Overview and quality assessment of health economic evaluations for homeopathic therapy: an updated systematic review

Figures & data

Figure 1. PRISMA 2020 flow diagram of study selection.

Table 1. Data extraction from newly identified studies.

Author/year/country	Study population	Intervention and comparator	Technique and perspective	Health outcome measure	Scope of costs and currency/price year	Time horizon and discount rates	Main results^a	Sensitivity analysis
Ostermann et al [20]/2021/Germany	Hypothetical (simulated) population of children (age 6 to <12 years) and adolescents/adults with moderate, recurrent tonsillitis (≥3 acute throat infections in the prior 12 months/≥2 in each of the previous 2 years)	SilAtro-5–90 (complex homeopathic medicinal product) as adjuvant homeopathic therapy (3 times 8-week cycles of 1 (children)/2 (adults) tablets 3 times a day) to STC vs. STC, comprising self-care with antiseptics and/or anesthetics, plus discretionary use of antibiotics and/or analgesics/antipyretics for the treatment of acute throat infections	Cost-effectiveness analysis Model-based economic evaluation (4- state Markov model) Societal perspective	Number of acute throat infection episodes avoided	Drugs, GP consultations, surgery, travel time, productivity loss €/2019	2 years 3% discount for costs and outcomes	Adults/adolescents over 12 years: SilAtro-5–90 + STC: 317.94 €, 0.46 acute throat infections. STC alone: 241.16 €, 0.92 acute throat infections. ICER: 167.42 € per acute throat infection avoided. Children 6 to <12 years: SilAtro-5–90 + STC: 234.87 €, 0.46 acute throat infections. STC alone: 241.16 €, 0.92 acute throat infections. SilAtro-5–90 + STC dominated STC alone. Assessment summary: health outcomes +, costs +	Univariate sensitivity analysis with values changed by 50%, threshold sensitivity analysis and probabilistic sensitivity analysis Cost-effectiveness results were most sensitive to the probability of having at least 1 acute throat infection with STC, the number of previous acute throat infections, and the expected number of acute throat infections with STC. The probability that SilAtro-5–90 + STC is cost-effective was 65% for adults and adolescents and 71% for children at a threshold value of 1,000 € per acute throat infection avoided.
Kass et al [22]/2020/Germany	2,524 adult or adolescent patients with allergic rhinitis, asthma, atopic dermatitis, migraine/headache, or depression	Treatment given by certified homeopathic physicians acc. to ICCH (HOM, n = 1,543) vs. STC (n = 981, matched on diagnosis, sex, and age)	Cost-utility analysis Comparative, prospective, observational study Primary endpoint: healthcare payer perspective; secondary analysis: societal perspective	Quality-adjusted life years (QALYs) based on Short Form Health Survey (SF-12) data	Primary analysis: costs acc. to ICCH (HOM group), medication costs, outpatient care costs, inpatient costs, other costs (for home healthcare, patient transportation, remedies and aids) Secondary analysis: productivity loss €/year not specified (submitted 2020)	1 year Discounts not applicable	Adjusted (for age, sex, education, residential state, complementary medicine affiliation, per protocol initial anamnesis and baseline utility value) total costs and adjusted mean QALY were significantly higher in the HOM group for migraine/headache (∆ costs: +442.16 €, p < 0.001; ∆ QALY: +0.034, p < 0.001) and for depression (∆ costs: +439.59 €, p < 0.001; ∆ QALY: +0.035, p < 0.001). For atopic dermatitis, adjusted total costs were non-significantly higher for HOM (+145.76 €, p = 0.250) whereas adjusted mean QALY was significantly higher (+0.038, p < 0.001).HOM was cost effective for migraine/headache (ICER: 12,863 € per QALY [95% CI: 12,490–13,235 €], depression (ICER: 12,413 € [95% CI: 12,101–12,726 €], and atopic dermatitis (ICER: 3,930 € per QALY [95% CI: 3,589 –4,271 €]) (assumed cost-effective threshold: ICER < 50,000 € per QALY).Assessment summary: health outcomes +, costs +	Sensitivity analyses on the variances of diagnosis-specific cost-effectiveness differences were operationalized using nonparametric bootstrapping. Based on these bootstrap results, cost-effectiveness acceptance curves were calculated to show probabilities of cost-effectiveness according to different values of the willingness to pay for a QALY gained. For migraine/headache, depression and atopic dermatitis, probability of cost-effectiveness was 100% at a threshold value of 50,000 € per QALY.
Colombo et al/2018 [23]/Italy	455 adult (n = 286) and pediatric (n = 169) patients from a single center, with ≥3 episodes of respiratory tract infections during the year preceding study inclusion	Oscillococcinum (Anas barbariae hepatis et cordis extractum 200k, 1 dose a week for 8 months per year) in addition to STC, comprising conventional treatment with symptomatic drugs (n = 246) vs. STC alone (n = 209)	Cost-effectiveness analysis Retrospective, observational study Health care payer perspective	Average number of episodes of respiratory tract infections per patient per year	Costs for medication and consultations €/year not specified (published 2018)	1 to 10 years (mean ± SD: 5.3 ± 2.6 years) No discounts reported	All patients: 0.66 ± 0.67 infections/year and costs of 23.77 € ± 28.78 € for Oscillococcinum + STC; 1.16 ± 1.18 infections/year and costs of 52.27 € ± 71.84 € for STC. Pediatric patients: 0.93 ± 0.80 infections/year and costs of 21.70 € ± 17.74 € for Oscillococcinum + STC; 1.69 ± 1.06 infections/year and costs of 43.97 € ± 34.69 € for STC. Assessment summary: health outcomes +, costs -	None reported
Frei [24]/2015/Switzerland	43 patients ≥20 years of age, ≥3 concurrent diagnoses (‘multimorbid’); single practice	Homeopathic single remedies prescribed according to polarity analysis Comparators for health outcome: pre-post treatment comparison costs: hypothetical patients with identical diagnoses treated with STC	Cost-effectiveness analysis Prospective case series study Perspective not reported	Patients’ rating of symptoms intensity (0=absent to 10=maximal intensity) and healing (0 to 10=complete healing)	Costs for medication and consultations €/year not specified (submitted 2014)	1 year Discounts not applicable	43 of 50 patients (86%) achieved an improvement of symptoms ≥80% and were counted as responders while 6 patients stopped treatment for lack of efficacy or other reasons. 1 patient showed improvement <80% and was thus also counted as treatment failures. The total costs were 657 € for HOM vs. an estimated 1,619 € for STC for the same diagnoses, i. e. HOM reduced the treatment costs by 59%. Assessment summary: health outcomes +, costs -	None reported
Roll et al [25]/2013/Germany	135 children aged 1–14 years, treated by homeopathic GP and conventional GPs) with mild to moderate atopic eczema (3 out 4 Williams’ criteria, Three-Item severity score between 2 and 7) for ≥6 months	Classical HOM based on homeopathic history case taking and prescription of single remedies according to the simile law (n = 48, 10 homeopathic GPs) recommendation of emollient creams and corticosteroids as rescue medication only vs. STC acc. to German disease management guidelines (n = 87, 16 conventional GPs)	Cost-effectiveness analysis Non-randomized, prospective, multicenter, open, comparative observational study Societal perspective	Main outcome: SCORAD (SCORing Atopic Dermatitis) score (range: 0–103 points; lower score indicates better outcome)	Costs of drugs, hospitali-zation, GP consultations, medical aids and adjuvant therapies, productivity loss (of parents) €/year not specified (submitted 2012)	36 months for health outcomes, 6 months (months 31-36) for costs Discount: 3% for costs	HOM: SCORAD total score 13.7 [95% CI: 7.9–19.5] after 36 months, total costs 261.14 € [95% CI: 185.46–336.85 €]. STC: SCORAD total score 14.9 [95% CI: 10.4–19.4] after 36 months, total costs 120.26 € [95% CI: 64.63–175.83 €]. Assessment summary: health outcomes 0, costs +	Non-parametric bootstrapping adjusting for confounders. Results support those of the main analysis.
Basili et al [26]/2011/Italy	Stratified sample of 82 patients treated for the common cold, influenza or para-influenza, who asked for reimbursement of 2 or more prescriptions during the follow-up. Participants were taken from CASAGIT, an Italian health insurance company for journalists and their families.	HOM including purely homeopathic, anthroposophical, and homeotoxicological remedies vs. STC. Participants were free to choose HOM, STC, or a combination of both interchangingly during follow-up.	Cost-effectiveness analysis Prospective cohort study Perspective not reported	Time between consecutive prescriptions	Costs of drugs Currency not reported but assumed to be €/year not specified (submitted 2008)	40 months No discounts reported	Intervals between consecutive HOM prescriptions were on average shorter than for STC. On the other hand, patients who favor homeopathy were at a reduced risk of re-prescriptions. Older patients required more frequent treatment while sex had no influence on treatment re-occurrence. Overall costs for HOM and STC were assessed to be similar for the indications studied (assessment based on intra-subject differences between HOM and STC presented graphically on the subject level). Assessment summary: health outcomes 0, costs 0	None reported

^aAll amounts from the original publication converted to € and a target price year of 2022. HOM: homeopathic treatment; STC: standard care (i.e. conventional medical care); ICER: Incremental cost-effectiveness ratio; QALY: Quality-adjusted life years; ICCH: German Integrated Care Contract ‘Homeopathy’ for the reimbursement of homeopathic treatments by statutory health insurance companies; GP: general practitioner;Assessment summary, HOM compared to applicable comparator: +: better health outcomes / higher costs; 0: similar health outcomes / similar costs; ‑: poorer health outcomes / lower costs.

