Abstract
Objectives
Randomized clinical trials (RCTs) are costly. We aimed to provide a systematic overview
of the available evidence on resource use and costs for RCTs to support budget planning.
Study Design and Setting
We systematically searched MEDLINE, EMBASE, and HealthSTAR from inception until November
30, 2016 without language restrictions. We included any publication reporting empirical
data on resource use and costs of RCTs and categorized them depending on whether they
reported (i) resource and costs of all aspects at all study stages of an RCT (including
conception, planning, preparation, conduct, and all tasks after the last patient has
completed the RCT); (ii) on several aspects, (iii) on a single aspect (e.g., recruitment);
or (iv) on overall costs for RCTs. Median costs of different recruitment strategies
were calculated. Other results (e.g., overall costs) were listed descriptively. All
cost data were converted into USD 2017.
Results
A total of 56 articles that reported on cost or resource use of RCTs were included.
None of the articles provided empirical resource use and cost data for all aspects
of an entire RCT. Eight articles presented resource use and cost data on several aspects
(e.g., aggregated cost data of different drug development phases, site-specific costs,
selected cost components). Thirty-five articles assessed costs of one specific aspect
of an RCT (i.e., 30 on recruitment; five others). The median costs per recruited patient
were USD 409 (range: USD 41–6,990). Overall costs of an RCT, as provided in 16 articles,
ranged from USD 43–103,254 per patient, and USD 0.2–611.5 Mio per RCT but the methodology
of gathering these overall estimates remained unclear in 12 out of 16 articles (75%).
Conclusion
The usefulness of the available empirical evidence on resource use and costs of RCTs
is limited. Transparent and comprehensive resource use and cost data are urgently
needed to support budget planning for RCTs and help improve sustainability.
Keywords
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References
- How to increase value and reduce waste when research priorities are set.Lancet. 2014; 383: 156-165
- Increasing value and reducing waste in research design, conduct, and analysis.Lancet. 2014; 383: 166-175
- Increasing value and reducing waste in biomedical research regulation and management.Lancet. 2014; 383: 176-185
- Increasing value and reducing waste: addressing inaccessible research.Lancet. 2014; 383: 257-266
- Reducing waste from incomplete or unusable reports of biomedical research.Lancet. 2014; 383: 267-276
- Potentially unnecessary and wasteful clinical trial research detected in cumulative meta-epidemiological and trial sequential analysis.J Clin Epidemiol. 2017; 82: 61-70
- The cost of drug development: a systematic review.Health Policy. 2011; 100: 4-17
- How to improve R&D productivity: the pharmaceutical industry's grand challenge.Nat Rev Drug Discov. 2010; 9: 203-214
- Demythologizing the high costs of pharmaceutical research. The London School of Economics and Political Science.Biosocieties. 2011; 6 (1745–8552): 1-17
- Estimating the cost of new drug development: is it really 802 million dollars?.Health Aff (Millwood). 2006; 25: 420-428
- Letter to Dr. DiMasi.2015 (Avaialable at)http://csdd.tufts.edu/files/uploads/UACTLetterDiMasi_Feb2015.pdfDate accessed: June 9, 2016
- Specific barriers to the conduct of randomized trials.Clin Trials. 2008; 5: 40-48
- Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials.Lancet. 2001; 357: 373-380
- Innovation in the pharmaceutical industry: new estimates of R&D costs.J Health Econ. 2016; 47: 20-33
- Transforming clinical research in the United States: challenges and opportunities: workshop summary.The National Academies Press, Washington, DC2010
- Rapidly rising clinical trial costs worry researchers.CMAJ. 2009; 180: 277-278
- Intergrated Addendum to ICH E6(R1): Guideline for good clinical practice.2015 (Available at)http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E6/E6_R2__Addendum_Step2.pdfDate accessed: July 6, 2017
- European move affects academic trials research.J Natl Cancer Inst. 2006; 98: 1100-1101
- Sensible approaches for reducing clinical trial costs.Clin Trials. 2008; 5: 75-84
- Europe's restrictive rules strangling clinical research.Nat Med. 2005; 11: 1260
- Prevalence, characteristics, and publication of discontinued randomized trials.JAMA. 2014; 311: 1045-1051
- Commentary on Sertkaya et al. and Larson, et al.Clin Trials. 2016; 13: 137-139
- How automation can help alleviate the budget crunch in public health research.Am J Public Health. 2015; 105: e19-e22
Organisation for Economic Co-operation and Development. Consumer Prices: Consumer Prices - Annual Inflation. Available at http://stats.oecd.org/index.aspx?queryid=22519#. Accessed July, 27 2017.
