david brulé, ba, dhms (can.), homeopath - toronto,...

David Brulé, BA, DHMS (Can.), Homeopath

Canadian Homeopathic Conference, Toronto, Canada - February 5, 2016

What is research and evidence

Research areas explored in Canada◦ Provings

◦ Social sciences

◦ Animal studies

◦ Clinical research

My experience with clinical research

Opportunities and ways forward

Canadian Homeopathic Conference,

Toronto, Canada - February 5, 2016



What

homeopaths do!

What we are

doing

today!



Writing up cases

in a formalized

manner.

Publication in

journals and

books – with

pertinent

information.

So far we are

hypothesis

generating…



A snapshot

in time.

Hypothesis

generating

and

hypothesis

testing!



You may have participated in this study!



Retrospective -

Compare two

groups by

looking back in

time.

Studies such as

comparing

outcomes of

conventional vs.

homeopathic

treatment of the

1918 Flu

epidemic



Prospective –

sets

parameters

prior to

enrolling

participants.



Patients who seek homeopathic treatment are likely to

improve considerably. These effects persist for as long as 8

years.



Reduces

various

biases

implicit in

other

designs.



Highly

dependent on

defining terms of

the review.

It’s position

at the top of

the pyramid

may mean it

is highly

political and

not driven

by science

and truth.

Practitioner case reports

Provings

Social sciences: studies on practitioner groups, physicians, pharmacists attitudes towards homeopathy and homeopathy regulation

Animal studies: One mouse model study conducted at University of Manitoba



Research in:◦ History of homeopathy

◦ Homeopathic philosophy

◦ Dispensing methods

◦ Homeopathy best practices

◦ Homeopathy use concurrent with conventional medications

◦ Homeopathy in infectious diseases

◦ Clinical homeopathy



4 clinical trials conducted or ongoing

Exploring:

Homeopathic treatment of ADHD

Homeopathic treatment of side effects of chemotherapy



Set out to explore a rigorous study design which will factor classical homeopathic methods within the context of the RCT design◦ Need to use best practices (classical homeopathy)

◦ Need to have model validity (typical of current homeopathic practice)

◦ Need to base design on consistent practitioners

Sample size estimates generated from experience and not guesswork



Frei, et al showed that it can take up to one year to get the right remedy when treating ADHD

Possible explanation for mixed results in prior studies



36 participants

Designed to see if a larger study was feasible, warranted and to calculate a sample size for future study

Results:◦ 63% had a significant decrease in ADHD symptoms

◦ Future study justified

◦ Sample size calculated based on 28 weeks of homeopathic treatment



Outcome scale Baseline

Group

Median

Final Group

Median

p-

value

% of

participants

with a

statistically

significant

change

Conners Global Index (CGI-P) T-score 85.5 74 0.001 63%

Conners ADHD Index Probability score 99 91 0.001 N/A *

Conners Content scale T-score for Inattention 85 75 0.001 34%

Conners Content scale T-score for

Hyperactivity/Impulsivity

84 78 0.001 51%

Conners DSM-IV-TR Symptom scale T-score

for the ADHD Inattentive sub-type

84 72.5 0.001 34%

Conners DSM-IV-TR Symptom scale T-score

for the ADHD Hyperactive-Impulsive sub-

type

81.5 74 0.001 51%



Attempt to maximize model validity – to emulate clinical practice as much as possible.◦ Appointments on a monthly basis

◦ Change remedies and potencies as needed clinically

◦ Total of 10 consultations

Primary restriction was remedy availability; study was limited to use of remedies carrying a DIN-HM # (medicines regulated for over the counter use in Canada).



Currently ongoing

Used data from pilot study to determine:◦ Sample size

◦ Length of study

◦ Optimal recruitment strategies

◦ All based on similar model as the pilot study including same practitioners, same treatment style, same primary outcome measure



Collaboration with team at SickKids Hospital

Novel environment – homeopathy has never been used in this setting (children undergoing chemotherapy in hospital setting in Canada)



To determine the feasibility of recruiting patients for a study of individualized homeopathy in paediatric patients receiving chemotherapy for cancer.



1. To determine the feasibility of administering individualized homeopathy in paediatric cancer patients receiving chemotherapy for cancer

by describing the proportion of participants who complete at least 10 days of treatment

2. To assess the acceptability of individualized homeopathy in paediatric cancer patients receiving chemotherapy for cancer.



3. Describe changes in fatigue scores according to:

Symptom Distress Scale

PedsQL Multidimensional Fatigue Scale

PedsQL Generic Core Scales and Acute Cancer Module.

4. Describe any adverse events possibly, probably or definitely related to the therapy.

5. Describe the clinical experience.



Study conducted from June 2012 to April 2014

Children (ages 2 to 18), diagnosed with any type of cancer who were receiving chemotherapy administered discontinuously in courses or cycles

A full case-taking (classical homeopathy) was performed at the home of the participant

Homeopathic medicines were lactose/sucrose pellet form or in 30% alcohol.



Participants were followed daily for 14 days.

Remedies and dosages could be changed on a daily basis.

Recruitment rates, adverse events and remedy selection were monitored

Changes in fatigue were measured using the Symptom Distress Scale (daily), the PedsQL Multidimensional Fatigue Scale and the PedsQL Generic Core Scales and Acute Cancer Module. (weekly)



Study clinician identified, through a review of case notes, patterns in homeopathic remedy prescribing as well as any adverse events.

Study clinician identified adverse events which could be considered homeopathic aggravations (clinically expected adverse event following the administration of a homeopathic remedy).



155 potential patients who fulfilled the inclusion/exclusion criteria were assessed.◦ Identified by the study team at the Hospital for Sick

Children

45 patients were eligible and 9 consented to participate.

8 participants received homeopathic treatment and one withdrew prior to treatment. All eight participants completed the 14 days of assessment.

We determined that provision of individualized homeopathy in this research setting (pediatric out-patient hospital in Toronto, Canada) was not feasible primarily due to difficulty in recruitment.



ScreenedN=155

Eligiblen=45

Refused n=36

Not interested (n=30)Too busy (n=3)Too sick (n=2)Fatigue not a problem (n=1)

Consentedn=9

Completed n=8

Withdrew n=1

Ineligible or Not Approached

n=110

Completion of chemotherapy (n=27)Health care team did not permit research team contact (n=23)Palliative (n=12)Too young (n=11)Living too far away (n=6)No fatigue (n=10)Ineligible protocol (n=7)Did not speak English (n=5)No discharge plan (n=4)Other (developmental delay, gastric tube) (n=5)



The proxy-report fatigue scores showed a significant improvement in general fatigue (β=1.7, SE=0.8; P=0.038) and sleep/rest fatigue (β=2.4, SE=0.7; P=0.004) over time. There was no change in cognitive fatigue with time (P=0.611).



Symptom Distress Scale scores significantly improved during the observation time frame (β=-0.08, standard error (SE)=0.02; P=0.0005).



At the initial consultation all of the study participants “fit” the homeopathic remedy picture of Cadmium Sulfuricum and that remedy was prescribed in either 6CH or 15CH potency at the beginning of each case.

The following homeopathic medicines were used:◦ Cadmium Sulphuricum (n=8)

◦ Lycopodium Clavatum (n=2)

◦ Calcarea Phosphorica (n=1)

◦ Nux Vomica (n=1)

◦ Phosphorus (n=1)



Clinically observed homeopathic aggravation◦ Occurred when given a “constitutional” remedy

based on the overall symptom picture of the patient and not on specific symptoms related to the chemotherapy.

◦ The remedy, Calcarea Phosphorica 6CH, was given as a single dose in pellet form.

◦ The remedy was given based on symptoms that emerged on days 5-6 of the treatment



1

2

3

4

5

SD

S S

core

Time

SDS score by Time

Calcarea

Phosphorica 6CH

administered here



Classical homeopathy selects individualized remedies based on the patient’s symptom picture

In some conditions, where there is a lack of individualized symptom picture, a condition specific “therapeutic” remedy may be considered

In this scenario, we found that Cadmium Sulphuricum in a low potency was an effective remedy and yielded significant results.



In a vulnerable population, it is important to mitigate as much as possible the occurrence of adverse events and/or aggravations

Elements that may have been a factor in this adverse event:◦ 1. Administration of the remedy in dry dose (pellet

form)

◦ 2. Administration of a constitutional remedy when the patient is undergoing chemotherapy treatment

◦ 3. Clinician error (not gauging patient sensitivity)



Homeopathic treatment may help children with chemotherapy related fatigue. (Just not seemingly feasible in a Canadian hospital).

Future study may consider a routine use of Cadmium Sulfuricum as part of the protocol.

To mitigate unwanted homeopathic aggravation, future study may discourage constitutional prescribing or may suggest the use of techniques such as liquid dosing or water dosing.



Collaboration with a team at the Canadian College of Naturopathic Medicine and the Ottawa Integrative Cancer Centre



Randomly assigned Randomly assigned Randomly assigned

chemo Verum/p

lacebo

chemo Placebo/

verum

chemo Placebo/v

erum

chemo Verum/

placebo

chemo Placebo/verum

chemo Verum/placebo



The n-of-1 design requires a “washout” period which returns the trial

participant to baseline before every intervention.

In this study, regular rounds of chemotherapy act as the “washout” period.

Rigorous scientifically

Inexpensive

Homogeneity - able to follow single participant and draw robust conclusions



Requires a condition that can be “washed out”.

Questionable generalizability (unsure whether the results of this study are typical of the population in general)



Is a study of this nature feasible in terms of:

◦ the ability of the participant to stay with the study and to fill out all of the questionnaires,

◦ the time it takes to recruit a single eligible patient and number of screens to find this patient,

◦ possible clinical effect size via changes in scores according to the Multi-dimensional Fatigue Inventory (MFI) and the EORTC-QLQ-C30



1 participant recruited at time of initial chemotherapy with scheduled 6 rounds of chemotherapy forthcoming

Homeopath followed the participant with in-person and telephone consultations (contact 2 times per week).

Able to prescribe and change remedy and potency at any time through the treatment period.



Study staff performed “coin-toss” randomization.

Clinician and participant blinded to randomization.

Remedy and instructions sent to participant immediately following prescription.



We recruited 1 participant after study recruitment period of 1 year

Participant completed full study (4 months of data collection)

Data analysis of effects of homeopathic treatment ongoing



Trial design is feasible

Need to explore other recruitment strategies



Know the literature

Design your study to answer your research question

As clinicians you can design with maximum model validity ◦ Questions that come up during clinical practice



Research networks - Collaboration is key!◦ IN-CAM

◦ Homeopathy Research Network

◦ ISCMR

Centre for Integrative Medicine (University of Toronto/Scarborough Hospital)

Funding ◦ SickKids Foundation

◦ Lotte and John Hecht Memorial Foundation

◦ Canadian CAM Research Fund

◦ CIHR

◦ otherCanadian Homeopathic Conference,


UCLAN

Canadian Universities◦ University of Toronto

◦ University of Alberta

◦ University of Lethbridge

◦ University of Calgary

◦ Université de Montréal



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