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Complementary Therapies in Medicine (2015) 23, 309—317
Available online at
www.sciencedirect.comScienceDirect
journal home page:
www.elsevierhealth.com/journals/ctimInfluence of adjunctive classical homeopathy on global health status and
subjective wellbeing in cancer patients — A pragmatic randomized controlled trial !
Michael Frass a,b , Helmut Friehs b , Christiane Thallinger a ,
Narinderjit Kaur Sohal a , Christine Marosi a , Ilse Muchitsch c ,
Katharina Gaertner a , Andreas Gleiss d , Ernst Schuster d ,
Menachem Oberbaum e,∗
a
Medical University of Vienna, Department of Medicine I, Clinical Division of Oncology,
Waehringer Guertel 18-20, 1090 Vienna, Austria
b
WissHom (Scientific Society for Homeopathy), Köthen, Germany
c
Austrian Chamber of Pharmacists, Department Vienna, HomResearch, Interdisciplinary Homeopathic
Research Group, Vienna, Austria
d
Medical University of Vienna, Center for Medical Statistics, Informatics and Intelligent Systems, Vienna,
Austria
e
Shaare Zedek Medical Center, The Center for Integrative Complementary Medicine, Jerusalem, Israel
Available online 23 March 2015
KEYWORDS
Cancer;
Homeopathy;
Additive
homeopathy;
Global health status;
Subjective well being
Summary
Objectives:
The use of complementary and alternative medicine has increased over the past
decade. The aim of this study was to evaluate whether homeopathy influenced global health
status and subjective wellbeing when used as an adjunct to conventional cancer therapy.
Design:
In this pragmatic randomized controlled trial, 410 patients, who were treated by
standard anti-neoplastic therapy, were randomized to receive or not receive classical homeo-
pathic adjunctive therapy in addition to standard therapy. The study took place at the Medical
University Vienna, Department of Medicine I, Clinical Division of Oncology.
Trial Registration: ClinicalTrials.gov: NCT00861432.
Corresponding author at:
Shaare Zedek Medical Center,
12 Shmu’el Bait Street,
91031 Jerusalem,
Israel.
Tel.: +972 2 6666395;
fax: +972 2 6666975.
E-mail addresses:
michael.frass@meduniwien.ac.at (M. Frass),
helmut.friehs@gmx.net (H. Friehs),
christiane.thallinger@meduniwien.ac.at (C. Thallinger),
narinderjit.sohal@meduniwien.ac.at (N.K. Sohal),
christine.marosi@meduniwien.ac.at (C. Marosi),
ilse.muchitsch@chello.at (I. Muchitsch),
katha gh@web.de (K. Gaertner),
andreas.gleiss@meduniwien.ac.at (A. Gleiss),
ernst.schuster@meduniwien.ac.at (E. Schuster),
oberbaum@netvision.net.il,
oberbaum@szmc.org.il (M. Oberbaum).
!
∗
http://dx.doi.org/10.1016/j.ctim.2015.03.0040965-2299/© 2015 Elsevier Ltd. All rights reserved.
310
M. Frass et al.
Main outcome measures: The main outcome measures were global health status and subjective
wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits),
patients filled in two different questionnaires.
Results: 373 patients yielded at least one of three measurements. The improvement of global
health status between visits 1 and 3 was significantly stronger in the homeopathy group by 7.7 (95%
CI 2.3—13.0, p = 0.005) when compared with the control group. A significant group difference was
also observed with respect to subjective wellbeing by 14.7 (95% CI 8.5—21.0, p < 0.001) in favor
of the homeopathic as compared with the control group. Control patients showed a significant
improvement only in subjective wellbeing between their first and third visits.
Conclusion: Results suggest that the global health status and subjective wellbeing of cancer
patients improve significantly when adjunct classical homeopathic treatment is administered in
addition to conventional therapy.
© 2015 Elsevier Ltd. All rights reserved.
The use of complementary and alternative medicine
(CAM), such as herbal, vitamin and nutritional supplements,
has increased over the past decade. 1 Various CAM techniques
are used by a substantial percentage of patients attempting
to ameliorate treatment outcome achieved by conventional
therapies. 20—60% of patients in the United States use some
form of CAM in various practice settings, with an estimated
16—20% using CAM along with prescribed medication. 2—4
In Austria, 27% of cancer patients (33% female vs. 20%
male) use interventions from the broad CAM category. 5 Their
administration is widely proposed by general practitioners
(44%) or at the patients’ own initiative (39%), but very rarely
(4%) recommended by the oncologist. Using a detailed inter-
view, the authors show that understanding of CAM methods
varies widely. 5 This is not surprising, as complementary
medicine includes a broad range of options, from intake
of herbal preparations, vitamins and extracts from various
natural sources to various religious and spiritual practices.