Bloomberg. Exchange rates. Available at https://www.bloomberg.com/markets/currencies. Accessed July, 27 2017.
- Key cost drivers of pharmaceutical clinical trials in the United States.Clin Trials. 2016; 13: 117-126
- Quantifying the magnitude and cost of collecting extraneous protocol data.Am J Ther. 2015; 22: 117-124
- Clinical trial metadata: defining and extracting metadata on the design, conduct, results and costs of 125 randomised clinical trials funded by the National Institute for Health Research Health Technology Assessment programme.Health Technol Assess. 2015; 19: 1-138
- The prostate, lung, colorectal, and ovarian cancer screening trial and its associated research resource.J Natl Cancer Inst. 2013; 105: 1684-1693
- Factors affecting workload of cancer clinical trials: results of a multicenter study of the National Cancer Institute of Canada Clinical Trials Group.J Clin Oncol. 2002; 20: 545-556
- An estimate of the cost of conducting phase II trials in lung cancer.Lung Cancer. 2000; 28: 85-95
- Research cost analyses to aid in decision making in the conduct of a large prevention trial, CARET. Carotene and Retinol Efficacy Trial.Control Clin Trials. 1993; 14: 325-339
- Patient recruitment to and cost of a prospective trial of medical treatment for benign prostatic hyperplasia.Eur Urol. 1992; 22: 9-13
- Recruiting pregnant indigenous women who smoke into a high contact incentivized cessation trial: a feasibility study.Nicotine Tob Res. 2016; 18: 2036-2040
- Recruitment techniques for alcohol pharmacotherapy clinical trials: a cost-benefit analysis.Addict Disord Their Treat. 2015; 14: 211-219
- Challenges in recruitment to a randomized controlled study of cardiovascular disease reduction in sleep apnea: an analysis of alternative strategies.Sleep. 2014; 37: 2035-2038
- An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.Clin Trials. 2014; 11: 141-149
- Effectiveness of newspaper advertising for patient recruitment into a clinical trial.Br J Clin Pharmacol. 2014; 77: 1064-1072
- An evaluation of the impact and costs of three strategies used to recruit acutely unwell young children to a randomised controlled trial in primary care.Clin Trials. 2013; 10: 593-603
- Recruitment strategy cost and impact on minority accrual to a breast cancer prevention trial.Clin Trials. 2013; 10: 292-299
- Effort required in eligibility screening for clinical trials.J Oncol Pract. 2012; 8: 365-370
- Efficacy and cost-effectiveness of an automated screening algorithm in an inpatient clinical trial.Clin Trials. 2012; 9: 198-203
- Efficiency and cost-effectiveness of recruitment methods for male Latino smokers.Health Educ Behav. 2011; 38: 293-300
- A comparative analysis of recruitment methods used in a randomized trial of diabetes education interventions.Contemp Clin Trials. 2010; 31: 549-557
- Effective and cost-effective clinical trial recruitment strategies for postmenopausal women in a community-based, primary care setting.Contemp Clin Trials. 2010; 31: 447-456
- Recruitment methods and costs for a randomized, placebo-controlled trial of chiropractic care for lumbar spinal stenosis: a single-site pilot study.J Manipulative Physiol Ther. 2010; 33: 56-61
- Recruiting hard-to-reach drug-using men who have sex with men into an intervention study: lessons learned and implications for applied research.Subst Use Misuse. 2009; 44: 1855-1871
- Evaluation of active and passive recruitment methods used in randomized controlled trials targeting pediatric obesity.Int J Pediatr Obes. 2009; 4: 224-232
- Effectiveness and cost of recruitment strategies for a community-based randomised controlled trial among rainwater drinkers.BMC Med Res Methodol. 2009; 9: 51
- Screening and enrolling subjects in a randomized clinical trial involving implant dentures.Int J Prosthodont. 2008; 21: 210-214
- Cumulative recruitment experience in two large single-center randomized, controlled clinical trials.Contemp Clin Trials. 2008; 29: 335-342
- Costs of recruiting couples to a clinical trial.Contemp Clin Trials. 2007; 28: 423-432
- Cost effectiveness of recruitment methods in an obesity prevention trial for young children.Prev Med. 2007; 44: 499-503
- Monitoring recruitment success and cost in a randomized clinical trial.Eur J Prosthodont Restor Dent. 2006; 14: 126-130
- Strategies, time, and costs associated with the recruitment and enrollment of nursing home residents for a micronutrient supplementation clinical trial.J Gerontol A Biol Sci Med Sci. 2005; 60: 1469-1474
