8/3/2019 Clinical Evidence Herbals
1/17
Clinical Evidence toEstablish Confidence in
Herbal ProductsGemiliano D. Aligui, MD, MPH, PhD
Associate Professor & Research Director, Ateneo School of Medicine & Public HealthHead of Research, The Medical City
Faculty, UERMMMCI Graduate SchoolPresident, Asian Foundation for Tropical Medicine, Inc.
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
2/17
Confidence
Public trust in determining safety andefficacy of the herbal product
Level of confidence must relate to:
Safety at specific conditions (drug-drug,
drug-food interactions)
Specific Indications (not a global claim)
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
3/17
This talk will limit to the medicinal productsonly in which the final product conforms
with the definition of a herbal medicine
Herbal Medicines - are finished, labelled
medicinal products that contain as active
ingredient(s) aerial or underground part(s)
of plants or any other plant material, or
combination thereof, whether the crudestate or as plant preparations.
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
4/17
Clinical Evidence
There are two Administrative Ordersreferring to Herbal Products
A.O. 184 s2004 - Guidelines on theRegistration of Traditionally-Used Herbal
Products
A.O. 172 s2004 - Guidelines on theRegistration of Herbal Medicines
by virtue of regulatory requirements
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
5/17
A.O. 184 s2004
The claim is limited to the folkloric use Required to state on the label
The Traditional application/use of thisproduct has not been evaluated by thePhilippine Food & Drugs Administration
If symptoms persist, consult your doctor Not allowed for use in pregnant, lactating
mothers, and children below 18 years.
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
6/17
A.O. 172 s2004
Galenicals - Phase 1 trial Pharmaceutical Dosage - Phase 1, II ClinicalTrials
Indications - Phase III Clinical trials
Establish the clinical efficacy
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
7/17
What constitutes Public
Trust?
Clinical Trials done under ethical standards
Good Clinical Practice Guidelines
Conform with the accepted norms orethical procedures by which the products
was evaluated in a clinical trial
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
8/17
A.O. 172 s2004 further
states that:
Validated by the National Integrated
Research Program on Medicinal Plants
(NIRPROMP of the PCHRD-DOST)
Validated by other competent research
centers accredited/approved by Phil FDA
This regulatory condition adds to the list of regulatory
requirements that establish confidence
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
9/17
Initiating the Trial
Clinical Trial Requirements
Investigators Brochure
Clinical Trial Protocol
ERC Review and Approval
a full documentation and process of review
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
10/17
Botanical Authentication and
Chemical Characterization
Taxonomic certification from source
Validation of plant chromatographicsignatures
Validation of amounts of active ingredients
in the raw material
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
11/17
Product Quality
Standards
Stability Biochemical Analysis
Molecular validation
Nutritional Analysis
Certifications (others)
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
12/17
Preparation of the
Investigators Brochure Pre-Clinical Studies, Safety Studies done
Comprehensive literature review of allknown active and inactive ingredients
Acute LD50, toxidrome
Pharmacologic (effects) tests inlaboratory animals and in vitro studies
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
13/17
Preparation of the
Investigators Brochure Safety Studies done
Non-mutagencity test Sub-chronic toxicity test of 90 days if
product is intended for a ten day use
Chronic toxicity test of at least 9 months(mice); 12 months (rats)
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
14/17
Clinical Trials
Phase I - Normal human volunteers forsafety (n=100)
Phase II - dose finding for efficacy,bioavailability (if applicable), (n=200)
Phase III - Randomized Clinical Trial(n=300)
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
15/17
Ethical Review ApprovalParadigm of Clinical Research
Natural History of Disease
PrimaryPrevention Secondary
Prevention Tertiary
Prevention
Indications - Disease
Disease progression
Clinical Trials
Phase I, II, III
SAFETY
Bioavailability ?
INVE
STIGATORBROCHURE
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
16/17
Paradigm of Clinical Research
Natural History of Disease
PrimaryPrevention Secondary
Prevention Tertiary
Prevention
Indications - Disease
Disease progression
Clinical Trials
Phase I, II, III
SAFETY
Bioavailability ?
Eth
icalReview
Approval
INVE
STIGATORBROCHURE
Wednesday, February 15, 12
8/3/2019 Clinical Evidence Herbals
17/17
Paradigm of Clinical Research
Natural History of Disease
PrimaryPrevention Secondary
Prevention Tertiary
Prevention
Indications - Disease
Disease progression
Clinical Trials
Phase I, II, III, IV
SAFETY
Bioavailability ?
Ethic
alReviewA
pproval
INVE
STIGATORBROCHURE