Page 29 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

be covered under some insurance scheme. Compensation should be
given by the sponsors but no undue inducement is allowed.

Phase II (Therapeutic Exploratory Trials) – After the
successful completion of phase I, an experimental drug is next
tested to determine therapeutic effects, effective dose range and
further evaluation of safety and pharmacokinetics in a limited
number of patients of either sex in patients.

Phase II trials are typically conducted in a small (usually 20-25
patients), well-defined homogeneous group of participants, and
generally limited to 3-4 centers. The dose used is lesser than the
highest dose used in phase I. Anesthesia and anticancer drugs are
allowed in this phase. An additional aim of this Phase II is
evaluation of potential study endpoints, therapeutic regimens,
concomitant medications and target populations e.g., age, gender,
disease stage / degree. It is advisable to include a clinical
pharmacologist as a co-investigator in such studies. Once the safety
is confirmed, a phase III trial can then be conducted.

Phase III (Therapeutic Confirmatory Trials) – Phase III
studies are conducted in patients with the target treatment using
the new chemical entity being tested successfully in the phase II.
The primary and secondary objectives are to evaluate the
pharmacological effectiveness and to study a short-term toxicity,
respectively. The number of the subjects in the phase II trials may
considerably increase up to several thousands depending on sample
size determination using a statistical method in conjunction with
the existing preliminary data. Usually there is a comparison with
standard drug and/or with a placebo if standard drug does not exist.
In the phase III trials, control procedures are implemented
beginning from subject selection, group randomization, treatment
allocation, follow up, and evaluation. The trial in this phase is
aimed to increase patient’s survival or to improve patient’s quality
of life. Then, the trial design should be randomized, double blinded,
i.e., both the investigators and the subjects do not know what drugs
either investigational or comparator are given. When the drug gives
the favorable results under the phase III trials, they are likely
authorized for marketing.

Phase IV (Therapeutic Use Trials) – This phase is also called a
post marketing surveillance study. The study is done after the drug
has been registered, with the objectives being to study the
therapeutic uses, any adverse effects, and toxicity of the drug in a
larger number of patients who have been using the drug for a
longer period of time, or to explore additional effectiveness for other
indications other than the approved ones. Also, the study in this

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