Table 2. Data extraction of previously identified studies, updated and extended.

Author/year/country	Study population	Intervention and comparator	Technique and perspective	Health outcome measure	Scope of costs and currency/price year	Time horizon and discount rates	Main results^a	Sensitivity analysis
Kooreman and Baars [27]/2012/The Netherlands	Data of patients of a Dutch health insurance and contributed by 1,992 GPs, including 28 homeopathic GPs	HOM by specialized GP (n = 1,181) vs. STC by conventional GP (n = 151,952)	Cost-effectiveness analysis Retrospective insurer dataset-based economic evaluation Health care payer perspective	Mortality rate	Costs of consultations, hospital care, medication, and paramedic care €/year not specified (submitted 2010)	4 years (2006–2009) No discounts reported	Crude mortality rates were 3.8% and 2.6% for HOM and STC, respectively (p < 0.05). In a regression model adjusting for confounders, HOM showed a non-significant reduction of mortality rates as compared to STC. Quarterly costs were 554.80 € for HOM compared to 589.12 € for STC. Assessment summary: health outcomes 0, costs -	None reported
Thompson et al [28]/2011/UK	35 children, 7–14 years old, with asthma (≥step 2 of the BTG (British Thoracic Society Asthma Guidelines)) recruited from 2 secondary care respiratory hospital clinics	Individualized HOM + STC (n = 17) vs. STC alone (n = 18)	Cost-effectiveness analysis Pragmatic randomized, controlled study Societal perspective	Pediatric Asthma Quality of Life Questionnaire (PAQLQ), Asthma Control Questionnaire (ACQ), measures of morning and afternoon peak flow	Healthcare costs (primary care consultations, secondary care and ambulance services, medication); personal costs (travel, loss of earnings) £/year not specified (submitted 2010)	16 weeks Discounts not applicable	No evidence for differences between groups for asthma control (ACQ) and asthma quality of life (PAQLQ); no clinical meaningful differences for peak flow or any other outcome measure. Average healthcare costs: HOM 1,299.66 €, STC 448.02 €; personal costs: HOM 149.80 €, STC 31.90 € Assessment summary: health outcomes 0, costs +	None reported
Kneis and Gandjour [29]/2009/Germany	113 adult patients aged 18–59 years with acute maxillary sinusitis (AMS, confirmed by radiography with mucosal thickening >6 mm, air-fluid level or complete opacification on the most AMS-affected side), 6 ear-nose-throat clinics and outpatient departments	Complex HOM (Sinfrontal®, n = 57) vs. placebo (n = 56) for 22 days. Concomitant paracetamol and saline inhalations were allowed.	Cost-utility analysis Double-blind, randomized controlled trial Societal perspective	Quality-adjusted life years (QALYs) gained, based on EQ-5D questionnaire	Costs of drug and productivity loss €/2005	3 weeks (main analysis), observational 8 week follow-up Discounts not applicable	Main analysis: compared to placebo, Sinfrontal® led to cost savings of 358 €/patient (95% CI: 134; 563 €) Utility gained: Sinfrontal® 0.0410 QALYs, placebo 0.0323 QALYs, incremental utility 0.0087 QALYs (95% CI: 0.0052–0.0123). Follow-up results support the main analysis. Assessment summary: health outcomes +, costs -	One-way sensitivity analyses based on different healthcare outcomes and cost estimates. Sinfrontal® led to cost savings and utility gains in 4 out of 5 sensitivity analyses and dominated placebo in 99.8 to 100% of cases. Non consideration of indirect costs led to a 100% cost -effectiveness at a willingness to pay of 3,600 € per QALY gained.
Pomposelli et al [30]/2009/Italy	61 patients with type-2 diabetes mellitus and diabetic polyneuropathy, single clinic with 4 participating physicians	Individualized, classical HOM (>10 different homeopathic remedies) + STC (diet, insulin or oral hypoglycemic agent, physiotherapy; n = 32) vs. STC alone (n = 29)	Cost-effectiveness analysis Non-randomized, prospective, observational study Perspective not reported	Diabetic Neuropathy Symptom (DNS) score, SF-36 quality-of-life questionnaire	Costs of medication €/2003 and 2004 (2004 used for cost conversion)	12 months Discounts not applicable	The DNS improved from 1.40 ± 1.21 to 1.07 ± 1.25 points at month 6 (p = 0.016) and to 1.22 ± 1.27 points at month 12 (p = 0.146) for HOM + STC. For STC alone, the DNS improved from 1.26 ± 1.06 to 1.06 ± 1.15 points at month 6 (p = 0.350) and to 0.94 ± 1.21 points at month 12 (p = 0.182). Significant improvements in SF- 36 scales were observed for HOM + STC. First 6 months’ costs for STC were 159 ± 157 € at baseline and were reduced to 132 ± 89 € in the HOM + STC group (p = 0.078) but increased to 109 ± 82 € (starting from 96 ± 77 € at baseline) for STC alone (p = 0.139). During months 7–12, STC costs in the HOM + STC group tended to increase but remained below the baseline level whereas costs in the STC-only group were comparable to the first 6 months. No between-group test statistics were reported. Assessment summary: health outcomes +, costs 0	None reported
