The Effectiveness of
Homeopathy
Peter Fisher FRCP, FFHom
Clinical Director and
Director of Research
Royal London
Homoeopathic Hospital
Royal
London
Homoeopathic
Hospital
Royal London Homoeopathic
Hospital
Recent Lancet publication

110 clinical trials of homeopathy, 110 of allopathy


21 of homeopathy, 9 of conventional medicine were
‘higher quality’


said to be matched
quality assessed by internal validity only
8 homeopathy, 6 conventional were ‘larger, highquality’
Recent Lancet publication:
conclusions
• ‘there was weak evidence for a specific effect of
homoeopathic remedies, but strong evidence for specific
effects of conventional interventions. This finding is
compatible with the notion that the clinical effects of
homoeopathy are placebo effects’.
Shang A et al Are the clinical effects of homeopathy placebo effects?
Comparative study of placebo-controlled trials of homeopathy and allopathy.
Lancet 2005;366:726-32
Recent Lancet publication:
criticisms
• 8 anonymous clinical trials.
• Not cited, no information (diagnoses, number of patients etc)
• 93% excluded.
• No sensitivity analysis
• what is result for all 110 or 21 homeopathy trials of ‘higher
quality’?
• Only internal validity
• The extent to which a study measures what it purports to
measure
• External validity, the extent to which a study measures
something meaningful in the ‘real world’
Recent Lancet publication:
quality
•
Recent Lancet publication
• ‘8 trials of homoeopathic remedies in acute infections of the upper
respiratory tract…indicated a substantial beneficial effect…no
evidence that the effect differed between the trial…of higher quality
and the remaining trials. Such sensitivity analyses might suggest
that there is robust evidence that the treatment under investigation
works. However, the biases that are prevalent in these
publications…might promote the conclusion that the results cannot
be trusted.’
• In fact homeopathic trials are generally of higher quality than
matched trials of conventional medicine and show less
heterogeneity
High quality research?
‘Classical’ homeopathy for
asthma

93 children 5-15 years with ‘mild to
moderate’ asthma




randomised to individualised homeopathy or
placebo
double-blind, placebo controlled
treated up to 6 times in one year, 3 NMQPs
76 children follow up data.
High quality research?
results


No significant difference between verum and
placebo in QoL
Statistically significant difference in severity
scores



severity treatment effect –8.0 (95% CI –13.7 to –2.2 ,
p=0.01, ANCOVA)
Other subscales differences, consistently favouring
homeopathy
post-hoc analysis of time lost from school, favoured
homeopathy, not clear whether statistically significant
High quality research?
Authors’ conclusions
‘No evidence that homeopathic remedies
were superior to placebo in improving the
quality of life of children with mild to moderate
asthma as an adjunct to normal treatment in
primary care.’
White A et al. Individualised homeopathy as an adjunct in the treatment of
childhood asthma: a randomised placebo controlled trial. Thorax 2003;58:317-321
‘Classical’ homeopathy for
asthma: outcome measures

Main outcome measure active QoL scale of the
Childhood Asthma Questionnaire (CAQ)
White et al
n=93 (mean)
CAQA
35.2
(4-7 years)
range 10-40
CAQB
28.1
(8-11)
range 7-35
CAQC
29.4
(12-16)
range 8-36
Higher values indicate better quality of life
validation study
n=535 (median)i
Asthmatic
Non-asthmatic
34
34
28
29
No data
No data
French DJ, Christie MJ, Sowden AJ. The reproducibility of the childhood asthma questionnaires:
measures of quality of life for children with asthma aged 4–16 years. Qual Life Res 1994;3:215–
24.
High quality research?


This study could not possibly have had a positive
result because of a ‘ceiling’ effect in the main
outcome measure. The (secondary) outcome
measures which could improve, did.
patients had normal QoL at entry



the scale cannot discriminate between normal and
asthmatic children
in order to achieve ‘clinically significant’ improvement
they would have had to finish with QoL scores > 100%!
also had normal PEFR at entry
• High internal validity, no external validity
High quality research?
self treatment for prevention of
URTIs

251 children <10y treated with Calc carb,
Pulsatilla or Sulphur 30c, selected by
parents




Recruited after attending A&E department in
winter
By mail, no contact with researchers
Constitutional medicine selected by parents
from brief written description, most frequently
prescribed medicines by homeopaths
Trondheim, Norway
Quality research?
self treatment for prevention of
URTIs



No difference in symptom scores over 12
weeks
But was there anything to treat? Were
these children really ill?
NO! They had symptoms 9% of days
• Normal 0-4 year olds have symptoms 20% of
days, 5-9 year olds 11.4% of days
• De Lange 49% of days
Steinsbekk A et al Self-treatment with one of 3 self-selected ultramolecular
homeopathic medicines for the prevention of upper respiratory tract infections in
children. A double blind-randomized controlled trial. Br J Clin Pharm 2005 59:447-55
Clinical
trials of
homeopathy:
metanalysis 1

89 RCTs
Clinical
trials of
homeopathy:
metanalysis 2
Combined odds
ratio 2.45
 (CI 2.05-2.93)

Clinical
trials of
homeopathy:
subgroup
analysis

Odds ratios
1.66-5.04
Metanalysis of clinical trials of
homeopathy: publication bias



Funnel plot for
publication bias
Some bias
present
923 unreported
trials required
to make
conclusions
insignificant!
Metanalysis of clinical trials of
homeopathy: conclusions

Not compatible with hypothesis that effects of
homeopathy are all placebo effects

Not clearly efficacious for any single condition

Further research warranted
Linde K et al. Are the clinical effects of homeopathy placebo effects? A metaanalysis of placebo controlled trials. Lancet 1997;350:834-43
European Commission Homeopathic
Medicine Research Advisory Group

17 randomised, placebo-controlled clinical trials
predefined primary outcome in patients
 total 2617 patients


Statistical significance


p = 0.000036
Conclusion

evidence that homeopathic treatments are more effective
than placebo; problems with methodological quality
Cucherat M. et al. Evidence of clinical efficacy of homeopathy. A metaanalysis of clinical trials. Eur J Clin Pharmacol 2000;56:27-33
Homeopathy in life-threatening
sepsis in ICU

RCT in University of Vienna, Intensive Care Unit
• Individualised homeopathy v placebo, double-blind
• 70 patients with severe sepsis
•standard criteria, mortality ~ 50%
• Outcome survival at 30 & 180 d
• Baseline characteristics well matched:
•age, sex, BMI, prior conditions, APACHE II score, signs of
sepsis, number of organ failures, mechanical ventilation,
vasopressors, haemofiltration, laboratory parameters
Homeopathy in life-threatening
sepsis in ICU

Results
Day 30 survival homeopathy 81.8%, placebo 67.7%, p = 0.19. Day 180
survival homeopathy 75.8%, placebo 50.0%, p = 0.043.
 No adverse effects
 NNT = 4
 1 patient saved for every 4 treated
 recombinant activated protein C NNT = 16, bleeding event 1:665.


Conclusions

Homeopathy may be an useful addition with long-term benefit for severely
septic patients. A constraint is limited number of homeopaths.
Frass M et al. Adjunctive homeopathic treatment in patients with severe sepsis: a
randomized, double-blind, placebo-controlled trial in an intensive care unit. Homeopathy
2005:94;75–80
Homeopathy in children with
recurrent URTIs

RCT in Free University of Amsterdam paediatric
outpatients


March 1987-January 1992
175 children with recurrent URTIs
18 months to 10 years
 stratified for age
 90 boys 80 girls

Homeopathy in children with
recurrent URTIs
Placebo
Homeopathy
2.61
3
2.21
60
50
40
53
49
30
2
20
10
0
1
0
Mean % days symptom free
Mean daily symptom score
25
20
77
75
50
25
0
59
21
16
15
10
5
0
No of courses of antibiotics
No of adenoidectomies
de Lange de Klerk ES. Et LEffect of homoeopathic medicines on daily burden of symptoms
in children with recurrent upper respiratory tract infections. BMJ. 1994: 309;1329-32.
Homeopathy in children with
Acute Otitis Media

RCT: 75 children with confirmed AOM
18 months to 6 years
 Individualised homeopathic treatment


Results
Fewer treatment failures with active at 5d, 2 & 6w
 Better diary scores at 24h & 64h with active (p<0.05)

Jacobs J et al. Homeopathic treatment of acute otitis media in children: a preliminary
randomised placebo-controlled trial. Pediatr Infect Dis J 2001;20:177-183
Homeopathy in the ‘real world’:
averting antibiotics for acute otitis media

Observational study of homeopathy in primary care
230 consecutive consultations
 Homeopathic treatment, if not pain free in 6 h, 2nd
homeopathic medicine, if not pain free at 12h, antibiotic
 University Paediatric Clinic, Berne

Results
 39% pain free in 6h, further 33% at 12h

28% antibiotics
 Resolution considerably faster than in reported series


14% cost savings
Frei H, Thurneysen A. Homeopathy in acute otitis media in children: treatment
effect or spontaneous resolution? Br Hom J 2001;90:180-182
Homeopathy in the ‘real world’:
cost-effectiveness in recurrent URTIs
• ‘Antibiotic’ v ‘homeopathic’ strategy
Non-randomised, pragmatic cost-effectiveness study
 Children 18m-5y, ≥ 5 episodes/year
 French GPs, with and without ‘homeopathic orientation’
 529 recruited, 499 followed at 6m

231 children treated by 62 non-homeopathic GPs
 268 by 73 homeopathic GPs


Outcomes episodes of URTI, complications, side-effects,
quality of life (Par-Ent-Qol), direct and indirect medical costs,
parents time off work to care for sick children
Homeopathy in the ‘real world’:
cost-effectiveness in recurrent URTIs

Results

Homeopathic strategy superior:
medical effectiveness (p<0.001)
 complications (p<0.001)
 number of consultations (p<0.001)
 quality of life (p<0.001)
 (p<0.001)
 parental time off work (p<0.001)

• Equivalent direct medical costs
• Confounders include smoking & day care
Trichard M et al. Pharmacoeconomic comparison between homeopathic and
antibiotic treatment strategies in recurrent acute rhinopharyngitis in children.
Homeopathy 2005:94:3-9
Homeopathy in the ‘real world’:
multinational study in upper & lower
respiratory tract complaints
• Homeopathy v conventional medicine for respiratory &
ear complaints in primary care
500 consecutive cases of upper, lower respiratory tract and ear
complaints
 6 primary care sites, 4 countries


Results
281 homeopathic, 175 conventional treatments
 Equivalent severity (HCQ-5)
 Treatment response 83% homeopathy, 68% conventional
 Homeopathy fewer adverse effects, greater satisfaction

Riley D. Open label trial of homeopathy vs conventional medicine for respiratory and ear
complaints seen in primary carte settings. J Altern Complement Med 2001;7:149-159
Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care

Comparative cohort study
Selected chronic diagnoses
 Adults: headache, low back pain, depression, insomnia,
sinusitis
 Children: atopic asthma, dermatitis, rhinitis
 Homeopathic v conventional GPs in Germany


Outcomes at 6 & 12 months
Severity of symptoms (numerical scale 0-10)
 Patient
 Doctor
 Quality of life (SF-36)
 Cost
 Consultations, medication, physiotherapy, hospitalisation,
sick pay, medical devices/appliances
 Conventional and homeopathic medication

Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care

Results
101 homeopathic, 59 conventional GPs
 493 patients (315 adults, 178 children)
 Generally well-matched

Homeopathic adults better educated,
 Conventional children heavier use of medical services

90% returned 6 month data, 80% 12 month
 Economic data from Krankenkasse (38%)
 Homeopathic v conventional GPs in Germany

Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care
Adults:
Conv 5.9 → 4.4
Homp 5.7 → 3.2
P=0.002
Patient assessment of severity
(0-10, 10 = worst possible) adjusted for gender, age, educational level, symptom
duration and gender/age interaction
Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care
Children:
Conv 3.9 → 2.7
Homp 4.6 → 2.0
p<0.001
Physician assessment of severity
(0-10, 10 = worst possible) adjusted for gender, age, educational level, symptom
duration and gender/age interaction
Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care
MCS
p=0.273
PCS
1st 6m
p=0.0.016
2nd 6m
P=0.649
Quality of Life scores
SF-36 adjusted for gender, age, educational level, symptom duration and
gender/age interaction
Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care

Health economics
 Total adjusted costs
Adults homeopathic €2155, conventional €2013,
(p=0.856)
 Children homeopathic €1471, conventional €786
(p=0.137)


Medication
Adults homeopathic €270, conventional €639
(p=0.117)
 Children homeopathic €334 conventional €424
(p=0.637)

Homeopathy in the ‘real world’:
Effectiveness of homeopathy in routine care

Conclusion

Patients seeking homeopathic treatment had
better outcomes overall, compared to patients
on conventional treatment, for similar costs
Witt C et al. Outcome and costs of homeopathic and conventional treatment
startegies: a comparartive cohort study in patients with chronic disorders. Comp
Ther Med 2005:13;79-86
Homeopathy in the ‘real world’: PEK
Programm Evaluation Komplementärmedizin
(Complementary medicine evaluation programme)
• 1998 - 2005 Switzerland
• Efficacy, appropriateness, cost-effectiveness: homeopathy, anthroposophy,
neural therapy, phytotherapy, Traditional Chinese Medicine
• During evaluation covered by compulsory health insurance
• Literature analysis & empirical research
• Literature analysis.
• Meta-analysis (Shang)
• Review of 22 systematic reviews
• 10 homeopathy as system
• 7 single condition
• 3 specific homeopathic remedy (Arnica)
• 2 specific homeopathic remedy in defined condition
• 20/22 at least trend in favour of homeopathy, 5 clear efficacy
• On 3-point scale (probable – questionable – improbable), efficacy probable
Homeopathy in the ‘real world’: PEK
• Empirical
• Prospective practice evaluation, cost-effectiveness
evaluation, population survey, clinical survey
Patient profile
conventional
homeopathy (CAM)
number of patients
3,078
2,934
serious
10.1%
16.2%
moderately serious
52.7%
60.5%
chronic
41.9%
41.9%
comorbidity
59.4%
64.1%
Homeopathy in the ‘real world’: PEK
Results
conventional
homeopathy (CAM)
number of patients
3,078
2,934
satisfied with treatment
43.3%
52.3%
side-effects
15%
9.1%
referrals
9.7%
5.7%
costs of treatment
931 SFR
708 SFR (CAM)
costs after correction
709 SFR
661 SFR (CAM)
• Costs include consultations, medication, lab tests and physical therapy
• Exclude referral, hospitalisation, side-effects, time lost from work
• Corrected for age, sex, doctor and practice-variables, accidents and home visits
• Not corrected for chronicity, severity, co-morbidity
Homeopathy in the ‘real world’:
homeopathy and acupuncture in
general practice
• Descriptive study of effects and benefits of acupuncture and/or
homoeopathy,
• Over 900 homeopathy patients in Germany insured by
Innungskrankenkasse
• SF-36 quality-of-life questionnaire and absence from work
• Medium to large improvements in SF-36
• Evidence of subjective benefit may account for the increase
in demand for these treatments
• Especially chronically ill and dissatisfied with previous
conventional treatment
Güthlin C et al. Measuring the effects of acupuncture and homoeopathy in general
practice: An uncontrolled prospective documentation approach. BMC Public Health
2004;4:6
Homeopathy in general practice:
SF-36 scores over 30 months
Homeopathy in general practice:
SF-36 scores over 6 months
Quality of life
Baseline
6 months
Effect size (d)
Physical functioning
N = 359
mean = 84
N = 301
mean = 89
d = 0.24
Role physical
N = 359
mean = 62
N = 301
mean = 83*
d = 0.51
Bodily pain
N = 373
mean = 57
312
mean = 73*
d = 0.52
General health
N = 368
mean = 53
N = 305
mean = 68*
d = 0.79
Vitality
N = 376
mean = 48
N = 309
mean = 61*
d = 0.72
Social function
N = 378
mean = 72
N = 314
mean = 84*
d = 0.48
Role emotional
N = 356
mean = 73
N = 298
mean = 87*
d = 0.36
Mental health
N = 376
mean = 59
N = 312
mean = 69*
d = 0.56
* Clinically relevant (>=10 % improvement)
d effect size (Cohen), d < 0.3 small, d < 0.8 moderate > 0.8 high
Homeopathy in general practice:
absence from work
Start of homeopathic treatment
Oscillococcinum® in influenzalike syndromes:
Cochrane review

Anas barbariae hepar et cordis extractum (HPUS)
Hearts and livers of wild ducks(!)
 Wildfowl are vectors of flu

7 RCTs: 4 treatment, 3 prevention
 Reduces duration of disease
 Patients more likely to consider active treatment effective
 Not effective for prevention
 Promising results, more research required

Vickers A, Smith C. Homoeopathic Oscillococcinum for preventing and treating
influenza and influenza-like syndromes. (Cochrane review). Cochrane Library 2001:1
Isopathy for respiratory allergy:
meta-analysis
Isopathy = treatment of ‘same with same’ eg homeopathic
dilutions of pollen for hayfever
 4 RCTs

2 hayfever (mixed pollen 30c)
 1 asthma (individualised allergen, mostly house dust mite 30c)
 1 perennial rhinitis (individualised allergen, mostly house dust mite 30c)
 Total n=253


Highly statistically significant

P=0.0007, 95% CI 4.2-15.4
Reilly D et al Randomised controlled trial of homoeopathy versus placebo in perennial
allergic rhinitis with overview of four trial series. BMJ 2000; 321:471-6
Isopathy in respiratory allergy:
summary of results
Isopathy in perennial rhinitis:
change in nasal inspiratory peak
flow
P=0.0001 ‘comparable to steroids’
Meta-analysis of homeopathy for
childhood diarrhoea
Rhus toxicodendron in primary
Fibromyalgia

Double-blind, crossover RCT


'Double selection': 30 patients with
primary fibromyalgia and Rhus tox indicated


Rhus tox 6c, identical placebo 4 weeks each
~25% of Fibromyalgia patients
Precautions
tests for contaminants
 after entry no contact between prescriber & patient
 assessment and dispensing by blinded metrologist

Rhus tox in Fibromyalgia
Tender point count
p=0.007
15
10
5
0
initial
active
placebo
Fisher P et al Effect of homoeopathic treatment on fibrositis
(primary fibromyalgia) BMJ 1989 299 365-6
Homoeopathic v conventional
topical treatment in OA knee

172 patients with OA knee

radiographically confirmed

SRL gel v Piroxicam gel

Change in VAS
SRL mean -16.5mm
 Piroxicam mean - 8.1mm


SRL fewer adverse events
Piroxicam
(n=86)
SRL
(n=86)
Van Haselen R, Fisher P. A randomised controlled trial comparing topical Piroxicam gel with
a homeopathic gel in osteoarthritis of the knee. Rheumatology 2000;39:714-719
Motives for attending the Royal London
Homoeopathic Hospital
(925 responses from 493 patients)
Personal
preference
22%
Other treatment
ineffective
32%
Other
6%
Adverse effects
from other
treatment
14%
Concern about
adverse effects
26%
Sharples F, Van Haselen R, Fisher P. NHS patients’ perspective
on complementary medicine. Comp Ther Med 2003;11:243-248.
Safety of homeopathy
• World literature search 1975-1995
• Enquiries with regulatory agencies (MCA and
FDA), companies
• Incidence of adverse effects very low
• mostly minor and transient
• under-reporting
• mistaken identity (herbal, not homeopathic)
Safety of homeopathy:
conclusions
• Generally very safe
• Main risks are indirect
• due to practitioner, not medicine
Dantas F, Rampes H. Do homeopathic medicines provoke adverse effects? A
systematic review. Br Hom J 2000;89:S35-38
The 'Benveniste Affair'
A slight disagreement...
Davenas E, Beauvais F, Amara J et al. Human basophil degranulation triggered by
very dilute antiserum against IgE. Nature 1988; 333: 816-818.
Hirst SJ, Hayes MA, Burridge J, Pearce FL, Foreman JC. Human basophil degranulation is
not triggered by very diluteantiserum against IgE. Nature 1993; 366: 525-7
Inhibition of basophil activation by
ultramolecular dilutions of Histamine


Multi-centre, peer-reviewed full paper on inhibition of
activation of basophils by ultramolecular dilutions of
Histamine
Blinded, uses multiple methods to corroborate
Belon P et al. Histamine dilutions modulate basophil activity. Inlamm Res
2004; 53:181-8
Human Basophil Degranulation
Test
Human Basophil Degranulation Test (HBDT) is wellestablished in-vitro model of allergy, described in
1960’s
 Basophils are circulating mast cells
 Contain basophilic granules in cytoplasm
 Granules stain blue with Alcian Blue
 Contain histamine and other immune mediators

Human Basophil Degranulation
Test
Degranulation is a manifestation of basophil
activation
 Activation is triggered by cross-linking of IgE on
surface, either by specific antigens in sensitive
individuals or by anti-IgE (IgG)
 Activation is inhibited by Histamine in supernatant (ie
negative feedback)
 Basophils also express CD63 antigen on their
surface when activated

Inhibition of activation of basophils by
ultramolecular dilutions of Histamine
4 labs (Paris, Utrecht, Belfast, Florence)
 Healthy donors


either sex basophils respond to anti-IgE, no medication
previous 4 weeks
Independent statistician (Brussels)
-30 -10-38M (15-19c), vortexed
 Histamine 10
 Main experiment inhibition of degranulation (Alcian
Blue) - all labs

Inhibition of degranulation with
histamine 15-19c
Paris
Utrecht
Belfast
Florence
Inhibition of degranulation (Alcian blue) with different concentrations
of anti-IgE and histamine 15-19c (pooled p<0.0001)
Effect of H2 antagonists on
activation
Ranitidine (10-4M) and Cimetidine (10-5M) partly block effects of
dilutions of histamine (Paris & Florence)
Inhibition of activation of basophils by
ultramolecular dilutions of Histamine:
discussion
Clearly positive
 Variations between labs due to sensitivity of donors
 No theoretical explanation

The Information Medicine
hypothesis
Water, and perhaps other polar solvents are,
under certain circumstances, capable of storing
information relating to substances with which they
have previously been in contact, and subsequently
transmitting this information to presensitised
biosystems.
Fisher 1995
How might water store
information? hypotheses
• Geometric models
• Formation of clathrates
• Information stored in bond lengths, angles
• Isotopicity
• Different isotopes form ordered framework
• Dynamic models
• Coherent regions displaying stable laser-like behaviour
• Del Guidice E, Preparata G, Vitiello G. Water as a free electric
dipole laser. Phys Rev Letts 1988; 61:1085-1088
Review Schulte J. Effects of potentisation in aqueous solutions. Br
Hom J. 1999;88:155-160
Thermoluminescence of ultramolecular
dilutions of NaCl and LiCl
• Method
•
•
•
•
•
dilutions of LiCl and NaCl in ‘heavy’ water (D2O)
cooled to 770K, bombarded with x- or γ-rays
excites electrons, creates +vely charged ‘holes’
warmed: +ve holes and excited electrons recombine
generates characteristic thermoluminescence ‘glow’
• Results
• high dilutions (15c = 10-30) of LiCl and NaCl have similar
spectrum to dilutions containing molecules of the same
substances, and different from D2O
• likely to be due to broken H-bonds
Thermoluminescence signature of
ultramolecular dilutions of NaCl and
LiCl
Rey L. Thermoluminesence of ultra-high dilutions of lithium chloride and
sodium chloride. Physica A 2003; 323:67-74
Thermoluminescence signature of
ultramolecular dilutions of NaCl and LiCl
Rey L. Thermoluminesence of ultra-high dilutions of lithium chloride and
sodium chloride. Physica A 2003; 323:67-74