title: The DiReCT study - improving recruitment into clinical trials: a mixed methods study investigating the ethical acceptability, feasibility and recruitment yield of the cohort multiple randomised controlled trials design.
abstract: BACKGROUND
  The 'cohort multiple Randomised Controlled Trial' (cmRCT) design has been proposed as a potential solution to poor recruitment into clinical trials. The design randomly selects participants eligible for experimental treatments from a pre-enrolled cohort of patients, recruiting participants to multiple trials from a single cohort. Controls remain unaware of their participation in specific trials.
  
  
  METHODS
  We undertook a mixed methods study to determine the ethical acceptability, the proportion of patients in a routine service consenting to cohort participation, the proportion of these who would consent to being hypothetically randomly selected to receive new treatments, and the views of clinicians on the acceptability of the design. We submitted our cmRCT design for ethical review and recruited participants from people with anxiety and depression attending a community mental health service of twenty-one clinicians. We recorded the proportion of patients who were offered participation in the DiReCT study and the proportion that consented to researcher contact, medical record sharing, and who accepted to be randomly allocated to active treatment procedures in future hypothetical unspecified clinical trials. We used a thematic framework analysis to analyse clinician interviews.
  
  
  RESULTS
  We obtained a favourable ethical opinion from the UK Health Research Authority. Clinicians approached 131/752 (17%) potentially eligible participants for consent. Of these 131, 84 (64%) initially consented to be contacted by a researcher and all but one consented to being randomised into future trials. We confirmed consent for 71 (54%) of participants approached by clinicians, of whom 69 (53%) consented to being randomised into hypothetical future trials, 9% (69/752) of all potentially eligible patients. The interviewed clinicians described issues impacting on their ability to recruit participants in terms of clinical concerns for patient wellbeing, work pressure, their views of both general research and the specific DiReCT study, and how they viewed patients' responses to being offered participation in the study.
  
  
  CONCLUSIONS
  The cmRCT system offers the potential to improve the recruitment into clinical trials and is acceptable ethically and to many patients. Overcoming the multiple factors driving the difficulties clinicians experience in patient recruitment is likely to require the application of significant implementation science-informed effort.
authors.affiliation: University of Exeter Medical School, Haighton Building, St Luke's Campus, Heavitree Road, Exeter EX1 2 LU, UK. d.a.richards@exeter.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Richards
authors.forename: Sarah
authors.initials: S
authors.lastname: Ross
authors.forename: Sarah
authors.initials: S
authors.lastname: Robens
authors.forename: Gunilla
authors.initials: G
authors.lastname: Borglin
mesh_terms: D000328:Adult; D001291:Attitude of Health Personnel; D005260:Female; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007258:Informed Consent / Q000941:ethics*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection / Q000941:ethics*; D016032:Randomized Controlled Trials as Topic / Q000941:ethics* / Q000523:psychology; D012108:Research Personnel / Q000941:ethics* / Q000523:psychology; D035842:Research Subjects / Q000523:psychology; D018401:Sample Size; D006113:United Kingdom