Introduction to

Clinical Research
Agenda
• Clinical Study/Trial
• Types of Clinical Trial
• Stages of Clinical Trial
• Phases of Clinical Trial
• Stakeholders in Clinical Trial
• Key document in Clinical Trial
• CR Industry & Career Prospects
Clinical Trials
• Any investigation in human subjects intended to discover or verify the clinical,
pharmacological and/or pharmacodynamics effects of an investigational
product(s), and/or to identify any adverse reaction to an investigational
product(s), and/or to study absorption, distribution, metabolism and excretion
of an investigational product(s) with the object of ascertaining its safety and/or
efficacy. The term clinical trial and clinical study are synonymous.

- Definition as per ICH GCP

Clinical Trial
• Clinical trial is a part of Clinical Study.
• 3 keywords in the clinical trial: Experimental unit, Treatment and Evaluation.
Experimental Unit: Subject from the targeted population under study. Eg.
Healthy human subjects or patients with certain disease.
Treatment: Procedure undertaken in the clinical trial. Eg.: New pharmaceutical
product/Placebo, new diet, surgical procedure, diagnostic test, medical device etc…
Evaluation: Intent of doing the study/trial. Eg.: safety or effectiveness of the test
treatment, QoL, Pharmacogenomics, Pharmacoeconomics etc…
Types of Clinical Trial
Based on the method:
• Observational Study
• Interventional Study
Based on the purpose
• Prevention Trial
• Screening Trial
• Diagnostic Trial
• Treatment Trial
• Quality of Life Trial
Types of Observational Study
Cohort Study (Longitudinal Study): Group of subjects followed over a period
of time. Can be prospective or retrospective study.
Cross-Sectional Study (Prevalence Study): Similar to cohort except all the
criteria measured at one point of time. No follow ups.
Case-Control Study: 2 group (Cases & Controls) are compared for various criteria
under study.
Stages of Clinical Trial
Phases of Clinical Trial
Phase 0: Human Microdosing study. Aims to speed up drug development
process.
Phase I: Human pharmacology/Clinical pharmacology. Aims to determine
pharmacological action and safety of the drugs in humans
Phase II: Therapeutic Exploratory Trials. Aims to determine therapeutic uses,
effective dose range and further evaluation of safety.
Phase III: Therapeutic Confirmatory Trial: Aims to determince safety and
efficacy of the drug in comparison to standard treatment.
Phase IV: Post Marketing Surveillance. Aims to determine new indication, new
method of administration, drug-drug interaction, drug-food interaction.
Phase 0
• Also known as Human Microdosing studies
• This are done to speed up the drug development process
• Aim to gather preliminary PK and PD parameters of the drug.
• A small sub-therapeutic dose (1/100th of therapeutic dose) is administered to a
small numbers of the subjects (i.e. 10-15 healthy volunteers)
• Phase 0 study gives no data on safety or efficacy of the drug, since the dose is
too low to cause any therapeutic effect.
• These are not mandatory
Phase I
• Also known as Human Pharmacology or Clinical Pharmacology studies.
• This is 1st in Human studies.
• Conducted in 20-80 healthy volunteers
• Main objective is to determine
▪ PK and PD profiles of the drug.
▪ Maximum tolerated dose.
▪ Safety evaluation of the drug.
PK & PD
Pharmacokinetic (PK): What body does to the drug.
• ADME –Absorption, Distribution, Metabolism and Excretion
• Cmax – Peak concentration of drug in blood
• Tmax – Time to achieve peak concentration.
• Elimination half life – Time taken to eliminate half of the drug from the body.
Pharmacodynamic (PD): What drug does to the body
Types of Phase I study
Single Ascending Dose (SAD):
A small group of patients are given a single dose of the drug and then are monitored over
a period of time. If they do not exhibit any adverse side effects, the dose is escalated and a
new group of patients is given the higher dose.
Multiple Ascending Dose (MAD):
A group of patients receives multiple low doses of the drug, while blood (and other fluids)
are collected at various time points and analyzed to understand how the drug is processed
within the body.
Phase II
• Also known as Therapeutic Exploratory Study.
• Conducted in 100-300 patients.
• Main objective is to determine
▪ Evaluate efficacy and short term safety of the drug.
▪ Effective dose –range
▪ Further evaluation of safety & PK parameters.
Types of Phase II study
Phase II a study:
Pilot clinical trial designed to assess the dosing requirements i.e. how much drugs
should be given.
Phase II b study:
Pivotal clinical trial designed to assess the drug efficacy i.e. how well the drug
response to the dose.
Phase III
• Also known as Therapeutic Confirmatory Trials
• Conducted in large number of patients (1000-3000)
• Most expensive and time consuming.
• Main objective is to determine safety and efficacy profile of the drug in broad
sample.
• To check how effective the drug is in comparison to the gold standard
treatment.
Types of Phase III study
Phase III a study:
Testing safety & efficacy of the drug in comparison to the gold standard treatment.
Phase III b study:
Provide information that can be used by marketing department to promote drug
after granting the license.
Phase IV
• Also known as Post Marketing surveillance.
• Conducted after marketing of the drug
• Conducted in large number of patients (1000-3000)
• Main objective is to determine
▪ new indication, new method of administration.
▪ drug-drug interactions, drug-food interactions
Phase No. of patients Duration Purpose

Phase I 20-80 Several months Mainly safety

Phase II 100-300 Several months to 2 years Mainly efficacy, but also safety

Phase III 1000-3000 2-5 years Safety, dosage, effectiveness

Stakeholders in Clinical Research
• Study Sponsors
• Investigator and site personnel
• Monitors
• IRB/IEC
• Regulatory Bodies
• Subjects
Key Documents in Clinical Trial
• Study Protocol
• Case Report Form (CRF)
• Informed Consent Form (ICF)
• Investigator’s Brochure
• Source Documents
• Clinical Study Reports
CR Industry
India is a hub for clinical research. It is the most favored destination for the
pharmaceutical R & D and Clinical Research.
• Standardized regulatory guidelines: DCGI, ICMR, DBT etc…
• Large pool of patient population.
• Highly skilled healthcare professionals
• Strong IT industry
• Cost and time effectiveness
Careers in Clinical Research
• Investigators
• Clinical Research Associates
• Clinical Research Co-ordinator
• Clinical Project Manager
• Data Manager
• Biostatistician
• Regulatory Affair Manager
• Clinical Trial Auditor
• Drug Safety Associate
• Medical Writer
“ More than 50,000 professionals will be required in the field of
clinical research in India alone.”

Thus science, pharmacy and medicine graduates can look forward

to exciting and rewarding career opportunities in clinical research.
Questions ???