ARTICLE IN PRESS

SYSTEMATIC REVIEW

Homeopathic Preparations for Preventing and

Treating Acute Upper Respiratory Tract
Infections in Children: A Systematic Review and
Meta-Analysis
David King, MBBS, MPH, FRACGP; Kate Hawke, BSc, MBBS;
Treasure M. McGuire, PhD, BPharm, BSc, GradDipClinHospPharm, GCHEd;
Mieke van Driel, MD, MSc, PhD, FRACGP
From the Primary Care Clinical Unit, Faculty of Medicine, The University of Queensland, Royal Brisbane & Women’s Hospital (D King and
M van Driel), Brisbane, Queensland, Australia; Princess Alexandra-Southside Clinical Unit, School of Clinical Medicine, Faculty of Medicine,
The University of Queensland, Translational Research Institute, Princess Alexandra Hospital (K Hawke), Woolloongabba, Queensland,
Australia; School of Pharmacy, The University of Queensland (TM McGuire), Woolloongabba, Queensland, Australia; Mater Pharmacy,
Mater Health (TM McGuire), South Brisbane, Queensland, Australia; and Faculty of Health Sciences and Medicine, Bond University
(TM McGuire), Robina, Queensland, Australia
The authors have no conflicts of interest to disclose.
Systematic Review Registration Number: CD005974.
Address correspondence to David King, MBBS, MPH, FRACGP, Primary Care Clinical Unit, Faculty of Medicine, The University of Queensland,
Royal Brisbane & Womens Hospital, Level 8, Health Science Building, Brisbane 4029, QLD, Australia (e-mail: d.king@uq.edu.au).
Received for publication November 1, 2019; accepted July 17, 2020.

TAGEDPABSTRACT
BACKGROUND: Acute upper respiratory tract infections (ARTIs)
are common and mostly self-limiting. A range of treatments
are used with the aim to cure or treat symptoms, including
widespread use of homeopathic treatments.
OBJECTIVE: To undertake a systematic review and meta-anal-
ysis of trials with the highest level of evidence, to establish the
benefits and risks for oral homeopathic remedies used to treat
and prevent ARTIs in children.
DATA SOURCES: MEDLINE, Embase, CINAHL, AMED,
CAMbase, British Homeopathic Library, CENTRAL, WHO
ICTRP and ClinicalTrials.gov registers to March 2018.
STUDY ELIGIBILITY, PARTICIPANTS, AND INTERVENTIONS:
Double-blinded randomized trials in children, treated with
oral homeopathic remedies versus placebo or conventional
treatments for ARTI.
APPRAISAL AND SYNTHESIS METHODS: Studies were reviewed
in duplicate for inclusion, data extraction, and risk of bias.
Meta-analysis was performed on only 4 outcomes. Other
outcomes were reported narratively.
RESULTS: Eight studies (1562 children) were included. Four
studies examined treatment and 4 prevention of ARTIs. Four
studies involved homeopaths individualizing treatment versus
four with non-individualized treatments. Three studies had high
risk of bias in at least 1 domain. All studies with low risk of bias
showed no benefit from homeopathy; trials at uncertain and high
risk of bias reported beneficial effects. Two individualized treat-
ment studies (N = 155) did not show benefit on short-term or
long-term cure. Prevention trials showed no significant outcomes:
recurrence of ARTIs. No serious events were reported.
LIMITATIONS: Methodological inconsistencies and heterogeneity.
CONCLUSIONS: The effectiveness for homeopathic remedies
for childhood ARTIs is not supported in higher quality trials.
TAGEDPKEYWORDS: child; complementary therapies; homeopathy;
infant; meta-analysis; otitis media; preschool; respiratory tract
infections; systematic review
ACADEMIC PEDIATRICS 2020;XXX:1−10

TAGEDPWHAT THIS SYSTEMATIC REVIEW ADDS
 After removing the potential for the placebo effect
and measurement bias, meta-analysis failed to find
any evidence of effectiveness for homeopathic reme-
dies for either treatment or prevention of ARTIs in
children.
HOW TO USE THIS SYSTEMATIC REVIEW
 Explain to patients considering using homeopathy to
treat or prevent ARTIs in children that no evidence
of benefit exists in high quality clinical trials.
 Chance, bias and the placebo effect can explain the
stated benefits of homeopathy in low quality trials.

