This document discusses special issues in clinical trials of phytopharmaceuticals and their drug development process. It defines phytopharmaceuticals as purified and standardized plant extracts containing a minimum of four bioactive compounds. The drug development process involves isolating bioactive ingredients, evaluating safety and efficacy using systematic pharmacological methods and conventional trials. Some challenges in clinical trials of phytopharmaceuticals include achieving patient homogeneity due to their personalized nature, issues with placebos and blinding due to complex mechanisms of action, and difficulty assessing effects of individual differences. The conclusion states that while demand is increasing and they are generally safe, standardization and quality of clinical trials needs improvement and the best approach is integrating traditional knowledge with modern technology

1. Special Issues in Clinical
Trial of
Phytopharmaceuticals
Dr. Shakeeb Dhorajiwala,
1st year DM resident,
Clinical Pharmacology

2. Outline
Conclusion
Certain challenges
Drug development process
Isolation of biologically active ingredients Evaluation Post- marketing procedures
Salient features of Phyto pharmaceutics
Historical aspect
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3. Historical Aspects
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4. Phytopharmaceuticals
Defined as purified & standardized fraction with:
• minimum 4 bioactive/ phytochemical compounds (qualitatively and quantitatively assessed) of
an extract
• of a medicinal plant/ its part,
for internal or external use of human beings or animals for
• Diagnosis
• Treatment
• Mitigation
• prevention
disease or disorder but does not include administration by parenteral route
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5. Can it be < 4?
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6. How does it differ from ASU?
fraction of crude
extract
distinctly
differentiated by
being purified
and standardized
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7. Drug development process
Isolation of
bioactive
ingredients
Evaluation of
safety & efficacy
using system
pharmacological
methods
Evaluation by
conventional
pharmacological
method
Regulatory
approval & post-
marketing
monitoring
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8. Isolation of bioactive ingredients
Three
staged
process:
Pre-drug: Drug
selection
Random
Ethnopharmacology
Zoopharmacognosy
quasi- drug:
Extraction
Conventional
Parallel
Sequential
Newer method
Semi-bionic
Microwave
Supercritical fluid
extraction
Full drug
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9. System Pharmacological method
Advantages
• Efficient and faster
process
• expansion of herbal
resources by finding new
targets
Disadvantages
• Costly
• Needs expertise
• Certain biological
systems too complex
to be evaluated
Computational analysis of
network between drugs and drug
targets
Predicts therapeutic effects
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10. Conventional Methods- Clinical Trials
Carried
out as per
ICMR
guidelines
Protocol reviewed by member with relevant expertise
Prospective CTRI registration
Co-investigator- One member conversant with that field
Benefit sharing with tribe/community Applying for IPR
Main
objectives:
Validate claim of S&E
Develop new preparation/ evaluate new indication
Change of formulation/ route of administration
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11. Ethical Considerations
Pre-requisites before conducting CT of phyto-pharmaceutics
Quality control check
Documentation of adulteration
Drug-drug interactions and drug-food interaction
Adequate preclinical data
• Organ toxicity
• fetotoxicity
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12. Special Issues (1/2)
Patient selection
Homogeneity-
difficult to
achieve
Soln : Double-
classification
system
Placebo & non-specific
effects
Soln:
Randomization
and blinding
Randomization: difficult
as Phytopharmaceutics
not based on linear-
cause-&-effect
assumption
Soln: Partial
randomization
Blinding: Double
blinding-too difficult
Soln: single
blinding/
assessor’s
blinding
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13. Special issues (2/2)
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Therapist & Protocol
variability: Phyto-
pharmaceutics 
Personalized care
forms its basis
Soln : > 1 therapist
employed
Outcomes: reliant on
subjective end-points
Soln: QOL  additional
end-point
Assessing effects of
individual
differences- Difficult
Expectation and
beliefs affect
outcome
Matching
Difficult
Acculturation plant
habitat destruction
Soln: Social mass
movements and
rallying

14. Conclusion
Global increase in demand
Generally considered safe
However, standardization and quality of CTs still not at par
Best way forward: Integration of ethnoscience with modern
technology
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