title: Missing steps in a staircase: a qualitative study of the perspectives of key stakeholders on the use of adaptive designs in confirmatory trials.
abstract: BACKGROUND
  Despite the promising benefits of adaptive designs (ADs), their routine use, especially in confirmatory trials, is lagging behind the prominence given to them in the statistical literature. Much of the previous research to understand barriers and potential facilitators to the use of ADs has been driven from a pharmaceutical drug development perspective, with little focus on trials in the public sector. In this paper, we explore key stakeholders' experiences, perceptions and views on barriers and facilitators to the use of ADs in publicly funded confirmatory trials.
  
  
  METHODS
  Semi-structured, in-depth interviews of key stakeholders in clinical trials research (CTU directors, funding board and panel members, statisticians, regulators, chief investigators, data monitoring committee members and health economists) were conducted through telephone or face-to-face sessions, predominantly in the UK. We purposively selected participants sequentially to optimise maximum variation in views and experiences. We employed the framework approach to analyse the qualitative data.
  
  
  RESULTS
  We interviewed 27 participants. We found some of the perceived barriers to be: lack of knowledge and experience coupled with paucity of case studies, lack of applied training, degree of reluctance to use ADs, lack of bridge funding and time to support design work, lack of statistical expertise, some anxiety about the impact of early trial stopping on researchers' employment contracts, lack of understanding of acceptable scope of ADs and when ADs are appropriate, and statistical and practical complexities. Reluctance to use ADs seemed to be influenced by: therapeutic area, unfamiliarity, concerns about their robustness in decision-making and acceptability of findings to change practice, perceived complexities and proposed type of AD, among others.
  
  
  CONCLUSIONS
  There are still considerable multifaceted, individual and organisational obstacles to be addressed to improve uptake, and successful implementation of ADs when appropriate. Nevertheless, inferred positive change in attitudes and receptiveness towards the appropriate use of ADs by public funders are supportive and are a stepping stone for the future utilisation of ADs by researchers.
authors.affiliation: School of Health and Related Research, Regent Court, University of Sheffield, 30 Regent Street, S1 4DA, Sheffield, UK. m.dimairo@sheffield.ac.uk.
authors.forename: Munyaradzi
authors.initials: M
authors.lastname: Dimairo
authors.affiliation: School of Health and Related Research, Regent Court, University of Sheffield, 30 Regent Street, S1 4DA, Sheffield, UK. j.boote@herts.ac.uk.|Centre for Research in Primary and Community Care, University of Hertfordshire, Hatfield, AL109AB, Hertfordshire, UK. j.boote@herts.ac.uk.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Boote
authors.affiliation: School of Health and Related Research, Regent Court, University of Sheffield, 30 Regent Street, S1 4DA, Sheffield, UK. s.a.julious@sheffield.ac.uk.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Julious
authors.affiliation: School of Health and Related Research, Regent Court, University of Sheffield, 30 Regent Street, S1 4DA, Sheffield, UK. j.nicholl@sheffield.ac.uk.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Nicholl
authors.affiliation: Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading, RG6 6AX, UK. s.c.todd@reading.ac.uk.
authors.forename: Susan
authors.initials: S
authors.lastname: Todd
mesh_terms: D000328:Adult; D001291:Attitude of Health Personnel; D017326:Clinical Trials, Phase III as Topic / Q000145:classification / Q000191:economics / Q000379:methods*; D032882:Comprehension; D005260:Female; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D010465:Perception; D017150:Public Sector / Q000191:economics; D036301:Qualitative Research; D012107:Research Design; D012108:Research Personnel / Q000523:psychology*; D012109:Research Support as Topic; D009626:Terminology as Topic