ACADEMIC PEDIATRICS Volume 000

Copyright © 2020 by Academic Pediatric Association 1 XX 2020
 ARTICLE IN PRESS
TAGEDEN2 KING ET AL
ACUTE RESPIRATORY TRACT INFECTION (ARTI) is a
major cause of morbidity and mortality worldwide. On
average, children have between 3 and 6 ARTIs annually,
and they are the most common cause of both illness and
mortality in children aged under 5 years outside the neona-
tal period.1 For the purposes of this review, we used
‘ARTI’ to represent both upper respiratory tract infec-
tions (URTIs) and lower respiratory tract infection.
Current conventional interventions to control ARTIs
are based on basic health care and environmental health,
such as the widespread use of vaccinations, simple case-
by-case management to diagnose and treat children
promptly using conventional pharmaceutical therapies,
and improvements in nutrition.2 Conventional medical
therapy for URTIs includes analgesics, decongestants,
antihistamines, expectorants, various types of antibiot-
ics and nutritional supplements.3
Complementary and alternative medicines are increas-
ingly popular.4 In addition, the overuse of antibiotics and
their lack of benefit against viral respiratory illnesses calls
for new approaches to treat common respiratory infec-
tions.5 Homeopathy, one of the many forms of comple-
mentary and alternative medicines, is based on treatments
using the principles of ‘similars’ and ‘dilutions’.6,7
Homeopathic remedies are produced by serial dilutions
with vigorous shaking between dilutions (potentization)
of a substance (such as an herb or trace element). This
process is thought to imprint information from the diluted
substance to the solvent.8 Homeopathic practitioners
claim benefit, especially for children, and in particular
when dealing with respiratory infections that account for
the most common cause of morbidity in children.9 One
of the basic tenets of homeopathic treatment is individu-
alization, whereby 2 or more patients with the same
medical diagnosis might receive different medicines,
based on the specific symptoms and duration of illness in
each patient.10 However, commercially available over-
the-counter remedies sold without an individualized
assessment or prescription are increasingly popular.
Whether or not homeopathy can be effective is a sub-
ject of debate, as actual doses of homeopathic drugs are
far below what is considered to have any medically quan-
tifiable effect. However, there are no established explana-
tory models for how highly diluted homeopathic remedies
might work. For this reason, homeopathy remains highly
controversial because the key concepts governing this
form of medicine are not consistent with the established
principles of conventional therapeutics.7
Most analyses of homeopathy studies conclude there is
little or no evidence to support homeopathy as an effective
treatment for any specific condition, based on flawed or
inadequate studies. However, some individual observa-
tional studies, randomized controlled trials, and laboratory
research have reported positive effects.11 Most reviews
failed to differentiate between the efficacy of nano-phar-
macological and behavioural components of homeopathic
care. Two recent systematic reviews examined separately
individualized and non-individualized placebo-controlled
trials.12,13 Both reviews found a small potential benefit
ACADEMIC PEDIATRICS
for homeopathy, but cautioned that low or unclear overall
quality of the evidence prompts caution in interpreting the
findings.
We reviewed the evidence for the effectiveness and
safety of oral homeopathic remedies for ARTIs in chil-
dren up to 16 years old, separately assessing individual-
ized homeopathy and non-individualized homeopathy.
We focused only on studies that were double-blind, as this
potentially removes biases that may account for the results
seen in earlier reviews.
TAGEDH1METHODSTAGEDEN
The review was conducted in accordance with the
recommendations of the Cochrane Collaboration.14
This review has been published as a Cochrane system-
atic review: Cochrane Database of Systematic Reviews
2018, Issue 9. Art. No.: CD005974.
TAGEDH2SEARCH METHODSTAGEDEN
We searched CENTRAL (2017, Issue 11), which contains
the Cochrane Acute Respiratory Infections Specialized Reg-
ister; MEDLINE (1946 to November 27, 2017); Embase
(2010 to November 27, 2017); CINAHL (1981 to November
27, 2017); AMED (1985 to December 2014); CAMbase
(searched March 29, 2018); British Homeopathic Library
(searched June 26, 2013—no longer operating). We used the
search strategy shown in Supplementary Figure 1. We also
searched the WHO ICTRP and ClinicalTrials.gov trials
registers (March 29, 2018), checked references, and
contacted study authors and content experts to identify
additional studies. This included searches of the NIHR Dis-
semination Centre (www.dc.nihr.ac.uk) for summaries of
new research (last searched March 29, 2018), the Database
of Abstracts of Reviews of Effects (DARE), and the NHS
Economic Evaluation Database (NHS EED).
TAGEDH2SELECTION CRITERIATAGEDEN
TAGEDPTYPES OF STUDIESTAGEDEN
Double-blind randomized controlled trials or double-
blind cluster-randomized controlled trials comparing oral
homeopathic remedies with placebo or conventional treat-
ments to prevent or treat ARTIs in children.
T YPES OF
AGEDPT PARTICIPANTSTAGEDEN
Children of either gender, aged up to 16 years with
ARTIs. We included children with other acute or chronic
comorbidities and who were not immune-deficient.
T YPES OF INTERVENTIONSTAGEDEN
AGEDPT
We included trials if one of the groups received any type
of oral homeopathic remedy (either ‘individualized’ fol-
lowing a homeopath consultation or ‘non-individualized’,
proprietary remedies without a consultation). Remedies
included either simple preparations involving single sub-
stances, or complex preparations involving more than 1
substance. The control group participants received either
standard treatments or identical oral placebo, usually the
biotherapy vehicle to ensure a similar colour and taste. We
 ARTICLE IN PRESS
TAGEDENACADEMIC PEDIATRICS HOMEOPATHY FOR CHILDHOOD RESPIRATORY INFECTIONS: A REVIEW
did not include herbal or other non-homeopathic medicinal
products available over the counter such as Echinacea.
TAGEDPSELECTION OF STUDIESTAGEDEN
Two review authors (D.K. and K.H.) independently
reviewed titles and abstracts to select potentially eligible
studies. Two review authors (K.H. and T.M.) indepen-
dently conducted a full text analysis to assess if these
studies met the eligibility criteria. Disagreements about
inclusion of one study were resolved first by discussion,
and supported by independent review by a third review
author (M.vD.).
T ATA
AGEDH2D
EXTRACTION AND MANAGEMENTTAGEDEN
Two review authors (K.H. and D.K. or T.M.) indepen-
dently extracted data from the included studies using a
standardized data collection form to minimize errors
and reduce potential bias. Discrepancies were rechecked
with a third reviewer (D.K. or T.M.) and discussed until
consensus was achieved.
T ISK OF
AGEDH2R BIAS IN INCLUDED STUDIESTAGEDEN
Two review authors (K.H. or T.M.) independently
assessed the risk of bias of each study using Cochrane’s
tool for assessing risk of bias. The tool assesses seven cri-
teria: random sequence generation; allocation conceal-
ment; blinding of participants and personnel; blinding of
outcome assessment; incomplete outcome data; selective
outcome reporting and other sources of bias. Each domain
is rated as low, high or unclear risk of bias. Disagreements
about inclusion of a study were resolved by discussion and
consensus, with any outstanding discrepancy arbitrated by
a third review author (D.K.).
T ATA
AGEDH2D ANALYSISTAGEDEN
TAGEDPOUTCOME DATATAGEDEN
The primary outcomes for which data were extracted
for the treatment studies were: 1) cure, defined as the
reduction or resolution of symptoms of ARTIs (fever/
body temperature, cough, pain, malaise/feeling of illness,
rhinorrhoea, etc.) in the short- (up to 14 days) and long-
term (up to 3 months); 2) disease severity as measured by
mean symptom scores. For the prevention studies primary
outcomes assessed were limited to disease severity and 3)
recurrence of ARTIs.
The following secondary outcomes were extracted, if
measured, for both treatment and prevention studies: 1)
duration of illness from time of randomization until reso-
lution of symptoms (measured longitudinally at intervals
of weeks, months or years); 2) need for hospitalization or
severe secondary illness; 3) days off school and days off
work for parents; 4) any adverse events; 5) quality of life
and 6) antibiotic use. We created a summary of findings
tables using the above outcomes.
T EASURES OF
AGEDPM TREATMENT EFFECTTAGEDEN
We expressed dichotomous data recording the primary
outcome of cure and secondary outcomes of adverse
3
events or requirement for parental absence from work as
odds ratios (OR) with 95% confidence intervals (CIs). We
expressed outcomes measured as continuous data (eg, for
number of antibiotic courses required) using the mean dif-
ference with standard deviations (SDs). We planned to
calculate the absolute risk reduction and numbers needed
to treat for an additional beneficial outcome if the results
were statistically significant. We contacted study authors
to request information on missing data wherever possible
and planned to perform an intention-to-treat analysis
TAGEDPDATA SYNTHESISTAGEDEN
We used Review Manager 5 to synthesize data.15 Pre-
vention and treatment studies were analysed separately.
We also analysed individualized homeopathy and
non-individualized homeopathy studies separately. In the
absence of heterogeneity we performed fixed-effect
meta-analysis. If important statistical heterogeneity was
detected, we applied a random-effects model. Where there
was obvious face value heterogeneity we did not pool data
but reported study results. We used the 5 Grade considera-
tions (study limitations, consistency of effect, impreci-
sion, indirectness and publication bias) to assess the
quality of a body of evidence as it relates to the studies
that contribute data to the meta-analyses for the pre-speci-
fied outcomes. For each of these Grade consideration limi-
tations present, we downgraded the strength of evidence
from ‘high quality’ another level: so one deficient consid-
eration was scored as ‘moderate quality’, 3 deficiencies
was graded ‘very low quality’. Sensitivity analysis was
not undertaken due to the small number of outcomes for
few included studies.
T SSESSMENT OF
AGEDPA HETEROGENEITYTAGEDEN
We assessed study heterogeneity in 2 ways. First, we
assessed face value heterogeneity by comparing study
populations, settings and methods. Second, the presence
of statistical heterogeneity was assessed by calculating
the chi-square test and I2 statistic.14 An I2 statistic >50%
was considered as important heterogeneity. Assessment of
reporting biases was not possible due to the small number
of included studies.
TAGEDH1RESULTSTAGEDEN
TAGEDH2LITERATURE SEARCHTAGEDEN
The results of the search are shown in Figure 1.
After de-duplication, we identified 1006 records. We
found no further records by checking reference lists of
included studies or by hand-searching. Searches of trial
registers identified 5 potential studies. We assessed
1006 records by title and abstract for inclusion and
excluded 979 records. Nine hundred seventy-seven
were either not trials, not related to oral homeopathic
remedies, or did not pertain to children. Two studies
(recommended by an expert in the field) were not
available at the time as full copy published papers and
were not included. The remaining 27 records were
obtained as full-text papers and checked against our
 ARTICLE IN PRESS
TAGEDEN4 KING ET AL
Figure 1. Flow chart of the literature search.
inclusion criteria. We excluded 19 papers that did not
meet inclusion criteria studies, leaving 8 studies for
inclusion in this review.
TAGEDH2STUDY CHARACTERISTICSTAGEDEN
The characteristics of the 4 prevention and the 4 treat-
ment studies are shown in Table 1.
T ETTINGS AND
AGEDPS PARTICIPANT CHARACTERISTICSAGEDNTE
The 8 included studies randomized a total of 1562 chil-
dren, from 0 to 12 years of age. Three studies originated
in European countries, 2 from the USA and 3 from other
continents. All included studies investigated URTIs.
Siqueira16 combined cold and flu diagnoses, so included
an unknown number of children with lower respiratory
tract infection.
Four studies16−19 examined the benefit of oral homeo-
pathic remedies for the prevention of ARTIs and the other
410,20−22measured aspects of cure from the treatment of a
recent ART infection. Four studies16,18,20,21 examined a
generic, commercially available product and the other
410,17,19,22 selected the remedy individually based on a
homeopath’s assessment of their illness and individual
characteristics.
ACADEMIC PEDIATRICS
TAGEDPRISK OF BIAS IN INDIVIDUAL STUDIESTAGEDEN
A ‘Risk of bias’ summary is shown in Figure 2. We
have adopted the Cochrane Collaboration method of
describing risk of bias based on the traffic light colour
code (red for high risk, yellow for uncertain and green
for low risk of bias). Two of the trials had concerns
about bias in the blinding process of participants and
researchers. Half of the included trials suffered from
concerns about selective reporting, particularly discrep-
ancies between predetermined outcomes and what was
reported in the results. Concerns about the high risk of
bias in the only trial that was not placebo controlled21
led to a lowering of the Grade of evidence for 2
combined outcomes that this study contributed to, as
reported in Table 4.
TAGEDH2OUTCOMESTAGEDEN
See Tables 2 to 4 for a summary of findings. There
was a lack of standardization of outcome assessment
among the included studies. Meta-analysis was there-
fore only able to be performed on four outcomes: short-
term and long term cure, recurrence of ARTIs and
antibiotic use. Due to the clinical heterogeneity of stud-
ies (regarding nature of illnesses, the time points of

