This presentation provides a comprehensive overview of clinical trials, the cornerstone of drug development and therapeutic validation. It covers phases of trials, study designs, ethical considerations, regulatory guidelines, and real-world challenges in conducting clinical research. Designed for medical students, researchers, and healthcare professionals, this resource emphasizes the scientific and ethical rigor required to translate experimental drugs into safe, effective therapies.

1. Clinical Trial & its phases
Presented by
Dr. Ipshita Jain
Junior Resident – 1
Department of Pharmacology & Therapeutics
KGMU, Lucknow

2. Contents
 History of clinical trial
 Definition
 Types
 Ethical considerations
 Measurable outcomes
Phases

3. History of Clinical Trials
• In 1906 no obligations to establish drug efficacy or safety.
• Amended in 1938 after the deaths of over 100 children from “elixir
sulfanilamide” requiring toxicity studies but no proof of efficacy.
• In 1960s, thalidomide taken early in pregnancy, was responsible for an
epidemic of Phocomelia.
• Amendments established the requirement for proof of efficacy as well as
documentation of relative safety in terms of the risk-to-benefit ratio for the
disease entity to be treated (the more serious the disease, the greater the
acceptable risk).

4. What is a Clinical Trial ?
 A prospective ethically designed investigation in human subjects to
objectively discover/verify/compare the results of two or more
therapeutic measures.
 Are designed to acquire information about the pharmacokinetic &
pharmacodynamic properties of a candidate drug in humans.

5.  Depending on the objective of the study, clinical trial may be
conducted in healthy volunteers or in volunteer patients.
 Both proof of efficacy as well as documentation of relative safety in
terms of the risk-to-benefit ratio for the disease entity to be treated is
needed for the conduct of clinical trial.

6. Types of Clinical Trials

7. Controlled Trial Multicentric Trial Sequential Trial
 The control group, which
should be as similar to the test
group as possible, receives
either a placebo (if ethically
permissible) or the existing
standard treatment (active
control
 Many large trials are
conducted at more than one
center by as many teams of
investigators, sometimes
spread over several countries
 Detect a significant result as
soon as it is achieved,
minimizing the number of
subjects
 Types –
o Parallel group design
o Cross over design
 Applicable only to certain
chronic diseases which remain
stable over long periods.
 The trial results are applicable
only to this chosen regimen
 Advantage –
o Larger number of patients can
be recruited in a shorter period
of time.
o Results are applicable to a
wider population base which
may cover several countries/
ethnic groups.
o Credibility of the trial is
enhanced
 The trial is conducted on
matched pairs of subjects and
is scored as ‘A’ treatment
better than ‘B’ or ‘B’ better
than ‘A’ or no difference
 Disadvantage – it may not
practicable to recruit matching
pairs of trial subjects

8.  Non-inferiority Trials : New treatment provides at least the same benefit
as the current treatment.
 Superiority Trials : Effect of new treatment must show clear superiority to
the effect of placebo, otherwise new treatment is not effective.
 Equivalence Trials : Old and new treatments are identical (in terms of
treatment outcomes) within some acceptable range defined clinically by a
+/- 20%.

9. Ethical Considerations in Clinical Trials
 All clinical trials must be conducted only after scrutiny and approval by an
independent ethics committee as per the ‘Good Clinical Practice’ (GCP)
guidelines.
 In India, the ICMR (2006) has brought out ‘Ethical guidelines, for
biomedical research on human participants’.

10.  Adherence to these provides assurance that the data and reported results
are credible and accurate, and that the rights, integrity and confidentiality
of trial subjects are protected as enunciated in the Helsinki Declaration of
the World Medical Association.
 The ethics committee has to ensure that the study does not breach the
following ethical principles : Autonomy, Beneficence, Non-maleficence &
Justice.

11. Social & clinical value
Scientific validity
Fair selection of subjects
Informed consent
Favorable risk benefit ratio
Independent review
Respect for potential & enrolled
subjects
Ethical Principles

12. What must be measured?
 The primary and secondary end points (cure, degree of improvement,
symptom relief, surrogate marker, avoidance of complication, curtailment
of hospitalization, survival, quality of life, etc.) of the trial must be specified
in advance.

13. Considerations in designing a Clinical Trial
 Confounders & Effect modifiers (presence of other diseases and risk
factors including genetic susceptibility ).
 Variable nature of disease.
 Subject and observer bias.
 Factors like Compliance/ Adherence.

14. Avoidance of Bias
There are three main strategies that aim to minimize bias in clinical trials,
namely:
 Randomization
 Blinding - Double blind RCT is the most credible method of obtaining
evidence of efficacy, safety or comparative value of treatments
 Rigorous follow-up & ascertainment of outcomes

15. Phases of Clinical Trial
PHASE NAME
0 Microdosing studies
1 Human Pharmacology Phase
2 Therapeutic Exploratory Phase
3 Therapeutic Confirmatory Phase
4 Post Marketing Surveillance

16.  Phase 0 use subpharmacological doses which are not expected to
produce any therapeutic or toxic effects, but yield human
pharmacokinetic information & may obviate the need for animal
pharmacokinetic studies.
Phases I-III are designed to establish safety and efficacy.
 Phase IV post marketing trials delineate additional information
regarding new indications, risks, and optimal doses and schedules.

17. Typical characteristics of the various phases of the clinical
trial required for marketing of new drugs

18. The phases, time lines, and attrition that characterize
the invention of new drugs

19. References
 Tripathi, K. D. (2018) Essentials of medical pharmacology. 8th ed. New
Delhi, India: Jaypee Brothers Medical
 Katzung BG, Basic and clinical pharmacology. 13th ed. New York: McGraw-
Hill Education; 2015. p 177-93.
 Goodman, L., Gilman, A., Brunton, L., Lazo, J. and Parker, K.,
(2006). Goodman & Gilman's the pharmacological basis of therapeutics.
New York: McGraw-Hill

20. THANK YOU