Witt et al [31]/2009/Germany	126 children aged 1-14 years with mild to moderate atopic eczema (duration of at least 6 months, fulfilling 3 of 4 Williams’ criteria, Three-Item Severity score between 2 and 7), 26 physicians	Individualized, classical, single-remedy HOM (41 different homeopathic remedies prescribed in total), emollient creams recommended, steroids as rescue therapy (n = 46, 10 physicians) vs. STC acc. to German disease management guidelines (n = 80, 16 physicians)	Cost-effectiveness analysis Prospective, multicenter, comparative observational study Societal perspective	Main outcome: SCORAD (SCORing Atopic Dermatitis) score (range: 0–103 points; lower score indicates better outcome) Quality-of-life (QoL) questionnaires assessing children and their parents	Costs of consultations, hospital stays, medication, number of sick leave days, medical aids and adjuvant therapies €/year not specified (submitted 2009)	12 months Discounts not applicable	Baseline-adjusted SCORAD scores were 22.5 ± 3.0 for HOM vs. 18.2 ± 2.3 for STC at month 6 (p = 0.290) and 17.4 ± 3.0 for HOM and 17.3 ± 2.3 for STC at month 12 (p = 0.974). QoL results in both groups were similar. Average 6 months costs were 1,162 € (95% CI: 813–1,512 €) vs 639 € (95% CI: 344–935 €) for HOM and STC, respectively (p = 0.026) and 12-month costs were 1,895 € (95% CI: 1,489–2,300 €) vs. 896 € (95% CI: 528–1,265 €) for HOM and STC, respectively (p = 0.001). Main cost drivers were consultations. Assessment summary: health outcomes 0, costs +	Per-protocol analysis, different missing data imputation strategies, non-parametric bootstrapping (1,000 times) adjusting for confounders. Bootstrapping results for 6 month-period: 8.1% probability of superior cost-effectiveness for HOM. For 12-month period probability is 35%. ≥94% probability of additional costs in the HOM group.
Sevar [32]/2005/UK	455 consecutive patients aged 1 month to 87 years from a single homeopathic clinic, various chronic conditions	Individualized, classical, single-remedy HOM (187 different single remedies prescribed in total), comparison of pre- vs. post-treatment	Cost-effectiveness analysis Prospective observational study Perspective not reported	Glasgow Homoeopathic Hospital Outcome Scale (GHHOS), successfully treated patients (GHHOS ≥1)	Costs of drug (savings of conventional drugs) £/2003	5 years total observation period Mean treatment /follow-up per patient: 11 months No discounts reported	304 patients were successfully treated (66.8%). In adults, success rates were higher in females (71.3% of n = 296) than in males (58.5% of n = 159). Age was not systematic associated with response. 148 patients (32.5%) stopped or substantially reduced their conventional medication, leading to average conventional drug cost savings of 65.14 €/patient/year. Assessment summary: health outcomes +, costs ­-	None reported
Witt et al [33]/2005/Germany	120* adults with diagnosis of headache, lower back pain, depression, insomnia or sinusitis and 68* children aged 1–16 years with diagnosis of bronchial asthma, atopic dermatitis or allergic rhinitis, treated by 101 homeopathic GPs and 59 conventional GPs *number estimated from available data in publication	HOM administered by homeopathic GPs vs. STC administered by conventional GPs	Cost-effectiveness analysis Prospective, multicenter, parallel group, comparative cohort study Health care payer perspective	Severity of symptoms assessed by patients and physicians (VAS scale from 0 to 10); adults: quality of life (MOS-SF-36)	Costs of medication, consultations, physiotherapy, hospitalization, productivity loss €/year not specified (published 2005)	12 months Discounts not applicable	Self-rated symptom improvement under HOM was significantly more pronounced than for STC in both adults (p = 0.002) and children (p = 0.029). In the physicians’ symptom rating HOM was superior to STC in children (p < 0.001) but not in adults (p = 0.251). Improvements in the SF-36 physical component were more pronounced for HOM during the first 6 months (vs. STC: p = 0.016) but not during the second 6 months (p = 0.649). No significant differences for the mental component (p = 0.273 favoring HOM). No significant differences for over-all adjusted costs: adults HOM 2,802 €, STC 2,617 €, p = 0.856; children HOM 1,912 €, STC 1,022 €, p = 0.137 Assessment summary: health outcomes +, costs 0	None reported
Trichard et al [34]/2005/France	431 children aged 18 months to 4 years with recurrent, acute, viral rhinopharyngitis (≥5 episodes during last 6 months)	Patients having received at least 1 homeopathic drug and no antibiotic (n = 241, 73 homeopathic GPs) vs. patients with at least 1 antibiotic and no homeopathic drug (n = 190, 62 non-homeopathic GPs). Other drugs such as mucus liquifiers, trace elements, corticosteroids, or antipyretics were allowed in both groups	Cost-effectiveness analysis Pragmatic, prospective observational study Societal perspective, health care payer perspective, patient perspective	Number of episodes of acute rhinopharyngitis, complications linked to episodes of acute rhinopharyngitis, adverse events; quality-of-life questionnaire (Par-Ent-Qol®) for parents of children with ear, nose, and throat infections	Costs of medication, consultations, complementary tests, productivity loss (number and duration, not economically evaluated) €/2000	6 months Discounts not applicable	Compared to patients on antibiotics, those on HOM had fewer episodes of rhinopharyngitis (2.71 vs. 3.97 on average, p < 0.001), fewer complications (1.25 vs. 1.95 on average, p < 0.001), and their parents made more favorable global quality-of-life ratings (21.4 vs. 30.4 points, p < 0.001). Adverse event rates were similar (4.6% vs. 4.2%, p = 0.86). Average direct costs were comparable (HOM 235 €, antibiotics 233 €, p > 0.05), but HOM caused less social security expenses (119 € vs. 134 €, p < 0.05) and more out-of-the-pocket costs (116 € vs. 99 €, p < 0.05). Fewer parents in the HOM group had to take leave to care for their sick child (9.5% vs. 31.6%, p < 0.001). Assessment summary: health outcomes +, costs 0	None reported
