Outcomes of patients who participate in randomised controlled trials compared to similar patients receiving similar interventions who do not participate.
BACKGROUND
Some people believe that patients who take part in randomised controlled trials (RCTs) face risks that they would not face if they opted for non-trial treatment. Others think that trial participation is beneficial and the best way to ensure access to the most up to date physicians and treatments.


OBJECTIVE
To assess the effects of patient participation in RCTs ('trial effects') independent both of the effects of the clinical treatments being compared ('treatment effects') and any differences between patients who participated in RCTs and those who did not.


METHODS
In May 2001, we searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, The Cochrane Methodology Register, SciSearch and PsycINFO for potentially relevant studies. Our search yielded over 10,000 references. In addition, we reviewed the reference lists of relevant articles and wrote to over 250 investigators to try to obtain further information.


METHODS
Randomised studies and cohort studies with data on clinical outcomes of RCT participants and similar patients who received similar treatment outside of RCTs.


METHODS
At least two reviewers independently assessed studies for inclusion, assessed study quality and extracted data. Study authors were contacted for additional information.


RESULTS
We included five randomised studies (yielding 6 comparisons) and 50 non-randomised cohort studies (85 comparisons), with 31,140 patients treated in RCTs and 20,380 patients treated outside RCTs. In the randomised studies, patients were invited to participate in an RCT or not; these comparisons provided limited information because of small sample sizes (a total of 412 patients) and the nature of the questions they addressed. There was statistically significant heterogeneity (P < 0.002, I(2) = 36.2%) among the 73 dichotomous outcome comparisons; none of the potential explanatory factors we investigated helped to explain this heterogeneity. No statistically significant differences were found for 63 of the 73 comparisons. Eight comparisons reported statistically significant better outcomes for patients treated within RCTs, and two comparisons reported statistically significant worse outcomes for patients treated within RCTs. There were no statistically significant differences in heterogeneity (P = 0.53, I(2) = 0%) or in outcomes (SMD 0.01, 95% CI -0.10 to 0.12) of patients treated within and outside RCTs in the 18 comparisons which had used continuous outcomes.


CONCLUSIONS
This review indicates that participation in RCTs is not associated with greater risks than receiving the same treatment outside RCTs. These results challenge the assertion that the results of RCTs are not applicable to usual practice.
Vist
G E
GE
Norwegian Knowledge Centre for Health Services, PO Box 7004, St Olavs Plass, Oslo, Norway, 0130. gunn.vist@kunnskapssenteret.no
Hagen
K B
KB
Devereaux
P J
PJ
Bryant
D
D
Kristoffersen
D T
DT
Oxman
A D
AD
D015331:Cohort Studies; D006801:Humans; D010342:Patient Acceptance of Health Care; D017064:Process Assessment, Health Care; D016032:Randomized Controlled Trials as Topic / Q000009:adverse effects*; D045808:Refusal to Participate; D018570:Risk Assessment; D016896:Treatment Outcome