A MULTICENTRIC CLINICAL VERIFICATION STUDY OF THE DRUGS PROVED BY THE COUNCIL
PROTOCOL TEAM
COORDINATORS including Programme Officers& Investigators
1. CHIEF CO-ORDINATOR:
DR. R.K. MANCHANDA, DIRECTOR GENERAL, CCRH, NEW DELHI.
2. CO-CHIEF CO-ORDINATOR:
DR. ANIL KHURANA, ASSISSTANT DIRECTOR, CCRH, NEW DELHI
3. CO-ORDINATOR:
DR. P.S. CHAKRABORTY, SCIENTIST-3, CCRH, NEW DELHI
4. Programme Officers and investigating officers
Sl.No.
Site
Code
City
Center
1.
Noida
Central Research
Institute
2.
Lucknow
3.
Kolkata
4.
Gudivada
5.
Puri
6.
Patna
7.
Port Blair
Homeopatic Drug
Research Institute
Regional Research
Institute for
Homoeopathy
Regional Research
Institute
Regional Research
Institute
Clinical Verification
Unit
Clinical Research Unit
1
Programme
Officers
Officer
incharge
Investigators
Officer
incharge
Officer
incharge
1.Dr. S. S. Nain,
Scientist -4
2. Dr. Pramodji
Singh
Scientist -4
Dr. N.R.Mondal
Scietnist -4
Dr. K.C. Das
Scientist -4
Officer
incharge
Officer
incharge
Officer
incharge
Officer
incharge
Dr. V.G. Prasad
Scientist -4
Dr. P.K. Pradhan
Scientist -2
Dr. V.K. Singh
Scientist -4
Dr. A.K. Prusty
Scientist -1
8.
Imphal
Regional Research
Institute
Regional Research
Institute
-do-
9.
Shimla
10.
Shillong
Clinical Research Unit
-do-
11.
Aizawl
Clinical Research Unit
-do-
12.
Agartala
Clinical Research Unit
-do-
13.
Dimapur
Clinical Research Unit
-do-
14.
Bhubaneswar Drug Proving
Research Unit
Guwahati
Regional Research
Institute
Chennai
Clinical Research Unit
-do-
15.
16.
1. INTRODUCTION
2
-do-
-do-do-
Dr. Ojit Singh
Scientist -4
Dr. Sunil S.
Ramteke
Scientist -4
Dr. U.K. Prusty
Scientist -1
Dr. T.S. Patole
Scientist -1
Dr. M.S. Ghosh
Scienist -4
Dr. M.R. Sarangi
Scientist -1
Dr. A.R. Sahoo
Scientist -1
Dr. Pratima Devi,
Scietnist -3
Dr. Ravi Kumar
Sadarla, Scientist-4
Homoeopathic Materia Medica is built upon signs and symptoms produced during proving
of the drug on healthy human volunteers, toxic effects as observed during accidental
poisoning or prolonged use of the drug, and clinical symptoms (observed to disappear
while drug is administered to sick person). The symptomatic data need to be clinically
verified on sick persons for their prescribing value before it is included in the
Homoeopathic Materia Medica, which forms the basis of clinical prescription of the
respective drug(s) on sick.
The Council had undertaken Clinical Verification of symptomatic data of 108 drugs,
including those proved by the Council and those, which have had fragmentary proving.
Studies on these medicines have already been completed. During the period of 2005 to
2013, the above said drugs completed their study. Consequently, another 16 such drugs
proved by the Council have been compiled and are proposed to be undertaken for clinical
verification in the present study.
1.1 Usefulness
Most of the medicines taken up for verification are of Indian origin. Provings of these
medicines indicate that many of these have vast potential for therapeutic use and thus their
verification will add help the profession. These findings assume significance in view of the
Government’s policy on indigenous medicinal plants, which lays emphasis on promoting
these drugs
2STUDY OBJECTIVES
2.1Hypothesis
The selected medicine on the basis of symptom similarity with those appearing in the drug
proving would result in annihilation of those symptoms or total relief of all the sign and
symptoms of the patient.
2.2Primary Objective
To clinically verify the symptomatology of the following 16 drugs
1.
Allium sativum
7.
Caesalpinia bonducella
2.
Amoora rohituka
8.
Cardiospermum halicacabum
3.
Asclepias currassavica
9.
Cyclosporin
4.
Avena sativa
10. Cynara scolymus
5.
Azathioprine
11. Foeniculum vulgare
6.
Buxus serpervirens
12. Gymnema sylvestre
3
13. Hygrophilla spinosa
14. Magnolia grandiflora
15. Persea americana
16. Psoralia corylifolia
4
2.3Secondary objective
To ascertain clinical symptoms (which were not observed during the proving but have
disappeared in the sick during the study either partially or completely and are not
mentioned in the referred literature).
3.STUDY DESIGN
3.1Type of Study
The study will be an open clinical trial in which patients will be enrolled from O.P.D. as and
when they come, after confirmation of their inclusion criteria as per protocol, till such time
that the target is achieved. The Homoeopathic medicines would be prescribed on the basis
of symptom similarity.
These individualistic symptoms of each case would be evaluated as per the Materia Medica
& ‘Repertorial index’, prepared on the basis of the symptoms obtained during the proving
of these drugs conducted under the Council and follow up of the patients would be
conducted periodically as specified in the protocol.
3.2Approach
The study designed to prove or disprove the hypothesis, i.e. “The selection of
Homoeopathic medicines on the basis of symptom similarity with those appearing in the
drug proving would result in annihilation of those clinical condition in the patients or total
relief of all the sign and symptom of the patient”.
3.3Duration of Study: Two years.
3.4 Study sites proposed
1.
Central Research Institute, Noida
2.
Homeopathic Drug Research Institute, Lucknow
3.
D.A.C. Regional Research Institute for Homoeopathy, Kolkata
4.
Regional Research Institute, Gudivada
5.
Regional Research Institute, Shimla
6.
Regional Research Institute, Puri
7.
Regional Research Institute, Imphal
8.
Regional research Institute, Guwahati
9.
Clinical Verification Unit, Patna
5
10. Clinical Research Unit, Port Blair
11. Clinical Research Unit, Shillong
12. Clinical Research Unit, Aizawl
13. Clinical Research Unit, Agartala
14. Clinical Research Unit, Dimapur
15. Clinical Research Unit, Chennai
16. Drug Proving Research Unit, Bhubaneswar
3.5Flow Chart of Study Design
Initial evaluation

History

Investigations as
needed

Screening of cases
Detailed screening for
assessment of symptom
similarity
Presence of severe
systemic diseases
If the indicated
medicine is from
outside the trial
drugs
Exclusion
(Treat the patients in
OPD)
Symptoms similarity with the
one of the trial drugs
No
Written informed
consent
Yes, register the
case
Prescription of
medicine from
assigned drugs
Assess the case
6
Change the
prescription, if no
response: refer the
case for appropriate
treatment
Reassess the case
if no improvement
4. SELECTION AND ENROLLMENT OF PATIENTS
4.1 Symptoms of assigned 16 drugs
4.2 Inclusion Criteria
1. Subjects from all age groups, irrespective of sex would be enrolled in the study.
2. Those presenting with minimum of three signs and symptoms matching with the
signs and symptoms ascribed to the selected drugs will only be enrolled in the
study.
3. Those who have not taken any medication for the past one week.
4.3 Exclusion Criteria
1. Those whose clinical presentations do not correspond with that of respective trial
medicines.
2. Those who are taking regular medication for systemic diseases such as Diabetes,
Hypertension etc.
5. STATISTICAL PLAN
5.1 Sample size

7200 cases will be initially be enrolled in the study.

480 cases of each drug.
5.2Statistical analysis
Data obtained during the study would be analyzed by using statistical method for each
symptom which will be verified on 30 or more patients.
7
6.PROCEDURES OF SELECTION OF MEDICINE
6.1 Case Recording:
A comprehensive case record on the specially evolved case recording proforma are
maintained and care is taken while recording the following

Detail evaluation of the complaints

Careful analysis of the characteristic nature of the symptoms: (Which should include
actuality of symptom(recent symptom or persistent old symptom); proving
symptom or symptom not described in previous published provings or clinical
symptoms modalities and level of detail, frequency of occurrence and accuracy)

Patient’s narration and Physician’s interrogation.

Past history.

Family history.

Menstrual history.

Obstetric history.

Physical and mental general.

Psychic features.

Constitution should be mentioned in respect to
 Physical makeup
 Colour in general
 Colour of hair and eyes
 Homoeopathic constitution
 Seasonal impact

Laboratory investigations

Totality of symptoms

Diagnosis
8
6.2 Selection of Medicine
Selection of medicine will be guided by the presenting signs and symptoms after
repertorisation. The prescription would finally be based on verifying the characteristic
symptoms of the medicine from Clinical Verification Materia Medica of the trial drugs
compiled by the Council for this study.
Any one of the selected medicine will be prescribed on the basis of presenting signs and
symptoms of the patient, which match the symptomatology of at least three symptoms of
the respective medicine.
A comprehensive case record on the specially developed case recording proforma will be
maintained.
The case so recorded will be analyzed and the evaluation of the symptomatology should
precede the selection of the medicine.
6.2.1 Justification of Prescription: Reasons for the initial choice of the medicine i.e.
totality, keynote(s); etiologic circumstances; clinical indications; global (physical, general
and mental) or repertorisation of symptoms; ‘meaning’ of patient’s problems (essence,
spirit, remedy problem) etc. are to be specified. More than one reason may be possible for a
case.
6.2.2 Potency & Dose
Assigned drugs will be available in 6C, 30C, 200C and 1M potencies and to be prescribed as
per the requirement of a case and to be given as per the direction laid down in Organon of
Medicine.
6.2.3 Follow up
For better confirmation, patient’s follow up may be for a longer period. Patients enrolled in
the study would be required to pay visit every week or earlier, if needed, for follow up &
assessment. In acute exacerbation state, frequency of visit should be on alternate day or
earlier. A pathological estimation to be made at a regular interval of 15 days or even earlier
as per the need.
In case of amelioration:
i.
If improvement continues → Placebo to continue.
ii.
If improvement stops → Repeat the medicine (first prescription) in the
same potency.
9
iii.
iv.
v.
Aggravation:
i.
ii.
iii.
Aggravation:
(i)
(ii)
If no further amelioration occurs even after medicine given in same
potency or improvement lasts for a very short period → next higher
potency of same medicine, may be given.
If amelioration of presenting complaints is accompanied by appearance
of old symptoms (according to Hering’s law of cure) → continue
placebo till the improvement continues.
If old symptoms come back to stay → repeat same medicine in same
potency and then followed as in (iii) above. In case there is no
perceptible improvement after adequate repetition of medicine in
different potencies, change of medicine is to be considered.
means
Worsening of existing symptoms.
Appearance of new symptoms.
Wrong direction of symptoms (if not according to Hering’s law).
Aggravation of presenting symptoms
a. Short aggravation followed by consistent amelioration
(homoeopathic aggravation):→ Continue placebo.
b. Aggravation of same symptoms without any relief: → change of
medicine is to be considered
Appearance of new symptoms
(a)
(b)
(c)
If new symptoms are mild and do not cause much concern to
the patient → placebo will be continued for one week.
If no improvement follows or worsening occurs after one week
→ change of medicine is to be considered.
If these new symptoms are severe and cause considerable
discomfort to patient → change of medicine/ therapy to be
considered.
No change:
No change in any of the symptoms either in frequency, duration or intensity (FDI).
In case of no change after first or subsequent prescriptions:
In case there is no perceptible improvement after adequate repetition of medicine in
different potencies, the investigator must look for any obstacle(s) for cure and steps
10
may be taken to remove them as far as possible. If no response, refer the case for
appropriate medical care.
6.3 Source of Medicine: Homoeopathic medicines for the trial would be procured from
licensed homoeopathic pharmacy, having GMP certification.
6.4 Change of Therapy: If there is no change in sign and symptoms of the patient after
adequate repetition of selected medicine or assigned medicines, in various potencies
judiciously, those patients will be treated in the general O.P.D. of the respective institution
and their records to be kept separately.
6.5 General supportive care: Advice the patient as follows:

Obstacle to cure for each cases must be find out and removed or minimized as
much as is possible.

A nutritious, well-balanced, healthy diet, regular exercise and hygiene must be
maintained.
6.6 Plan of treatment
The general management i.e. Non-medicinal and the indicated medicine together, to be
advised.
Non Medicinal Management: Advice the patient as follows:


Each and every case should be evaluated in depth to find out any known causative
factors etc., which should be removed or minimized.
A nutritious, well-balanced, healthy diet is recommended.
7. PROCEDURES AND METHODS
7.1 Enrollment
The enrollment procedure after presentation of participant to a specific site is as
follows:
Four stages for Participant selection
Stage 1:
Preliminary verbal screening by the OPD doctor for presence of inclusion criteria
Participants will be recruited from those coming to Out Patient Department (OPD) in
the institutes where the study has been assigned. While each site will evolve its own
advocacy procedures for attracting research subjects (advertisements, media, camps,
11
handouts, etc.), they will all follow the standard recruitment procedure. The procedure
involves a two stage screening prior to initiation of the consent procedure. The first
screening is a verbal screening by the attending physician in the OPD.
The OPD doctor will verbally screen the patients presenting with symptoms related to
the indicated medicine (s).
No details will be kept on the number of participants screened by the OPD doctors. It is
expected that the site investigators will ask the OPD doctor to screen as many patients
as possible. participants, who are of relevant sign & symptoms, will be sent to the
investigating officer for detailed and recorded screening.
Stage 2:
Detailed screening by the investigating officer for presence of inclusion criteria and
absence of all exclusion criteria (FORM A)
The investigating officer will examine the patient for the presence of inclusion criteria
and exclusion criteria. Those who are potentially eligible for the study will then be
subjected to Case Record Performa by the investigating officer.
A record will be maintained of the potentially eligible patients coming to for the detailed
screening in all the participating sites.
For a site to stay in the study a minimum of 30 patients must be enrolled in any month
period with proper follow-up must be more than 95%. In addition, the site must follow the
clinical and investigational parts of the protocol stringently. To complete the study within
the stipulated time frame, each site is required to make all efforts to enroll at least 30 cases
per month into the study.
Stage 3: Informed written consent of potentially eligible subjects
The purpose of the study will be explained to patients and oral informed consent to
participate obtained. The patients eligible to enter the study will be fully informed about
the study. The content of the explanation provided to the patients is described in the
attached consent form (FORM B1). The site investigator from all the Institutes/ Units
involved in the study will obtain the freely given, written consent of the patients in local
language & Hindi/ English, to participate in the study. A proposed written consent form is
attached (FORM B2). If the patient is not literate, a thumbprint may be substituted for
signature, duly witnessed by somebody in addition to the person requesting consent.
The Case history by using FORM C, will be performed as quickly as possible after the
second detailed screening.
12
The history should include daily living and typical activities for the patient.
Patients who are no longer eligible for the study at the completion of Case-taking will not
be enrolled in the study and receive usual care as clinically indicated. All the data will be
recorded.
The study personnel will explain and demonstrate to the patient how to take the medicine
at home at recruitment and at all subsequent follow-up visits.
Enrolled into study---
yes/no
Enrollment of consenter and registration
Drug pathogenesis is composed of the signs and symptoms obtained during the proving
conducted by the Council with the citation of references (as mentioned in bibliography).
7.2 Selection of rubrics for repertorisation
It will depend upon the presenting signs and symptoms of the cases enrolled. A list of
rubrics to be repertorized need to be enumerated.
7.3 Basis of prescription – to be indicated by the investigator in the Case Record.
8. ASSESMENT:
8.1 Periodical:
The ‘Zero’ will be the time of enrollment. The study personnel will call the patient
every week or earlier, if, need be, for the follow up visit and will examine the patient.
All the patients will be taught to recognize the signs of worsening illness. They will
be advised to report to the Institute/Units if any of the signs develop at any time
before the scheduled visit.
If the patient doesn’t report on a date (fixed) effort shall be made to contact him/her
in any way.
For uniformity, reaction of the patients are graded as per the international classification in
a systematic pattern as follows:
Mark Condition of patient
5
Observation by the
physician
Very spectacular changes in the total picture, all
symptoms are disappearing and the general state of
13
4
3
2
1
0
-1
-2
-3
-4
-5
health is completely improved
Spectacular disappearance of all symptoms with
improved general state of health
Disappearance of symptoms, start of a general health state
improvement
Good effect during the treatment but we are not convince
it will improve the patient completely, other therapies are
still needed
Some effect during the treatment but it could be due to
other factors (like placebo)
No effect
Some deterioration or aggravation during and/or after the
treatment but it could due to other factors (like nocebo)
Clear deterioration of the symptoms during and/or after
the treatment
Deterioration of the symptoms and start of alteration of
the general health state
Clear alteration of patient’s general state of health
Very spectacular alteration of complete patient’s health
state
5 (very spectacular changes in the total picture, all symptoms are disappearing and
the general state of the health is completely improved),
4 (symptoms disappeared, general state of health is also improved, but it is not too
rapid)
3 (disappearance of symptoms, with starting of improvement of general state of
health)
2 (good effect during the treatment, but it may requires other supportive
management)
1 (Some effect during the treatment but it could be due to other factors)
O (no effect)
-1 (Some deterioration or aggravation during and/or after the treatment but it
could due to other factors)
-2 (Clear deterioration of the symptoms during and/or after the treatment)
-3 (Deterioration of the symptoms and start of alteration of the general health state)
-4 (Clear alteration of patient’s general state of health)
-5 (Very spectacular alteration of complete patient’s health state)
14
For assessing causal relationship in homoeopathy, the following scale shall be used. A total
score of more than five, helps to assess causal relationship between remedy reaction and
remedy choice. (The table is given below)
Yes No Don’t know
1. Was the case similar to other cases with this medicine?
+1
0
0
2. Did the effect appear after administration of the
medicine?
+1
-1
0
3. Did the effect after one dose subside after a period of
time?
4. Was the improvement resumed after repeated
administration of the medicine?
5. Was there an initial aggravation?
6. Did the effect comprise more than the presented
complaint, e.g. wellbeing and other complaints, like in the
scale above
7. Did the course of improvement follow Hering's rule?
8. Did old symptoms reappear for a while in the course of
the improvement?
9. Are there alternate causes (other than the medicine)
that solely could have caused the improvement?
10. Did the patient have the same response to other
homeopathic medicines?
11. Was the effect confirmed by objective evidence?
8.2Degree of improvement:
+1
0
0
+2
-1
0
+1
+2
0
0
0
0
+2
+1
0
0
0
0
-3
+1
0
-1
+1
0
+1
0
0
1. Cured – complete disappearance of all signs & symptoms with restoration of all
biological functions.
2. Improved – reduction in duration, frequency and intensity of symptoms
3. Not Improved – no change in symptoms after sufficient trial of prescribed medicines
4. Worse – increase of number, frequency, intensity and duration of symptoms
5. Referred – referred for other therapy in the eventuality of any adverse event.
6. Withdrawal – case withdraws consent or refuses for further treatment.
7. Drop out – does not fulfil conditions as per the protocol.
8.3Schedule of Treatment Events
15
Sl.
No.
Time
Event
1
Day 1
Screening
2
Day 1-2
Consent, case recording and
repertorisation, inclusion into study
3
Day 1-2
Homoeopathic therapy initiated
4
Day 7
Weekly follow up, alternate day, as
required for a case
8.4 Criteria for withdrawal of patients
 It is the responsibility of the site investigator to maintain the patient in the study,
provided it is safe to do so.
 A patient may be discontinued from the study for any of the following reasons,
which must be documented on the appropriate case record form
a. Clinical failure after complete treatment
b. No change in symptomatology of the subject
c. Aggravation of complaints of the patient
d. Occurrence of a serious adverse events
e. No adverse events are expected during Homoeopathic therapy. But
adverse events may occur as the natural course of disease.
f. Patient withdraws consent
g. Protocol is not followed
8.5Data Collection and clinical care of withdrawal subjects
 Such patients will receive medical treatment as directed by their physician in the
O.P.D. of the Institute/ Unit
 Procedures at discontinuation of enrollment:
The site investigator is responsible for completion of all appropriate case report
forms up to the time that the patient is discontinued from the study.
16
8.6Record handling:
 Confidentially: All the evaluation forms, reports and other records are kept in
locked file cabinet. The patient is issued an identity card with unique
identifier number.
 There are forms that are completed by all the sites for each subject recruited,
including two consent form for the patient’s information and his/her written
consent for the enrolment in the study. All the reports are sent to
Headquarter at specified time.
Patient Identity Card for follow up
Name of the patient _________
__/___/__/__/
Unique Identifier No.
Project _Clinical Verification
enrollment:
Date of
Name of Investigator
Date of starting of Treatment __________
Follow up visits( to be mentioned on the back page)
P. T.O
Remark
s
Date
Week/da
y
Back side
17
8.7Dissemination, notifications and reporting:
 All data derived from the multi centric study are the property of Council.
 The principle papers on the primary and secondary outcomes emerging from
the multicentric study will be published under joint authorship (task force
study). The names of the scientists who have participated in the proposal
development and data analysis will be listed at the end of the paper in
alphabetical order and their specific contribution to the study will be
mentioned.
 Sites participating in the multi centric study will then be listed according to
their status in alphabetical order. Authorship issue for site investigators will
rest with the Director General of the Council. Each site team will be
encouraged to produce scientific manuscripts and technical reports based on
their site-specific data. Scientists will be encouraged to present the findings
at scientific conference and meetings with the prior approval of the Director
General, CCRH.
8.8 Study management at site
Each site will be responsible for setting up an information system to keep track of all
patients screened and enrolled and a filing system to keep all study records – case history
records, study protocol and or related documentation and drug distribution records. The
site investigator is responsible for the completeness and accuracy of the study material.
8.9 Case History records
These include the Case Report Forms (CRFs) that will contain information and
documents the subject’s ability to participate in the study (including a copy of a sign on
consent form) and information from tests and examinations. Whenever possible
copies of supporting documentation of the information contained in the study case
report forms should be kept with each patient’s case history records. All information in
the case history records should be attributable to a specific individual. Each subject’s
case history record will be evaluated to verify the validity and completeness of the data
on the CRF when a study monitor visits the study site.
Each CRF should be complete with follow up sheets and are to be maintained properly.
All corrections to the CRFs must be made without obscuring the original entry. The
revised entry should be inserted and the person making the correction should sign and
18
date the correction. Only authorized study personnel may complete or correct case
report forms.
8.10 Records retention
Retention of accurate and complete records is essential to establish the validity and
completeness of the study. All records must be retained for 5 years after the data set is
published.
9. Monitoring and Inspection:
9.1 Project Monitoring and Reviews
 Site visit is made by the monitoring officer between 3-6 months after
commencement of studies.
 Presentation of interim data by the investigator is made at Hqrs.
 Data review board will monitor the information with respect to deviation
from the study protocol, inappropriate enrolment of study subject, missed
observation etc. And suggest plan to rectify any problems at the site.
9.2 Interim assessment of the study
On the basis of interim report received from the different centers involved in the
clinical study, assessment will be made regarding progress of the clinical study,
Interim analysis will be placed before the Data Review Board for suggestions in
improvement or modifications, if required in the protocol. Data Review Board (DRB)
will also assess for compliance of protocol by the study site. Non compliance may
result into closure of study at particular site.
9.3 Quality control




Once the project has been approved cleared by the Scientific Advisory Committee
and Ethical Committee, a centralized workshop will be organized for research
officers (to be involved in specific study) to ensure standardization and quality
control.
A periodical review will be made at all the sites for quality assurance.
A random subset of records from each site will be evaluated for quality control.
Investigators will be asked to bring all medical records for selected subjects to data
analysis workshop. Information in the medical records will be compared with the
data on the case report form to assess completeness and accuracy of reported data.
10.DATA ANALYSIS AND MANAGEMENT
10.1Reporting Guidelines
19






All centers will send monthly report on case recruitment to headquarters
either by fax or e-mail on 1st to 4th of each month.
An interim assessment report of all the cases enrolled is to be submitted on
completion of 3rd, 6th, 9th month of the study.
An interim assessment report of all the cases enrolled is to be submitted on
completion of 1 year of the study.
Data review board will assess the research data as reported in 6 months
assessment form as well as first and second interim report.
On completion of each year a Master Chart is to be submitted.
Final assessment report on completion of the study is to be submitted to
Hqrs. in form of Concluding Report.
10.2 Data analysis Plan

Co-ordinating cell at CCRH Hqrs. will finally compile and analyze data
received from all the centers in consultation with Data Review Board.
10.3 Institutional Data Review Board

Institutional Data Review Board (IDRB) shall make Interim review of the data
of the study every six months
11.TRAINING
 A training module will be prepared detailing out various modes of training to
be imparted to the concerned staff at each of the centers of trial.
12.ETHICAL REVIEW
 Ethical clearance of the study has been obtained in the 11th meeting of the
ethical committee of CCRH.
13. SAFETY ASPECTS OF TRIAL DRUGS
All the drugs used in the study are homoeopathic pharmacopoeal preparations
and does not contain any toxic property posing threat to the human beings
except two drugs viz. Azathioprine and Cyclosporine, which are frequently been
used under modern system of medicine as immunosuppressive agents. But,
since these drugs will be used in 6C, 30C, 200C and 1M potencies, these are far
beyond the toxic levels in human beings, hence could safely be used for the
study.
14.LIMITATIONS OF STUDY
20
Non achievement of sample size at a particular site/centre –

In case of non achievement of sample size in the study period, there will be
option for extension of the study for a further limited period after due approval
of Scientific Advisory Committee of the Council.

