title: Cluster randomized trials utilizing primary care electronic health records: methodological issues in design, conduct, and analysis (eCRT Study).
abstract: BACKGROUND
  There is growing interest in conducting clinical and cluster randomized trials through electronic health records. This paper reports on the methodological issues identified during the implementation of two cluster randomized trials using the electronic health records of the Clinical Practice Research Datalink (CPRD).
  
  
  METHODS
  Two trials were completed in primary care: one aimed to reduce inappropriate antibiotic prescribing for acute respiratory infection; the other aimed to increase physician adherence with secondary prevention interventions after first stroke. The paper draws on documentary records and trial datasets to report on the methodological experience with respect to research ethics and research governance approval, general practice recruitment and allocation, sample size calculation and power, intervention implementation, and trial analysis.
  
  
  RESULTS
  We obtained research governance approvals from more than 150 primary care organizations in England, Wales, and Scotland. There were 104 CPRD general practices recruited to the antibiotic trial and 106 to the stroke trial, with the target number of practices being recruited within six months. Interventions were installed into practice information systems remotely over the internet. The mean number of participants per practice was 5,588 in the antibiotic trial and 110 in the stroke trial, with the coefficient of variation of practice sizes being 0.53 and 0.56 respectively. Outcome measures showed substantial correlations between the 12 months before, and after intervention, with coefficients ranging from 0.42 for diastolic blood pressure to 0.91 for proportion of consultations with antibiotics prescribed, defining practice and participant eligibility for analysis requires careful consideration.
  
  
  CONCLUSIONS
  Cluster randomized trials may be performed efficiently in large samples from UK general practices using the electronic health records of a primary care database. The geographical dispersal of trial sites presents a difficulty for research governance approval and intervention implementation. Pretrial data analyses should inform trial design and analysis plans.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN 47558792 and ISRCTN 35701810 (both registered on 17 March 2010).
authors.affiliation: Department of Primary Care and Public Health Sciences, King's College London, Capital House, 42 Weston St, London SE1 3QD, UK. martin.gulliford@kcl.ac.uk.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Gulliford
authors.forename: Tjeerd P
authors.initials: TP
authors.lastname: van Staa
authors.forename: Lisa
authors.initials: L
authors.lastname: McDermott
authors.forename: Gerard
authors.initials: G
authors.lastname: McCann
authors.forename: Judith
authors.initials: J
authors.lastname: Charlton
authors.forename: Alex
authors.initials: A
authors.lastname: Dregan
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D054976:Clinical Governance; D016000:Cluster Analysis; D003661:Decision Support Techniques; D057286:Electronic Health Records; D006801:Humans; D010818:Practice Patterns, Physicians'; D011320:Primary Health Care / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents