CHALLENGES IN CONDUCTING CLINICAL TRIAL (STUDY) FOR … · Dabur India Ltd 1. DISCLAIMERS •The...

CHALLENGES IN CONDUCTING CLINICAL TRIAL (STUDY) FOR

AYUSH AND HERBAL MEDICINES

CLINICAL TRIAL (STUDY) ON AYUSH & HERBAL MEDICINE

Dr.Vedula Sasibhushan

Senior manager; DRDC,

Dabur India Ltd

1

DISCLAIMERS

• The views and opinions expressed in this presentation are of presenter and do not necessarily represent the official position of Company / Institute

• Current and future legislation must be taken in to account when referring to the views expressed in this presentation

• These slides should not be copied or reproduced as such without the permission of the presenter.

227-06-2019CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE

AYURVEDA

• Ayurveda is ancient medical system with sound philosophical and

experimental basis.

• Main principal of Ayurveda is “ Swasthyasya Swasthya Lakshanam”

• Ayurveda comprised of physical, psychological, philosophical, ethicals and

spirutual health

27-06-2019CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE 3

HERBAL PRODUCT CATEGORIES

• ASU Drug - India

• Phytopharmaceuticals - India

• Nutraceuticals– India

• Dietary Supplements – USA

• Natural Health Products – Canada

• THMPD (Traditional Herbal Medicinal Product) – EU

• Complementary Medicine – Australia / Newzealand

• Traditional Medicines: GCC / Saudi Arabia

27-06-2019

CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE

4

27-06-2019


5

Laws Regulating Herbal Product in India

• ASU Drugs - Drug & cosmetic Act 1940 & rules 1945, Chapter IV A

• Schedule T - Good manufacturing practices (GMP)

•Drugs & Magic Remedies Act (DMRA)

• Biodiversity Act 2002 & Rules 2004

• Indian Patents Act

•ASU GCP

• Legal Metrology Act 2009

• Nutraceuticals—FSS Act 2006—FSS Regulation 2011—Nutraceuticals– 2016

• Phytopharmaceuticals –2015

HERBAL DRUG DEVELOPMENT _ KEY STEPS

• Traditional text search

• Modern literature search

• License type

• Formulation development

• Packaging development

• Stability studies


• Efficacy screening

• Safety studies

• Clinical studies

• License application

• Label design

• Claims

• Marketed…

ASU DRUGS

27-06-2019


10

“Phytopharmaceutical drug” includes purified and standardized

fraction with defined minimum four bio-active or phyto-

chemical compounds (qualitatively and quantitatively assessed)

of an extract of a medicinal plant or its part, for internal or

external use of human beings or animals for diagnosis,

treatment, mitigation or prevention of any disease or disorder

but does not include administration by parenteral route.

Phytopharmaceutical Drug


27-06-2019

HERBAL DRUG DEVELOPMENT IN INDIA

12Total 99 books including Sidha and Unani

SCHEDULE E(1): LIST OF POISONOUS SUBSTANCES IN AYURVEDA

27-06-2019

HERBAL DRUG DEVELOPMENT IN INDIA

13‘to be taken under medical supervision’

AYUSH GUIDELINE

27-06-2019 14CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE

NPD

• Conventional method for

molecular drug approach- New

chemical entity

• First In Human


NEUTRACEUTICALS

• Vitamins

• Micro nutrients

• Functional Food

• Nootropics


HERBAL MEDICINE

• Years of Human consumption

Food, Medicine, Cosmetic

• Extensive data on Herbs available –

Monographs, Compendia, Pharmacopeia

• Do we need to test safety on Rodents?


LICENSE REQUIREMENT FOR CLASSICAL FORMULATIONS

27-06-2019

CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE 18

LICENSE REQUIREMENT FOR P & P FORMULATIONS


LICENCE REQUIREMENT FOR EXTRACT BASED FORMULATIONS

27-06-2019CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE20

• Prospective

• Randomized

• Blind

• Controlled

• Placebo

• Active

27-06-2019HERBAL DRUG DEVELOPMENT IN INDIA 21

CLINICAL RESEARCH STUDY DESIGN

AYURVEDA CLINICAL STUDIES - CTRI REGISTRATIONS

• Total 208 studies registered (2010 to 2015)

• 167/208 were single centred i.e., 80.2% and only 41/2018 (19.7%) were

multi centred

• Total of 13 /208 are sponsored by pharmaceutical companies (6.25%)

• 2/3 i.e, 130 are RCT and 2/208 are non-RCT

• Out of 130 Only 21 (16.2%) are double blind, 18 (13.8%) are single blind, 8

(6.2%)

• 70/208 (33.6%) did not describe the blinding technique

• 91/208 (43,75%) are opened labelled27-06-2019CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE 22

➢ Identification of investigators / sites

➢Few CRO with knowledge of science and Ayurveda both

➢Formulations – consistent quality

➢Dose, regimen & duration

➢Concept of flexi dose therapy

➢Complex study design

➢ Involvement of biostatisticians

➢GCP compliance

➢Not fully regulated

➢Etc

Challenges in clinical studies on ayurvedic & herbal products


ANUPANA(Vehicle for drug administration)

Most of the time the drug is administered with avehicle Honey, sugar, jaggery, butter milk, curd, ghee,warm water, Expressed juice of a herb etc.

