Protocol for a phase 1 homeopathic drug proving trial

<p>Abstract</p> <p>Background</p> <p>This study protocol adapts the traditional homeopathic drug proving methodology to a modern clinical trial design.</p> <p>Method</p> <p>Multi-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.</p> <p>Discussion</p> <p>Homeopathic 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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT01061229.</p

a randomised placebo-controlled trial

Hintergrund: Homöopathische Arzneimittelprüfungen sind ein Grundpfeiler der Homöopathie. Ziel der Studie war es zu prüfen, ob die Einnahme einer homöopathischen Arznei arzneispezifische Symptome hervorruft, verglichen mit Placebo. Methoden: Die Studie wurde als randomisierte, doppelblinde, placebokontrollierte, multizentrische klinische Prüfung der Phase 1 durchgeführt. Sie bestand aus einer 1-wöchigen Run-in-Phase, einer 5-tägigen Interventions-Phase und 16-tägigen Nachbeobachtungs-Phase. Verblindet waren Probanden, Prüfärzte und der Statistiker in Bezug auf Allokation und Identität der Prüfarznei. Probanden in der Interventionsgruppe erhielten Okoubaka aubrevillei in der Potenz C12, Probanden in der Placebo-Gruppe erhielten optisch und geschmacklich identische Globuli aus Saccharose. Einnahmeschema war 5x5 Globuli pro Tag, 5 Tage lang. Erfassungsdokument war ein semistrukturiertes digitales online geführtes Symptomentagebuch, in welchem die Probanden ihre Symptome dokumentierten. Primärer Endpunkt war die Differenz der Anzahl charakteristischer Symptome, die unter Okoubaka aubrevillei und unter Placebo auftraten. Die Identifikation von charakteristischen Symptomen erfolgte mittels qualitativer Inhaltsanalyse. Sekundäre Endpunkte waren die qualitativen Unterschiede der Symptomenprofile von Verum und Placebo, sowie die Anzahl der Prüfsymptome insgesamt in beiden Gruppen. Für die quantitative Auswertung wurden die Anzahl der Symptome in einer Intention-to-treat-Analyse an ein univariates Kovarianzanalysemodell angelegt, in dem die Gruppe, die Erwartungshaltung und die Anzahl der Symptome in der Run-In-Phase als Einflussvariablen modelliert wurden. Ergebnis: 31 Probanden (19 Okoubaka und 12 Placebo) wurden eingeschlossen, davon wurden die Datensätze von 29 Probanden ausgewertet. Es konnte kein statistisch signifikanter Unterschied in der Anzahl charakteristischer Symptome zwischen der Interventionsgruppe (Mittelwert ± Standardabweichung 5,4 ± 6,0) und der Kontrollgruppe (Mittelwert ± Standardabweichung 4,9 ± 5,6) festgestellt werden. Der Gruppenunterschied für das Auftreten eines charakteristischen Symptoms betrug 1,11 (95% Konfidenzintervall: 0,40 bis 3,05, p=0,843). Frauen und Probanden, die sich vorab als sehr reaktionsfähig in Bezug auf Homöopathika eingestuft hatten, beschrieben deutlich mehr Symptome unabhängig ob sie der Verum- oder Placebo-Gruppe zugeteilt waren. Die Interrater- Reliabilität (Cohens Kappa) der qualitativen Analyse lag mit 0,69 knapp unterhalb des im Vorfeld als Gütekriterium festgelegten Wertes von 0,7 (95%-Konfidenzintervall: 0,62 bis 0,76). Der qualitative Vergleich der Symptomenprofile zeigte ebenfalls keinen eindeutigen Gruppenunterschied. Schlussfolgerung: Die Verbindung von qualitativen und quantitativen Methoden erbrachte keinen signifikanten Unterschied zwischen der Anzahl charakteristischer Symptome unter Verum bzw. Placebo. Nicht nur die Häufigkeit charakteristischer Symptome in der Placebogruppe, sondern auch das Auftreten arzneispezifischer Symptome unter Placebo wirft Fragen auf. Der Nocebo-Effekt könnte eine plausible Erklärung für einige Phänomene sein, die in dieser Studie beobachtet wurden.Background: Homeopathic drug proving is a basic concept in homeopathy. This study aimed to record symptoms produced by a homeopathic drug compared with placebo. Methods: This 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. Results: Thirty-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. Conclusions: Combined 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

Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the dsd-LIFE study

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Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the dsd-LIFE study

Objective To investigate fertility outcome in individuals with different forms of disorders of sex development (DSD), if assisted reproductive technology (ART) was used, and the patients' satisfaction with the information they had received. Design A cross-sectional multicenter study, dsd-LIFE. Setting Not applicable. Patient(s) A total of 1,040 patients aged ≥16 years with different DSD diagnoses participated. Intervention(s) A web-based questionnaire was filled out by all participants. The participants could chose to take part in somatic investigations including ultrasonography. Main Outcome Measure(s) Information on partner, number of children, ART, adoption and step-children, general health, presence of gonads and uterus, current education and economic situation, received information on fertility issues, and satisfaction with the information, was collected. Result(s) In the total cohort, mean age 32 years, 33% lived with a partner, but only 14% reported having at least one child including 7% with ART, 4% adopted. Only 3.5% of the total cohort had been able to reproduce without ART, most frequently women with congenital adrenal hyperplasia, and only 0.7% of participants with other diagnoses. Of the participants, 72% had received information on fertility, but 17% were not satisfied with the information. Conclusion(s) Fertility outcome is significantly reduced in all types of DSD; however, fertility potential should be assessed individually. The satisfaction with how fertility problems have been discussed can be improved. The care of patients with DSD is complex, should be individualized, and new treatment possibilities incorporated. A close collaboration in multidisciplinary teams is therefore essential to improve the situation for individuals with DSD

Andes Hantavirus Variant in Rodents, Southern Amazon Basin, Peru

We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted

Fertility outcome and information on fertility issues in individuals with different forms of disorders of sex development: findings from the dsd-LIFE study

International audienceOBJECTIVE:To investigate fertility outcome in individuals with different forms of disorders of sex development (DSD), if assisted reproductive technology (ART) was used, and the patients' satisfaction with the information they had received.DESIGN:A cross-sectional multicenter study, dsd-LIFE.SETTING:Not applicable.PATIENT(S):A total of 1,040 patients aged ≥16 years with different DSD diagnoses participated.INTERVENTION(S):A web-based questionnaire was filled out by all participants. The participants could chose to take part in somatic investigations including ultrasonography.MAIN OUTCOME MEASURE(S):Information on partner, number of children, ART, adoption and step-children, general health, presence of gonads and uterus, current education and economic situation, received information on fertility issues, and satisfaction with the information, was collected.RESULT(S):In the total cohort, mean age 32 years, 33% lived with a partner, but only 14% reported having at least one child including 7% with ART, 4% adopted. Only 3.5% of the total cohort had been able to reproduce without ART, most frequently women with congenital adrenal hyperplasia, and only 0.7% of participants with other diagnoses. Of the participants, 72% had received information on fertility, but 17% were not satisfied with the information.CONCLUSION(S):Fertility outcome is significantly reduced in all types of DSD; however, fertility potential should be assessed individually. The satisfaction with how fertility problems have been discussed can be improved. The care of patients with DSD is complex, should be individualized, and new treatment possibilities incorporated. A close collaboration in multidisciplinary teams is therefore essential to improve the situation for individuals with DSD

Sexuality in Adults with Differences/Disorders of Sex Development (DSD): Findings from the dsd-LIFE Study

For various reasons, sexuality of individuals with differences/disorders of sex development (DSD) may be affected. The aim of the study was to describe sexual activity, satisfaction with sex life, satisfaction with genital function, and sexual problems in people with different DSD conditions. Data were collected from 1,040 participants in Europe. Many people with a variety of DSD conditions do not appear to be satisfied with their sex life, experience a variety of sexual problems, and are less sexually active than the general population; therefore sexuality should be explicitly addressed in the care of people with DSD