Similar to allopathic medicine, further study is needed to
prove that CAM therapies are effective. This is a major
concern because patients do not routinely report use of
CAM when providing a medication history. 6,7 This observa-
tion is complicated by the fact that many oncology patients
use several complementary techniques together with their
conventional treatment. One example: in a phase I clini-
cal study of 309 patients, 162 (52%) used one or more CAM
methods. 8 This rising interest in CAM has been acknowledged
by the medical community, 9 with homeopathy, in particular,
increasingly used by cancer patients. 10,11
The aim of this prospective, controlled study was to eval-
uate whether adjunctive homeopathic treatment has any
influence on global health status and subjective wellbeing
in patients with various types of cancer. Homeopathy, one
of the most popular CAM forms, is based on the ‘Law of Sim-
ilars’, which determines that substances causing symptoms
in healthy individuals can be used to stimulate healing in
patients who have similar symptoms due to their illness. 12
The remedies are produced by serial dilution and vigorous
shaking (called succussion) between every dilution. In clas-
sical homeopathy, treatment consists of two main elements:
taking the individual case history and prescribing individu-
ally selected homeopathic medicines, which correspond to
the sum of symptoms presented by the patient. The purpose
of the homeopathic case history is to ascertain the totality
of signs and symptoms of the patient, enabling the selec-
tion of an individualized homeopathic medicine based on the
broad themes and idiosyncratic characteristics elicited from
the totality of presenting symptoms physical, mental and
emotional. 12 Classical homeopaths generally use one rem-
edy at a time, usually highly diluted and agitated and in rare
repetitions only rarely combining two or more remedies.
In this study, we focused on the homeopathic method.
We used standardized questionnaires to assess global health
status as well as subjective wellbeing. The study was not
designed to evaluate the effect of specific homeopathic
remedies used for specific symptoms, such as vomiting and
nausea.
Patients and methods
Study design
The study was approved by the Ethical Committee of
the Medical University of Vienna on November 4, 2008; #
513/2008. Included were all patients over 18 years of age
prior to their first conventional treatment (chemotherapy,
radiation therapy, surgical therapy) who signed an informed
consent form. The only exclusion criteria were inability to
comply with the study protocol, and the mental inability
to fill out the questionnaires. On their first visit, patients
were told by an administrative staff member about the
availability of a study exploring the effect of additive home-
opathy on global health status and subjective wellbeing,
and were given a patient’s information sheet. Once written
informed consent was given, eligible patients were random-
ized to receive standard anti-cancer care (control group), or
standard anti-cancer care together with adjunctive homeo-
pathic therapy (homeopathy group).
The random allocation was made by a computer-
generated code using sequentially numbered containers.
The random allocation sequence (Microsoft Excel) was gen-
erated by an individual uninvolved in the study, and study
participants were assigned to the groups according to the
randomization list. The homeopathy group received individ-
ually tailored homeopathic treatment daily, according to the
guidelines described by Hahnemann, 12 using the Complete
Repertory, 13 Kent’s Materia Medica 14 and the Pocket Manual
311
Influence of adjunctive classical homeopathy and subjective wellbeing in cancer patients
of Homeopathic Materia Medica & Repertory of William
Boericke. 15 Classical homeopathic treatment requires selec-
tion of one homeopathic medicine (remedy) at a time for
each individual, based on the broad themes and idiosyn-
cratic characteristics elicited from the totality of presenting
symptoms —physical, mental and emotional. Homeopathy is
defined by the Law of Similars, which means that symp-
toms which appear after intake of a certain remedy in
healthy persons may heal a person suffering from similar
symptoms (‘‘Like cures like’’). A detailed clinical history is
recorded by the homeopath, relying mainly on the symp-
toms described by the patient. The symptoms are then listed
and repertorized. Participation in the study required three
visits. Patients were prescribed one homeopathic medicine
at each visit, but treatment could be changed at any clinic
attendance. A single homeopath (MF) with forty years’ expe-
rience as a classical homeopath, holding a diploma from
the Austrian Medical Chamber and training at the Austrian
Medical Association of Classical Homeopathy, consulted and
prescribed the remedies. The first visit was 60 min long, and
the follow-ups were 30 min each. Remedies were taken daily.