Trichard et al [35]/2004/France	499 children aged 18 months to 4 years with recurrent, acute, viral rhinopharyngitis (≥5 episodes during last 6 months)	Treatment by specialized homeopathic physician (HOM; n = 268, 73 GPs) vs. treatment by non-homeopathic physician (STC; n = 231, 62 GPs). In both groups, physicians were free to prescribe any treatment according to their medical judgment	Cost-effectiveness analysis Pragmatic, prospective, observational study Societal perspective, health care payer perspective, patient perspective	Number of episodes of acute rhinopharyngitis, complications linked to episodes of acute rhinopharyngitis, adverse events; quality-of-life questionnaire (Par-Ent-Qol®) for parents of children with ear, nose, and throat infections	Costs of medication, consultations, complementary tests, productivity loss (number and duration, not economically evaluated) €/1999 and 2000 (2000 used for cost conversion)	6 months Discounts not applicable	Compared to patients on STC, those on HOM had fewer episodes of rhinopharyngitis (2.77 vs. 3.83 on average, p < 0.001), fewer complications (1.40 vs. 1.81 on average, p = 0.009), and their parents made more favorable global quality-of-life ratings (21.979 vs. 28.125 points, p = 0.010). Adverse event rates were similar (4.9% vs. 3.0%, p = 0.42). Compared to STC, HOM was associated with higher average costs to society (262 € vs. 223 €, p = 0.012) and to the patient (129 € vs. 93 €, p < 0.001) but with similar costs to social security (133 € vs. 130 €, p = 0.73). Fewer parents in the HOM group had to take leave to care for their sick child (13.1% vs. 27.4%, p = 0.001). Assessment summary: health outcomes +, costs +	None reported
Slade et al [36]/2004/UK	97 consecutive patients aged 0–90 years with various complaints, referred to 1 homeopathy service run by 1 GP	HOM by qualified practitioner (no details reported), pre- vs. post-treatment comparison	Cost-effectiveness analysis Prospective observational study Perspective not reported	Self-rated symptom severity, activity limitation, and wellbeing were scored using the MYMOP (Measure Yourself Medical Outcome Profile, 7-point scale) tool	Costs of savings on conventional drug £/year not specified (submitted 2003)	Health outcomes: Primary symptoms individual follow-up: mean duration of 134 (25–222) days. Secondary symptoms, activity limitation and wellbeing: mean duration of 126 (25–222), 141 (27–222) and 132 (25–222) days respectively Consultation/medication fees: 6/12 months before vs. 6/12 months after initial consultation Conventional medication costs savings: mean duration of 146 (19–222) days Discounts not applicable	Average improvements between 1.41 and 2.49 points for primary and secondary symptoms, ability to undertake activities, and well-being between initial visit and final assessment (p < 0.0001 for each item). The average number of consultations decreased from 6.33 during 6 months before inclusion to 5.26 during 6 months after inclusion (p = 0.004). 28 of 49 evaluable patients (57%) reduced or stopped the use of conventional medication after the start of HOM. For the 22 patients, for whom clear information was available, the annual cost saving was 4,582.81 €. Assessment summary: health outcomes +, costs -	None reported
Van Wassenhoven and Ives [37]/2004/Belgium	782 patients with mainly chronic diseases of all major organ systems; 80 specialized homeopathic practices	Classical HOM, including a total of 333 different single remedies, 21 of them accounted for about half of the prescriptions, pre- vs. post-treatment comparison	Cost-effectiveness analysis Prospective observational study Perspective not reported	Patients and physicians’ ratings of severity of physical and psychological symptoms; patient’s perceived effectiveness of current and previous treatment; satisfaction with current and previous treatment	Medication and consultation fees €/year not specified (submitted 2003)	Health outcomes estimated by patients and physicians on 1 specific day comparing before and after homeopathic treatment. Cost calculations based on a 1-year period Discounts not applicable	The proportion of patients with no appreciable symptom burden was 18.2% before and 64.2% after HOM for physical symptoms and 24.8% and 66.6% for psychological symptoms, respectively. 89% of patients stated that HOM had improved their physical condition. 95% of patients reported to be fairly or much satisfied with homeopathic treatment, compared to 18.9% for previous conventional treatment. Patients rated the effectiveness of their homeopathic treatment as very effective. Patients’ estimated average annual expenditure on drugs was 377 € during HOM, compared to 486 € before HOM. Homeopathic GPs’ (data from 47 GPs) expenditure on conventional drugs was on average about ^1/3 of the national GP average amongst them ^1/5 for antibiotics Assessment summary: health outcomes +, costs -	None reported
