Haley Rafferty
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Elisa Rocha
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Paola Gonzalez-Mego
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Clara Ramos
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Mirret M El-Hagrassy
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Muhammed E Gunduz
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Elif Uygur-Kucukseymen
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Hanan Zehry
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Swapnali Chaudhari
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Paulo EP Teixeira
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Gleysson R Rosa
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Ana L Zaninotto
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Christopher Connor
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham & Women's Hospital, Boston, MA
Uri Eden
Boston University, Boston, MA, USA
Ciro Ramos-Estebanez
Case Western Reserve University, Cleveland, Ohio
Felipe Fregni
Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Charlestown, MA, USA.
Laura Dipietro
Highland Instruments, Inc. Cambridge, MA, USA
Timothy Wagner
Highland Instruments, Inc. Cambridge, MA, USA
Abstract
Introduction: Run-In (RI) periods can be used to improve the validity of randomized controlled trials (RCTs), but their utility in Chronic Pain (CP) RCTs is debated. Cost-effectiveness analysis (CEA) methods are commonly used in evaluating the results of RCTs, but they are seldom used for designing RCTs. We present a step-by-step overview to objectively design RCTs via CEA methods and specifically determine the cost effectiveness of a RI period in a CP RCT.
Methods: We applied the CEA methodology to data obtained from several noninvasive brain stimulation CP RCTs, specifically focusing on (1) defining the CEA research question, (2) identifying RCT phases and cost ingredients, (3) discounting, (4) modeling the stochastic nature of the RCT, and (5) performing sensitivity analyses. We assessed the average cost-effectiveness ratios and incremental cost-effectiveness ratios of varied RCT designs and the impact on cost-effectiveness by the inclusion of a RI period vs. No-Run-In (NRI) period.
Results: We demonstrated the potential impact of varying the number of institutions, number of patients that could be accommodated per institution, cost and effectiveness discounts, RCT component costs, and patient adherence characteristics on varied RI and NRI RCT designs. In the specific CP RCT designs that we analyzed, we demonstrated that lower patient adherence, lower baseline assessment costs, and higher treatment costs all necessitated the inclusion of an RI period to be cost-effective compared to NRI RCT designs.
Conclusions: Clinical trialists can optimize CP RCT study designs and make informed decisions regarding RI period inclusion/exclusion via CEA methods.
Key terms: cost-effectiveness analysis (CEA), randomized controlled trial design (RCT design), Chronic Pain Trials, Run-In Period, Noninvasive Brain Stimulation, Neuromodulation
