Whole Medical Systems (WMSs) are complete systems of medical theory and practice; they assume the human being as a hierarchically structured and interrelated system; they see diseases within this holistic paradigm, affecting and being affected by different parts of the human individual, a disease or condition thus having general and unique aspects in each patient; besides the physical and (patho-)physiological level, also the emotional, biographical, social, and spiritual dimensions are regarded to be important. This introduces a person-centered, individualized approach. Many complementary therapy systems are WMSs (e.g., Anthroposophic Medicine, Ayurveda, Homeopathy, Naturopathy, Traditional Chinese Medicine). They have distinct nosological conceptions, diagnostic procedures, and integrate sometimes thousands of treatment approaches, e.g. remedies, non-pharmacological interventions, lifestyle recommendations, counseling, and support the patient pursuing his or her own goal. The treatments are mostly deduced from the WMSs concept or derived from its medical practice, but rarely from molecular reasoning or preclinical experiments. Indications for remedies from WMSs are not restricted to singular disease entities; one remedy is often applied in a large variety of diseases, depending on the individual condition and situation of the patient (see below the contribution by Hamre et al. in this article). In general, these complementary therapy systems are integrated with conventional medicine, representing a form of integrative and personalized health care [1].

WMS therapies often are multimodal in order to address both the typical as well as the individual presentation of the disease, to address different conditions of the patient presumed to be connected with the disease, and also to strengthen his or her salutogenetic potentials. Thus, multimodal interventions often intend to support each other’s working principle. Frequently, the treatments are delivered by cooperating providers (physicians, therapists, nurses, nutritionist, etc.), the delivery depending on characteristics and competence of the provider and the patient. Many of the interventions are to be flexibly and individually tailored. Due to these characteristics, WMSs present challenges for the scientific and medical comprehension and evaluation. The traditional research model (1 trial for 1 intervention in 1 disease) does not suffice due to a variety of reasons, particularly as it does not account for the system synergies and patient centeredness. It would also produce an unsurmountable number of trials (e.g., 1 WMS with 1,000 remedies, 50 potential indications each, would require 50,000 trials, necessitating millions of study patients, billions of Euros, without addressing multimodal and individualized application). Research strategies have been proposed to adequately evaluate WMSs and address their complexity, the system aspects, and the patient centeredness [2]. Whole-system research assumes that in a system the whole is more than the parts, producing emergent effectiveness. It is crucial to study the intact, whole, and complex system, including the synergies of multimodal treatments, the system context, the patientprovider relationship, and the treatment individualizations (system research is equally pursued for complex interventions in conventional medicine, such as stroke care or diabetes care). In further steps, exemplary individual treatments are to be investigated in more detail and depth, using modern clinical and preclinical re-