If a particular site/centre fails to achieve the sample size in first 6 months, or
is not complying to the protocol, the study will be discontinued and there will be
an option for inclusion of one more centre after due approval of Scientific
Advisory Committee.
15.TIME LINE
Sl.
No.
1
EVENT
Period for the
Event
Draft protocol, submit to EC IDRB
Constitution and 1st meeting of the Data Monitoring
committee
2
Pre-trial preparations:
already available
Organize purchase of drugs, equipment, furniture, etc.,
printing of programmes for data entry and management
3
Quality assurance workshops
(For standardized training of appointed investigators at all
centres in outcomes assessment, data collection, reporting,
etc.)
Will be conducted
latter, if required
4
Recruitment in main study
Already available
5
6
Quality assurance site visits:
Interim analysis
3-6 months
At every 3 months
7
Subsequent meetings of Data Monitoring Committee*
As and when will
be required
8
Data compilation and analysis
At conclusion of
study
*The Data Monitoring Committee can meet at any time on the call of the Chairperson.
21
FORM A
Site Code ______________________ Date ________________
O.P.D. Registration No. …………………….. Screening number __________
Detailed Screening Form
1. Name of the Patient ………………………………………………………………
2. Age _____________
3. Sex:
Male/Female
4. Reason for OPD attendance: (symptoms for which the patients has reported in the
OPD)
1.
22
2.
3.
4.
5.
5. Whether Suffering From:
H/o Systemic disease severe (Diabetes mellitus/
Hypertension, etc.)
Yes
No
Taken any other medication in the past one week
Yes
No
If ‘Yes’ to the above in Column 5, exclude the patient from the study.
If ‘No’ to Column 5, then include.
IF INCLUDED, PROCEED TO FORM B (informs the patient as per information sheet FORM
B1 and get the written consent as per FORM B2)
Selected for Case taking
Yes / No
Signature
Investigator
Signature
In-charge of the Institute /Unit
23
FORM B1
Patient Information Sheet
Unique identifier _ _ _/ _ _ _ / _ _ _/ _ _ _/CV/I1/I2/I3
(Site code/ O.P.D. Regd. No./Screening No./Research case No.)
Clinical Verification of the reliability of symptoms of 35 drugs includes drugs proved by the
Council, mostly of indigenous origin and scattered in homoeopathic literature.
Purpose of the study
Clinical Verification of all or part of the symptom picture established in a homoeopathic
drug proving is designed to further demonstrate the potential clinical applicability of
homoeopathic medication.
Study procedures
Now you have been screened. We invite you to enroll yourself in this study. If you are
willing to enroll in the study, you will be assessed for the trial for inclusion criteria and you
will be required to undergo certain laboratory investigations, if required, from time to time
free of cost as deemed fit by the Research Scientist. You would also be examined by the
attending Research Scientist for the status of the disease. Once enrolled into the study you
will be given certain Homoeopathic medicines for your complaints. The medicines would
be prescribed free of cost to you. You will not know the contents of the medicines
prescribed to you during the trial period but this information will be available to the
Research Scientist. Medicine will be supplied in the form of sugar globules, which will have
to be given in doses as deemed fit for you. You would not be allowed to take any other
medication Allopathic, Homoeopathic, Ayurvedic, Herbal etc., without the prior permission
of your attending Research Scientist. If you were already taking any medicine you would be
required to tell the Research Scientist concerned. You will be required to be present for
follow up every week after commencing the treatment.
Risks from the study
No serious risks are anticipated in this study. We are assuming that you will recover after
homoeopathic treatment given in this trial. However, it is possible that you may not
recover completely. You will be closely followed up and additional treatment will be
administered, if necessary. The homoeopathic treatment is one of the commonly used
treatments. It has a good safety profile.
Benefits from the study
The benefits to you will be that you will be provided close medical follow up free of cost by
a separate physician and will not be required to wait. All medications and investigations for
this study will be provided free of cost. The results of this study may benefit society at
24
large, by providing information that may justify treatment of patients that will result in
considerable cost savings.
Complications
We do not anticipate any serious complications during the study. However, complications
may rarely arise during the course of the study, due to the medicinal aggravation.
Treatment of such complications will be carried out as required at no cost to you. No
financial compensation, however, will be provided for such complications.
Compensation
There will be no other financial compensation for participation in the study.
Confidentiality
All information collected in this study will be kept strictly confidential except as may be
required by law. You will not be identified by name if the results of the study are
published.
Rights of the participants
Participation in the study is voluntary. Refusal to participate will not influence your care in
this centre in any way. Though we would like all study participants to complete the study,
you are free to withdraw from the study at any time during the course of the study. If at
any time during the course of the study, you have any questions or concerns related to the
study, you are free talk to your doctor. In case of any further enquiry, you may contact the
following doctor:
Director General, Central Council of Research in Homoeopathy, 61-65, Institutional area,
opp. D-block, New Delhi 110058. Phone numbers 28525523, Fax:91-11-28521060, e mailccrh@del3.vsnl.net.in
Alternatives to participation in the study
You will be seen by one of the doctors in the Institute/ Unit and provided treatment
according to the regular treatment protocol of the institute.
25
FORM B2
Informed Written Consent Form
Unique identifier _ _ _/ _ _ _ / _ _ _/ _ _ __/CV/I1/I2/I3
(Site code/ O.P.D. Regd. No./Screening No./Research case No.)
Consent
I have had the study explained to me and have read the contents of this form / had the
contents of this form read to me and I have understood the same. I have been given the
opportunity to ask questions and have them answered to my satisfaction. I am willing to be
enrolled in the study.
Name of the Patient :
Signature of patient ______________________________ Date _______________
Signature of Investigator __________________________ Date __________
(Name of the Investigator __________________________________________________)
Signature of Attendant/Witness (in case, if patient is minor) ______________________
Date _______
(Name of Attendant /Witness __________________________________________)
26
FORM C
UNIT/INSTITUTE___________________________________________________________________
_________________________________________________________________________________
Under
Central Council for Research in Homoeopathy,
Deptt. of AYUSH, Ministry of Health & Family Welfare, Govt. of India, New Delhi.
CASE RECORDING PROFORMA (CLINICAL VERIFICATION)
Registration No:……………………………….
Date of Registration: ………………………………
Name: ---------------------------------------------------Father/Husband’s Name: -----------------------------------
Age: ------------Sex. ………Religion…………….. Marital status:……………. Occupation:----------------
Address:…………………………………………………………………………………………………….
…………………………………………………………………………Tel. No.…………………………..
Provisional diagnosis: ………………………………………………………………………………………
27
A. INTERROGATION:
I.
PRESENTING COMPLAINTS:
(a)
Chief Complaints with Duration (Verbatim)
1.
2.
3.
4.
5.
(b)
Location
Further details about presenting complaints in respect of location,
sensation, extension, modalities and concomitants.
Sensation
Modalities
c) History of present complaints:
28
Concomitants
Extension
II.
CHARACTERISTIC PHYSICAL GENERALITIES