Apart from the initial assessment for homeopathic treat-
ment, conventional medical attention regarding length and
frequency of medical contacts was identical in both study
groups. All patients — both control and treatment groups —
were seen in the same clinic, for both their conventional
and study treatment. Patients in both groups filled out the
questionnaires in this same clinic. Those in the control group
received similar assistance and instructions concerning the
questionnaires as those in the treatment group.
At all three visits, two different questionnaires were
filled out by the study subjects. Time to complete the two
questionnaires was an estimated 10 min. The first was the
standardized questionnaire of the European Organization for
Research and Treatment of Cancer, EORTC-QLQ-C30, focus-
ing on quality of life (QoL) and global health status. 16 The
second evaluated subjective wellbeing using a visual ana-
log scale (VAS). The primary outcomes were global health
status and subjective wellbeing. Further, several function-
ing parameters as well as side effects of chemotherapy and
radiation such as nausea, appetite loss and constipation
were evaluated. The second questionnaire was developed
at the Medical University Vienna in Vienna, Austria, and
addressed use of other CAM methods, such as acupuncture,
mistletoe therapy, herbals, Schuessler cell salts, Bach flow-
ers and vitamins.
Study subjects completed the questionnaires at baseline
prior to initial assessment for homeopathic treatment, as
well as at the two follow-up visits scheduled at intervals
of two months. The prospective endpoint for evaluation of
outcomes was therefore four months per patient. Overall,
including patient recruitment and recording of outcomes,
the study ran from December 2008 to July 2010. The types,
frequency and duration of concurrent conventional can-
cer therapy during the study, as well as the use of other
palliative therapies (including antidepressants and cortico-
steroids) were recorded. Since the study was designed as an
open pragmatic trial, we did not use placebo in the control
group.
We followed the SPIRIT (Standard Protocol Items: Recom-
mendations for Interventional Trials) statement at the time
of protocol development 17 and our reporting followed the
RedHOT guidelines (homeopathy specific CONSORT). 18
Patients
A total 453 patients with malignancies of the breast,
lungs, gastrointestinal tract, brain, kidneys and other were
screened for enrollment into the study. Of them, 43 did
not consent to participation and 410 were, therefore,
enrolled (Table 1). All patients received conventional can-
cer treatment during the trial at the Medical University
of Vienna, Department of Medicine I, Clinical Division of
Oncology.
Homeopathic treatment
Homeopathic treatment consisted of individualized reme-
dies, prescribed after careful anamnesis and repertorization
Table 1
Patients’ characteristics (n = 373). All patients had stage III or IV tumors.
Age (years, mean ± SD)
Gender (f, %)
Diagnoses
Breast cancer
Hematological cancer
Gastrointestinal cancer
Lung cancer
Renal cell cancer
Sarcoma
Brain cancer
Gynecological cancer
Other
Metastatic disease (yes, %)
Chemotherapy (yes, %)
Radiation (yes, %)
Homeopathy group (n = 194) Control group (n = 179)
55.4 ± 12.5
129 (66.5%)
—
74
26
23
21
7
6
7
4
26
48 (24.7%)
86 (44.3%)
25 (12.9%) 58.1 ± 11.2
116 (64.8%)
—
79
19
25
22
8
1
6
1
18
43 (24.0%)
97 (54.2%)
33 (18.4%)
312
following the rules of Samuel Hahnemann, the founder
of homeopathy. It was administered daily as oral globules
and/or dilutions. The homeopathic remedies were prepared
according to the European Pharmacopeia and the Home-
opathic Pharmacopeia (HAB 2009; Maria Treu Apotheke,
Vienna, Austria). The specific remedy dilutions used were
Q-potencies, which patients were advised to take daily.
Therapy was started with Q1 and then continued in ascend-
ing order with Q2, Q3, etc. In addition, C- and LM-potencies
were used, especially for treating side effects of chemo-
and radiation therapy. The primary outcome measures were
global health status and subjective wellbeing in the home-
opathy group.
Statistical analysis
The VAS-values for subjective wellbeing in the second ques-
tionnaire were re-scaled 0—100, for the sake of comparison
with the EORTC-QLQ-C30 questionnaire. The subscores of
the latter were transformed to 0—100, as proposed in the
manual.