- The Diabetes Prevention Program: recruitment methods and results.Control Clin Trials. 2002; 23: 157-171
- Response to direct and indirect recruitment for a randomised dental clinical trial in a multicultural population of elders.Community Dent Oral Epidemiol. 2002; 30: 377-381
- Recruiting phobic research subjects: effectiveness and cost.Anesth Prog. 2001; 48: 3-8
- Two recruitment strategies for a clinical trial of physically frail community-living older persons.J Am Geriatr Soc. 2001; 49: 1039-1045
- Cost effectiveness of screening for clinical trials by research assistants versus senior investigators.J Psychiatr Res. 1999; 33: 81-85
- Challenges faced in recruiting patients from primary care practices into a physical activity intervention trial. Activity Counseling Trial Research Group.Prev Med. 1999; 29: 277-286
- Therapeutic trial participants: where do we find them and what does it cost?.Psychopharmacol Bull. 1997; 33: 75-78
- Monitoring recruitment effectiveness and cost in a clinical trial.Control Clin Trials. 1993; 14: 52S-67S
- What is the most cost-effective advertising strategy for alcohol pharmacotherapy clinical trials?.Drug Alcohol Depend. 2015; 146: e5
- The impact of protocol amendments on clinical trial performance and cost.Ther Innov Regul Sci. 2016; 50: 436-441
- Improving protocol design feasibility to drive drug development economics and performance.Int J Environ Res Public Health. 2014; 11: 5069-5080
- The costs associated with adverse event procedures for an international HIV clinical trial determined by activity-based costing.J Acquir Immune Defic Syndr. 2007; 46: 426-432
- Cost-evaluation model for clinical trials in a hospital pharmacy service.Pharm World Sci. 1995; 17: 172-176
- Quality assurance within the scope of Good Clinical Practice (GCP) - what is the cost of GCP-related activities? A survey within the Swedish Association of the Pharmaceutical Industry (LIF)'s members.Qual Assur J. 2009; 12: 3-7
- Conducting a fully mobile and randomised clinical trial for depression: access, engagement and expense.BMJ Innov. 2016; 2: 14-21
- Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.Clin Trials. 2016; 13: 127-136
- Economic return from the Women's Health Initiative estrogen plus progestin clinical trial: a modeling study.Ann Intern Med. 2014; 160: 594-602
- Eliminating the “expensive” adjective for clinical trials.Am Heart J. 2014; 167: 419-420
- Toward more specific and transparent research and development costs: the case of seasonal influenza vaccines.Vaccine. 2014; 32: 3336-3340
- Chelation-therapy heart trial draws fire.Nature. 2012; 491: 313-315
- Estimated research and development costs of rotavirus vaccines.Vaccine. 2009; 27: 6627-6633
- The economic returns of pediatric clinical trials of antihypertensive drugs.Am Heart J. 2008; 156: 682-688
- Economic return of clinical trials performed under the pediatric exclusivity program.JAMA. 2007; 297: 480-488
- Assessing the costs and benefits of medical research: the diabetic retinopathy study.Soc Sci Med. 1992; 34: 973-981
- Are clinical trials a cost-effective investment?.JAMA. 1989; 262: 1795-1800
- Using economic analysis to determine the resource consequences of choices made in planning clinical trials.J Chronic Dis. 1985; 38: 753-765
- Controlled trial of propranolol for the prevention of recurrent variceal hemorrhage in patients with cirrhosis.N Engl J Med. 1983; 309: 1539-1542
- Multiple risk factor intervention trial - risk factor changes and mortality results.JAMA. 1982; 248: 1465-1477
- Series: pragmatic trials and real world evidence: Paper 1. Introduction.J Clin Epidemiol. 2017; 88: 7-13
- Central challenges facing the national clinical research enterprise.JAMA. 2003; 289: 1278-1287
- Education section - studies within a trial (SWAT).J Evid Based Med. 2012; 5: 44-45
- The price of innovation: new estimates of drug development costs.J Health Econ. 2003; 22: 151-185
- How much do clinical trials cost?.Nat Rev Drug Discov. 2017; 16: 381-382
Article info
Publication history
Published online: December 26, 2017
Accepted:
December 20,
2017
Footnotes
Funding: This project was partially funded by the Swiss Federal Office of Public Health. Benjamin Speich is supported by the Research Foundation of the University of Basel. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of interest statement: All authors have declared that no competing interests exist.
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