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
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
The need for organised study
 EVALUATION OF DRUG X FOR
OSTEOARTHRITIS
 How many patients improved?

approximately 150 /200

 What was the percentage of
improvement?
 80-90%
 CLINICAL TRIAL -I
 Any drop outs?
 May be 10-12

 Reasons?
 ------may be they did not get symptomatic
relief???

 Any side effects?

 Gastritis,headache,diarrhoea etc.
Clinical trial-2
 EVALUATION OF DRUG Y FOR
OSTEOARTHRITIS
 How many patients improved?

 Ifthe criteria of 40% is considered as

improvement, 150/200 showed
improvement(p<.01)
Clinical trial-2
 What was the percentage of
improvement?
 100 patients 40-50%
 40 patients 50-60%
 10 patients 60-70%
Clinical trial-2
 Any drop outs?
 There were 10 drop outs due to
following reasons
 3 –gastritis
 4 no improvement
 3 reasons not known
Clinical trial-2
 Any side effects?
 Gastritis,
 headache,
 diarrhoea etc.
 tingling and numbness
 1,2,3, were due to the drug.
OUTCOME
Clinical trial-1
Trial poorly designed
no definite outcome,
results ambiguous

Clinical trial –2
trial well designed,organised and conducted
definite outcome.
Results-conclusive.
Scope of clinical research?
 Total cost of the drug development
900 million US $

 Total time taken for the drug development

10-12 years

 2/3rds of the cost and time is spent on

clinical trials.
Historical review
19TH CENTURY

 Ancient pharmacy practice

 Drugs given on trial and error basis

 Practicing physician decided all.

History: The concept of Ethics
20th CENTURY

 Growth of Pharma industry

 1947 Nuremberg code after the trials by

the Nazi physicians

 Emphasized on the informed consent

History: The concept of Ethics
 1950s
Proper testing of drugs on
human beings started

 Theconcept of randomised
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
Declaration of Helsinki

 Thalidomide disaster brought about an

exponential growth in Pharmaceutical
legislation
Ethical issues today
 International
conference on
hormonisation- 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
organisations(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
 Synthesis
 Drug designing
 Target validation(Preliminary in-vitro
screening)
 Pharmacological assays
NEW DRUG DEVELOPMENT
PROCESS
Drug development
 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,teratogenecity
genotoxicity,
effects on fertility and reproduction
PRECLINICAL STUDIES
 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- marketting 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
hormonisation(ICH)
 Good clinical practice(GCP)
 Independent ethics committee IEC
 Institutional Review board IRB
 Informed consent
Good clinical practice
 Itis 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
MONITORING
 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
 Internaldepartment of the CRO
 Avoids unnecessary risks to the
patients.
 Essential to improve the quality of all
the processes of the trial.
AUDIT
 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
PHARMACOVIGILANCE
 Collectionof data on adverse effects
of the drugs that are already in the
market
PHARMACOEPIDEMIOLOGY

 Collectionof data in terms of both

efficacy and safety after being
prescribed to large number of
patients.
OUTSOURCING
 Outside source utilisation for conducting
a clinical study.

 Transferring
part of the activity of drug
development to any other independent
organisations (contractual research
organisations).
STANDARD OPERATING
PROCEDURES

 Written
instructions to achieve
uniformity in the performance.
FRAUD

 Generation of a false data with an

intention to deceive.
MISCONDUCT

 Behaviour which falls short of good

ethical or scientific standards(-
carelessness)
BIOAVALABILITY STUDIES

 Tounderstand 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
 Organised collection of accurate
data from the clinical trial,

 Capture the data from the data base

 Toprovide a clean data to the

statistician to facilitate analysis.
BIOSTATISTICS
 During the protocol designing
 to calculate number of patients to be
included in the trial(sample size)
 randomisation
 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
 Toprepare reviews on the drug
based on the available literature.

 Preperation of research papers.

 Medico-marketting 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.