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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 uses of existing drugs, devices,
drug delivery systems etc.
Why do we need clinical trials?
to prove the efficacy and safety in human beings. 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
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.
OF DRUG Y FOR OSTEOARTHRITIS How many patients improved?
the criteria of 40% is considered as improvement, 150/200 showed improvement(p<.01)
was the percentage of improvement? 100 patients 40-50% 40 patients 50-60% 10 patients 60-70%
drop outs? There were 10 drop outs due to following reasons 3 –gastritis 4 no improvement 3 reasons not known
Any side effects? Gastritis, headache, diarrhoea etc. tingling and numbness 1,2,3, were due to the drug.
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.
Ancient pharmacy practice Drugs given on trial and error basis Practicing physician decided all.
History: The concept of Ethics
Growth of Pharma industry 1947 Nuremberg code after the trials by the Nazi physicians Emphasized on the informed consent
History: The concept of Ethics
Proper testing of drugs on human beings started 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
conference on hormonisation- Good clinical practices (ICH-GCP) Guidelines
review board/Institutional ethics committee informed consent,
Regulatory guidelines today
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
companies Clinical/contract research organisations(CROs) Biotech companies Central diagnostic laboratories Clinical research training institutes
Understanding clinical research
New drug development
discovery and development 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
studies conducted on Experimental animals for safety and efficacy
toxicity studies LD50 Sub- acute toxicity studies Chronic toxicity studies Special toxicity studiescarcinogenecity,teratogenecity 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
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?
Who participates in the trial?
Ethical issues and guidelines
conference on hormonisation(ICH) Good clinical practice(GCP) Independent ethics committee IEC Institutional Review board IRB Informed consent
Good clinical practice
is the international standard for conducting the clinical trials which lays down the standard for Design, Conduct Monitoring Termination Analysis and Documentation.
written free consent of the subjects to participate in a clinical trial after receiving complete information about the new product
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
trial Ensuring that it is conducted according to the approved protocol, GCP, SOPs and the regulatory requirements. Usually done by Clinical research associates.
the progress of a clinical
Quality control and quality assurance
department of the CRO Avoids unnecessary risks to the patients. Essential to improve the quality of all the processes of the trial.
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
of data on adverse effects of the drugs that are already in the market
of data in terms of both efficacy and safety after being prescribed to large number of patients.
source utilisation for conducting a clinical study. part of the activity of drug development to any other independent organisations (contractual research organisations).
STANDARD OPERATING PROCEDURES
instructions to achieve uniformity in the performance.
of a false data with an intention to deceive.
which falls short of good ethical or scientific standards(carelessness)
understand how much of drug is available for action.
for new formulations, Compare the new formulation of any established drug with the existing formulation.
Data management,analysis and validation
collection of accurate data from the clinical trial, the data from the data base
provide a clean data to the statistician to facilitate analysis.
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
any event or step in the data management Necessary for retrospective analysis for the purpose of audit
prepare reviews on the drug based on the available literature. of research papers. literature.
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.