Sample size calculation
Since to our knowledge the standard deviation of intra-
individual differences was not reported in the relevant
literature at the time of study planning, the study was
designed to detect an effect of one third of a standard
deviation (Cohen’s d = 1/3). Accounting for an expected
drop-out rate of up to 25%, a study with 2 × 191 patients
would give 80% power based on a two-sided significance
level of 5%. We used the multiple imputation method with
50 simulation runs and constraints between 0 and 100 to
impute missing values for the second and the third visits. 19
Due to a non-monotone missing pattern, the Fully Con-
ditional Specification (FCS) method was employed. Each
group-specific imputation model comprised age, chemother-
apy (yes/no), metastases (yes/no), use of any other CAM
treatment (yes/no) as well as available measurements of
the respective outcome. Linear imputation models with
predictive mean matching were used, other than for dys-
pnea, insomnia, constipation, appetite loss and diarrhea.
For these, logistic imputation models were used since these
outcomes have only four categories each.
ANCOVA models were calculated on each of the 50
imputed data sets and results were summarized using
Rubin’s rules (proc mianalyze of SAS 9.3). In each model, the
difference between visits 3 and 1 of the respective outcome
was the dependent variable. The independent variables
were the randomized group, the respective baseline out-
come value (visit 1), age, use of any other CAM treatment,
chemotherapy, and metastases (gender and radiation ther-
apy did not prove significant nor to have any relevant impact
on the other effect estimates). For an unadjusted estimate
of the group difference, the group comparison was adjusted
solely for baseline outcome values. For the group-specific
changes, least squares estimates (with 95% confidence
intervals = 95% CI) depend on the values of the other
independent variables in the model. They are therefore
evaluated at median values for the covariates and factors
and are thus given for typical patients. Group differences
M. Frass et al.
of these changes are independent of the co-variables and
other factors (there are no interactions in the model due to
insignificance) and are presented as least squares means and
95% confidence intervals. p-Values for the secondary out-
comes (functioning scales and side effects) are corrected
for multiple testing using the method of Bonferroni—Holm.
p-Values of the two primary outcomes were not corrected
since the protocol planned reporting of the results of both
outcomes independently of their significance.
We performed a sensitivity analysis to investigate the
robustness of our assumptions concerning missing values at
visits 2 or 3 for the primary outcomes. For this purpose, the
imputed values were shifted in favor of the control group by
an increasing amount of 5, 10, 15 and 20 units (half of the
shift added in the control group and half of it subtracted in
the homeopathy group) using the ‘‘mnar’’ statement with
‘‘adjust’’ option within proc mi of SAS.
All p-values are the result of two-sided tests at the
(overall) significance level of 0.05. All computations were
performed with SAS software 9.4 (SAS Institute Inc., Cary,
NC, USA, 2012).
Results
Patients’ characteristics (Fig. 1 and Table 1)
The study screened 453 patients, of whom 43 did not consent
to participate. The remaining 410 were randomized. After
randomization, 37 patients dropped out (16 in the home-
opathy group, 21 in control). Thus, 373 patients received
allocated treatment (194 in the homeopathy group, and
179 in the control group). 335 patients 173 patients in
the adjunctive homeopathy group and 162 controls made
the first two of the planned three clinic visits and com-
pleted the two sets of questionnaires. 137 patients in the
homeopathy group and 145 controls attended the third visit
and completed the questionnaires (Fig. 1). Missing values
after baseline were imputed (see statistical analysis sec-
tion), whereas no information was available for the 37
patients who declined after randomization. Our analysis
set, therefore, comprises 373 patients. All were treated
as intended. Despite randomization, there was a marked
difference in age between the two groups (homeopathy:
55.4 ± 12.5 vs. control: 58.1 ± 11.2 years). There were no
relevant differences between the groups regarding gen-
der distribution, cancer diagnoses and metastatic disease
(Table 1). All patients were in tumor stages III or IV. The
type, frequency and duration of concurrent conventional
cancer therapy during the study, as well as the degree of
use of other palliative therapies, were similar in the two
groups, as was the use of antidepressants and corticoste-
roids. No adverse effects of the homeopathic treatment
were observed.
