Clinical research on homeopathic preparations: protocol template for a series of systematic reviews

BACKGROUND: The clinical benefits of homeopathic preparations (HPs) used in anthroposophic medicine and homeopathy remain a topic of debate. Systematic reviews (SRs), with or without meta-analyses (MAs), that assess the literature in line with scientific standards and account for the complex nature of these interventions are lacking for many health conditions. This project aims to conduct SRs to evaluate the efficacy, effectiveness, and safety of HPs for selected patient populations, using a pluralistic approach that considers internal and model validity. METHODS: This protocol follows PRISMA-P. A comprehensive literature search will include the HOMIS database, MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, LILACS, topic-specific sources, citation indices, trial registers, and grey literature, including preprint servers. Eligible studies will have a prospective, longitudinal design and include randomized controlled trials and non-randomized comparative studies published in various languages, evaluating HP interventions for efficacy, effectiveness, and/or safety in health conditions preselected through expert consensus. All patient types, interventions, co-interventions, therapeutic goals, and comparison groups will be eligible. Research questions and outcomes will be developed with consideration of the patient perspective. Each SR will be conducted by a multidisciplinary team, supported by an advisory group. Risk of bias will be assessed using ROB-2 and ROBINS-I. Model validity and the efficacy-effectiveness spectrum will be evaluated using MVHT and RITES. Intervention complexity will be analyzed with an adapted iCAT_SR. Where meta-analysis is not feasible, a narrative synthesis following SWiM will be conducted; otherwise, quantitative synthesis will be performed. Certainty of evidence will be assessed using GRADE. DISCUSSION: This series of SRs and MAs will investigate the effects of HPs as complex interventions in healthcare and aims to establish an evidence base regarding their efficacy, effectiveness, and safety. By integrating assessments of internal and model validity and potential effect modifiers, the reviews aim to provide a more comprehensive understanding of the conditions under which HPs may yield clinical benefits. In addition, the project may identify research gaps and methodological shortcomings to inform future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420251017029.