Paterson et al [38]/2003/UK	60 adult patients aged 29–84 years with dyspepsia (upper abdominal or retro sternal pain, discomfort, heartburn, nausea, vomiting ≥2 weeks), single clinic	Classical, individualized HOM by qualified GP (n = 21) vs. treatment by conventional GP (STC; n = 19) or acupuncture (n = 20)	Cost-effectiveness analysis Open, randomized clinical trial Health care payer perspective	Measure Yourself Medical Outcome Profile (MYMOP) and General Well-being Index (GWBI), SF-36 health survey	Costs for medication, consultations, referrals (National Health Service, NHS costs) £/1998 and 1999 (1999 used for cost conversion)	Health outcomes at 6 weeks (primary), 4 and 6 months (trial period) and 12-month follow-up (MYMOP only); costs during 6-month trial period and 12- month follow-up Discounts not applicable	MYMOP score mean changes at week 6 (primary outcome measure) were 0.44 ± 1.41 points for HOM and 0.53 ± 1.76 points for STC, mean difference −0.09 (95% CI: −1.19; 1.01) points. No significant differences at week 6 or at any other time point. Little change over time and no appreciable group differences for GWBI and SF36. Average total dyspepsia-related NHS primary care costs per patient for 6-month period: HOM 104.22 ± 132 €, STC 129 ± 148 €. Assessment summary: health outcomes 0, costs -	None reported
Frei and Thurneysen [39]/2001/Switzerland	230 patients between 0 and 16 years with acute otitis media (acute ear pain, hearing loss, signs of inflammation of the eardrum), single clinic	Classical, individualized HOM (n = 230, 27 different remedies given).Comparator for health outcome: placebo group; comparator for economic analysis: costs for STC	Cost-effectiveness analysis Prospective, observational study Perspective not reported	Proportions of patients free of pain at 6 h after start of HOM needing a 2^nd HOM and free of pain at 12 h after start of treatment	Costs for medication and consultations CHF/price year not specified (submitted 2000)	12 h Discounts not applicable	90 patients (39%) pain-free at 6 h after 1^st HOM, 76 patients (33%) pain-free after 12 h and 2^nd HOM; 64 patients (28%) not recovered within 12 h and received antibiotics. Based on literature comparison, improvement with HOM 2.4 times faster than with placebo. Total costs/patient 14% cheaper for HOM treatment than for STC (69 € vs. 80 €) Assessment summary: health outcomes +, costs -	None reported
Bachinger et al [40]/1996/Germany	114 patients with chronic arthritis of the knee with arthrosis therapeutics	HOM (n = 57): Zeel® comp. (homeopathic complex remedy) intra-articular injections (3 cycles of 10 injections for 5 weeks each) vs. STC (n = 57): hyaluronic acid intra-articular injection (3 cycles of 5 injection for 5 weeks each). In both groups: concomitant therapy: heat applications and movement therapy	Cost-effectiveness analysis Model-based economic evaluation (decision tree) Societal perspective	Treatment response, defined as pain reduction of 30% compared to baseline after 5 weeks (visual analogue scale)	Costs within the healthcare system, costs of intervention, travel, sick leave, adverse effects DM/year not specified (published 1996)	1 year Discounts not applicable	Average total direct + indirect costs, HOM: 788 € per patient, 1,728 € per successfully treated patient (26 out of 57); STC: 1,454 € per patient, 2,688 € per successfully treated patient (34 out of 57). Assessment summary: health outcomes 0, costs -	Probabilistic sensitivity analysis varying the probability of discontinuation of therapy Based on different proportions of premature treatment discontinuation the adjusted costs per successfully treated patient were always lower for HOM as compared to STC.
Feldhaus [41]/1993/Germany	Dental surgery patients with statutory insurance, single dental practice, sample size not reported	HOM: Arnica 12X before and after every planned surgical treatment and at least after every unplanned surgical treatment (1 tablet per day for 3 days before and up to 1 week after the procedure, other homeopathic single remedies as indicated), comparison of pre- vs. post-treatment STC for costs: averages from other dental practices acc. to reimbursement plan of statutory insurance	Cost-effectiveness analysis Retrospective analysis of health records Health care payer perspective	Frequency of post-operative treatments and sick certificates before and after the introduction of Arnica 12X	Costs related to postoperative follow-up treatment (medication, consultations, surgery) and due to productivity loss (number of sick certificates) DM/year not specified (originally published in German 1992)	Time horizon not reported (analysis of health records from 1983 to 1990) No discounts reported	After the introduction of HOM using Arnica 12X, the number of post-operative follow-up treatments decreased by an average of 54.7% compared to before the introduction, resulting in average annual savings of 934 € for the insurance company. The average number of sick certificates issued by the practice per quarter was reduced from 7.0 to 2.6 compared to pre-HOM. Assessment summary: health outcomes +, costs -	None reported

