Recruitment to Clinical Trials: Adwoa Hughes-Morley What are the Strategies for Success?

How easy is it to recruit to clinical trials? Across all contexts (McDonald et al, 2006) –53% of trials are awarded an extension –45% recruit less than 80% of their target –31% of trials recruit successfully In the pharmaceutical sector (Barnes, 2006) –80% of all trials fail to meet their recruitment target In primary care (Bower et al, 2007) –29% recruit according to schedule We dont know about the scale of the problem for mental health trials

Consequences of under recruitment 1.Unrepresentative sample = lack of external validity 2.Reduction of statistical power = increased probability of type II error 3.Inhibits the development of reliable evidence and delays adoption of effective interventions. 4.Costly 5.Is it ethical?

Barriers to recruitment (Spaar et al, 2009) SYSTEM RELATED Lack of study staff Multi-centre trials Inexperienced/ine fficient governance bodies Availability of the intervention INDIVIDUAL Treatment preferences of health care providers Patient aversion to randomisation TRIAL-DESIGN- RELATED Doubted scientific rationale of trial question Doubted relevance of the trial question Complexity of the trial Restrictive eligibility criteria

Strategies used to improve recruitment to RCTs (Treweek et al, 2010) 1.Open RCT versus blinded RCT 2.Placebo versus other comparator 3.Other change to trial design versus conventional RCT design 4.Modification to the consent form or process –Opt-out consent versus opt-in consent –Consent to experimental care versus usual consent –Consent to standard care versus usual consent –Refusers choose treatment versus usual consent –Physician modified consent versus usual consent –Participant modified consent versus usual consent 5.Financial incentives for participants 6.Telephone reminders 7.Modification to the training given to recruiters 8.Greater contact between trial coordinator and trial sites 9. Modification to the approach made to potential participants –Educational video versus standard information –Educational video with written information versus written information –Telephone screening versus face-to-face screening –Enhanced recruitment package versus standard recruitment package –Enhanced recruitment package with baseline data collected by telephone versus standard recruitment –package –Enhanced recruitment package with recruitment at churches versus standard recruitment package –Clinical trial booklet with standard information versus standard information –Home safety questionnaire with trial invitation versus trial invitation –Positive framing of side effects versus neutral framing –Negative framing of side effects versus neutral framing –Interactive computer presentation of trial information versus audio-taped presentation –Writing treatment effect is 'twice as fast' in trial information versus writing 'half as fast' –Total information disclosure versus standard disclosure –Electronic completion of screening questionnaire versus standard paper completion –Oral completion of screening questionnaire versus standard paper completion

Which recruitment methods have evidence of effectiveness? 1.Telephone reminders to non-responders (Nystuen 2004) 2.Opt-out procedures requiring potential participants to contact the trial team if they do not want to be contacted about a trial (Trevena 2006)] 3.Open label trials rather than blinded (Avenell 2004; Hemminki 2004)

CADET Recruitment

ACUDep Trial

Why was recruitment in these trials Successful? GP practice database searches Broad inclusion criteria Simple study procedures –(assessments not lasting more than 1.5hours) Identifying problems early through close monitoring Compensating for under-recruitment, by over- recruiting elsewhere Telephone follow ups (CADET) The MHRN and PCRN involvement Ensuring adequate therapist capacity

Barriers to recruitment in your trials SYSTEM RELATEDINDIVIDUAL TRIAL-DESIGN-RELATED

Adwoa Hughes-Morley Mood Disorders Centre University of Exeter, Washington Singer Laboratories, Exeter, EX4 4QG.