title: Challenges of maintaining research protocol fidelity in a clinical care setting: a qualitative study of the experiences and views of patients and staff participating in a randomized controlled trial.
abstract: BACKGROUND
  Trial research has predominantly focused on patient and staff understandings of trial concepts and/or motivations for taking part, rather than why treatment recommendations may or may not be followed during trial delivery. This study sought to understand why there was limited attainment of the glycaemic target (HbA(1c) ≤6.5%) among patients who participated in the Treating to Target in Type 2 Diabetes Trial (4-T). The objective was to inform interpretation of trial outcomes and provide recommendations for future trial delivery.
  
  
  METHODS
  In-depth interviews were conducted with 45 patients and 21 health professionals recruited from 11 of 58 trial centres in the UK. Patients were broadly representative of those in the main trial in terms of treatment allocation, demographics and glycaemic control. Both physicians and research nurses were interviewed.
  
  
  RESULTS
  Most patients were committed to taking insulin as recommended by 4-T staff. To avoid hypoglycaemia, patients occasionally altered or skipped insulin doses, normally in consultation with staff. Patients were usually unaware of the trial's glycaemic target. Positive staff feedback could lead patients to believe they had been 'successful' trial participants even when their HbA(1c) exceeded 6.5%. While some staff felt that the 4-T automated insulin dose adjustment algorithm had increased their confidence to prescribe larger insulin doses than in routine clinical practice, all described situations where they had not followed its recommendations. Staff regarded the application of a 'one size fits all' glycaemic target during the trial as contradicting routine clinical practice where they would tailor treatments to individuals. Staff also expressed concerns that 'tight' glycaemic control might impose an unacceptably high risk of hypoglycaemia, thus compromising trust and safety, especially amongst older patients. To address these concerns, staff tended to adapt the trial protocol to align it with their clinical practices and experiences.
  
  
  CONCLUSIONS
  To understand trial findings, foster attainment of endpoints, and promote protocol fidelity, it may be necessary to look beyond individual patient characteristics and experiences. Specifically, the context of trial delivery, the impact of staff involvement, and the difficulties staff may encounter in balancing competing 'clinical' and 'research' roles and responsibilities may need to be considered and addressed.
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Edinburgh, EH8 9AG, UK. J.Lawton@ed.ac.uk
authors.forename: Julia
authors.initials: J
authors.lastname: Lawton
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jenkins
authors.forename: Julie L
authors.initials: JL
authors.lastname: Darbyshire
authors.forename: Rury R
authors.initials: RR
authors.lastname: Holman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Farmer
authors.forename: Nina
authors.initials: N
authors.lastname: Hallowell
mesh_terms: D000368:Aged; D001291:Attitude of Health Personnel; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D054796:Drug Dosage Calculations; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D019983:Guideline Adherence; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D061267:Insulin Aspart; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D036301:Qualitative Research; D012107:Research Design; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human