Page 44 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

Category I –Phase 1 studies may not be necessary for
formulations belonging to category 1. In Phase II dose ranging
should be explored to find the effective dose as also maximum
tolerated dose. To validate the statement with placebo or standard
drug depending on the ethical requirements, RCTs would be the
preferable methodology. The clinical trials would mostly fall in the
non-inferiority group if literature is not available regarding the
proven efficacy of the formulation. Superiority trial could be
designed if the control arm is placebo or modern medicine, which is
only less effective. If the outcome is encouraging, sometimes a pilot
observational study to explore feasibility of conducting larger trials
for validation can be designed.

The substance to be tested which is already in use in Bangladesh
Systems of Medicine or has been described in their texts, the need
for testing its toxicity in animals has been considerably reduced.
Neither would any toxicity study be needed for Phase II trial. This
is the unique reverse pharmacology approach for evaluating
traditional formulations for traditional indication. If there are
reports suggesting toxicity or when the herbal preparation is to be
used for more than 3 months it would be necessary to undertake 4 -
6 weeks toxicity study in 2 species of animals in the circumstances
described above or when a larger multicentric phase III trial is
subsequently planned based on results of phase II study. Clinical
trials with ASU preparations should be carried out only after these
have been standardized and markers identified to ensure that the
substances being evaluated are always the same. However, for
phase I and phase II trials, for the formulations to be tried, Good
manufacturing Practices (GMP) standards would not be required.
But for Phase III GMP standards would be required for the
formulations to be used in the trial as the number of participants
would be larger and this will be followed by marketing approvals.

Category II and III: Like the other synthetic drugs, all the steps
involved for regulatory approvals should be followed. However, for
formulations falling under category two only limited toxicities as
mentioned for category I would apply.

All formulations involving herbal component should satisfy
following criteria as prescribed by WHO document “Operational
Guidance: Information needed to support clinical trials of herbal
products (2005)”:

BMRC ETHICAL GUIDELINE ON HUMAN SUBJECTS Page 40