^aAll amounts from the original publication converted to € and a target price year of 2022. HOM: homeopathic treatment; STC: standard care (i.e. conventional medical care); QALY: Quality-adjusted life years; GP: general practitioner;Assessment summary, HOM compared to applicable comparator: +: better health outcomes / higher costs; 0: similar health outcomes / similar costs; ‑: poorer health outcomes / lower costs.

Figure 2. Summary of economic evaluation of homeopathic treatment vs. comparator.

*studies with health outcomes + and costs -: Colombo 2018, Frei 2015, Kneis 2009, Sevar 2005, Slade 2004, van Wassenhoven 2004, Frei 2001, Feldhaus 1996; studies with health outcomes + and costs 0: Pomposelli 2009, Witt 2005, Trichard 2005; studies with health outcomes 0 and costs -: Kooreman 2012, Paterson 2003, Bachinger 1996; studies with health outcomes + and costs +: Ostermann 2021, Kass 2020, Trichard 2004; studies with health outcomes 0 and costs 0: Basili 2011; studies with health outcomes 0 and costs +: Roll 2013, Thompson 2011, Witt 2009.

**studies with health outcomes + and costs -: Kneis 2009; studies with health outcomes + and costs +: Ostermann 2021, Kass 2020, Trichard 2004; studies with health outcomes 0 and costs +: Roll 2013, Witt 2009.

Read the detailed description of this figure

HOM: homeopathic treatment; +: better health outcomes / higher costs for HOM; 0: similar health outcomes / similar costs for HOM; ‑: poorer health outcomes / lower costs for HOM; green colored boxes: favors HOM; yellow colored boxes: needs further consideration, i.e. incremental analysis; red colored boxes: favors comparator.

