Vol. 147 No. 4546 (2017)
Insufficient recruitment and premature discontinuation of clinical trials in Switzerland: qualitative study with trialists and other stakeholders
AIMS OF THE STUDY
Premature discontinuation occurs in about 25% of randomised clinical trials in Switzerland; it mainly affects investigator-initiated trials and is mostly due to problems with recruitment of patients. The aim of this study was to qualitatively investigate reasons for trial discontinuation due to poor patient recruitment and suggestions to address those reasons in the Swiss context.
We conducted semi-structured interviews with trialists whose trials were discontinued because of recruitment problems, other experienced trialists, and stakeholders in clinical research in Switzerland. Interviews were audio-recorded, transcribed verbatim, and anonymised. We analysed the transcripts using deductive coding and built up themes that were continuously discussed within the research team.
Of 65 invited Swiss trialists and stakeholders, 39 (60%) agreed to be interviewed and contributed to this analysis. We identified four main themes of reasons for poor recruitment: (1) Switzerland has a decentralised healthcare system with many small hospitals and few patients per hospital, many research regulations, no standardisation of medical records across hospitals, and a heterogeneous ethics assessment of study protocols. There is little collaboration of different stakeholders in clinical research and a lack of prioritisation of projects. (2) Limited human and financial resources, especially in the academic setting, compromise research questions and size of clinical trials. When funding is used up this typically triggers discontinuation of already delayed clinical trials. (3) Investigators face underdeveloped research networks and a limited collaborative attitude among clinical researchers. They typically embark on clinical studies with a great deal of optimism but insufficient preparation. (4) Swiss patients have universal health coverage and many treatment options. Negative media coverage of clinical research and a lack of accessible information for patients about ongoing clinical studies frequently make participation in clinical trials less attractive. More interactive structures and collaboration across stakeholders were mentioned as potential solutions to tackle the problems.
Recruitment of participants into clinical trials in Switzerland is challenging because of various, often interlinked factors related to the Swiss health system, available funding, investigators, and patients. Common goals and concerted efforts by involved stakeholders appear necessary to achieve improvement.
- Kasenda B, von Elm E, You J, Blümle A, Tomonaga Y, Saccilotto R, et al. Prevalence, characteristics, and publication of discontinued randomized trials. JAMA. 2014;311(10):1045–51. doi:.https://doi.org/10.1001/jama.2014.1361
- Donovan JL, Paramasivan S, de Salis I, Toerien M. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials. 2014;15(1):5. doi:.https://doi.org/10.1186/1745-6215-15-5
- Donovan JL, de Salis I, Toerien M, Paramasivan S, Hamdy FC, Blazeby JM. The intellectual challenges and emotional consequences of equipoise contributed to the fragility of recruitment in six randomized controlled trials. J Clin Epidemiol. 2014;67(8):912–20. doi:.https://doi.org/10.1016/j.jclinepi.2014.03.010
- Fayter D, McDaid C, Eastwood A. A systematic review highlights threats to validity in studies of barriers to cancer trial participation. J Clin Epidemiol. 2007;60(10):990–1001. doi:.https://doi.org/10.1016/j.jclinepi.2006.12.013
- Spaar A, Frey M, Turk A, Karrer W, Puhan MA. Recruitment barriers in a randomized controlled trial from the physicians’ perspective: a postal survey. BMC Med Res Methodol. 2009;9(1):14. doi:.https://doi.org/10.1186/1471-2288-9-14
- Toerien M, Brookes ST, Metcalfe C, de Salis I, Tomlin Z, Peters TJ, et al. A review of reporting of participant recruitment and retention in RCTs in six major journals. Trials. 2009;10(1):52. doi:.https://doi.org/10.1186/1745-6215-10-52
- Mills E, Wilson K, Rachlis B, Griffith L, Wu P, Guyatt G, et al. Barriers to participation in HIV drug trials: a systematic review. Lancet Infect Dis. 2006;6(1):32–8. doi:.https://doi.org/10.1016/S1473-3099(05)70324-8
- Mills EJ, Seely D, Rachlis B, Griffith L, Wu P, Wilson K, et al. Barriers to participation in clinical trials of cancer: a meta-analysis and systematic review of patient-reported factors. Lancet Oncol. 2006;7(2):141–8. doi:.https://doi.org/10.1016/S1470-2045(06)70576-9
- Abraham NS, Young JM, Solomon MJ. A systematic review of reasons for nonentry of eligible patients into surgical randomized controlled trials. Surgery. 2006;139(4):469–83. doi:.https://doi.org/10.1016/j.surg.2005.08.014
- Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R, et al.; STEPS group. Recruitment to randomised trials: strategies for trial enrollment and participation study. The STEPS study. Health Technol Assess. 2007;11(48):iii, ix-105. doi:.https://doi.org/10.3310/hta11480
- Kaur G, Smyth RL, Williamson P. Developing a survey of barriers and facilitators to recruitment in randomized controlled trials. Trials. 2012;13(1):218. doi:.https://doi.org/10.1186/1745-6215-13-218
- Briel M, Olu KK, von Elm E, Kasenda B, Alturki R, Agarwal A, et al. A systematic review of discontinued trials suggested that most reasons for recruitment failure were preventable. J Clin Epidemiol. 2016;80:8–15. doi:.https://doi.org/10.1016/j.jclinepi.2016.07.016
- Bowen GA. Naturalistic inquiry and the saturation concept: a research note. Qual Res. 2008;8(1):137–52. doi:.https://doi.org/10.1177/1468794107085301
- Braun V, Clarke V. Using thematic analysis in psychology. Qual Res Psychol. 2006;3(2):77–101. doi:.https://doi.org/10.1191/1478088706qp063oa
- Gayet-Ageron A, Rudaz S, Perneger T. Biobank attributes associated with higher patient participation: a randomized study. Eur J Hum Genet. 2016;25(1):31–6. doi:.https://doi.org/10.1038/ejhg.2016.132
- McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, et al. What influences recruitment to randomised controlled trials? A review of trials funded by two UK funding agencies. Trials. 2006;7(1):9. doi:.https://doi.org/10.1186/1745-6215-7-9
- Ziebland S, Featherstone K, Snowdon C, Barker K, Frost H, Fairbank J. Does it matter if clinicians recruiting for a trial don’t understand what the trial is really about? Qualitative study of surgeons’ experiences of participation in a pragmatic multi-centre RCT. Trials. 2007;8(1):4. doi:.https://doi.org/10.1186/1745-6215-8-4
- Cullati S, Courvoisier DS, Gayet-Ageron A, Haller G, Irion O, Agoritsas T, et al. Patient enrollment and logistical problems top the list of difficulties in clinical research: a cross-sectional survey. BMC Med Res Methodol. 2016;16(1):50. doi:.https://doi.org/10.1186/s12874-016-0151-1
- Swiss National Science Foundation. Investigator Initiated Clinical Trials (IICT) 2017 [July 19, 2017]. Available from: http://www.snf.ch/en/funding/programmes/iict/Pages/default.aspx
- Swiss National Science Foundation. Protected research time for clinicians 2017 [July 19, 2017]. Available from: http://www.snf.ch/en/funding/supplementary-measures/protected-research-time-clinicians/Pages/default.aspx.
- Federal Office of Public Health (FOPH). Roadmap for developing the next generation of clinical researchers 2017 [July 19, 2017]. Available from: https://www.bag.admin.ch/bag/en/home/themen/mensch-gesundheit/biomedizin-forschung/biomedizinische-forschung-und-technologie/masterplan-zur-staerkung-der-biomedizinischen-forschung-und-technologie/roadmap-nachwuchsfoerderung-klinische-forschung.html.
- The Coordination Office for Human Research. (kofam). Searching for a clinical trial [July 19, 2017]. Available from: https://www.kofam.ch/en/snctp-portal/searching-for-a-clinical-trial/.
- Ross S, Grant A, Counsell C, Gillespie W, Russell I, Prescott R. Barriers to participation in randomised controlled trials: a systematic review. J Clin Epidemiol. 1999;52(12):1143–56. doi:.https://doi.org/10.1016/S0895-4356(99)00141-9
- Bower P, Brueton V, Gamble C, Treweek S, Smith CT, Young B, et al. Interventions to improve recruitment and retention in clinical trials: a survey and workshop to assess current practice and future priorities. Trials. 2014;15(1):399. doi:.https://doi.org/10.1186/1745-6215-15-399
- Preston NJ, Farquhar MC, Walshe CE, Stevinson C, Ewing G, Calman LA, et al. Strategies designed to help healthcare professionals to recruit participants to research studies. Cochrane Database Syst Rev. 2016;2:MR000036. doi:.https://doi.org/10.1002/14651858.MR000036.pub2
- Treweek S, Lockhart P, Pitkethly M, Cook JA, Kjeldstrøm M, Johansen M, et al. Methods to improve recruitment to randomised controlled trials: Cochrane systematic review and meta-analysis. BMJ Open. 2013;3(2):e002360. doi:.https://doi.org/10.1136/bmjopen-2012-002360
- Rick J, Graffy J, Knapp P, Small N, Collier DJ, Eldridge S, et al. Systematic techniques for assisting recruitment to trials (START): study protocol for embedded, randomized controlled trials. Trials. 2014;15(1):407. doi:.https://doi.org/10.1186/1745-6215-15-407
- Weisskopf M, Bucklar G, Blaser J. Tools in a clinical information system supporting clinical trials at a Swiss University Hospital. Clin Trials. 2014;11(6):673–80. doi:.https://doi.org/10.1177/1740774514546702