Vol. 148 No. 0304 (2018)
Funding characteristics of randomised clinical trials supported by the Swiss National Science Foundation: a retrospective cohort study
- Alain Amstutz
- Stefan Schandelmaier
- Roy Frei
- Jakub Surina
- Arnav Agarwal
- Reem Alturki
- Belinda von Niederhäusern
- Erik von Elm
- Matthias Briel
- on behalf of the MAking Randomized Trials Affordable (MARTA) Group
AIMS OF THE STUDY
Failure to publish publicly funded research represents a waste of scarce research resources across medical disciplines and countries. In Switzerland, about 40% of randomised clinical trials (RCTs) supported by the Swiss National Science Foundation (SNSF) were not published. We aimed to describe funding characteristics of published and unpublished RCTs supported by the SNSF, to quantify the amount of money spent for unpublished studies, and to compare our results to a similar study performed in the UK.
We established a retrospective cohort of RCTs funded by the SNSF up to 2015. For each RCT proposal, two investigators independently identified corresponding publications in electronic databases and trial registries. Teams of two investigators independently extracted details from the original SNSF proposal and, if available, from trial registries or publications. In addition, we surveyed principal investigators about trial costs and additional sources of funding.
We included 101 RCTs supported by the SNSF between 1986 and 2015. Most were single-centre RCTs with a median of 138 participants (interquartile range [IQR] 76–400). Overall, 67 (67%) principal investigators responded to our main survey questions. Median total costs per RCT were CHF 428 000 (IQR 282 000–900 000) of which the SNSF provided a median CHF 222 000 (67% of total costs, IQR 40–80%). Most investigators (70%) mentioned additional funding, mainly from their own institution or private foundations. A total of CHF 6.7 million was granted to RCTs that remained unpublished. Funding characteristics were similar to publicly funded trials in the UK.
A third of the total SNSF grant sum spent on healthcare RCTs between 1986 and 2015 did not result in peer-reviewed scientific publications. New SNSF grant schemes might improve publication outcomes but their effectiveness needs to be evaluated.
- Ann B. Research Methods In Health: Investigating Health And Health Services. McGraw-Hill Education (UK); 2014.
- Devereaux PJ, Yusuf S. The evolution of the randomized controlled trial and its role in evidence-based decision making. J Intern Med. 2003;254(2):105–13. doi:.https://doi.org/10.1046/j.1365-2796.2003.01201.x
- Sinha G. European move affects academic trials research. J Natl Cancer Inst. 2006;98(16):1100–1. doi:.https://doi.org/10.1093/jnci/djj349
- Eisenstein EL, Collins R, Cracknell BS, Podesta O, Reid ED, Sandercock P, et al. Sensible approaches for reducing clinical trial costs. Clin Trials. 2008;5(1):75–84. doi:.https://doi.org/10.1177/1740774507087551
- Duley L, Antman K, Arena J, Avezum A, Blumenthal M, Bosch J, et al. Specific barriers to the conduct of randomized trials. Clin Trials. 2008;5(1):40–8. doi:.https://doi.org/10.1177/1740774507087704
- Chakma J, Sun GH, Steinberg JD, Sammut SM, Jagsi R. Asia’s ascent--global trends in biomedical R&D expenditures. N Engl J Med. 2014;370(1):3–6. doi:.https://doi.org/10.1056/NEJMp1311068
- Holler B, Forgione DA, Baisden CE, Abramson DA, Calhoon JH. Interactive financial decision support for clinical research trials. J Health Care Finance. 2011;37(3):25–37.
- DiMasi JA, Hansen RW, Grabowski HG. The price of innovation: new estimates of drug development costs. J Health Econ. 2003;22(2):151–85. doi:.https://doi.org/10.1016/S0167-6296(02)00126-1
- Bodenheimer T. Uneasy alliance--clinical investigators and the pharmaceutical industry. N Engl J Med. 2000;342(20):1539–44. doi:.https://doi.org/10.1056/NEJM200005183422024
- 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
- Dwan K, Altman DG, Arnaiz JA, Bloom J, Chan AW, Cronin E, et al. Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS One. 2008;3(8):e3081. doi:.https://doi.org/10.1371/journal.pone.0003081
- Amstutz A, Schandelmaier S, Frei R, Surina J, Agarwal A, Olu KK, et al. Discontinuation and non-publication of randomised clinical trials supported by the main public funding body in Switzerland: a retrospective cohort study. BMJ Open. 2017;7(7):e016216. doi:.https://doi.org/10.1136/bmjopen-2017-016216
- De Angelis C, Drazen JM, Frizelle FA, Haug C, Hoey J, Horton R, et al.; International Committee of Medical Journal Editors. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. Lancet. 2004;364(9438):911–2. doi:.https://doi.org/10.1016/S0140-6736(04)17034-7
- Chan A-W, Upshur R, Singh JA, Ghersi D, Chapuis F, Altman DG. Waiving confidentiality for the greater good. BMJ. 2006;332(7549):1086–9. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458595/. Accessed March 27, 2014. doi:.https://doi.org/10.1136/bmj.332.7549.1086
- Decullier E, Lhéritier V, Chapuis F. Fate of biomedical research protocols and publication bias in France: retrospective cohort study. BMJ. 2005;331(7507):19. doi:.https://doi.org/10.1136/bmj.38488.385995.8F
- Stern JM, Simes RJ. Publication bias: evidence of delayed publication in a cohort study of clinical research projects. BMJ. 1997;315(7109):640–5. doi:.https://doi.org/10.1136/bmj.315.7109.640
- Sully BGO, Julious SA, Nicholl J. A reinvestigation of recruitment to randomised, controlled, multicenter trials: a review of trials funded by two UK funding agencies. Trials. 2013;14(1):166. doi:.https://doi.org/10.1186/1745-6215-14-166
- Walters SJ, Bonacho Dos Anjos Henriques-Cadby I, Bortolami O, Flight L, Hind D, Jacques RM, et al. Recruitment and retention of participants in randomised controlled trials: a review of trials funded and published by the United Kingdom Health Technology Assessment Programme. BMJ Open. 2017;7(3):e015276. doi:.https://doi.org/10.1136/bmjopen-2016-015276
- Incentives for Clinical Trialists to Share Data - NEJMp1608351. http://www.nejm.org/doi/pdf/10.1056/NEJMp1608351. Accessed December 4, 2017.
- 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
- Briel M, Elger B, von Elm E, Satalkar P. Insufficient recruitment and premature discontinuation of clinical trials in Switzerland: qualitative study with trialists and other stakeholders. Swiss Med Wkly. 2017;147:w14556. doi:10.4414/smw.2017.14556.