Changes in global health status and subjective
wellbeing between the first and third visits
The changes between visits 1 and 3 are summarized in
Table 2. In the homeopathy group, a significant improvement
in global health status by 10.6 (95% CI 5.3—15.9, p < 0.001)
and in subjective wellbeing by 20.9 (95% CI 15.6—26.2,
313
Influence of adjunctive classical homeopathy and subjective wellbeing in cancer patients
Assessed for eligibility (n=453)
Declined before consenting to
participate (n=43)
Randomized (n=410)
Allocated to intervention (n=210)
♦ De clined to parti cipate (n =16)
♦ Received allocated intervention (n=194)
st
♦ Answered questionnaires at 1 visit (n=194) Allocated to control (n=200)
♦ De clined to parti cipate (n =21)
st
♦ Answered questionnaires at 1 visit (n=179)
Answered questionnaires at 2 nd vi sit (n =173 ) Answered questionnaires at 2 nd vi sit (n =162 )
Answered questionnaires at 3 rd visit (n=137) Answered questionnaires at 3 rd visit (n=145)
Figure 1 Flow Chart
p < 0.001) were detected between the first and third visits
(numbers given are for typical patients of median age,
median respective baseline value, without chemotherapy
and without metastases — see statistics section). In the
control group, global health status (3.0; 95% CI 2.5—8.4,
p = 0.288) did not change significantly between the first
and third visits, while subjective wellbeing (6.1; 95% CI
0.3—11.9, p = 0.039) changed significantly.
Comparison of Changes in Global Health Status and
Subjective Wellbeing between the Adjunctive Homeopathy
Group and Control Patients (Table 2 and Fig. 2). The improve-
ment in global health status between visits 1 and 3 was
significantly greater in the homeopathy group by 7.7 (95%
CI 2.3—13.0, p = 0.005). A significant group difference was
also observed regarding subjective wellbeing by 14.7 (95%
CI 8.5—21.0, p < 0.001) in favor of the homeopathic as com-
pared with the control group. The scenarios of our sensitivity
analysis show that clinically relevant and statistically signif-
icant results are maintained for subjective wellbeing, even
for shifts of up to 20 units to the imputed values in favor of
the control group (Fig. 2).
Changes in Functioning Scores and Side Effects of
Chemotherapy between the First and Third Visits in Adjunc-
tive Homeopathy and Control Patients (Table 2).
In the homeopathy group, a clear improvement in func-
tioning (physical, role, cognitive, social and emotional) was
observed, all of it statistically significant after multiplicity
correction with the exception of physical functioning. Symp-
toms of fatigue also decreased significantly (p ≤ 0.001) while
changes in levels of pain, dyspnea, insomnia and appetite
loss did not reach statistical significance. Nausea, constipa-
tion and diarrhea worsened, albeit not significantly.
In the control group, a significant deterioration of phys-
ical functioning was detected. Except for fatigue, all side
effects increased, nausea and diarrhea increased even sig-
nificantly.
Comparison of Changes of Functioning Scores and
Side Effects of Chemotherapy between Adjunctive
Homeopathy and Control Patients (Table 2)
Compared with control patients, those in the homeopathy
group experienced a significant improvement in physical,
cognitive, social and emotional functioning. Homeopathic
therapy induced significantly less fatigue, pain, dyspnea and
appetite loss, compared with the control group. Nausea,
insomnia, constipation and diarrhea were also reduced,
albeit not significantly.
314
M. Frass et al.
Table 2 Comparison of first vs. third visits in the group with adjunctive homeopathy and in the group receiving conventional
treatment without adjunctive homeopathy (control), and differences of third vs. first visit between the two groups. Least squares
means and confidence intervals.
Homeopathy group
Mean a
b
Global health status
Subjective wellbeing b
Physical functioning b
Role functioning b
Cognitive functioning b
Social functioning b
Emotional functioning b
Fatigue c
Nausea and vomiting c
Pain c
Dyspnea c
Insomnia c
Constipation c
Appetite loss c
Diarrhea c
10.6
20.9
7.0
17.0
16.1
12.4
15.3
−19.5
4.0
−8.5
−9.7
−7.2
5.5
−0.9
8.2
LCL
5.3
15.6
1.8
9.3
10.2
5.2
8.7
−25.8
−1.6
−15.6
−17.8
−14.7
−2.6
−9.1
0.4
UCL
15.9
26.2
12.2
24.7
21.9
19.6
21.8
−13.1
9.7
−1.4
−1.6
0.2
13.6
7.2
16.1
Control group
Mean a
p
*
<.001
3.0
<.001 *
6.1
0.008 −6.5
<.001 *
8.4
<.001 *
2.4
<.001 * −1.1
<.001 *
0.9
<.001 * −0.9
0.163
8.9
0.018
8.4
0.018
2.2
0.057
1.0
0.184
9.5
0.822
9.0
0.039 12.5
Homeopathy vs. Control
LCL UCL p
−2.5
0.3
−11.0
0.6
−3.3
−7.8
−5.2
−6.9
3.9
1.9
−5.7
−6.3
2.6
1.9
5.2 8.4
11.9
−2.0
16.2
8.1
5.6
7.1
5.1
13.9
15.0
10.2
8.3
16.5
16.1
19.8 0.288
7.7
0.039
14.7
0.005 *
13.5
0.034
8.6
0.411
13.7
0.738
13.6
0.767
14.3
0.766 −18.6
<.001 * −4.9
0.011 −17.0
0.580 −11.9
0.790
−8.2
0.007
−4.1
0.013
−9.9
<.001 * −4.2
Mean
LCL UCL p
2.3
8.5
8.6
0.4
7.7
6.7
8.0
−24.7
−10.0
−23.8
−19.6
−15.6
−11.0
−17.1
−11.2 13.0
21.0
18.4
16.9
19.7
20.4
20.7
−12.4
0.3
−10.1
−4.3
−0.9
2.9
−2.7
2.8 0.005
<.001
<.001 *
0.040
<.001 *
<.001 *
<.001 *
<.001 *
0.066
<.001 *
0.002 *
0.029
0.251
0.007 *
0.235
a Least squares group means vary with covariate and factor values; the values reported here are evaluated at a median age of 57,
median baseline value of the respective outcome and without chemotherapy, metastases or any other CAM treatment.
b Positive change corresponds to improvement.
c Negative change corresponds to improvement.
* Significant after adjustment for multiple secondary outcomes using the method of Bonferroni—Holm.
LCL, lower confidence limit; UCL, upper confidence limit; confidence limits are the limits of a 95% confidence interval.
Figure 2 Forest Plot for the change in the primary outcome variables between visits 1 and 3 in homeopathic (H) and control
(C) group and for the group difference (H—C) of these changes. Error bars show least squares means and 95% confidence intervals.
Unadjusted results of unadjusted analysis (i.e. only adjusted for baseline outcome); adjusted results of the full model; S5, S10,
S15, S20: results of sensitivity analysis with shifts of 5, 10, 15 and 20 units added to imputed values in favor of the control group
(for details see statistics section). Confidence intervals not including zero indicate statistical significance.
315
Influence of adjunctive classical homeopathy and subjective wellbeing in cancer patients
Table 3 Use of other alternative/complementary meth-
ods (multiple answers possible, patients reported up to four
different methods).
Homeopathy
group
(n = 194)
Nutritional supplements,
such as vitamins
Bach flowers
Schuessler cell salts
Herbals (phytotherapy)
Mistletoe therapy
Acupuncture
Others
None
Control
group
(n = 179)
36 37
35
15
16
10
18
61
106 17
5
14
6
17
8
66
Patients’ use of CAM (Table 3)
A marked difference was demonstrated regarding the use of
other CAM methods, such as acupuncture, mistletoe ther-
apy, herbals, Schuessler cell salts, Bach flowers and vitamins
(Table 3). Control group patients used nutritional supple-
ments such as vitamins, as well as acupuncture, equally
often than those in the homeopathy group (Table 3), and
they used them throughout the study period. Table 4 lists the
homeopathic remedies used most frequently in the home-
opathy group. The remedies were prescribed at different
dosages (potencies from Q1 to Q30, as well as C6 to C200,
and as LM1 to LM30).
Discussion
In this phase II study, we offered cancer patients with
different malignancies structured access to homeopathy
Table 4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Most frequently used homeopathic remedies.
Phosphor
Sulphur
Natrium muriaticum
Lachesis
Pulsatilla
Arsenicum album
Nux vomica
Calcium carbonicum
Silicea
Lycopodium
Conium
Mercurius solubilis
Thuja
Sepia
Rhus toxicodendron
Ignatia
Kalium muriaticum
Chininum arsenicosum
Natrium sulphuricum
Staphisagria
133
84
64
63
47
46
39
38
27
26
25
25
19
17
16
14
12
11
11
10
in addition to their conventional treatment. The study
investigated the homeopathic method as such, not specific
remedies. In a pragmatic trial, we evaluated the whole
‘‘homeopathic package,’’ including exploration and med-
ication. To our knowledge, this is the first prospective
randomized controlled phase II study that has evaluated
the influence of complementary homeopathic treatment in
patients with malignancies treated at the same institution.
A non-randomized study was performed by Rostock et al.
where treatment of the two groups was administered in four
different institutions. 11 Their findings were similar to ours,
namely an improved quality of life (QoL) and a tendency to
decreased fatigue symptoms.
We observed that homeopathy used as a complemen-
tary modality to state-of-the-art cancer treatment improved
both global health status and subjective well-being, com-
pared with control group patients who did not receive
adjunctive homeopathic treatment. The improvement in
global health status and subjective wellbeing occurred
between the first and third visits in the homeopathy
group and was statistically significant. During the same
period, patients who received solely state-of-the-art onco-
logic treatment experienced a markedly lower decrease of
global health status and subjective wellbeing, in agreement
with recently reported data. 16 Thus, homeopathy patients
improved in contrast to control patients. Patients from
the adjunctive homeopathy group reported a significantly
greater improvement in physical, cognitive, social and emo-
tional functioning, as well as decreased fatigue, pain and
appetite loss, compared with control patients. We ruled
out the possibility that these improvements were associ-
ated with other additional supportive treatments, such as
increased use of antidepressants or corticosteroids in the
adjunctive homeopathy group, since we found no statistical
difference in their use between the two groups.
The factors influencing the increasing use of CAM meth-
ods by cancer patients were addressed in a recent study
in the context of whether their use may be associated
with perceived distress or poor compliance with standard
treatment. 20 In this study, the predictors for use of CAM were
younger age, progressive cancer and active coping behav-
ior. Surprisingly, use of CAM was not associated with poor
compliance regarding conventional medical treatment.
We added a complex homeopathic setting to conven-
tional care and tested it against conventional care alone
and found that it improves both wellbeing and QoL. The
study was not designed to show which component of homeo-
pathic treatment was effective, only that, from a pragmatic
point of view, patients benefit from additional homeopathic
treatment.
This study was an ‘add-on’ trial: the ‘standard anti-
cancer care’ and all other treatments were the same in both
groups, the only difference being addition of classical home-
opathic treatment for the patients in the treatment group.
In classical homeopathic treatment, other types of inter-
vention (e.g., nutritional supplements and acupuncture) are
normally discouraged. On the other hand, as is customary in
pragmatic trials, other complementary interventions were
not prohibited. Some patients, therefore, used additional
CAM techniques. It may be suggested that this could have
created additional variability and possible bias. By adding
use of other CAM methods to the multi-variable analysis of
316
M. Frass et al.
the primary outcomes as an additional factor, the treat-
ment effect estimate is adjusted for different use of any
other CAM in the two groups. With this being a pragmatic
trial, we were interested in the ‘net effect’ which reflects
effectiveness rather than efficacy. 21
A limitation of the study may be the heterogeneity
of cancer entities that it included. There were, however,
no significant differences between patients in the two
groups regarding gender distribution, cancer diagnosis and
metastatic disease. The type, frequency and duration of
concurrent conventional cancer therapy during the study
were similar in the two groups. Another possible limitation
of the study is the high attrition rate which may introduce
some bias; to counter this, we employed multiple imputa-
tion techniques. A sensitivity analysis showed that, at least
for subjective well-being, the results presented prove robust
to deviations from the missing at random assumption under-
lying the multiple imputation method.
The number of patients completing the third set of ques-
tionnaires was, however, low, and not for reasons of death or
clinically significant deterioration. We have no explanation
for the high attrition rate.
Despite randomization, we observed differences
between the groups at baseline with respect to the primary
outcome measures. ANCOVA models were used to adjust
the group comparisons not only for potential confounders
such as age or oncological therapy but also for different
levels of the outcome measures at the first visit. In this
way, potential regression-to-the-mean effects that may
be stronger in the group with poorer baseline values
were adequately met. 22 We have no explanation as to
why the number of patients completing the third set of
questionnaires was lower in the homeopathy than in the
control group. Another of the study’s limitations is that
outcome assessment took place on an unblinded basis and
that 37 patients quit the study after randomization without
even baseline measurements. The reason for declining
after randomization was obviously driven either by disap-
pointment at being allocated to the undesired group or by
late awareness of the additional pressure of homeopathic
consultations. Some participants allocated to the control
group were resentful or demoralized because they did not
receive the homeopathic treatment they had hoped for.
Resentful demoralization, however, may actually not have
been so great a problem, because only five more patients
in the control group declined to participate compared with
the homeopathy group.
The study’s limitations are those of all pragmatic trials:
frequently, treatments with moderate effects may bene-
fit from the lack of blindness and allocation concealment,
and patient preferences or beliefs can influence the out-
come of the study. This has been shown in empirical studies
which demonstrated that trials without or with inappro-
priate blinding and/or allocation concealment are often
(erroneously) more statistically significant than RCTs, which
are better controlled. 21,23,24 Whereas a pragmatic trial can
shed light on the overall performance of a treatment, it will
very often be difficult to identify the specific components
(or even biases) that explain this effectiveness.
A further limitation is the absence of a placebo control
group. This, however, does not disqualify a study, since many
conventional cancer studies are not placebo-controlled. 25,26
To overcome this limitation, we are currently performing a
double-blind placebo-controlled study to test whether the
results of the present study are reproducible under more
stringent conditions with longer follow-up.
The issue of ‘equipoise’ is often a controversial issue
in trials of treatment modalities where patients are likely
to have a strong preference for the treatment, which is
often applicable in CAM/homeopathy. The concern is that
only patients with a weaker preference will be prepared
to be included in the trial, with possible negative effects
on outcomes as compared with patients seen in routine
practice.
Homeopathy is controversial within the medical scien-
tific community, with heated discussion relating mainly to
the effectiveness of high potencies. Interestingly, thermo-
luminescence investigations have shown that high potencies
beyond Avogadro’s number exhibit physical properties, 27 and
a scattering of preclinical trials in homeopathy can already
be seen within conventional literature. 28,29 The role of the
homeopathic consultation vs. the homeopathic remedy as
being the possible main effect of the whole practice of
homeopathy must be kept in mind. Discussions about home-
opathy often include the role of placebo. This, however,
seems to be overemphasized. Hróbjartsson and Gøtzsche
have recently conducted a systematic review of clinical
trials in which patients were randomly assigned to either
placebo or ‘‘no treatment’’ groups. The authors found
little evidence in general that placebo has powerful clin-
ical effects, 30,31 and its role should thus be reconsidered.
The observed beneficial effects of homeopathic adjunc-
tive treatment, the lack of side effects as well as the low
cost of homeopathic remedies contrast with other poten-
tial medically or financially ‘toxic’ CAMs, taken without the
knowledge of the medical oncologist. The attitude toward
CAM was assessed in a study evaluating current knowledge,
attitudes and interests of medical students, general physi-
cians and gynecologists. 32 Doctors believed that CAM is most
useful in general medicine, supportive oncology, pediatrics,
dermatology and gynecology, whereas students believed
that dermatology, general medicine, psychiatry and rheuma-
tology offer opportunities.
Our findings may also be important because health-
related QoL is regarded as an important end-point in
oncological clinical trials. According to the results of our
study, QoL may be influenced on an individual level by
the described procedure or possibly by other CAM inter-
ventions that influence QoL. 33,34 It may be speculated that
such interventions could also influence the outcome in one
or other treatment branch, resulting in mistaken conclu-
sions about the study drug in question, particularly if there
is an imbalance in patient inclusion regarding the patient
characteristics mentioned above. It may thus be concluded
from the obvious frequency of CAM use by patients as well
as from the present data that clinical report forms should
include an analysis of CAM use during clinical trials to enable
statisticians to accurately analyze study outcome.
Conclusions
The results achieved in some three decades of research into
homeopathic cancer treatment do not yet justify use of
317
Influence of adjunctive classical homeopathy and subjective wellbeing in cancer patients
homeopathy as an alternative to conventional cancer ther-
apy. On the other hand, there is a growing corpus of evidence
indicating that homeopathy may play a significant role in
integrative oncology as a supportive therapy. We believe
our results bolster this view and suggest that global health
status and subjective wellbeing of cancer patients can be
significantly improved with homeopathic treatment. Addi-
tive homeopathic treatment could therefore be considered
a safe and supportive therapy for cancer patients.
Conflict of interest
No competing financial interests exist. No funding had been
obtained for this study from any source.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at
http://dx.doi.org/10.1016/j.ctim.2015.03.004.
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