Complementary and Alternative Therapies: Herbal Medicines

1
Complementary and Alternative Therapies Herbal
Medicines
Uncritical enthusiasm
Uninformed repulsion
Current methodologies not adequate
Where is the evidence?
2
Dr. Ranjit Roy Chaudhury Dr. Urmila Thatte India
Challenges in clinical evaluation of alternative
medicines
3
1. Literature search

• Paucity of published data
• Local Clinical Practice not documented
• Good literature search difficult
• Journals not indexed, not peer reviewed, poor
  quality data
• Information in local language needs correct
  interpretation

4
2. Starting material

• Identification and source of herb

Bacopa monnieri
Centella asciatica
Brahmi
5
2. Starting material

• Single herb? Multiple herbs?
• Purity WHO criteria
• Continuous Supply, Quality Control and Stability
  of batches multi-centric studies
• Standardisation of extract bioassay guided

6
Chemical markers vs. activity

• Estrogenic activity found in a vegetable oil
• Plant obtained in July Active that obtained
  in April Inactive
• HPTLC fingerprinting

7
Chemical markers July Active vs. April
Inactive
Mobile phase - II
Mobile phase - I
Mobile phase - III
8
3. Pre-clinical work-up

• How much toxicity testing is needed?
• Local Regulatory status (India Categories)
• Lack of pre-clinical data difficulty to
  extrapolate animal studies

9
4. Clinical Studies

• Which formulation traditional/new
• What dose (crude/extract), regimen, duration no
  pre-clinical data, rely on traditional literature

10
4. Clinical Studies planning protocol

• Sample size
• Choosing efficacy and safety variables and end
  points
• Inclusion/Exclusion criteria
• Individualisation constitution

11
Response to medications depends on prakriti
(constitution)
Anti-epileptic medication
responders
Non- responders
12
4. Clinical Studies Design

• open label
• observational
• n1 studies
• Add-on design ethics
• Blinded studies difficult Assessor blind
  possible (ksharasootra)

13
4. Clinical Studies use of placebo

• Ethics
• Difficult to match colour, taste, odour, flavour
  or formulation of herbal product
• Should be truly inert

14
Ethanol induced gastric mucosal damage in rats
Evans blue leakage in gastric tissue content
(ug/g)
IMP011

NS

placebo
plt 0.05 vs. D/W NS not significant vs.
IMP-011.
15
4. Clinical Studies RCTs

• Reduces bias  
• Difficult to design RCTs for alternative
  medicines
• Involve complex interventions
• Cultural and social influences
• Are holistic in nature
• Focus on symptoms
• Intra inter variation in responses
• Require long duration of therapy 

16
5. Pharmacokinetics

• Plasma estimation of active molecules difficult
  
• May be more than one active molecule
• Metabolic changes during absorption possible
• Effect kinetics attractive option

17
6. Ethics

• Coinvestigator from alternative system
• Standards of care of control group HIV research
• Informed consent Meaningful, vernacular, easier?
• Attitude towards alternative therapy safe
  patient information sheet may mislead

18
6. Ethics

• Cultural overtones
• Translating research findings into components of
  accessible care
• Commercialisation of folklore medicine
  rights/share of tribe or community to be given

19
7. Regulatory Scenario

• US FDA Europe food supplements FDA guidelines
  available
• India
• DCGI, State FDAs
• Special emphasis on herbal research Categories

20
8. Analysis

• What degree of improvement to expect?
• What should be criteria for defining success?
• Comparison with modern potent medicines?

21
8. Analysis
Rate of decrease in wound score

Students unpaired t-test plt0.01vs. GA

Recurrence of diarrhea in malnourished children
Chi square test plt0.001 vs. Control
22
5 rules for Clinical Research in Alternative
Medicines

• Literature review look at traditional
  literature, collate experiential data, proper
  interpretation
• Consult qualified expertise
• GMP for investigational products
• Plan a good protocol keep in mind the
  traditional medicine philosophy
• Adhere to ethical and regulatory aspects