An ‘Anupana’ is a half-medicine in itself.


DOUBLE BLIND PLACEBO CONTROLLED CLINICAL TRIAL

• Follow Rx Regimen model

• Identify one product for CT

• Replace it with Placebo in control group


CHALLENGES - Blinding

• Difficult to match Odour, taste, colour of the placebo

• Placebo response

• Most of the time might not be possible….


CHALLENGES - Phases

• Phase I has practically no meaning

• Phase II and III are usually merged

• Phase IV is actually happening most of the times


CLINICAL STUDIES

• Design- Why do we need Prakruthi?

• Saara, Satwa, Samhanana, Desha,

kala, Vaya- Study specific

• Focus on the End point=Data required


DESIGNING THE STUDY

Processing technique

(Samskara)

Formulation (Samyoga)

Herb properties (Swabhava

Indication (Sampraptighataka)

Primary End points (Roga)

Secondary End points

(Anubandha)


TESTING AND IMAGING IN CLINICAL STUDIES

• Specific Markers

• MRI

• 3D

• Reduces sample size

• Improves value of evidence


APPLICATION SCIENCES

• Quality of life

• Behavioural science

• Integrative approach

• Epidemiological study

• Single person studies

• Demographics for sustaining

ecology


DESIGN AND MEDICINES**STUDIES AVAILABLE ON CTRI

• Comparing with specific OHA

• In combination with OHA

• Comparing with Non specific OHA

regimen

• Chikitsa/Upasaya

• Yogas for All types of Prameha

• Dhatri Nisha yoga

• Vamana karma

• Snehapana

• Dashamoola yavagu

• Khadira kramuka kasaya ghanavati

• Varadi ghanavati/Samsodhana+VG/GBL

• Chitrakadi Kw/Vamana+Chit Kw

• Basti-NA churna/ Udwartana-NA churna

• Diet

• Lodhrasava/ Basti +Lodhrasava27-06-2019 32CLINICAL TRIAL ON AYUSH & HERBAL MEDICINE

CRITERIA EMPLOYED

• Signs and symptoms

• FBS, PPBS

• HOMA-IR = fasting insulin (mU/L) × fasting glucose (mg/dL)/405

• Random blood glucose concentration greater than 200 mg dL OR

Fasting blood glucose greater than 126mgdL OR

Two hours blood glucose greater than 200 mgdL during an oral glucose tolerance test

Adopted by American Diabetic Association

• All the symptoms

• Prameha Purvarupa- Diabetes symptoms- DM complications


BALANCING THE NEEDS

Principles of treatment

Specificity

VariablesObjective methods

Data collection

Analysis


DEVELOPMENT OF DISEASE WISE PROTOCOLS

• Sulphonylureas act primarily by stimulating the islet cells of pancreas to produce

Insulin

• Biguanides reduce absorption of carbohydrates from gut

• Gymnema sylvestre, Cinnamomum tamala, Inula racemosa have been demonstrated to

bring about blood glucose homeostatis by increasing serum insulin levels

• Caesalpinia bonducella, Mangifera indiac act by reducing carbohydrate absorption.

• None of the studies reporeted te hypoglycemic cativity in Insulin resistance conditions

and also not attempted to explain the drug activity against Dushyas in prameha


DEVELOPMENT OF DISEASE WISE PROTOCOLS

• Similarly in the clinical studies on Amavata, assesment criteria can be of American

college of Rheumatology but at the same time Ayurvedic Diagnostic criteria should

also be considered (Angamarda (Body aches), Thrishna (Thrist), Alasya (Laziness),

Gaurava (Heaviness), Jvara (Fever)).


STRATEGIES• Improvement in Research Methodology (Like MedRA the language should be same)

• Encouragement of research on Ayurvedic fundamentals

• Validation of Ayurvedic drugs with reverse pharmacology

• Drug Interaction studies (Cytochrome P 450)

• Encouragement of Interdisciplinary research (Giolden Triangle project, Genomic studies,

NIH study for RA)

• Improvement of Quality of herbs

• Active involvement of government

• Revalidation of Clinical trails

• Resolution of controversies in Ayurvedic Drugs

• Manpower Training


Herbal drug development & clinical research

should take care of the best possible design,

methodologies, using modern tools but taking

care of Ayurveda principles in mind……and above

all….give top priority to your Patients….

27-06-2019 38HERBAL DRUG DEVELOPMENT IN INDIA


[email protected]

Thank you

CHALLENGES IN CONDUCTING CLINICAL TRIAL (STUDY) FOR … · Dabur India Ltd 1. DISCLAIMERS •The...

Documents

Transcript of CHALLENGES IN CONDUCTING CLINICAL TRIAL (STUDY) FOR … · Dabur India Ltd 1. DISCLAIMERS •The...