none of our a priori explanatory factors helped explain this heterogeneity. The 18 comparisons of continuous outcomes showed no significant differences in heterogeneity (I2 = 0%). The overall pooled estimate for continuous outcomes of the effect of participating in an RCT was not significant (standardised mean difference 0.01, 95% confidence interval −0.10 to 0.12).

Conclusion No strong evidence was found of a harmful or beneficial effect of participating in RCTs compared with receiving the same or similar treatment outside such trials.


  • Contributors GEV carried out the literature search. GEV and KBH selected the studies. GEV, KBH, PJD, and DB extracted the data. GEV, DTK, and ADO analysed the data. GEV, KBH, PJD, DB, and ADO drafted the manuscript. GEV, KBH, PJD, and ADO developed the protocol and review. DB hand searched the five medical journals. GEV is guarantor for the paper.

  • Funding Norwegian Health Services Research Centre, McMaster University, and the Nuffield Trust.

  • Competing interests None declared.

  • Ethical approval Not required.

  • Accepted 31 March 2005
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