Table 3. Quality assessment of included studies by means of the CHEC list.

		Ostermann 2021 [20]	Kass 2020 [22]	Colombo 2018 [23]	Frei 2015 [24]	Roll 2013 [25]	Kooreman 2012 [27]	Basili 2011 [26]	Thompson 2011 [28]	Kneis 2009 [29]	Pomposelli 2009 [30]	Witt 2009 [31]	Sevar 2005 [32]	Witt 2005 [33]	Trichard 2005 [34]	Trichard 2004 [35]	Slade 2004 [36]	v. Wassenhoven 2004 [37]	Paterson 2003 [38]	Frei 2001 [39]	Bachinger 1996 [40]	Feldhaus 1993 [41]
1	Study population	✓	✓	✓	⃠	✓	⃠	✓	✓	✓	✓	✓	⃠	✓	✓	✓	✓	⃠	✓	⃠	⃠	⃠
2	Competing alternatives	✓	⃠	⃠	⃠	⃠	⃠	⃠	⃠	✓	✓	✓	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	✓	⃠
3	Research question	✓	✓	✓	⃠	✓	⃠	⃠	✓	✓	⃠	✓	✓	✓	✓	✓	✓	⃠	✓	✓	✓	✓
4	Study design	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓
5	Time horizon	✓	✓	✓	✓	⃠	✓	✓	⃠	✓	⃠	✓	⃠	⃠	✓	✓	⃠	⃠	⃠	⃠	✓	⃠
6	Perspective	✓	⃠	✓	⃠	✓	⃠	⃠	✓	✓	⃠	✓	⃠	⃠	✓	✓	⃠	⃠	✓	⃠	✓	✓
7	Cost identification	✓	✓	⃠	⃠	✓	✓	⃠	✓	⃠	⃠	⃠	⃠	✓	✓	✓	⃠	⃠	⃠	⃠	✓	⃠
8	Cost measurement	✓	⃠	✓	⃠	⃠	⃠	⃠	⃠	✓	⃠	⃠	✓	⃠	⃠	⃠	⃠	⃠	✓	⃠	⃠	⃠
9	Cost valuation	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠
10	Outcome identification	✓	✓	✓	✓	✓	⃠	⃠	✓	✓	✓	✓	⃠	✓	✓	✓	⃠	⃠	✓	⃠	⃠	⃠
11	Outcome measurement	✓	✓	⃠	⃠	✓	⃠	⃠	✓	✓	✓	✓	⃠	✓	✓	✓	✓	⃠	✓	⃠	✓	⃠
12	Outcome valuation	n/a	✓	n/a	n/a	n/a	n/a	n/a	n/a	✓	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a	n/a
13	Incremental analysis	✓	✓	⃠	⃠	⃠	⃠	⃠	⃠	✓	⃠	✓	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠
14	Discounting	✓	n/a	⃠	n/a	⃠	⃠	⃠	n/a	n/a	n/a	n/a	⃠	n/a	n/a	n/a	n/a	⃠	n/a	⃠	n/a	⃠
15	Sensitivity analysis	✓	✓	⃠	⃠	✓	⃠	⃠	⃠	✓	⃠	✓	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	✓	⃠
16	Conclusions	✓	✓	✓	⃠	✓	✓	⃠	✓	⃠	⃠	✓	✓	✓	⃠	⃠	✓	✓	✓	⃠	✓	⃠
17	Generalizability	✓	✓	⃠	⃠	⃠	✓	✓	✓	✓	⃠	✓	✓	✓	✓	✓	⃠	✓	✓	⃠	✓	⃠
18	No conflict of interest	⃠	✓	✓	✓	✓	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	⃠	✓	⃠	⃠	⃠	⃠	⃠	⃠
19	Ethical/distributional issues	✓	⃠	✓	⃠	✓	⃠	⃠	⃠	⃠	⃠	✓	⃠	✓	✓	✓	⃠	⃠	⃠	⃠	⃠	⃠
	Number of ✓	16	13	10	4	11	5	4	9	13	5	13	5	9	10	11	5	3	9	2	10	3
	Proportion of ✓*	89%	72%	56%	24%	61%	28%	22%	53%	72%	29%	77%	28%	53%	59%	65%	29%	17%	53%	11%	59%	17%

✓: Sufficient attention is given to this aspect; ⃠: insufficient attention is given to this aspect; n/a = not applicable; *proportions based on number of quality criteria that apply.

Figure 3. Association between publication year (predictor) and CHEC quality score – linear regression analysis results (regression line and 95% confidence interval; data points are studies included in the analysis).

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