Table 1. Characteristics of Included Studies
Reference Population
de Lange de 170 children with at least 3
Klerk 199416 URTIs in past year.
18 months−10 years
86/84 intervention vs control
The Netherlands
Jacobs 200110 N = 75 (36/39)
18 months−6 years
Clinical diagnosis of otitis
media
Private paediatric practice,
USA
Jacobs 201620 263 children aged 2−5 years
with URTI, duration
<7 days.
(128/133) from a primary
care practice, USA
Malapane 30 primary school students
201421 (15/15) who had a sore
throat or tonsillitis.
6−12 years, South Africa
Pedrero-Escalas 95 children (45/50) referred
201617 to tertiary hospital for otitis
media with effusion
2 months to 12 years, Spain
Intervention
Homeopathic treatment indi-
vidualized by homeopathic
practitioners: for long-term
wellness and acute
symptoms
Individualized remedies,
including Pulsatilla nigri-
cans, Chamomilla, Sulpur,
Calcerea carbonica
Commercial formulation
(Hyland’s Cold ‘n Cough 4
Kids), 5 mls up to 6 times
daily as needed
Commercial homeopathy
tablets (Tonzolyt)—2 tabs
4 times daily under tongue
3 months of 2 different rem-
edies daily, 5 granules
twice daily. Both groups
received daily aerosol
solution of Ambroxol,
saline and Budesonide
TAGEDENACADEMIC PEDIATRICS
Control Measurements Outcomes Results
Identical 1-year duration Mean daily symptom score, mean Mean daily symptom score 2.61
placebo Patient diaries, obser- percentage of days symptom- (placebo group) vs 2.21 (treatment
vations collected free, number of antibiotic group), difference 0.41; 95% CI 0.02
second weekly with courses, number of adenoidec- to 0.83). In both groups antibiotic use
telephone interviews tomies, and tonsillectomies over was greatly reduced compared with
1-year follow-up year before entering the trial. Propor-
tion having adenoidectomies lower in
the treatment group (16%, 8/50 vs
21%, 9/42). Proportion having tonsil-
lectomies same in both groups (5%).
Identical 6 weeks duration Number of treatment failures at Non-significant reduction in treatment
placebo Follow-up visits were 5 days, 2 and 6 weeks; diary failures at all time points with active
made by an otolaryn- symptom score during first 3 homoeopathy. Lower diary scores in
ARTICLE IN PRESS
gology resident days; middle ear effusion at 2 the homoeopathy group at all time
and 6 weeks. points. This was statistically signifi-
Outcomes provided by correspon- cant at 2 time points.
dence with author: cure rate;
daily symptom scores; adverse
HOMEOPATHY FOR CHILDHOOD RESPIRATORY INFECTIONS: A REVIEW
events
Identical Parents assessed cold Overall symptom severity at 7- to Data on 957 doses of study medication
placebo score at baseline, 10-day follow-up; change in in 154 children analysed. Improve-
twice daily on study severity 1 hour after dose for ments in sneezing, cough, and the
days 1−3, and at the first 10 doses; adverse events; composite cold score severity was
7- to 10-day follow- functional status; and non-spe- significantly greater at both 7 and
up cific symptoms 10 days in active vs placebo
recipients.
Identical 6-day duration Pain score (daily for 6 days) Significant improvement in treatment
placebo Unspecified timing and Pain on swallowing group vs placebo for the following
number of consulta- Referred ear pain symptoms: pain associated with ton-
tions for assessing Tonsil size sillitis, pain on swallowing, erythema
symptoms Erythema of pharynx and inflammation of the pharynx, and
Vital signs tonsil size.
FACES pain rating scale and
Symptom Grading Scale
Identical Study duration for 12 Presence of otitis media 61.9% of experimental group (EG)
placebo months with effusion cured compared with 56.8% of pla-
Occurrence of acute otitis media cebo group. Recurrence 4.8% in EG
Adverse events vs 11.4% in the placebo group. No
significant difference. Adverse events
distributed similarly, except in the case
of URTIs, less frequent in EG (3 of 46
vs 13 of 50; P = .009).
(Continued)
5

Table 1. (Continued)
Reference Population
Sinha 201222 80 children (40/40) with ear-
ache of <36-hour duration,
bulging tympanic mem-
brane.
2−6 years. Homeopathic
paediatric clinic, India
Siqueira 201618 600 children from low-
income families; InfluBio
(200), homeopathic com-
plex (200), placebo (200)
1−5 years
Brazil
Steinsbekk 199 children who had pre-
2005a19 sented to emergency
department with a diagno-
sis of URTI (97/102)
0−10 years
Norway
CI indicates confidence interval; URTI, upper respiratory tract infections; ARTIs, Acute upper respiratory tract infections; and MD, mean difference.
*Abstract states placebo was used but no details are provided in the paper. Comparator group received conventional treatment with analgesics & antipyretics, but as parents were blinded to allocation,
the homeopathy group could presumably receive these as well. Antibiotics if <50% improvement by day 3.22
Intervention
Individualized treatment by
homeopath
2 different homeopathic sol-
utions administered twice
daily for 30 days by child’s
tutor
Assignment to 1 of 3 reme-
dies based on child’s
symptoms.
2 pills twice weekly for 12
weeks
TAGEDEN6
Control Measurements Outcomes Results
Conventional Tympanic Membrane Change of symptoms (0−21 days) All patients cured by day 21, except 2
KING ET AL
treatment* Examination scale Time to cure (5%) lost to last 2 follow-ups in treat-
on days 3, 7, 10, and Examination signs ment group. By the 3rd day, 4 patients
21 Need for antibiotics were cured in homeopathy group but
only one in conventional group. Antibi-
otics were prescribed in 39 (97.5%) of
conventional group, no antibiotics
were required in the homeopathy
group.
Identical 1 year of follow-up Number of episodes of influenza 445 (74.17%) of 600 children completed
placebo and URTIs in 1 year (duration of the study. The number of ARTIs
days of illness and adverse detected in this trial was low. Number
events, neither reported in the of ARTIs in 12 months (0.40 pooled
ARTICLE IN PRESS
publication) homeopathy groups and 1.07 in pla-
cebo group (MD 0.67, 95% CI 0.69
to 0.25)
Identical Daily symptom diaries Median daily symptom score, No difference in predefined primary out-
placebo days with URTI, antibiotic use, come between the two groups
analgesic use, days off work for (P = .733). Median URTI scores over
parents, adverse events 12 weeks in the homeopathic medi-
cine group were 26.0 (95% CI 16.3
−43.7) and for placebo 25.0 (95% CI
14.2−38.4). No statistical difference
between groups in median number of
days with URTI symptoms or use of
conventional medication/care.
ACADEMIC PEDIATRICS
 ARTICLE IN PRESS
TAGEDENACADEMIC PEDIATRICS
Figure 2. Risk of bias assessment.
outcome measures, and the measurement scales of out-
come measures), quantitative meta-analyses must be
interpreted with caution.
TAGEDH2PREVENTION STUDIESTAGEDEN
Table 2 presents the outcome measures for 2 stud-
ies16,19 that examined the prevention of ARTIs using indi-
vidualized oral homeopathic remedies.
Both studies used different, non-validated scoring tools
for disease severity; therefore, we did not pool data for
this outcome. De Lange de Klerk16 reported mean daily
symptom scores on 4 dimensions with a scale of 0 to 56
and over 1 year. The mean score in the homeopathy group
was 2.21 (86 children) and 2.61 in the placebo group,
mean difference 0.41 (95% CI 0.02 to 0.83; P = .06),
which was not statistically or clinically significant. Steins-
bekk19 reported median daily symptom scores for 12
weeks (scale 0−11). The median additive scores across
the study period was 26 (homeopathic group, n = 97) ver-
sus 25 (placebo group n = 102), P = .73. The need for
antibiotics was the only secondary outcome from these
2 studies that could be combined with meta-analysis,
with a non-significant result (OR 0.79 [95% CI 0.35 to
1.76]).
HOMEOPATHY FOR CHILDHOOD RESPIRATORY INFECTIONS: A REVIEW 7
Recurrence of ARTI was the only outcome reported
(Table 3) by both non-individualized prevention trials17,18
that could be combined, with a non-significant result.
In Siqueira,18 the mean number of ARTI episodes in
12 months (calculated by the review authors) was 0.40
(SD 0.57) in the pooled homeopathy groups and 1.07 (SD
1.60) in the placebo group (mean difference 0.67, 95%
CI 0.69 to 0.25). Yet the paper reports on the number
who developed 3 or more ARTIs the first year post-inter-
vention; 46 of 151 (30.5%) in the placebo group versus
only 1 subject in the 2 homeopathic groups (P < .001).
This was not a pre-specified outcome measure. This study
had a 26% loss to follow-up rate. No other pre-specified
outcomes were reported by either study.
TAGEDH2TREATMENT STUDIESTAGEDEN
The outcomes for individualized and non-individual-
ized treatments studies are reported together in Table 4,
due to the small number of reported outcomes. Only
short-term cure (OR 1.31 [95% CI 0.09−19.54]), and
long-term cure (OR 0.99 [95% CI 0.10−9.67]) could be
combined in meta-analysis from 2 studies.10,22 It was not
possible to pool the results for disease severity due to dif-
ferent methods of reporting symptom scores between the
studies and significant clinical heterogeneity. The individ-
ualized homeopathy treatment studies10,22 did not find a
consistent effect: higher symptom scores were observed
in the placebo or conventional treatment groups at some
time points and lower scores were observed at other time
points. The non-individualized homeopathy studies did
not find a consistent effect: Jacobs (2016)20 found a differ-
ence in symptom scores in favour of the homeopathy
group at day 1 (among participants who returned symp-
tom diaries), but otherwise no significant effect of symp-
tom scores was seen. Malapane21 only found a significant
difference at day 6, but not days 1 to 5, in children with
viral sore throat treated with homeopathy.
We decided not to report on the need for antibiotics that
was reported in the Sinha22 study, due to concerns with
major protocol deviation. The methods described involved
antibiotic prescription for both homeopathy and conven-
tional treatment participants after 3 days if less than 50%
improvement had occurred. However, the mean symptom
score for homeopathy participants reduced by <50%
(from 14.28 to 8.18) at day 3, making it impossible that all
homeopathy group participants had a >50% improvement.
However, no homeopathy participants were commenced on
antibiotics, yet the authors assert ‘In Homeopathy group
antibiotics were not required for any case’, while 98% of the
control group was prescribed antibiotics.
TAGEDH1DISCUSSIONTAGEDEN
TAGEDH2SUMMARY OF EVIDENCETAGEDEN
Our review found only 8 trials that used a double-blind
randomized methodology investigating the effect of
homeopathic treatment in 1562 children with ARTIs.
Four trials focused on prevention and 4 on treatment. For
 ARTICLE IN PRESS
TAGEDEN8 KING ET AL ACADEMIC PEDIATRICS

