Dr Peter FisherDr Peter Fisher
Clinical DirectorClinical Director
The Efficacy and Real World The Efficacy and Real World
Effectiveness of HomeopathyEffectiveness of Homeopathy
Clinical DirectorClinical Director
Director of Research Director of Research
Royal London Hospital Royal London Hospital
for Integrated Medicinefor Integrated Medicine
Editor in Chief, Editor in Chief,
HomeopathyHomeopathy
Efficacy and Effectiveness
• Efficacy: ideal circumstances
• Does it do what it is supposed to do in ideal
circumstances?
• eg randomized controlled in university hospital• eg randomized controlled in university hospital
• Effectiveness: routine circumstances
• Does do what it is supposed to do in routine
circumstances?
Validity
• Internal validity
• How much a trial minimises or avoided bias
• External validity
• How generalisable are the results• How generalisable are the results
• Ecological validity
• How well it approximates to the real world
• Model validity
• How well it reflect good practice
Scientific questions raised by
homeopathy• Do homeopathic medicines have beneficial effects that are not
placebo effects?
• Does homeopathy as a whole system of medicine provide benefit in terms of effectiveness and cost-effectiveness?
• Do substances cure diseases or syndromes similar to those that they cause?
• Can substances diluted beyond the Avogadro limit have effects in living systems?
• How might any such effects be mediated?
• Do symptoms reported by healthy volunteers in homeopathic pathogenetic trials (‘provings’) reflect the therapeutic potential of substances?
• Is homeopathy safe?
Lancet 2005 Meta-analysis
(Shang A...Egger M)
� 110 matched trials of homeopathy and conventional medicine
� Reduced to 21 ‘higher quality’ trials of homeopathy, 14 conventional
� Further reduced to 8 homeopathy, 6 conventional ‘larger higher quality’
� Further reduced to 8 homeopathy, 6 conventional ‘larger higher quality’• ‘weak evidence for a specific effect of homoeopathic remedies, but
strong evidence for specific effects of conventional interventions. 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
Shang et al funnel plots:
standard error v log odds ratio
SE 0.12-1.65 SE 0.13-01.52
homeopathyconventional
Small SE (lowest quartile) = larger
Shang et al: criticisms
• 8 anonymous clinical trials.
• Not cited, no information (diagnoses, number of patients etc)
• 93% excluded.
• Data ‘dredged’•Why 8/21? ‘larger’ added post-hoc •Why 8/21? ‘larger’ added post-hoc
•No sensitivity analysis •What is result for all 110 or 21 trials of ‘higher quality’?
•What if homeopathy works for some indications, not others?
•Did not comply with QUOROM guidelines•No descriptive data for trials, no summary results,
no consideration of external validity etc
Shang et al
vital details emerge
• Christmas Eve 2005 identity of the 8/6 trials
published on website
• Enough detail to enable approximate
reconstruction of methodsreconstruction of methods
• ‘conclusions not as definite as reported’
Rutten ALB, Stolper CF. The 2005 meta-analysis of homeopathy: analysis of
post-publication data. Homp 2008;97:169–177.
Lüdtke R, Rutten ALB. The conclusion on the effectiveness of homeopathy
depend highly on the set of analysed trials. J Clin Epidem 2008:61:1197–1204.
Odds Ratios:
Shang’s original set
8 studies Odds Ratio (OR)=0.88, 95% CI 0.66-1.18
21 studies OR=0.76, CI 0.59-0.99 p=0.039
Highly sensitive to one trial and
one indication
Excluding 4 trials on post-exertion muscle stiffness
OR=0.68, CI=0.52-0.90 p=0.007 (n=17)
Arnica in long-distance
running� 519 long-distance runners
� mostly London marathon 1997
� Arnica 30x (30dH) v placeboArnica 30x (30dH) v placebo� randomised double-blind
� No difference between groups� muscle soreness
� time
Vickers A, Fisher P et al. Homoeopathic Arnica 30x is ineffective for
muscle soreness after long-distance running: a randomized, double-
blind, placebo-controlled trial. Clin J Pain 1998;14:227-231
Odds ratios without muscle
stiffness but including Linde’s
high quality studies
OR 25 trials 0.74 (95% CI: 0.59–0.94).
Focussed systematic reviews
and meta-analyses: positive
• Adverse effects of cancer management (Kassab et al
2009)
• Fibromyalgia (Perry et al 2010)
• Childhood diarrhoea (Jacobs et al., 2003)• Childhood diarrhoea (Jacobs et al., 2003)
• HIV/AIDS (Ullman, 2003)
• Influenza treatment with Oscillococcinum® (Anas
barbariae hepatis et cordis extractum HPUS) (Vickers
& Smith, 2006)
• Osteoarthritis (Long & Ernst, 2001)
Focussed systematic reviews
and meta-analyses: positive 2
• Post-operative ileus (Barnes, Resch & Ernst, 1997).
• Rheumatic diseases (Jonas, Linde & Ramirez, 2000).
• Seasonal allergic rhinitis (Lüdtke & Wiesenauer, 1997)
• Seasonal allergic rhinitis (Taylor et al., 2000)
• Upper respiratory tract infections & allergy (Bornhöft et al, • Upper respiratory tract infections & allergy (Bornhöft et al,
2006)
• Upper respiratory tract diseases, including otitis media
(Bellavite et al, 2006)
Focussed systematic reviews
and meta-analyses: negative
• Arnica (Ernst & Pittler, 1998)
• Delayed-onset muscle soreness (Ernst & Barnes, 1998)
• Headache and migraine prevention (Ernst, 1999)• Headache and migraine prevention (Ernst, 1999)
• Influenza prevention with Oscillococcinum® (Vickers &
Smith, 2006)
• Insomnia (Cooper 2010)
Focussed systematic reviews and
meta-analyses: inconclusive
• Anxiety (Pilkington et al. 2006)
• Arnica (Lüdtke & Hacke 2005)
• Attention deficit hyperactivity disorder (Coulter & Dean 2007)
• Cancer (Milazzo, Russell & Ernst 2006) • Cancer (Milazzo, Russell & Ernst 2006)
• Childhood and adolescence ailments (Altunç et al 2007)
• Chronic asthma (McCarney, Linde & Lasserson, 2004)
• Dementia (McCarney et al 2004)
• Depression (Pilkington et al 2005)
• Headache and migraine treatment (Owen & Green 2004)
• Induction of labour (Smith 2004)
‘Vote count’ clinical research
in homeopathy
• 142 human RCTs in human medicine of homeopathy
published in peer-reviewed literature to end 2009
• 40 individualised homeopathy
• 122 single medicines• 122 single medicines
• 74 conditions
• 44% positive for homeopathy
• 8% negative
• 48% inconclusive
Meta-analysis of homeopathy
for childhood diarrhea
Jacobs J et al. Homeopathy for childhood diarrhea: combined results and
meta-analysis from three randomized, controlled clinical trials. Pediatr
Infect Dis J, 2003;22:229–34
Homeopathy for prophylaxis
diarrhoea
• Biological Farming Systems Group, Wageningen
University, Netherlands
• Commercial pig farm
• Randomised, observer blind placebo-controlled
- in piglets
• Randomised, observer blind placebo-controlled
• 52 sows last month of gestation
• Coli 30K (Unda) or placebo sprayed on vulva x2/week
• 525 piglets followed for 1 week
Homeopathy for prophylaxis of
diarrhoea in piglets: results
Treatment Sows Piglets Diarrhoea (%)
Placebo 26 265 63 (23.8)Placebo 26 265 63 (23.8)
Coli 30k 24 260 10 (3.8)**
**p<0.001 GLM corrected for parity, season, group
Camerlink I et al. Homeopathy as replacement to antibiotics in the case
of Escherichia coli diarrhoea in neonatal piglets. Homp 2010 99: 57–62
Arnica for knee surgery
• 3 RCTs double blind, Arnica montana 30x v placebo
• Arthroscopy (n=227), total arthroplasty (n=35) cruciate ligament reconstruction (n=57).
• Postoperative swelling and pain
• Before surgery 1 x 5 globules
• After surgery, 3×5 globules 8-11 days
• Results Overall (p = 0.040)• Results Overall (p = 0.040)
• Arthroscopy (p = 0.204) Total arthroplasty (p = 0.184) Cruciate ligament (p = 0.019).
• Overall positive treatment effect
• no strong evidence that the effectiveness of Arnica depends on the type of surgery
Brinkhaus B et al, Homeopathic arnica therapy in patients receiving
knee surgery: Results of three randomised double-blind trials. Comp
Ther Med 2006 14, 237—246
Arnica for knee surgery
ART =
Arthroscopy
CLR = Cruciate
ligament
reconstruction
AKJ = Total
Effects on swelling over time (standardised effects and 95% CIs). 0 = no
between group difference, positive favours Arnica
AKJ = Total
arthroplasty
RCTs of Homeopathy for
Fibromyalgia
• 3 RCTs
• All showed benefit
• 2 v placebo, 1 v normal care
• Particularly function, Quality of Life• Particularly function, Quality of Life
Fisher P et al Effect of homoeopathic treatment on fibrositis (primary fibromyalgia). Br Med J
1989; 299: 365-366.
Bell IR et al. Improved clinical status in fibromyalgia patients treated with individualized
homeopathic... Rheumatology 2004; 43:577–582.
Relton C et al.Healthcare provided by a homeopath as an adjunct to usual care for
Fibromyalgia (FMS): results of a pilot Randomised Controlled Trial. Homp 2009;98:77-82
Individualised homeopathy
in insomnia• Double blind RCT in
South Africa
• n=30
• Top 5 30
35
40
45
50
Me
dia
n h
ou
rs s
lee
p/w
ee
k (
da
iry
)
ns
** ** *
**p<0.01, *p<0.05, Kruskal-Wallis
• Top 5
• Lachesis
• Nux vomica
• Medorrhinum
• Sepia
• Lycopodium
0
5
10
15
20
25
Baseline week 2 week 3 week 4
Me
dia
n h
ou
rs s
lee
p/w
ee
k (
da
iry
)
Homeopathy Placebo
Naudé D et al. Chronic primary insomnia: Efficacy of
homeopathic simillimum. Homp 2010:99, 63–68
Homeopathy v Fluoxetine:
non-inferiority trial
• Double dummy RCT
• Mild to moderate depression
• Referred to Homeopathy and Depression clinic Jundiaí
Medical School (São Paulo, Brazil) by public health Medical School (São Paulo, Brazil) by public health
system professionals
• Individualised homeopathy LM/Q potencies x3/week
• 20 medicines v Fluoxetine 20-40mg/day
• Outcomes: MADRS, tolerability
• ITT analysis
Adler U et al. Homeopathic Individualized Q-potencies versus Fluoxetine
for Moderate to Severe Depression: Double-blind, Randomized Non-
inferiority Trial eCAM 2009 doi:10.1093/ecam/nep114
Homeopathy v Fluoxetine:
non-inferiority trial
• Results
• 91 entered, 55 completed
• Homeopathy non-inferior
• No significant differences
side effects side effects
• but 21% fluoxetine, 11%
homeopathy ‘side effects that
interfere markedly with
performance’ (p=0.275).
Homeopathy and ADHD: what happens when treatment is stopped?
• 83 children 6-16 years, ADHD (DSM-IV).
• Double blind, placebo controlled crossover RCT of individualised homeopathy• 62 responders (50% improvement in CGI), participated in the trial.
• 13 non-responders
• Responders received verum and placebo for 6 weeks, random • Responders received verum and placebo for 6 weeks, random sequence• Cognition had improved significantly with open treatment (P<0.0001).
• During trial CGI better on verum than placebo (P<0.05). • Long-term CGI improvement 12 points (63%, P <0.0001).
• Suggests effectiveness of homeopathy in ADHD particularly behavioural and cognitive.
Frei H et al. Homeopathic treatment of children with attention deficit hyperactivity
disorder: a randomised, double blind, placebo controlled crossover trial. Eur J
Peds 2005; 164:758-67.
Homeopathy and ADHD 2:
negative result
• Double-blind, RCT, private homeopathic clinic, Seattle WA
• 43 children 6–12 y DSM-IV criteria for ADHD.
• homeopathic consultation and individualized treatment or placebo. follow up every 6 weeks for 18 weeks.
