Table 1.

Characteristics of the selected reviews and meta-analyses evaluating the benefits of participation in Randomized Clinical Trials (RCTs).

Author, Year	Objective	No. of Databases Searched, Date Range of Searching, and Publication Data Range (PDR) of Primary Studies	QUALITY ASSESSMent on Primary Studies	RCT Participant Characteristics (No. Comparisons)	Non-Participant Characteristics (No. Comparisons)	Outcomes (Measurement)
Vist [30], 2008	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	5 databases: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, The Cochrane Methodology Register, SciSearch and PsycINFO. Up to March 2007. PDR: 1978–2006	Per review. No validated tool used. The criteria followed to assess the validity of comparisons was scored as: “met”, part, “partially met”, “not imbalance”, “not met”, “unclear”.	Patients in different clinical areas and interventions: oncology (31), cardiology (22), other internal medicine subspecialties (27), obstetrics and gynaecology (29), psychology or drug abuse (15), and paediatrics (12), surgery or other procedures (33), drug therapy (28), radiotherapy (15), counselling or education (9), usual care (45), and active monitoring/watchful waiting (6).	Patients receiving similar treatment outside of RCTs (80), eligible refusers (1), patients not invited to participate (2), eligible non-participants who do not meet the above categories (2).	Mortality (dichotomous) morbidity and changes in self-reported pain, quality of life, and function (continuous).
Fernandes [28], 2014	To compare 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.	MEDLINE (1966 to November 2010), Embase (1980 to November 2010), Cochrane Central Register of Controlled Trials (CENTRAL; 1960 to last quarter of 2010) and PsycINFO (1880 to November 2010). From 1880 to 2010. PDR:1979–2009	Per review. No validated tool used.	Patients in different clinical areas and interventions: surgery or medical procedures (46); drug therapy (57); radiotherapy (5); counselling or education (27); other therapy (12).	Patients with the same diagnoses who did not enter RCTs known as “outsiders” (147).	Mortality (dichotomous), patient-reported or other clinically important outcomes (continuous outcomes)
Gross [31], 2006	To quantify the differences in health outcomes between randomized trial participants and eligible non-participants.	Medline, the Web of Science citation database, and manuscript references. From 1984 to 2002. PDR: 1084–2002.	Per review. No validated tool used.	Patients in different clinical areas (oncology, cardiovascular diseases, obstetrics and gynaecology) and interventions: diagnostics (2), medical (14) or surgical (9).	Patients sharing healthcare settings at recruitment, participants recruited in a similar way, eligible non-participants, non-participants allowed to access agents used in a trial.	Mortality, treatment acceptability, and proportion of time or number of days with a given condition.
Peppercorn [32], 2004	To assess the empirical evidence that patients with cancer who enrols in clinical trials have better outcomes than those who do not enrol.	Medline. Search range nor defined. PDR: 1971–2002.	Per review. Not validated tool. Pilot-tested forms recording potential sources of bias.	Cancer patients (24).	Eligible refusers (4), patients in retrospective cohort (21), participants in natural experiment (1).	Health benefits in cancer patients in RCTs (trial effect)
Braunholtz [33], 2001	To assess whether there is evidence that randomized controlled trials are systematically beneficial, or harmful, for patients.	Databases not defined. Up to August 1996. PDR: 1879–1996.	Per review. Not validated tool. Sources of bias of concern were conceptualized as: “patient selection bias”, clinician selection bias”, “detection bias”, “transfer bias” and “study induced bias”.	Patients in cancer therapy (10), cardiovascular (2), other medical interventions (2).	Indirect comparisons (2); patients in at least one concurrent non-trial control group (11): eligible refusers (3), refusers and eligible non-recruited patients (4), all non-randomized patients of recruiting clinicians (1), all non-recruited patients of recruiting and non-recruiting clinicians (3); no control group (1).	Health benefits in cancer patients in RCTs,
Nijjar [29], 2017	To determine whether participation in randomised controlled trials (RCTs), compared with non-participation, has a beneficial effect on women’s health.	MEDLINE (1966 to December 2015), Embase (1980 to December 2015), Cochrane Central Register of Controlled Trials (CENTRAL; 1960 to last quarter of 2015) and PsycINFO (1880 to December 2015). PDR:1981–2015.	Per review. Jadad scale and Newcastle Ottawa score (NOS).	Women in obstetrics-gynaecology interventions: medical (12), surgical (6), and other (3).	Comparable non-participants cohort (21).	Health benefits in women, fetuses or new-borns (dichotomous).