Patients
A total of 2,055 patients suffering from at least one chief complaint (acute runny nose, sore throat, ear pain, sinus pain or cough) were enrolled in the study and given either homeopathic (H: n = 1,220) or conventional treatment (C: n = 829) (Figure 1). Six patients did not receive any treatment and were excluded from further analysis. All patients from the USA and Spain (H: n = 216; C: n = 29) were excluded since telephone interviews were not performed according to the study protocol. For another 227 patients no follow-up data were available because either interviews could not be carried out or the patient withdrew from the study. Data of 1577 patients with at least one follow-up contact were evaluated (full-set analysis), 857 patients in the homeopathy group and 720 patients in the conventional treatment group. For 1116 patients (H: n = 576; C: n = 540) follow-up data on day 14 were documented, being the per-protocol set (Figure 1).
Upon enrolment in the study, patients, or the patients' legal guardians were asked for their treatment preference. In the homeopathy group, 81% of patients had a preference for homeopathy, 18% had no treatment preference. In the conventional group, 55% of the patients' preferred conventional treatment, 2% homeopathy and 43% had no treatment preference. Patients at mixed centres were additionally asked whether they would agree to be randomized if the choice of treatment was made randomly. With 68.1%, the majority of patients in the homeopathy group refused to be randomized, 30.6% had no problem with randomisation and in 1.3% no remark was given. In the conventional group willingness and unwillingness to be randomized were equally distributed (51.9% yes, 47.9% no, 0.1% no remark).
Baseline characteristics
Demographic data of children (1. The proportion of children under 18 years was 47% of patients receiving homeopathic compared to 35% receiving conventional treatment. Within this subpopulation the average age and Body Mass Index (BMI) differed significantly between both treatment groups. In adults, the distribution of males and females, average age and BMI differed significantly between the homeopathic and conventional group.
As shown in Table 2, cough was the most frequently reported chief complaint in children, followed by sore throat and ear pain. In adults sore throat was the most frequent, followed by cough and runny nose. The overall distribution of the five chief complaints in children was comparable in both treatment groups, but differed significantly in adults (p = 0.0026, Chi-square test). The mean severity score differed significantly at baseline for 2 out of 5 chief complaints, both in children and adults (Table 2).
With regard to the diagnosis of the chief complaints, in children otitis media was most frequently diagnosed (H: 18.9%; C: 13.5%) followed by bronchitis (H: 16.7%; C: 10.7%) and laryngitis (H: 12.3%; C: 12.7%). In adults, pharyngitis (H: 23.1%; C: 14.7%), bronchitis (H: 11.5%; C: 17.1%) and tonsillitis (H: 13.9%; C: 8.9%) were most frequently diagnosed. In adults, no significant differences were observed with respect to concomitant medical problems (H: 34.2%; C: 36.6%) or concomitant medication (H: 20.7%; C: 20.1%). In the homeopathic group 21.6% of the children had concomitant medical problems versus 13.5% in conventional group (p = 0.0098; Fisher's exact test). The proportion of children receiving concomitant medication was higher in the homeopathic group (9.1%) than in the conventional group (6.7%) as well but did not reach a statistical significant level (p = 0.3098; Fisher's exact test).
Medication
A total of 62 different homeopathic remedies were prescribed primarily on an individual basis. The top 10 (Table 3) of the most frequently prescribed homeopathic remedies included typical 'acute' remedies and accounted for about 60% of the prescriptions. In the conventional group 190 different medications were prescribed. Most of them were antibiotics followed by nasal preparations and analgesics (Table 3).
Treatment outcome
The primary outcome criterion, defined as the percentage of patients with complete recovery or major improvement after 14 days, was first calculated for the total patient population. The one-sided test of the full-set analysis showed non-inferiority of homeopathic in comparison with conventional treatment (H: 86.9%; C: 86.0%; p = 0.0003). These results were confirmed by the analysis on the per-protocol set (including all patients with data at day 14) since similar response rates were obtained in both treatment groups (H: 87.7%; C: 86.9%; p = 0.0019).
The response rates at various time points in children and adults are shown in Figure 2. The primary outcome criterion (response rate at day 14) in children was 88.5% after homeopathic and 84.5% after conventional treatment. In addition, response rates after 7 days (H: 68.8%; C: 64.3%) and 28 days (H: 93.1%; C: 92.5%) did not differ between both treatment groups either. In adults, the response rates after 7 days (H: 71.2%; C: 68.8%), 14 days (H: 85.6%; C: 86.6%, LOCF) and 28 days (H: 93.9%; C: 95.9%; LOCF) of treatment were not significantly different as well.
Since the majority of patients (> 84%) were fully recovered or major improved after 14 days of treatment, it was of relevance to look at outcome differences within the first 7 days. As shown in Figure 3, the percentage of children experiencing a first improvement at different time points within the first week of treatment was significantly higher in the homeopathy group compared to the conventional group (p = 0.0488). For adults, a similar significant difference in favour of homeopathy (p = 0.0001) was observed.
Additional analysis on the primary outcome criterion in order to correct for demographic differences at baseline was carried out (Figure 4). The unadjusted odds ratio (OR) of the primary outcome criterion was 1.40 (0.89–2.22) for children and 0.92 (0.63–1.34) for adults. In the subgroup of children, adjustments for age, mean severity and concomitant medical problems had little effect on the OR. The unadjusted OR for the Body-Mass-Index was 1.92 (1.03–3.60) and the only one showing a significant difference in favour of homeopathy. Adjustment for BMI differences between both treatment groups at baseline minimally reduced the OR to 1.89 (1.00–3.57). In adults, individual adjustments for all variables had little to no effect on the OR of the primary outcome criterion (Figure 4).
Another outcome measure was the occurrence of adverse drug reactions. The percentage of children experiencing a suspected adverse drug reaction was not significantly different in both groups (H: 2.0%; C: 2.4%, p = 0.7838, Fisher's exact test). In adults, the number of suspected adverse drug reactions was significantly higher after conventional than after homeopathic treatment (C: 7.6%; H: 3.1%; p = 0.0032, Fisher's exact test). Both in children and adults, the suspected adverse drug reactions occurred predominantly in the body as a whole (upon homeopathic treatment) or in the gastro-intestinal system (upon conventional treatment).
In addition, patients' satisfaction with treatment and healthcare provider was evaluated. Almost all patients in both treatment groups were either satisfied or very satisfied with the treatment after 28 days (children: 95% H; 93% C, adults: 91% H; 95% C). A very high percentage of children (H: 98%; C: 95%) and adults (H: 97%; C: 97%) were either satisfied or very satisfied with the healthcare provider.
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