Economic evaluation protocol for the PRevention Of sudden cardiac death aFter myocardial Infarction by Defibrillator implantation: the PROFID EHRA trial.

INTRODUCTION: The implantable cardioverter defibrillator (ICD) is a cardiac device recommended for use to prevent the occurrence of sudden cardiac death (SCD) in post-myocardial infarction (MI) patients with reduced left ventricular ejection fraction (LVEF). The evidence informing this guidance comes from landmark trials that are now more than 20 years old. The risk-benefit profile of ICD for the contemporary target population may have changed substantially since then, which raises the question of whether there is evidence for sparing patients a procedure associated with potentially severe complications and high healthcare costs. A main part of the PRevention Of sudden cardiac death aFter myocardial Infarction by Defibrillator implantation (PROFID) project is the PROFID EHRA trial, which is supported by the European Heart Rhythm Association. PROFID EHRA is a European Union-funded, prospective, randomised, multi-centre, non-inferiority study designed to compare optimal medical therapy (OMT) alone to ICD with OMT, for post-MI patients with reduced LVEF. The study also describes economic evaluation methods to quantify the cost and health implications of using OMT alone in place of ICD implantation plus OMT in this group of patients. METHODS AND ANALYSIS: The economic evaluation has been designed to conduct a pre-trial cost-effectiveness analysis (CEA) prior to the availability of trial data, followed by a within-trial cost-consequences analysis (CCA) and a long-term post-trial CEA, conducted from the National Health Service and Personal Social Service perspective in England. The pre-trial CEA uses simulation modelling informed by available evidence to assess the lifetime costs and quality-adjusted life years of OMT alone and ICD+OMT in post-MI patients with reduced LVEF at risk of SCD, as defined in the PROFID EHRA trial. The within-trial CCA is intended to summarise the health-related quality of life (HRQoL), healthcare resource use and associated costs observed during the PROFID EHRA trial follow-up period. The post-trial CEA updates the pre-trial model by incorporating contemporary evidence about the HRQoL and costs observed during the trial and the occurrence of those events and outcomes accruing during the trial follow-up period and projecting them into the expected lifetime of the patients. Sensitivity analyses are performed to assess the robustness of the CEA results with respect to both model assumptions and uncertainty in the value of the model input parameters. Finally, a value of information analysis will identify the key drivers of uncertainty surrounding the model conclusions regarding the optimal treatment strategy, establishing if further research may be required. ETHICS AND DISSEMINATION: The PROFID EHRA trial, under legal sponsorship of Charité-Universitätsmedizin Berlin, Germany, received its first ethics approval by the Medicine Research Ethics Committee of the La Paz University Hospital in Madrid, Spain (reference number LHS-2019-0209). Before including patients, for all participating study centres, the required local, central and/or national ethical approval has to be obtained. As of the date 13 November 2025, at least one participating study centre in the following countries has received ethical approvals from relevant ethics committees: Austria, Belgium, Czech Republic, Denmark, France, Germany, Great Britain, Hungary, Israel, the Netherlands, Poland and Spain. Results will be shared with the general public through various media channels and additionally with healthcare professionals and the scientific community through scientific meetings, conferences and publications. TRIAL REGISTRATION NUMBER: NCT05665608.