Thermal reaction(Relation to heat and cold): - hot/chilly/ambithermal/sensitive to
both





Desires/Craving: Aversion/Dislikes: Intolerance to:Appetite (loss of/decreased/increased/voracious) : Thirst (absent/decreased/increased/small quantity/large quantity/short
interval/long interval): Tongue :Taste (loss of/bad/bitter/ saltish / soapy/ sweetish/ if any other specify……) : Stool (character & frequency): Urine [(character & frequency- (D/N)]: Perspiration (scanty/normal/profuse): (location & character) :-








Sleep [position & character( disturbed/light/deep/refreshing)] :Dream: - (nature)
Others: -
III. Characteristic Mental Features:
IV. PAST HISTORY:
V. FAMILY HISTORY:
VI. PERSONAL HISTORY (Additional information including Menstrual/Obstetric History)
VII. TREATMENT HISTORY:
29
GENERAL STATUS & PHYSICAL EXAMINATION:
Built: ………………….
Nutrition:………………
Height:……………
Weight:………………….
Anaemia: ……………….
Jaundice: …………….
Cyanosis:……………….
Oedema: ……………….
Skin-----------------
Lymph nodes:(cervical, auxiliary, inguinal) ……………………………………
Blood pressure: ………/………. Pulse rate: ……………………………………
Temperature: …………………….Respiratory rate: …………………………….
Tongue: ------------------------------------
C. SYSTEMIC EXAMINATION:

Respiratory system: -

Cardiovascular system: -

Central Nervous system: -

Gastro-intestinal system: -

Genito - urinary system

Musculo-skeletal system: -

Special organs-Eye, Nose, Ears: -
30
D. LABORATORY INVESTIGATIONS:






Hematological investigations: - (mandatory)
Urine examination (R/M): - (mandatory)
Stool examination (R/M): -(mandatory)
Radiological investigation: Ultrasonography: Others: -
E. SYMPTOMS
Sl.
No.
Symptoms of the
patient
Corresponding rubrics
31
Verification Drugs
covering the symptom
Sl.No.
Symptoms not seen in any of the clinically verified drug
F. REPERTORIZARION RESULT
G. BASIS OF SELECTION OF DRUG (Justification of prescription)
(Any peculiar indication as regard to - location, sensation, modality, extension &
concomitant, characteristic indication, uncommon, peculiar indication, keynote indication,
pathological or clinical indication, others- (if any) etc.)
H. PRESCRIPTION
Date
Name of medicine and potency
Dosage
Number of days
NOTE: - 1. Case taking should be in legible writing
2. No column should be left blank
3. NP- nothing particular
4. NK – not known
Signature
Signature
Investigator
Incharge of the Institute /Unit
32
FOLLOW UP PROFORMA:
1.
Name of Patient…………………………………………..
Date
Symptoms of the patient at
previous visit
Case No. ……………
Response to Treatment
Additional symptoms in this visit
New Symptoms in this visit
Analysis /Remarks
33
2. For uniformity, reaction of the patients are graded as per the international
classification in a systematic pattern as follows:
Mark Condition of patient
5
4
3
2
1
0
-1
-2
-3
-4
-5
Observation by the
physician
Very spectacular changes in the total picture, all
symptoms are disappearing and the general state of
health is completely improved
Spectacular disappearance of all symptoms with
improved general state of health
Disappearance of symptoms, start of a general health state
improvement
Good effect during the treatment but we are not convince
it will improve the patient completely, other therapies are
still needed
Some effect during the treatment but it could be due to
other factors (like placebo)
No effect
Some deterioration or aggravation during and/or after the
treatment but it could due to other factors (like nocebo)
Clear deterioration of the symptoms during and/or after
the treatment
Deterioration of the symptoms and start of alteration of
the general health state
Clear alteration of patient’s general state of health
Very spectacular alteration of complete patient’s health
state
3.
Yes No Don’ know
1. Was the case similar to other cases with this medicine?
+1
0
0
2. Did the effect appear after administration of the
medicine?
3. Did the effect after one dose subside after a period of
time?
4. Was the improvement resumed after repeated
administration of the medicine?
5. Was there an initial aggravation?
6. Did the effect comprise more than the presented
complaint, e.g. wellbeing and other complaints, like in the
+1
-1
0
+1
0
0
+2
-1
0
+1
+2
0
0
0
0
34
scale above
7. Did the course of improvement follow Hering's rule?
8. Did old symptoms reappear for a while in the course of
the improvement?
9. Are there alternate causes (other than the medicine)
that solely could have caused the improvement?
10. Did the patient have the same response to other
homeopathic medicines?
11. Was the effect confirmed by objective evidence?
+2
+1
0
0
0
0
-3
+1
0
-1
+1
0
+1
0
0
4.Degree of improvement:
Sl. No.
Degree of improvement
1
2
3
4
5
6
Cured
Improved
Not Improved
Referred
Withdrawal
Drop out
Remark
After how many
days and dose
ADDITIONAL REMARKS
1.
Most indicated and efficacious Homoeopathic medicine
2.
Clinical symptoms of Homoeopathic medicine found to be effective
3. Relapse of the symptoms during observation period
(i)
No. of Relapses
(ii)
Duration of each Relapse
4. Any Homoeopathic aggravation, if yes, specify
Medicine causing aggravation
5. PRESCRIPTION:
Date ………….. Name of medicine and potency ………………………..….
Dosage ………
Number of days……………….
35
6. Justification of the prescription
7. Name of the medicine whether same or changed, with justification –
S. No.
Date
Medicine
Potency
Justification
Signature
Response
Signature
Investigator
Incharge of the Institute /Unit
36
Contd. till
(mention
the date)
Reporting Proforma I
MONTHLY REPORTING PROFORMA
(To be submitted to Hqrs.)
Reporting Month …………………….
1.
Name of the Institute/Unit:
2.
Title of Study
council
3.
Name of Investigator (s)
4.
Staff Engaged in the Project:
5.
No. of cases attended in GENERAL O.P.D. of the Institute / Unit
A Multicentric clinical verification of pathogenesis of the drugs proved by the
New
Old
Total
6.
No. of cases screened for the Study
7.
No. of Research Cases enrolled for the study during reporting
period:
Allium sativum
Amoora rohituka
Apium graveolens
Asclepias currassavica
Avena sativa
Azathioprine
37
T
M
F
Buxus serpervirens
Caesalpinia bonducella
Cardiospermum halicacabum
Cyclosporin
Cynara scolymus
Foeniculum vulgare
Gymnema sylvestre
Hygrophilla spinosa
Magnolia grandiflora
Persea americana
Psoralia corylifolia
Total Research Cases
8.
No. of cases not included in the study
9.
No. of Research Cases Registered since inception
1
0.
Registration no. of case records enclosed
Note: Enclose photo copies of two case records and summary of all the cases registered
during the reporting month and follow up sheet for the case record submitted with the
previous monthly reports.
38
11. Follow-up action report in respect of Cases not included in the study
S.No. Ref. No.
Name
Age Sex
(OPD reg.
No./Screening
no.)
Signature
Reason
Action
taken
Rx
Signature
Investigator
Incharge of the Instt./Unit
39
Reporting Proforma II
INTERIM REPORT
( After 3,6,9 months)
(To be submitted to Hqrs.)
Period of Interim Report: ……………………………………………..
1
.
Name of the Institute/Unit:
2
.
Title of Study
the council
A Multicentric clinical verification of pathogenesis of the drugs proved by
Primary Objective of the Study: To evolve clinically verified complete pathogenesis of the
35 drugs under study
Secondary Objectives of the Study:
To ascertain –


