Introduction To Clinical Research

What is clinical research?

Organized research on human beings intended to provide adequate information on the drug use as a therapeutic agent on its safety and efficacy.

Also referred to as Clinical trial management

Clinical research - position in drug development

Discovery research Formulation and development Clinical development (trials) Commercialization

When do we need clinical trials?

new drugs for new uses of existing drugs, medical devices, new drug delivery systems etc.

Why do we need clinical trials?

Evidence to prove the efficacy and safety in human beings.

Only a well designed clinical study on a defined population can give meaningful results- (positive or negative) about any therapeutic intervention

Scope of clinical research?

Total

cost of the drug development 900 million US $ time taken for the drug development 10-12 years of the cost and time is spent on clinical

Total

2/3rds

trials.

Historical review
19TH CENTURY
20th CENTURY
Ancient

pharmacy practice

Growth of Pharma industry 1947 Nuremberg code after the trials by the Nazi physicians Emphasized on the informed consent

Drugs given on trial and error basis Practicing physician decided all.

1950s Proper testing of drugs on human beings started The concept of randomized controlled clinical trials appeared.

Further growth in ethical issues

WMA (1964) (world medical association) guidance to physicians and other participants in medical research involving human subjects. Thalidomide disaster brought about an exponential growth in pharmaceutical legislation Declaration of Helsinki

Ethical issues today

International conference on harmonization- Good clinical practices (ICH-GCP) Guidelines

Institutional review board/Institutional ethics committee Patients informed consent,

Regulatory guidelines today

Drugs and cosmetics act 1940 schedule-Y Indian GCP guidelines ICMR Guidelines WHO Guidelines ICH-GCP Guidelines

Clinical research then and now

Clinical

research 50 years ago Investigator driven informal activity

Clinical research now Multidisciplinary, multinational, multibillion dollar global business governed by many complex and interrelated regulations and guidelines.

Clinical research -a multi-disciplinary approach

Sponsor Investigators Monitors Auditors and the quality control personnel. Biostatisticians.

Data management group. Regulatory Affairs. Reporting and Documentation medical writing. Business development group

Players in Clinical Research Industry

Pharma companies Clinical/contract research organizations (CROs) Biotech companies Central diagnostic laboratories Clinical research training institutes

Understanding clinical research

New drug development

Drug discovery and development

Clinical trials

NEW DRUG DEVELOPMENT PROCESS

Drug discovery

Drug development

Synthesis Drug designing Target validation(Preliminary in-vitro screening) Pharmacological assays

Safety Efficacy Kinetics Formulation

PRECLINICAL STUDIES

Include studies conducted on Experimental animals for safety and efficacy

Toxicity studies: Acute toxicity studies LD50 Sub- acute toxicity studies Chronic toxicity studies Special toxicity studies: carcinogenecity, teratogenicity genotoxicity, effects on fertility and reproduction

Efficacy studies In- vitro assays : Studies conducted using only animal tissues or cells or enzyme systems In- vivo assays: Experiments using whole animals

CLINICAL TRIAL PHASES

Phase-I - Clinical pharmacology, safety of new drugs Phase-II - Safety and efficacy of new drug in patients, exploratory trial.

Phase-III - Multicentric confirmatory trial. Phase-IV - Post marketing surveillance

Who conducts the clinical trial?

Investigators

Principal investigator Co-investigator

Who participates in the trial?

Subjects

Healthy Human Volunteers Patients

Ethical issues and guidelines

International conference on harmonization(ICH) Good clinical practice(GCP) Independent ethics committee IEC Institutional Review board IRB Informed consent

Good clinical practice

It is the international standard for conducting the clinical trials which lays down the standard for

Design, Conduct Monitoring Termination Analysis and Documentation.

Informed consent

A written free consent of the subjects to participate in a clinical trial after receiving complete information about the new product

Regulatory requirements

Drugs and cosmetics act 1940 Schedule-Y DCGI Drug controller General of India US-FDA United states-Food and drug administration act. MHRA Medicinal and health care products regulatory agency

MONITORIN G
Overseeing the progress of a clinical trial Ensuring that it is conducted according to the approved protocol, GCP, SOPs and the regulatory requirements.

Usually done by Clinical research associates.

Quality control and quality assurance

Internal department of the CRO Avoids unnecessary risks to the patients. Essential to improve the quality of all the processes of the trial.

AUDI T

Systematic and independent examination of the trial related documents and activities

Checks whether the trial is going on as per the Protocol, GCP, SOP. Whether reported accurately or not

PHARMACOVIGILANC E
Collection of data on adverse effects of the drugs that are already in the market

PHARMACOEPIDEMIOLO GY
Collection of data in terms of both efficacy and safety after being prescribed to large number of patients.

OUTSOURCI NG

Outside source utilization for conducting a clinical study.

Transferring part of the activity of drug development to any other independent organizations (contractual research organizations).

STANDARD OPERATING PROCEDURES

Written instructions to achieve uniformity in the performance.

FRAU D
Generation of a false data with an intention to deceive.

MISCONDUC T
Behavior which falls short of good ethical or scientific standards(carelessness)

BIOAVALABILITY STUDIES

To understand how much of drug is available for action.

Bioequivalence studies

Conducted for new formulations, Compare the new formulation of any established drug with the existing formulation.

Data management, analysis and validation

Organized collection of accurate data from the clinical trial, Capture the data from the data base To provide a clean data to the statistician to facilitate analysis.

BIOSTATISTIC S

During the protocol designing To calculate number of patients to be included in the trial(sample size)

Randomization Review of data and For the final analysis of results by applying suitable statistical methods.

DOCUMENTATION AND REPORTING

Record any event or step in the data management Necessary for retrospective analysis for the purpose of audit

MEDICAL WRITING

To prepare reviews on the drug based on the available literature. Preparation of research papers. Medico-marketing literature.

SUMMARY

Clinical research is an integral part of drug development Unlike the past, today the process has gained a unique position due to the regulatory requirements and ethical guidelines available globally..

Designing, conducting, monitoring, appropriate quality assurance and data management determine the success of the clinical research.

The End

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