Basics of Clinical Research

Mr.Siva Kartheek Matam M.PharmPatient Safety SpecialistMumbai

Any research conducted on humans with ethical values to show that a device, drug, or treatment method is safe and effective.

It is a process of taking a new drug molecule in to the market through the regulatory approvals.

1937 – Elixir Sulfanilamide disaster

105 US citizens died after treatment with sulfanilamide elixir containing diethylene glycol (DEG)

The incident hastened final enactment in 1938 of the Federal Food, Drug and Cosmetic Act

1950’s - Thalidomide tragedy

Prescribed for controlling nausea and vomiting in pregnant women

Teratogenic – children born with deformed limbs.

1962 – Ban of thalidomide use in pregnant women.

PHASE I: Objective:

Objective of Phase 1 studies is to determine the maximum-tolerated dose with well-defined potential toxicities Initial assessment of safety, drug tolerability, and dose range in humans To study pharmacokinetic and pharmacodynamic parameters of the drug in human beings Healthy volunteers Small subject population (20-80)

PHASE II: Objective:

Objective of Phase 2 Studies is to define the dose regimen of the drug that elicits the desired therapeutic benefit and that outweighs the observed clinical risks

Initial assessment of efficacy (proof-of-concept) and further assessment of safety

Involve patients who have the indicated disease or condition

Small patient population (100-300)

PHASE III: Objective:

To provide sufficient data to convince the regulatory authorities of the favourable benefit/risk ratio of the drug under investigation

Large-scale studies aimed at verifying efficacy establishing safety, and establishing the optimum dosage

Phase-3 studies also called as confirmatory studies

Involve a larger number of patients (1000-3000)

Protocol Investigator’s Brochure (IB) Form 1572 (FDA) – Statement by

Investigator Undertaking by Investigator (CDSCO –

ScheduleY) Financial Disclosure form Ethical Committee approval Directorate General for Foreign Trade

(DGFT) approval

Informed Consent Form (ICF) Source Documents Case Report Form (CRF) Serious Adverse Event (SAE) Reporting

form Investigator Trial File (ITF) Correspondence file

Filing NDA

(New Drug Applications) at

FDA

POST MARKETING SURVEILLANCE (PMS): Objective:

To assess the long term effects of the drug

To determine drug behavior in huge patient pool

To determine new therapeutic benefits or indications

Regulatory requirement: Structured Adverse Events reporting system Periodic Safety Update Reports (PSURs)

The PSURs are required to be submitted to DCGI – Once in every six months for the first two

years of the drug approval

Yearly once for the next two years

Then to be submitted annually.

The Periodic Safety Update Report (PSUR) is required as part of the FDA Post Marketing Drug Risk Assessment (PMDRA) program. 

USFDA-quarterly reports during first 3 years, then annual reports

EMEA - Report should be submitted every 6 months for first 2 years, annually for next three years and then five yearly after the first renewal

Country: India Authority: Central Drug Standard

Control Organization (CDSCO) Head: Drug controller general of India

(DCGI)

The CDSCO, headed by the DCGI, is primarily responsible for coordinating the activities of the State Drugs Control Organization, formulating policies and ensuring uniform implementation of the Drugs and Cosmetics Act of 1940 (DC Act) and the Drugs and Cosmetics Rules of 1945 (DC Rules) throughout India.

Schedule Y: The legislative requirements of pharmacovigilance in India are guided by specifications of Schedule Y.

United States of America Authority: United States Food and Drug

administration (USFDA)

United Kingdom Authority: Medicines and Healthcare

products Regulatory Agency (MHRA)

European countries Authority: Evaluation agency for

European medicines (or) European medicines evaluation agency (EMEA)

Australia Authority: Therapeutic Goods

Administration (TGA)

Country: Canada Authority: Health Canada

PharmaMedical

Statistician

StatisticianOther

LifeSciences

TherapeuticsGuidelines

AndRegulations

Clinical Research Coordinator (CRC) or Clinical Trial Assistant (CTA)

Clinical Research Associate (CRA) Pharmacovigilance Specialist Clinical Data Associate Medical coder Medical Writer Regulatory Affairs or Medical Affairs Associate Literature Expert Medical Adviser or Medical Monitor (Medical

background) Biostatistician

JOB PROFILES

Questions???

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