Int J Stroke. 2014 Aug;9(6):811-3. doi: 10.1111/ijs.12259.

Financial management of a large multisite randomized clinical trial.

Sheffet AJ, Flaxman L, Tom M, Hughes SE, Longbottom ME, Howard VJ, Marler JR, Brott TG; CREST Investigators.

Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.

 

Abstract

BACKGROUND: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites.

AIMS: Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials.

METHODS: Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated.

RESULTS: Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model.

CONCLUSIONS: Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity.

KEYWORDS: carotid endarterectomy; carotid stenting; clinical trial; cost factors; economics; stroke

PMID: 24661748

 

SUPPLEMENT

The Carotid Revascularization Endarterectomy (CEA) vs Stenting (CAS) Trial (CREST) assesses the safety, efficacy, and durability of carotid stenting versus surgery in 2502 symptomatic and asymptomatic patients in 117 clinical sites in the United States and Canada. The trial was awarded funding from the National Institutes of Health (NIH) from 1999 through 2016.

Before the start of the trial, converting the grant budget from salaries and other direct costs to reimbursement for data (study visits and tests) submitted allowed for:

  • Conservation of funds in times of crisis (e.g. when the study was temporarily stopped)
  • Expansion of the number of sites using the same budgeted amount
  • Attainment of recruitment goals
  • Operating eight years on a five-year awarded budget
  • Extension of follow-up to 10 years through 2016

The trial received funding in three segments shown in the table below:

 

NIH Awards Trial Progress
1999 – 2006 Trial initiation and recruitment
2007 – 2011 Enrollment completed and primary and secondary results published
2012 – 2016 Long-term follow-up ongoing to compare ipsilateral stroke and restenosis in CAS versus CEA patients

 

At 103 US and Canadian sites, 1188 (72.5% of surviving subjects) are active; 111 completed 10 years’ follow-up, and 1155 have consented to CMS database linkage to compare CREST patient outcomes to those in national databases for future publication.

Primary and secondary aims have been published in the New England Journal, Lancet Neurology, Circulation, Stroke, Clinical Trials and the Journal of Vascular Surgery. CREST and European trial investigators are merging data for meta-analysis and publications relating to carotid disease as part of the Carotid Stenosis Trialists Collaboration (CSTC). We continue to focus on retention, data compliance and quality in preparation for publication of the long term follow-up results planned in 2016.

 

 

 

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