Introduction To Clinical Research Class 1

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  for

drugs

new uses of existing drugs,

 ,medical  new

devices,

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?  If

the 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

 The

concept 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 multidisciplinary 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 studiescarcinogenecity,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  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

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  Internal

department 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  Collection

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

PHARMACOEPIDEMIOLOGY  Collection

of 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

 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  Organised

collection of accurate data from the clinical trial,

 Capture  To

the data from the data base

provide 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  To

prepare 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. 