3
.
Additional symptoms, which respond to the respective drugs.
Clinical symptoms (which were not observed during proving but seen to have
disappeared in the sick during the study).
Name of Reporting Officer
4. Staff Engaged in the Project:
Name
Qualification
Designation
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
40
…………………………
5.
………………………………
…………………………….
No. of cases attended in GENERAL O.P.D. of the Institute / Unit
New
Old
Total
6.
No. of cases screened for the Study
7.
No. of Research Cases Studied during reporting period:
Allium sativum
Amoora rohituka
Asclepias currassavica
Avena sativa
Azathioprine
Buxus serpervirens
Caesalpinia bonducella
Cardiospermum halicacabum
Cyclosporin
Cynara scolymus
Foeniculum vulgare
Gymnema sylvestre
Hygrophilla spinosa
Magnolia grandiflora
Persea americana
Psoralia corylifolia
41
T
M
F
Total Research Cases
8.
No. of cases not included in the study
9.
No. of Research Cases Registered since inception
3. Problems faced, if any
3.1
Suggestions for rectifying these problems
4.
Any Special Achievement
5. Number of sheets attached*: ____________________________
*Attach one supplementary sheet for each individual drug
Signature
Signature
Investigator
In-charge of the Institute./Unit
42
43
Prescribing Symptoms /
Additional Symptoms/
Clinical Symptoms
T M F T M F
Signature
Investigator
44
T M F T M F
T
M F
Signature
In-charge of the Institute./Unit
Remark
Clinical conditions verified for each
symptom
Duration of Treatment
No. of cases wit worsened
(and clinical condition found worsen
mentioned in Remark column)
No. of cases with no change
(and clinical condition found no change
mentioned in Remark column)
No. of cases improved
(and clinical condition found improved,
mentioned in Remark column)
No. of cases completely disappeared
(and clinical condition found cured,
mentioned in Remark column)
Duration of complaints
Potency
No. of cases prescribed
Supplementary sheet
(Analysis of symptoms)
NAME OF THE DRUG:
Response to treatment
Reporting Proforma III
ANNUAL REPORT
(On completion of 1 yr.)
(To be submitted to Hqrs.)
Period of Annual Report: ……………………………………………..
1
.
Name of the Institute/Unit:
2
.
Title of Study
council
A Multicentric clinical verification of pathogenesis of the drugs proved by the
Primary Objective of the Study: To evolve clinically verified complete pathogenesis of the 35 drugs
under study
Secondary Objectives of the Study:
To ascertain –


3
.
Additional symptoms, which respond to the respective drugs.
Clinical symptoms (which were not observed during proving but seen to have disappeared in the
sick during the study).
Name of Reporting Officer
4. Staff Engaged in the Project:
Name
Qualification
Designation
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
45
5.
No. of cases attended in GENERAL O.P.D. of the Institute / Unit
New
Old
Total
6.
No. of cases screened for the Study
7.
No. of Research Cases Studied during reporting period:
Allium sativum
Amoora rohituka
Asclepias currassavica
Avena sativa
Azathioprine
Buxus serpervirens
Caesalpinia bonducella
Cardiospermum halicacabum
Cyclosporin
Cynara scolymus
Foeniculum vulgare
Gymnema sylvestre
Hygrophilla spinosa
Magnolia grandiflora
Persea americana
Psoralia corylifolia
Total Research Cases
46
T
M
F
8.
No. of cases not included in the study
9.
No. of Research Cases Registered since inception
3. Problems faced, if any
3.1
Suggestions for rectifying these problems
4.
Any Special Achievement
5. Number of sheets attached*: ____________________________
*Attach one supplementary sheet for each individual drug
Signature
Signature
Investigator
Incharge of the Institute./Unit
47
Prescribing Symptoms /
Additional Symptoms/
Clinical Symptoms
T M F T M F
Signature
Investigator
48
T M F T M F
T
M F
Signature
In-charge of the Institute./Unit
Remark
Clinical conditions verified for each
symptom
Duration of Treatment
No. of cases wit worsened
(and clinical condition found worsen
mentioned in Remark column)
No. of cases with no change
(and clinical condition found no change
mentioned in Remark column)
No. of cases improved
(and clinical condition found improved,
mentioned in Remark column)
No. of cases completely disappeared
(and clinical condition found cured,
mentioned in Remark column)
Duration of complaints
Potency
No. of cases prescribed
Supplementary sheet
(Analysis of symptoms)
NAME OF THE DRUG:
Response to treatment
Reporting proforma IV
Master Chart of One year
Sl.
No
.
Reg.
No.
Age
Sex
P/
D
Symptom
s
Duratio
n of
sympto
m
Dru
g
Poten
cy
Dosag
e
Durati
on of
treat
ment
Signature
Signature
Investigator
Incharge of theInstitute./Unit
49
Respon
se
Observ
tion
Reporting Proforma V
CONCLUDING REPORT
(To be submitted to Hqrs. after completion of project)
Period of Study: ……………………………………………..
1
.
Name of the Institute/Unit:
2
.
Title of Study
council
A Multicentric clinical verification of pathogenesis of the drugs proved by the
Primary Objective of the Study: To evolve clinically verified complete pathogenesis of the 35 drugs
under study
Secondary Objectives of the Study:
To ascertain –


