2. Phase II
• It is also known as therapeutic exploratory trial.
• 50-500 subjects.
• Confirms the effectiveness, monitors side effects and further evaluated
the safety.
• Duration: 6 months to several years.
• For new actions of a marketed drug, clinical trial can start from phase II i.e
phase I is exempted.
• Phase II trials involves:
a) Phase IIa: Designed to assess dosing requirements
b) Phase IIb: Designed to assess efficacy
3. • It is now common to conduct Phase II trials with a control
group in conjunction with the test group given the drug.
The control group is given either the current standard
treatment or placebo (an inert non-drug substance).
• Another practice is to blind the trial, which means that the
subjects are not aware to whether they receive the placebo
or drug (single blind study).
• In some trials, even the investigator is unaware of whether
the subject is in the control or active group (double blind
study).
• The rationale is to eliminate the possibility of bias affecting
the trial results.
4. • Specific clinical endpoints or markers are used to
assess interaction of drug and disease.
• There are two types of markers: definitive and
surrogate.
• For example, in the case of cancer or hypertension, the
definitive markers are mortality and stroke,
respectively.
• The surrogate markers may be tumor size, or cancer –
associated proteins p53, TGF - α in the case of cancer,
and blood pressure or cholesterol level in
hypertension.
5. Information obtained from Phase IIa
studies
• Proves primary hypothesis
• Efficacy
• Effect Size
• Adverse events (ADR of special interest)
• Biomarker profiling
6. Information obtained from Phase IIb
studies
• Dose-response
• Frequency
• Additional ADR
• Identifying confounding factors
• Type of patients more responsive to
treatment.
7. Phase III
Objectives:
* To confirm safety and effectiveness of the drug
* Basis for marketing approval (NDA application).
Subjects: Several hundred to 3000.
The study can be randomized & controlled or can
be blinded.
8. • Phase III trial is normally conducted in several
hospitals in different demographic locations
(Multisite trial), to determine the influence of
ethnic responses, together with incorporation of
new criteria for fine - tuning the trial.
• Because the results are crucial to the
determination of the drug ’s effectiveness, the
Phase III trial is referred to as the pivotal trial, as
it can make or break the success of a drug.
9. • The methodology of the trial has to be carefully prepared
so that meaningful results can be gathered at the
conclusion of the trial.
• Extensive statistical analyses are performed to evaluate the
data.
• If for any reason the drug does not show significant
advantage over current treatment, the result may be
refined and certain subgroups are analyzed to determine if
the effects are greater in one group than in the other.
• The study results provide comprehensive data for
understanding the critical parameters of safety and
effectiveness of the drug.
10. • These results enable the pharmaceutical
company to set the dosage, treatment frequency,
duration, and target patient groups for the drug.
• The analysis done, together with chemistry &
manufacturing are submitted to regulatory
authorities to seek approval to market the drug.
• The duration may range from 3-5 years.
11. Phase IV
• Phase IV clinical trials are postmarketing approval trials to monitor the
efficacy and side effects of the drug in an uncontrolled real - life situation.
• This is also known as a postmarket surveillance trial.
• Information about the effectiveness of the drug is compared with
established treatment.
• Also information on the side effects, patient’s quality of life, and cost
effectiveness is collected.
• Any adverse events are reported and acted on to ensure patients’ welfare
is not compromised by the drug.
• Serious events are reported to regulatory authorities within a specified
time and, if deemed necessary, the drug is recalled or doctors and patients
are notified.
