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.

BackgroundHomeopathic drug proving is a basic concept in homeopathy. This study aimed to record symptoms produced by a homeopathic drug compared with placebo.MethodsThis multicentre, randomised, double-blind, placebo-controlled phase 1 trial consisted of a 7-day run-in period, a 5-day intervention period and a 16-day post-intervention observation period. Subjects, investigators and statisticians were blinded for intervention groups and identity of the homeopathic drug. Subjects in the intervention group received Okoubaka aubrevillei (potency C12) and subjects in the placebo group received the optically identical sucrose globules. Dosage in both groups was five globules taken five times per day over a maximum period of 5 days. Subjects documented the symptoms they experienced in a semistructured online diary. The primary outcome parameter was the number of characteristic proving symptoms compared with placebo after a period of 3 weeks. Characteristic symptoms were categorised using content analysis. Secondary outcome parameters were the qualitative differences in profiles of characteristic and proving symptoms and the total number of all proving symptoms. The number of symptoms was quantitatively analysed on an intention-to-treat basis using analyses of covariance with the subject’s expectation and baseline values as covariates.ResultsThirty-one subjects were included (19 Okoubaka and 12 placebo). Data for 29 participants could be analysed. No significant differences in number of characteristic symptoms in both groups were observed between Okoubaka (mean ± standard deviation 5.4 ± 6.0) and placebo (4.9 ± 5.6). The odds ratio for observation of a characteristic symptom was 1.11 (95% confidence interval 0.4 to 3.05, P = 0.843). Females and subjects expecting a higher number of symptoms at baseline or feeling more sensitive to homeopathic drugs experienced more characteristic symptoms regardless of allocation. The qualitative analysis showed an inter-coder reliability of 0.69 (95% confidence interval 0.62 to 0.76). The qualitative comparison of symptom profiles was inconclusive.ConclusionsCombined results of qualitative and quantitative methods did not result in a significant difference of characteristic proving symptoms between O. aubrevillei C12 and placebo. The qualitative comparison of the symptom profiles leaves some open questions. The nocebo effect might be a plausible explanation for most of the phenomena observed in this trial.Trial registrationClinicalTrials.gov: NCT01061229

Homöopathische Arzneimittelprüfungen (HAMPs) werden seit über 200 Jahren von homöopathischen Ärzten durchgeführt und stellen eine traditionell in der homöopathischen Ärzteschaft verankerte Form des Arzneimittelselbstversuches dar. Nach Einschätzung durch die Bundesbehörden handelt es sich bei der homöopathischen Arzneimittelprüfung um eine klinische Prüfung Phase I, für die das Arzneimittelgesetz anzuwenden ist. Die Adaptation eines 200 Jahre alten, primär qualitativen Studiendesigns an das moderne Arzneimittelgesetz und die Good Clinical Practice Guidelines führt zu einer Reihe von Schwierigkeiten, die primär Verblindung, «informed consent» und die Einordnung unerwünschter Ereignisse betreffen. Heilpraktiker sind von der Leitung einer HAMP ausgeschlossen. Darüber hinaus steigen Kosten und organisatorischer Aufwand einer HAMP enorm. Der Artikel diskutiert Folgen und Konsequenzen für die Zukunft.

Zusammenfassung Die qualitativen Ergebnisse der hom?opathischen Arzneimittelpr?fung von Okoubaka aubrevillei wer- den im Vergleich zu Placebo und vorangegangenen Arzneimittelpr?fungen und klinischen Erfahrungen dargestellt und diskutiert.

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