title: Clinical trial participation improves outcome: a matched historical cohort study.
abstract: BACKGROUND
  Well-conducted, investigator-led randomized controlled trials (RCTs) are the gold standard for evaluating the efficacy of new treatments and are a key component of evidence-based medicine. It is unclear whether participating in an RCT is beneficial to the individual before the results of RCTs are known.
  
  
  OBJECTIVE
  In a matched historical cohort study, we examined whether participation in RCTs was associated with improved health outcomes.
  
  
  METHODS
  Participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE), Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), or Telmisartan Randomized Assessment Study in ACE-intolerant Subjects with Cardiovascular Disease (TRANSCEND) studies and non-participant controls were selected from patients attending outpatient clinics at Middlemore Hospital between 2001 and 2003.
  
  
  RESULTS
  A total of 251 RCT participants and 502 randomly selected patients not enrolled in a trial but who met study entry criteria were matched for age, gender, and ethnicity. There was a significant difference in all-cause mortality for trial participants versus non-participants over the study period (unadjusted relative risk reduction (RRR) = 63%; 95% confidence interval (CI) = 28%-81%) and a significant reduction in cardiovascular mortality (unadjusted RRR = 81%; 95% CI = 17%-95%) favouring RCT participants. Allowing for co-morbidity, the adjusted RRR of all-cause mortality associated with trial participation was 55% (95% CI = 10%-77%). Active treatment in an RCT was found to be less explanatory than trial participation. The adjusted RRR for cardiovascular mortality associated with active treatment in a trial was 86% (95% CI = -2% to 98%), with trial participation found to be less explanatory than active treatment.
  
  
  CONCLUSIONS
  The main limitations of this trial relate to its design as a retrospective study with a historical cohort comparison group. Limitations include lack of complete data for some patients, bias in selection of the comparison group, and the effects of confounding variables. However, the study design and analysis were planned so as to minimize these as much as possible.
  
  
  CONCLUSIONS
  This study revealed significantly lower all-cause mortality among participants in industry-sponsored RCTs compared with non-participants who received routine hospital outpatient care. This effect was independent of study drug.
authors.affiliation: aMiddlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
authors.forename: John R
authors.initials: JR
authors.lastname: Baker
authors.forename: Alain C
authors.initials: AC
authors.lastname: Vandal
authors.forename: Joey
authors.initials: J
authors.lastname: Yeoh
authors.forename: Irene
authors.initials: I
authors.lastname: Zeng
authors.forename: Selwyn
authors.initials: S
authors.lastname: Wong
authors.forename: Stuart N
authors.initials: SN
authors.lastname: Ryan
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000401:mortality; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D035842:Research Subjects; D012189:Retrospective Studies; D014652:Vascular Diseases / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents