Abstract
BACKGROUND: Evidence synthesis for whole medical systems, defined as complete systems of theory and practice that have evolved independently from biomedicine. is challenging. This paper provides a framework for evidence synthesis of Traditional, Complementary and Integrative Medicine (TCIM) systems incorporating context and complexity. A systematic review program on the effects of homeopathic preparations is used as a practical illustration of the proposed framework. PROPOSED SOLUTION: A systems perspective considers the patient as a complex system of interconnected regulative subsystems embedded in a complex environment, and disease as a dysregulation of the dynamic adaptive state of the organism. Most TCIM systems, including homeopathy, aim to stimulate regulative systems and their functions to regain homeostasis. The consequences of these principles for the approach to evidence synthesis of TCIM systems are explored and explained. FRAMEWORK COMPONENTS: A systems perspective takes into account a plurality of evidence sources, including 'real-world' clinical data such as case reports, case series and cohort studies. The systematic review program focuses on comparative studies of homeopathy in various clinical indications and includes both non-randomized prospective studies of interventions (NRSIs) and randomized controlled trials (RCTs). For risk-of-bias assessments, use is made of respectively ROBINS-I and ROB2. Evidence certainty is graded transparently and rigorously based on the GRADE framework. An experienced patient advocate is involved in the research program and input from patient advisors who experienced the clinical indication under investigation is incorporated. DISCUSSION: RCT and NRSI evidence on homeopathic preparations for a range of clinical indications will be synthesised. A limitation, from a complex systems perspective, is that the implication of these findings will still need to be contextualized within the broader context of the existing state of knowledge. An 'evidence eco-system' that includes complementary sources of information will be required to inform decisions. CONCLUSION: Evidence synthesis of TCIM systems can move beyond conventional approaches by framing evidence within its complexity and context, together with real-world data and patient perspectives. This approach entails methodological challenges and will require gap analyses to guide future research and improve the applicability for public health and individualized patient care.