3
.
Additional symptoms, which respond to the respective drugs.
Clinical symptoms (which were not observed during proving but seen to have disappeared in the
sick during the study).
Name of Reporting Officer
4. Staff Engaged in the Project:
Name
Qualification
Designation
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
…………………………
………………………………
…………………………….
50
5..
No. of cases screened for the Study
6.
No. of Research Cases Studied during reporting period:
Allium sativum
Amoora rohituka
Asclepias currassavica
Avena sativa
Azathioprine
Buxus serpervirens
Caesalpinia bonducella
Cardiospermum halicacabum
Cyclosporin
Cynara scolymus
Foeniculum vulgare
Gymnema sylvestre
Hygrophilla spinosa
Magnolia grandiflora
Persea americana
Psoralia corylifolia
Total Research Cases
7.
No. of cases not included in the study
51
3. Problems faced, if any
3.1
Suggestions for rectifying these problems
4.
Any Special Achievement
5. Number of sheets attached*: ____________________________
*Attach one supplementary sheet for each individual drug
Signature
Signature
Investigator
Incharge of the Institute./Unit
52
CONCLUDING REPORT
Period of study:
1.
Name of the Institute/Unit:
2.
Title of Study:
Primary Objective of the study: To evolve clinically verified complete
pathogenesis of the 34 drugs under study.
Secondary objectives of the Study:
To ascertain
Additional symptoms, which respond to the respective drugs.

Clinical symptoms (which were not observed during proving but seen to
have disappeared in the sick during the study).
3.
Name of Reporting Officer :
4.
Staff engaged in the project:
Name
Designation
5.
Qualification
No of cases attended in
general O.P.D of the
Institute/Unit
T
M
F
New
Old
Total
6.
No. of cases screened for the
Study
7.
No. of research cases studied
during reporting period:
So far (June
2010- March
2013)
T
53
M
F
During the reporting
period(April’12March’13)
T
M
F
Agave americana
8.
Total Research Cases
9.
No. of cases not included in
the study -
10.
No. of Research Cases
Registered since inception
Signature
Signature
Investigator
Incharge of the Institute./Unit
54
Prescribing Symptoms /
Additional Symptoms/
Clinical Symptoms
T M F T M F
Signature
Investigator
55
T M F T M F
T
M F
Signature
In-charge of the Institute./Unit
Remark
Clinical conditions verified for each
symptom
Duration of Treatment
No. of cases wit worsened
(and clinical condition found worsen
mentioned in Remark column)
No. of cases with no change
(and clinical condition found no change
mentioned in Remark column)
No. of cases improved
(and clinical condition found improved,
mentioned in Remark column)
No. of cases completely disappeared
(and clinical condition found cured,
mentioned in Remark column)
Duration of complaints
Potency
No. of cases prescribed
Supplementary sheet
(Analysis of symptoms)
NAME OF THE DRUG:
Response to treatment
Reporting proforma VI
Master Chart of Enrolled Cases
Sl.
No
.
Reg.
No.
Age
Sex
P/
D
Symptom
s
Duratio
n of
sympto
m
Dru
g
Poten
cy
Dosag
e
Durati
on of
treat
ment
Signature
Signature
Investigator
Incharge of theInstitute./Unit
56
Respon
se
Observ
tion
References:
1. Central Council for Research in Homoeopathy; Homoeopathic Drug Provings (Conducted by
Central Council for Research in Homoeopathy); CCRH, New Delhi.
2. Allen, Timothy F.; The Encyclopedia of Pure Materia Medica; B. Jain Publishers Pvt. Ltd.,
New Delhi; Reprint Edition, 1986.
3. Allen, Timothy F.; Handbook of Materia Medica and Homoeopathic Therapeutics; B. Jain
Publishers Pvt. Ltd., New Delhi; Reprint Edition, 2001.
4. Anshutz, E. P. Dr.; New, Old & Forgotten Remedies; B. Jain Publishers Pvt. Ltd., New Delhi;
Second edition 1996, Reprint Edition 2002.
5. Boericke, William; Boericke’s New Manual of Homoeopathic Materia Medica; B. Jain
Publishers Pvt. Ltd., New Delhi; Third Revised and Augmented Edition Based on Ninth
Edition, 2007.
6. Clarke, John Henry; A Dictionary of Practical Materia Medica; B. Jain Publishers Pvt. Ltd.,
New Delhi; Reprint Edition, 2006.
7. Cowperthwaite, A. C.; A Text-book of Materia Medica and Therapeutics, Characteristics,
Analytical and Comparative; B. Jain Publishers Pvt. Ltd., New Delhi; Reprint Edition, 2001.
8. Ghose, Sarat Chandra; Drugs of Hidoosthan with Their Homoeopathic Uses, Provings and
Clinical Veifications; Hahnemannn Publishing Co. Pvt. Limited, Calcutta; 8th Edition, 1980.
9. Hering, C.; The Guiding Symptoms of Our Materia Medica; B. Jain Publishers Pvt. Ltd., New
Delhi; Reprint Edition, 1986.
10. Ministry of health and family welfare, Indian system of medicine and homoeopathy, Govt. of
India; Homoeopathic Pharmacopoeia of India;
11. Hughes, Richard and Dake. J. P; A Cyclopaedia of Drug Pathogenesy; World Homoeopathic
Links; New Delhi; First Indian Edition, 1979.
12. Lippe .Adloph Von Dr.; Key Notes and Red Line Symptoms of The Materia Medica; B. Jain
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