Table 2. Summary of Findings: Homeopathic Remedies (Individualized Treatment) Compared to Placebo or Usual Care for Preventing Acute Respiratory Tract Infection (ARTI) in Children (De Lange de

Quality of the Evidence

*Effect size for the primary outcome “Disease severity” not estimable, as we could not pool the 2 studies,16,19 due to different, non-validated scoring tools used, assessing different symptom combina-
the primary outcome of cure, there was both clinical face
value and statistical heterogeneity between studies, with

Moderate

Moderate

Moderate
Moderate
(Grade)
important differences in definition of cure and disparate

Low
time points for outcome assessment. In treatment studies
short-term cure data showed little difference between
homeopathy and control groups for resolution of symp-
toms of otitis media.10,22 These cure rates are reflective of
the natural history of untreated otitis media.23 For pooled
short-term cure data, there was an OR of 1.31 (95% CI
0.09−19.54) favouring the placebo group. The wide CI
Number of Participants

reflects that 2 studies found opposite directions of effect

369 (2 studies16,19)
199 (1 study19)

199 (1 study19)

170 (1 study16)
199 (1 study19)
at these time points. Long-term cure data also revealed lit-
(Studies)

tle difference between the homeopathy and control

tions. Neither study found a clinically or statistically significant difference at the P = .05 level between homeopathy and placebo for daily URTI symptom scores.
groups, with 95% to 100% cure rates at day 21. For pooled
long-term cure data, there was an OR of 0.99 (95% CI
0.10−9.67), favouring the homeopathy group. Again, the
wide CI reflects that 2 studies found opposite directions of
effect at these time points.
None of the included studies assessed symptoms using
the same symptom score scales; therefore, it was not pos-
Relative Effect Odds

sible to pool data for this outcome. It is noteworthy that in

Ratio (95% CI)

(0.64−2.70)

(0.83−2.55)

(0.35−1.76)

(0.75−8.42)

many studies, low rates of return of symptom diaries

OR 1.31

OR 1.46

OR 0.79

OR 2.51

resulted in fewer children being evaluated for symptom

—

score outcomes compared to other outcomes. Most of the

time points reported by individual studies had non-signifi-
cant differences between means.
The prevention studies found either no difference or
non-significant differences in median daily symptom
scores. In summary, qualitative analysis of disease sever-
ity suggests there is no clear difference between placebo
Mean difference 0.19 lower

and homeopathy for disease severity. Both individualized

Homeopathy Group
Benefit/Risk in

and non-individualized studies showed varied results for

835 per 1000

495 per 1000

268 per 1000

93 per 1000

ARTI recurrence.
We could not pool data for most secondary outcome
measures due to scarcity of reporting. The 2 prevention
studies that reported on need for antibiotics found out-
comes with opposite directions of effect. This low-quality
evidence suggests that homeopathy has little impact on
the need for antibiotic usage. We assessed most outcomes
as providing low-quality evidence, with some outcomes
judged as providing very low-quality and a few moderate-
Mean 0.80 courses
Benefit/Risk in
Control Group

quality evidence. A number of studies failed to report on

794 per 1000

402 per 1000

317 per 1000

39 per 1000

adverse events.
CI indicates confidence interval; OR, odds ratio.

T IMITATIONS OF THE
AGEDH2L REVIEWTAGEDEN
There were several limitations related to the quality of
the available evidence, in particular some studies had
Klerke 199416 & Steinsbekk 200519)

methodological inconsistency, small sample sizes, high

Number of courses of antibiotics

attrition rates, failure to conduct intention-to-treat analy-

ses, selective reporting and apparent protocol deviations.
Days off work for parents

For example, Siqueira18 reported an outcome measure not

Outcomes*
Recurrence of ARTI

Need for antibiotics

pre-specified and had a 26% loss to follow-up rate. Note

also the low total number of ARTIs during the 12-month
Adverse events

follow-up period for both groups, compared to the year

before and to normal incidence of ARTI in childhood.
This suggests that the monthly assessments for URTI may
not have detected all cases. The use of different measures
 ARTICLE IN PRESS
TAGEDENACADEMIC PEDIATRICS HOMEOPATHY FOR CHILDHOOD RESPIRATORY INFECTIONS: A REVIEW 9

Table 3. Summary of Findings: Homeopathic Remedies (Non-Individualized Treatment) Compared to Placebo or Usual Care for Prevent-
ing Acute Respiratory Tract Infection (ARTI) in Children. (Pedrero-Escalas 201617 & Siqueira 201618)

Number of Quality of the

Benefit/Risk in Benefit/Risk in Relative Effect Odds Participants Evidence
Outcomes Control Group Homeopathy Group Ratio (95% CI) (Studies) (Grade)
Recurrence of ARTI 448 per 1000 481 per 1000 OR 1.14 695
(0.83−1.57) (2 studies17,18) Low*
Number of ARTIs The mean number of ARTIs Mean difference - 0.47 − 600
was 1.3 episodes episodes lower (1 study17) Moderate*
Adverse events 80 per 1000 22 per 1000 OR 0.26 95
(0.03−2.42) (1 study18) Very low†
CI indicates confidence interval; OR, odds ratio.
*Large loss to follow-up—likely to result in a biased assessment of the intervention effect.18
†Homeopathy was used for a different indication (Otitis media with effusion—a chronic condition not an ARTI) in this trial.17

Table 4. Homeopathic Medicinal Products Compared to Placebo or Usual Care for Treating Acute Respiratory Tract Infection in Children.
Individualized (Jacobs 200110 & Sinha 201222) and Non-Individualized (Jacobs 201620 & Malapane 201421) Studies Combined