• CGI parent and teacher; Brief performance test
• No statistically significant differences homeopathy v placebo • No statistically significant differences homeopathy v placebo
• Statistically and clinically significant improvements both groups
• No evidence of effect of individualised homeopathy.
• Future studies should be longer and include a control group not receiving homeopathic consultation.
• Comparison to conventional stimulant?
Jacobs J et al. Homeopathy for Attention-Deficit/Hyperactivity Disorder: A
Pilot Randomized-Controlled Trial. J Alt Comp Med 2005;11:799–806
Homeopathy and ADHD:
treatment comparison• Frei et al
Lycopodium
Calcarea carbonica
Sulphur
Belladonna
Causticum
Phosphorus
• Jacobs et al
Medorrhinum
Saccharum officinalis
Calcarea carbonica
Calcarea phosphorica
China officinalis
StramoniumPhosphorus
Total 24 medicines
LM3-30, every 1-2 days
Stramonium
Total 41 medicines
Dilutions, regime not given
Or Dopamine muriaticum and Serotinin?
But Frei randomised after optimal homeopathic medicine found
(mean 3 attempts)
Jacobs randomised before 1st prescription
•Homeopathy to avert Methylphenidate (Ritalin®) in ADHD� Attention Deficit Hyperactivity Disorder DSM-IV criteria � 115 children 3-17y, mean 8.3y. 92♂, 23♀. � One withdrawal� Conners Global Index (CGI) ≥14, mean 20.63 at entry
Homeopathy in the ‘real world’Averting Ritalin® for ADHD
� Conners Global Index (CGI) ≥14, mean 20.63 at entry� University Paediatric Clinic, Berne
� Results� 86 (75%) improved sufficiently not to require Methylphenidate
�Mean improvement (parent ratings) 73%, Conners 55%�Mean treatment period 3.5m
� 25 (22%) eventually required methylphenidate�Mean treatment period 22m
Frei H, Thurneysen A. Treatment for hyperactive children: homeopathy and
methylphenidate compared in a family setting. Br Hom J 2001;90:183-188.
� 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
Homeopathy in the ‘real world’:Effectiveness of homeopathy in routine care
� 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
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
P=0.002
Homeopathy in the ‘real world’:Effectiveness of homeopathy in routine care
MCS
p=0.273PCS
1st 6m
p=0.0.016
2nd 6m
Quality of Life scores SF-36 adjusted for gender, age, educational level, symptom duration and gender/age
interaction
2nd 6m
P=0.649
Homeopathy in children with recurrent URTIs
� RCT in Free University of Amsterdam paediatric
outpatients
175 children with recurrent URTIs� 175 children with recurrent URTIs� 18 months to 10 years
� stratified for age
� 90 boys 80 girls
Homeopathy in children with recurrent URTIs
2.612.21
0
1
2
3
Placebo Homeopathy
49 53
0
10
20
30
40
50
60
Mean % days symptom freeMean daily symptom score
7759
0
25
50
75
No of courses of antibiotics
21
16
0
5
10
15
20
25
No of adenoidectomies
Mean % days symptom free
de Lange de Klerk ES.et al. Effect 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
� 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
Homeopathy in the ‘real world’:averting antibiotics for acute otitis media
� 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
•‘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
Homeopathy in the ‘real world’:cost-effectiveness in recurrent URTIs
� 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
� Results� Homeopathic strategy superior:
�medical effectiveness (p<0.001)�complications (p<0.001)�number of consultations (p<0.001)
Homeopathy in the ‘real world’:cost-effectiveness in recurrent URTIs
�number of consultations (p<0.001)�quality of life (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’:
eczema
• Cohort study homeopathy v conventional treatment for eczema
• Signs/symptoms, quality of life over 12 months
• 118 children 1-16y
• homeopathy mean age 5.1y, 56% boys• homeopathy mean age 5.1y, 56% boys
• conventional 6.2y, 61% boys
• Conclusions
• Similar symptomatic improvement both groups
• Similar QoL improvement
• But slightly better with conventional in 8-16 subgroup
Homeopathy in the ‘real world’:
eczema
adjusted for sex, age, parent’s educational level, log
symptom duration and interaction age x sex
Change in symptoms over 12m
patients’ or parents’ assessment
Change in symptoms over 12m
physicians’ assessment
Homeopathy in the ‘real world’:
eczema
Adjusted change in eczema-related QoL over 12m, all children
Keil T et al Homoeopathic versus conventional treatment of
children with eczema: A comparative cohort study, Comp
Ther Med (2006), doi:10.1016/j.ctim.2006.10.001
Homeoprophylaxis against
Leptospirosis epidemic in Cuba
• Nosode 200c, 10M
• 2.3 million, 3 provinces , 92% coverage
• Oct-Dec 2007
• Sharp, significant reduction, rise expected
• 38 → 3-4 cases/week/100,000 in 3 weeks
• Rest of Cuba (8.8m) followed historical trends
and rainfall
Bracho G et al. Large-scale application of highly diluted bacteria for
Leptospirosis epidemic control. Homp 2010; 99:156-166.
Homeoprophylaxis against
Leptospirosis epidemic in Cuba
Start of
programme
Intervention
region
n=2.3m
(no of cases)(no of cases)
Rest of
country
n=8.8m
(no of cases)
RCT of Homeopathy for
Dengue Fever
• Double-blind, placebo-controlled RCT in Honduras.
• 60 patients who met case definition
• fever +2 ancillary symptoms
• Homeopathic complex or placebo for 1 week • Homeopathic complex or placebo for 1 week
• Aconite, Belladonna, Bryonia, Eupatorium, Gelsemium,
Rhus tox 12c. 2 pills x 4/day
• + standard analgesic
RCT of Homeopathy for
Dengue Fever
• No difference in outcomes between two groups
• days of fever, pain analgesic use, complications
• But only 3 had lab-confirmed dengue!• But only 3 had lab-confirmed dengue!
• 3 had malaria
• Rapid tests for Dengue now available
Jacobs J et al. The use of homeopathic combination remedy
for dengue fever symptoms: a pilot RCT in Honduras.
Homeopathy (2007) 96, 22–26
Homeopathic complex for
Dengue: pain scores
Sinfrontal: low potency complex
• Cinnabaris D4 Ferrum phosphoricum D3 Mercuriussolubilis D6 all triturations
• Multi centre double-blind, placebo-controlled RCT in Ukraine
• Acute maxillary sinusitis • Acute maxillary sinusitis
• 113 patients, 22 days
• Outcomes • Sinus severity score D0 – D7: Sinfrontal reduction 5.8
placebo 2.3 p<0 .0001
• Complete remission D21: Sinfrontal 39 (68.4%) placebo 5 (8.9%)
Zabolotnyi D et al. Efficacy of a complex homeopathic medication
(Sinfrontal) in patients with acute maxillary sinusitis. Explore 2007;
3:98-109.
Sinfrontal: economic analysis
• Same RCT, extended follow up
• 113 patients with AMS 11 weeks
• Economic data collected • indirect comparison to placebo-controlled trials of
antibacterials
• Sinfrontal associated with significant cost savings • Sinfrontal associated with significant cost savings compared to placebo, mostly due to reduced work absence • Indirect comparison with antibacterials suggested
significantly higher cure rate at similar or lower cost.
• Sinfrontal may be a cost-effective treatment for AMS.
Kneis KC et al Economic evaluation of Sinfrontal in the treatment of acute maxillary sinusitis in adults. Applied Health Economics and Health Policy. 2009; 7:181-191
Cost benefit of Homeopathy in
chronic respiratory disease
Asthma: change in
prescribing costs (%)
Year 1 Year 2
specific -71 -54
homeopathy
specific -71 -54
general -64 -50
controlspecific +11 +4
general +31 +16
**
**
**
** p<0.01 v baseline
Rossi E et al. Cost–benefit evaluation of homeopathic v conventional
therapy in respiratory diseases Homp (2009) 98:2-10
Homeopathy in long term
conditions: observational study• Prospective, multicentre cohort study 103 homeopathic
primary care practices Germany and Switzerland• All new patients age >1 year
• Outcomes: Patients' perceived change in complaint severity (1-10) QoL SF-36 at 0, 2 & 8 years.(1-10) QoL SF-36 at 0, 2 & 8 years.• 3,709 patients 73% 8-year follow-up.
• Diagnoses• Adults: allergic rhinitis, headache
• Children atopic dermatitis, recurrent infections
• Significantly improvement disease and QoL (p < 0.001)
0
0.5
1
SF36 physical SF36 mental
Change in QoL scores
Normalised
-2
-1.5
-1
-0.5 Baseline 2 years 8 years
Effect size
Physical 0.39 p<0.001
Mental 0.54 p<0.001
Witt C et al. How healthy are chronically ill patients after eight
years of homeopathic treatment? BMC Public Health 2008, 8:413
Bristol Homoeopathic Hospital
outcome study: methods
• National Health Service (NHS) Hospital, Teaching Trust
• 6544 consecutive follow-up patients over 6 years
• 23,473 consultations
• Every patient attending a follow-up appointment over the study period included, commencing at first follow-up the study period included, commencing at first follow-up attendance.
• Outcome measure: 7-point Likert scale (ORIDL) at end of consultation compared to baseline
Bristol Homoeopathic Hospital
outcome study: results
• A total of 6544 consecutive follow-up patients were
given outcome scores.
• 70.7% (4627) reported improvement
• 50.7% (3318) better (+2) or much better (+3).• 50.7% (3318) better (+2) or much better (+3).
• Conclusions: Homeopathy associated with positive
health changes to a substantial proportion of a large
cohort of patients with a wide range of chronic
diseases.
Spence D et al Homeopathic Treatment for Chronic Disease: A
6-Year, University-Hospital Outpatient Observational Study J
Alt Comp Med 2005;11:793–798
Bristol outcome study:
diagnostic groups
6 2 2
Dermatology Neurology* Rheumatology Gastrointestinal
Psychiatry ENT Oncology Other**
Respiratory Cardiovascular Genitourinary
19
16
109
9
8
7
6
6 2 2
* includes chronic fatigue,
** includes endocrinology, opthalmology, ‘polysymptomatology’
Bristol outcome study:
outcomes in 5 most frequent diagnoses
404550
Eczema chidren (n=448) Chronic fatigue syndrome (354)
Cancer (301) Arthritis (245)
Depression (201)
05
10152025303540
Homeopathic outcomes at RLHIMall patients receiving homeopathic treatment in March
2007 for top 5 conditions (n=187/797)
20
25
30
CFS Osteoarthritis Eczema Depression Rheumatoid Arthritis
0
5
10
15
Motives for attending the Royal London Hospital for Integrated Medicine
(925 responses from 493 patients)
Other
6%
Adverse effects
from other
treatment
14%
Personal
preference
22%
Concern about
adverse effects
26%
Other treatment
ineffective
32%
Sharples F, Van Haselen R, Fisher P. NHS patients’ perspective on
complementary medicine. Comp Ther Med 2003;11:243-248.
Change in medication in patients attending the
Royal London Hospital for Integrated Medicine
2468101214
No of
patients CancerMusculoskeletal/Rheumatology
5
10
15
20
25
30
35
02
Stopped Reduced Unchanged Increased0
5
Stopped Reduced Unchanged Increased
Skin
0
2
4
6
8
10
12
14
Stopped Reduced Unchanged Increased
Respiratory
0
2
4
6
8
10
12
14
16
18
Stopped Reduced Unchanged Increased
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• 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
Recent Homeopathic Pathogenetic
Trials (HPTs, provings)• 2 small scale (25-30 volunteers)
• All double blind randomised
• Aconitum napellus 30c v placebo, crossover• were symptoms qualitatively different?
• statistically-significant difference, enabling discrimination• statistically-significant difference, enabling discrimination
• Arsenicum album 30c v Natrum muriaticum 30c v placebo, 3-arm • were symptoms specific?
• judged by blinded expert using decision support software.
• significantly more specific symptoms
• total symptoms highest with placebo, but mostly non-specific
Recent Homeopathic
Pathogenetic Trials (HPTs)
• In both symptoms qualitatively but not quantitatively different, specific to medicine compared to placebo
Piltan D et al. Test of a homeopathic dilution of Aconitum napellus. A clinical, randomized, double-blind, controlled crossover study in healthy volunteers. Forsch Komplementärmed 2009;16:168-73.
Möllinger H et al. Homeopathic pathogenetic trials produce specific symptoms different from placebo. Forsch Komplementärmed. 2009;16:105-10.
Scientific questions raised by
homeopathy• Do homeopathic medicines have beneficial effects that are not
placebo effects?
• Does homeopathy as a whole system of medicine provide benefit in terms of effectiveness and cost-effectiveness?
• Do substances cure diseases or syndromes similar to those that they cause?
• Can substances diluted beyond the Avogadro limit have effects in living systems?
Hormesis in animalshormesis = stimulatory or beneficial effect of low dose of toxin
v linear (threshold) model
Stebbing ARD Hormesis - the stimulation of growth by low levels of
inhibitors. Sci Tot Environ 1982;22:213-234
Similarity v survival in cell
culture
Reuber H35 Hepatoma cells
% similarity between heat shock
proteins triggered by
heat shock (primary stimulus) and
secondary low dose
conditioning response:
survival factor
% similarity
conditioning response:
1µM arsenite (As)
0.3 µM cadmium (Cd)
0.1µM mercury (Hg)
10 µM lead (Pb)
10 µM copper (Cu)
20 µM menadione (men)
1 µM diethyldithiocarbamate (ddtc)
Wiegant FAC , Van Wijk R. The similia principle; results obtained in a cellular
model system. Homp 2009. 98:3-14
survival factor
In vitro evidence of effect of
ultramolecular dilutions:
systematic review• 67 in-vitro experiments
• Stepwise agitated dilutions <10−23
• 75 publications (33%• 75 publications (33% replications)
• Quality assessed by modified SAPEH score.
• 73% effect with ultramolecular dilutions
• including 68% of 18 with SAPEH score ≥6
• 73% replications positive
In vitro evidence of effect of
ultramolecular dilutions:
systematic review • Conclusions
• Design and experimental models heterogenous
• High quality experiments can demonstrate effect • High quality experiments can demonstrate effect
of ultramolecular dilutions
• No positive result reproduced by all investigators.
Witt C et al. The in vitro evidence for an effect of high
homeopathic potencies - A systematic review of the
literature. Comp Ther Med 2007;15:128–138.
Jacques Benveniste
1935-2004
Human Basophil
Degranulation Test (HBDT)
� 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)anti-IgE (IgG)
� Activation is inhibited by Histamine in supernatant (ie
negative feedback)
� Basophils express CD63 & CD203c antigens on t surface
when activated
HBDT:
Benveniste model
Anti
gen
IgE Histamine
Histamine
HBDT & ultramolecular dilutions of
histamine (Ste Laudy)
IgE
Histamine
Bibliometric study:
inhibition of basophil activation by
ultramolecular histamine
Initial Positive repetitionRepetition with different
resultsNegative repetition
Single centre
Ste Laudy 1991 Ste Laudy 1993 Ste Laudy 2001
Ste Laudy 1996
Ste Laudy 1997
Ste Laudy 2006 Ste Laudy 2006
Ste Laudy 2008
Multi
centre
Ste Laudy 2004 Wiegant 2004
Ennis 2004
Mannaioni 2004
Independent
Brown 2001 Guggisberg 2005
Lorenz 2003
Lorenz 2003 Lorenz 2003
Chirumbolo 2009
Summary: inhibition of basophil activation in 13/17 experiments
Endler PC et al. Repetitions of fundamental research models for homeopathically
prepared dilutions beyond 10-23. Homeopathy (2010) 99, 25–36
25
30
35
p=0.028
NS
The specificity of histamine:
histamine v histidine
Effects of histamine and histidine (inactive analogue) 16c on
basophil activation. Mean of 10 experiments in triplicate
0
5
10
15
20
Negative control Positive control Histamine 16CH Histidine 16 CH
% CD63
Recent independent replication
Chirumbolo S et al. Inhibition of CD203c membrane up-regulation in human basophils by
high dilutions of histamine: a controlled replication study. Inflamm
Res DOI 10.1007/s00011-009-0044-4
dilutions of histamine (A) succussed water (B)
% inhibition of basophils activated by IgE
Modulation of prothrombotic
effect of ultramolecular aspirin
• Previous experiments indicate that ultramolecular dilutions of acetylsalicyclic acid (ASA) are prothrombotic
• 120 Wistar rats treated ASA 15c or control and specific COX-1 (SC 560) and COX-2 (NS 398) inhibitors
• ASA 15c Significantly increased the number and duration of emboli v controlcontrol
• ASA 15c + COX-1 inhibitor further increased embolisation and decreased bleeding time
• ASA 15c + COX-2 inhibitor not different from control
• Prothrombotic activity of ultramolecular ASA may be due to inhibition of COX-2 mediated PGI2 production in vascular endothelium
Doutremepuich C et al. Thrombogenic properties of ultra-low-dose of acetylsalicylic acid in a
vessel model of laser-induced thrombus formation.Thrombosis Res, 1994 76: 225-229.
Eizayaga FX et al. Modification produced by selective inhibitors of cyclooxygenase and ultra
low dose aspirin on platelet activity in portal hypertension. World J Gastroenterol
2007;13:5065-5070.
Number of emboli
n
ASA 15c - + - + - +
control Sc-560 Ns-398
Duration of embolisation
ASA 15c - + - + - +
control Sc-560 Ns-398
2
4
6
8
10
12 *
1
2
3
4
5
6
minutes
***
Effect of COX-1 and 2 inhibitors on prothrombotic
effect of ultramolecular ASA
control Sc-560 Ns-398 control Sc-560 Ns-398
Bleeding time
seconds
ASA 15c - + - + - +
control Sc-560 Ns-398
50
100
150
200
250
*
COX-1
inhibitor
COX-2
inhibitor
Bibliometric study:
ultramolecular thyroxine/thyroidinum
and rate of amphibian metamorphosis
InitialPositive
repetition
Repetition with
different results
Negative
repetition
Single
centre
Welles 2007
Pongratz 2007
Suanjak 2007
Weber 2007centre
Suanjak 2007
Multi
centre
Endler 1991
Pongratz 1991
van Wijk 1991
Zausner 2002
Pongratz 2002
Lassnig 2002
Independent Guedes 2004
Summary: decreased speed of metamorphosis in 10/11 experiments
Endler PC et al. Repetitions of fundamental research models for homeopathically
prepared dilutions beyond 10-23. Homeopathy (2010) 99, 25–36
Gelsemium in mouse model
of anxiety• In Light-Dark test, Gelsemium 5, 9 and 30c were
associated with statistically significant increase in
number of transitions
between compartments
• Indicates anxiolytic activity• Indicates anxiolytic activity
• comparable to buspirone.
• non-linear
• Includes ultramolecular
dilutions.
Bellavite P et al. Assays of homeopathic remedies in rodent behavioural
and psychopathological models. Homp 2009; 98, 208–227
Gelsemium in mouse model
of anxiety
Magnani P et al Dose-effect study of Gelsemium sempervirens in high
dilutions on anxiety-related responses in mice Psychopharmacology
DOI 10.1007/s00213-010-1855-2
Effect of Gelsemium in rat
limbic system
Effect of Gels on
production of the
neurosteroid
allopregnanolone
(3a,5a-THP)
production in rat
hippocampus
and amygdala
slices
Venard C et al. Comparative Analysis of Gelsemine and Gelsemium
sempervirens activity on Neurosteroid Allopregnanolone formation in
the Spinal Cord and Limbic System. eCAM 2009
doi:10.1093/ecam/nep083
Conclusion
• There’s a lot going on!
• A scientific revolution, generating reaction?
• Too early to say
• Stick to our core values, don’t be tempted to
make excessive claims
The challenges facing
homeopathy
• ‘Plausibility Bias’
• ultramolecular dilutions
• mechanism of action not understood
• ‘OJ Simpson effect’
• Because of unsustainable claims
• immunisation, prophylaxis
• metaphorical theories
To find
out
more...
www.sciencedirect.com/science/journal/14754916www.sciencedirect.com/science/journal/14754916www.sciencedirect.com/science/journal/14754916www.sciencedirect.com/science/journal/14754916
[email protected]@uclh.nhs.uk
