clinical trial phase 3 and 4

CLINICAL TRIAL PHASE 3 AND 4

BY

SANCHIT RASTOGI

Monday, April 10, 2023 1icri,dehradun

PHASE 3• Also known as therapeutic confirmatory trials• randomized controlled • multicenter trials• on large patient groups (300–3,000 or more depending

upon the disease/medical condition studied) • Safety ,drug interactions are accessed on a larger scale• Additional pharmacokinetic data may be obtained.• Phase III trials are the most expensive• time-consuming

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PHASE 3 (CONTINUES)

• difficult trials to design • especially in therapies for chronic medical

conditions• continue while the regulatory submission is

pending at the appropriate regulatory agency.


PHASE 3 CONSIST OF TWO PARTS

PHASE 3A

• Trials carried out on a large number-or in a special category – Regulatory requirement for NDA

PHASE 3B

• Extended trials of IIIa after applying for approval but before launch.

• Phase 3b studies are known as "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug.


New Drug Application (NDA)

• NDA filing process is applying for marketing approval to regulatory body.

• Aplication contains often in hundreds of volumes, full reports of all preclinical and clinical data.

• Review and decision of approval may take 3 years or longer.

• Controlled marketing allowed for life threatening diseases


POST MARKETING SURVEILLANCE

• Used to describe the research and studies associated with product safety evaluation after the drug has been approved for marketing.

• Pms=Pharmacovigilance+Pharmacoeconomics+Pharmacoepidemiology.

• No fix duration


SOME DATES IN THE HISTORY OF PHARMACOVIGILANCE

• 1848

The Lancet starts collecting notifications of side effects after a death caused by anaesthesia

• 1906

US Federal Food and Drug Act requires that pharmaceuticals be “pure” and “free of any contamination”

• 1937

USA: 107 lethal cases after diethylenglycol was mistakenly used to solubilize sulphanilamides

• 1952

France: 100 lethal cases after diethyl tin diodide was mistakenly used in a skin preparation


CONTI……..• 1959-61 Reports of foetal abnormalities in relation with the use of a new sleep-

inducing drug thalidomide (biggest number in Germany) • 1962 USA revised law requiring to prove safety and efficacy before issuing

marketing authorisation• 1964 UK starts “yellow cards” system• 1967 WHO’s International Drug Monitoring Programme• 1976 Drugging of the Americas: inadequacy of safety information


OBJECTIVES OF PMSConform the efficacy and safety profile in large populations during

practice

Detect the unknown adverse drug reaction/s

Evaluation of over-dosage and treatments

Identifications of new indications

Evaluation of new formulations, dosages, durations of treatment

Evaluation in different age groups / types of patients


PMS METHODOLOGIES

• Spontaneous reporting system• Case reports• Cross sectional studies• Cohort studies


SPONTANEOUS REPORTING SYSTEM

• Health care personal suspects that a particular medication is associated with an adverse event observed during the course of caring for a patient, reports the ADE to a formal reporting system.

Various reporting systems are: WHO INTERNATIONAL SYSTEM USFDA –MEDWATCH UK –YELLOW CARD SYSTEM NATIONAL PHARMACOVIGILANCE SYSTEM


WHO INTERNATIONAL SYSTEM

• Established in 1968• Headquaters in geneva• Who collaborating centre for international

drug monitoring-uppsala monitoring centrein sweden

• Individual case reports of suspected adr are collected and stored in a common database.



Official member countriesAssociate member countries

WHO Drug Monitoring ProgrammeParticipating countries 1999

USFDA –MEDWATCH

• Allows health care professionals and consumers to report serious adr that they suspect are associated with the drugs and medical devices they prescribe,dispense or use.

• Reporting can be done on line, by phone, or by submitting the medwatch 3500 form by mail or fax


UK –YELLOW CARD SYSTEM

• Came into existence in 1964• States that “every member of the medical and

dental profession in the uk..” to report ..”promptly the details of any untoward condition in a patient which might be the result of drug treatment.

• Example:halothane in jaundice


NATIONAL PHARMACOVIGILANCE SYSTEMINDIA

• launched by CDSCO in november,2004

• Aim-to develop the culture of ADR notifications by heatlh care workers country is divided into zone and regions

CDSCO, new delhi at the top followed by SETH GS MEDICAL COLLEGE,MUMBAI AND AIIMS IN NEW DELHI

• Then there are 5 regional centers i.e KOLKATA.MUMBAI,NAGPUR,DELHI,PONDICHERRY

• 28 peripheral systems spread across the country


COHORT STUDIES

• Groups of individuals are identified • Followed over time to time to determine the

incidence of some predetermined outcome• Generally is of two types:• Prospective study• Retrospective study


CASE CONTROL STUDY

• Allow health care workers to share their individual experiences in published medical literature.

• Play important role in communicating previously unidentified uses and dangers of drug.


CROSS SECTIONAL STUDIES

• It is an observational study in which drug exposure and diseased status or symptoms are determined at a single point in time


COMPUTERS IN PMS

• Arisg• Dsnavigator• Oracle• Argus assurance• Expert direct• sas



“There are 3 actions of a drug: the one we want , the one you don’t want , and the one you don’t know about”

FUTHER READING

• Edwards IR, Aronson Jk , adverse drug reactions: definitions, diagnosis, and management. Lancet 2000:356:1255-9

• Goyal R.K, basics of hospital and clinical pharmacy,1st edition, B.S Shah publication, Ahmadabad, pg 261 -277

• Tripathi KD,”essentials of medical pharmacology”,jaypee brothers medical publishers,6th edition,pg no.78-86



QUESTIONS?COMMENTS?

Monday, April 10, 2023 27icri,dehradun

THANK YOU

clinical trial phase 3 and 4

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