Benefit/Risk in Benefit/Risk in Relative Effect Odds Number of Participants Quality of the Evidence
Outcomes*,† Control Group Homeopathy Group Ratio (95% CI) (Studies) (Grade)
Short-term cure 816 per 1000 773 per 1000 1.31 (0.09−19.54) 155 (2 studies10,22) Very low
Long-term cure 696 per 1000 698 per 1000 0.99 (0.10−9.67) 155 (2 studies10,22) Very low
Adverse events 41 per 1000 133 per 1000 OR 3.55 (1.27−9.96) 263 (1 study20) Low
CI indicates confidence interval; OR, odds ratio.
*Effect size for primary outcome “disease severity” not estimable as none of the studies assessed symptoms using the same symptom
scoring scales.
†Antibiotic use outcome cannot be interpreted as a valid study outcome due to apparent protocol deviations.22

and time points meant quantitative meta-analyses could
not be conducted for many outcomes.
There was significant clinical face value heterogeneity
among studies. Data that were amenable to quantitative
meta-analysis showed high statistical heterogeneity. ORs
were generally small with wide CIs, often in association
with contributing studies reporting opposite directions of
effect. The study protocol of Sinha22 involving different
treatment of groups raises concerns for allocation conceal-
ment and blinding, as the clinicians prescribing the antibi-
otic must have been aware of the allocations.
Potential biases in the review process were minimized
by following the Cochrane review process for selection of
included studies and extraction of data. Sources where
homeopathic studies are referenced are not as easily
accessible as mainstream therapies; therefore, it is possi-
ble that we missed assessing some studies that were poten-
tially eligible for inclusion. Our decision to combine the
only trial using conventional treatment as the control
group22 with one other using identical placebo10 for 2
meta-analysed outcomes was for pragmatic purposes, and
did not materially affect the conclusion our conclusions.
AGEDH2C WITH EXISTING LITERATURETAGEDEN
T OMPARISON
Our results are in agreement with other reviews of the
effectiveness of homeopathy. In March 2015, the Austra-
lian National Health and Medical Research Council pub-
lished an information paper that summarised the evidence
on the effectiveness of homeopathy for treating a wide
range of health conditions.24 The overview considered
57 systematic reviews and 176 individual studies that
compared homeopathy to placebo or other treatment for treat-
ing 61 health conditions.25 The reviewers identified 3 system-
atic reviews assessing the effectiveness of homeopathy for the
treatment of ARTI.26−28 Based on the body of evidence the
reviewers determined that homeopathy is not more effective
than placebo, and there is no reliable evidence that homeopa-
thy is as effective as the other therapies, for the treatment of
ARTIs. One of these reviews explored homeopathy for
childhood illnesses by categories,26 with the findings regard-
ing otitis media being similar to those of our review.
Another recent systematic review examining complemen-
tary and alternative medicine treatment (including homeopa-
thy) for otitis media,29 found that research into the effects of
homeopathic treatment for otitis media is scant and its qual-
ity limited, which is a similar finding to our Cochrane
Review. Another review found a large proportion of com-
pleted trials of homeopathy were not published within
2 years, leading to potential publication bias.30 Reporting
bias was also high as a quarter of the trials that had been
published had altered their primary endpoint.30
TAGEDH2IMPLICATIONS FOR FUTURE RESEARCHTAGEDEN
Funders and study investigators contemplating research of
oral homeopathic remedies to prevent or treat paediatric
ARTIs need to consider whether further research will
advance our knowledge, given the poor outcomes associated
with higher quality evidence, the uncertain mechanism of
action and lack of a measurable dose in such products. How-
ever, if undertaken, rigorous attention to study design is
required to reduce the methodological inconsistencies and
heterogeneity identified in this systematic review.
 ARTICLE IN PRESS
TAGEDEN10 KING ET AL
TAGEDH1CONCLUSIONSTAGEDEN
The 8 included studies that assessed a spectrum of oral
homeopathic medicinal products for preventing and treat-
ing ARTIs in children did not find any significant and con-
sistent benefit for cure, disease severity, recurrence of
ARTI or any of the secondary outcomes defined for this
review. We focused only on studies that were double-
blind, as this potentially removes biases inherent in studies
of lower quality of evidence. Half of included studies had
questions raised about reporting bias, which may explain
some of the reported positive benefit of homeopathy for a
handful of selected outcomes in some of the studies.
Homeopathy is generally considered safe and well tol-
erated, but the reporting of adverse events across trials
was poor and inconsistent, so this assertion is not sup-
ported by conclusive evidence. Overall, the findings of
this review do not support the use of homeopathic reme-
dies for ARTIs in children in clinical practice.
TAGEDH1ACKNOWLEDGMENTSTAGEDEN
We would like to acknowledge the contributions of Annika Mascare-
nhas and Jacqueline Seebold, who wrote the protocol under the guidance
and supervision of Mieke van Driel and Treasure McGuire, and Benja-
min Buffington who contributed to the Cochrane Review as an author.
TAGEDH1SUPPLEMENTARY DATATAGEDEN
Supplementary data related to this article can be found
online at https://doi.org/10.1016/j.acap.2020.07.016.
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