Protocol for a phase 1 homeopathic drug proving trial

Abstract

BackgroundThis study protocol adapts the traditional homeopathic drug proving methodology to a modern clinical trial design.MethodMulti-centre, randomised, double-blind, placebo-controlled phase 1 trial with 30 healthy volunteers. The study consists of a seven day run-in period, a five day intervention period and a 16 day post-intervention observation period. Subjects, investigators and the statisticians are blinded from the allocation to the study arm and from the identity of the homeopathic drug. The intervention is a highly diluted homeopathic drug (potency C12 = 1024), Dose: 5 globules taken 5 times per day over a maximum period of 5 days. The placebo consists of an optically identical carrier substance (sucrose globules). Subjects document the symptoms they experience in a semi-structured online diary. The primary outcome parameter is the number of specific symptoms that characterise the intervention compared to the placebo after a period of three weeks. Secondary outcome parameters are qualitative differences in profiles of characteristic and proving symptoms and the total number of all proving symptoms. The number of symptoms will be quantitatively analysed on an intention-to-treat basis using ANCOVA with the subject's expectation and baseline values as covariates. Content analysis according to Mayring is adapted to suit the homeopathic qualitative analysis procedure.DiscussionHomeopathic drug proving trials using the terminology of clinical trials according GCP and fulfilling current requirements for research under the current drug regulations is feasible. However, within the current regulations, homeopathic drug proving trials are classified as phase 1 trials, although their aim is not to explore the safety and pharmacological dynamics of the drug, but rather to find clinical indications according to the theory of homeopathy. To avoid bias, it is necessary that neither the subjects nor the investigators know the identity of the drug. This requires a modification to the informed consent process and blinded study materials. Because it is impossible to distinguish between adverse events and proving symptoms, both must be documented together.Trial registrationClinicalTrials.gov identifier: NCT01061229.

A Minimum Protocol for Randomised Homeopathic Drug Proving as Basis for Further Research

“…Therefore, there is little consensus on the exact number of volunteers needed in the placebo arm in HDPs. Teut et al [9] published a HDP protocol with symmetrical arms (both n = 15). However, the main purpose of this HDP protocol was not to generate a characteristic symptom picture of the HMP, but to investigate a possible group difference between verum and placebo.…”

“…Most frequent design flaws described were absence of proper randomisation, blinding, placebo control and well-defined criteria for inclusion of symptoms [5]. Before and since this review [5], most studies on HDPs have focussed on interpretation and usefulness of the generated symptoms, rather than on improvement of the symptom collection process as such [6,7,8,9]. Walach [10] proposed to keep HDPs for collecting new symptoms epistemologically separated from those designed to quantitatively test hypotheses about the generation of new symptoms.…”

“…Some regulatory authorities consider HDPs as phase I clinical trials [9]. Table 1 summarises the similarities and differences between phase I clinical trials and HDPs [11].…”

Homeopathic drug proving of Okoubaka aubrevillei: a randomised placebo-controlled trial

“…Within this study we developed a study design methodology and a study protocol that fulfils the criteria of the Good Clinical Practice, Declaration of Helsinki and German drug regulations and also tests its applicability and feasibility in practice [12]. German drug regulation authorities classified this HDP as a phase 1 trial, which can be misleading and has been discussed as controversial [12].…”

“…German drug regulation authorities classified this HDP as a phase 1 trial, which can be misleading and has been discussed as controversial [12]. …”