title: Financial management of a large multisite randomized clinical trial.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Surgery, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sheffet
authors.forename: Linda
authors.initials: L
authors.lastname: Flaxman
authors.forename: MeeLee
authors.initials: M
authors.lastname: Tom
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hughes
authors.forename: Mary E
authors.initials: ME
authors.lastname: Longbottom
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Howard
authors.forename: John R
authors.initials: JR
authors.lastname: Marler
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Brott
mesh_terms: D016894:Endarterectomy, Carotid / Q000191:economics; D005376:Financial Management / Q000379:methods*; D005381:Financing, Organized; D006801:Humans; D015337:Multicenter Studies as Topic / Q000191:economics* / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000191:economics* / Q000379:methods; D015607:Stents / Q000191:economics; D020521:Stroke / Q000517:prevention & control* / Q000601:surgery
keywords: carotid endarterectomy; carotid stenting; clinical trial; cost factors; economics; stroke