S eminar on - PowerPoint Presentation

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Seminar on CLINICAL TRIALS

Presented byY.SRUTHIM.Pharmacy –II sem

DEPARTMENT OF INDUSTRIAL PHARMACYUNIVERSITY COLLEGE OF PHARAMACEUTICAL SCIENCESKAKATIYA UNIVERSITYWARANGAL-506009Slide2

ContentsIntroduction on Drug Development ProcessUnderstanding Clinical TrialsTypes of clinical trialsClinical trial protocolRegulatory bodies governing clinical trials

Ethics in Clinical Drug ResearchPhases of clinical trialsStudy DesignsClinical Trials in IndiaReferencesSlide3

New chemical Entity

Preclinical studies

Investigational New Drug ApplicationPreclinical studies plusProduct formulationMfg & controlsPackage & label designLT animal toxicityClinical trialsPhase IPhase IIPhase III

New Drug Application

Submission

FDA review

Pre approval plant inspection

FDA action

Post marketing

Phase IV,Clinical pharmacology/toxicology, Adverse drug reactions &product defects reporting, product line extension

Schematic representation of new drug development processSlide4

These are biomedical or health related research studies in human beings that follow a predeter

mined protocol.

CLINICAL TRIALSSlide5

Understanding Clinical trialsWhy participate in a clinical trial?

Who can participate in a clinical trial?What happens during a clinical trial?What are the risks and benefits of participating in a clinical trial?What should people consider before participating in a trial?Slide6

Types of clinical trials:

Treatment trialsPrevention trialsDiagnostic trialsScreening trialsQuality of life trialsSlide7

The clinical protocolContents:

Statement of purpose and objective of the studyOutline of the investigational plan and design including the kind of control group and methods to minimize bias on the part of the subjects, investigators and analysts.Estimate the number of patients to be involved.Basis for subject selection, including inclusion and exclusion criteriaDescription of dosing plan, including dose levels, route of administration and duration of patient exposure.Slide8

…contdDescription of the patients observations, measurements and tests to be usedClinical procedures, lab tests and monitoring to be used to minimize patient’s risk.Names, addresses and credentials of the principal investigator and sub-investigators.Location and description of research facilities.Approval of authorized IRBSlide9

Regulatory bodies governing clinical trialsFDA-The Food, Drug and Cosmetics Act, as regulated through Title 21 of the U.S Code of Federal regulations, requires a new drug to be approved by the Food and Drug administration.Advisory Committee-The FDA often seeks the opinion of outside experts to aid the agency in making decision on approvability of the drug .

One or more advisory committee comprising scientific experts from academic medicine, a consumer representative, biostatistician and other members deemed to be importantInstitutional Review Boards-A committee governing the conduct of clinical trials at the local institution.Members who have the professional competence in scientific, legal, regulatory and moral perspective are included.Slide10

Clinical trials in India are regulated by Schedule Y of the Drug and Cosmetics Rules, 1945.The Central Drugs Standard Control Organization (CDSCO), headed by the Drugs Controller General (India) (DCG(I)), discharges the functions allocatedto the Central Government (similar to the US Federal Government) under the Drugs and Cosmetics Act,1940.DCG(I), along with the Indian Council of Medical Research (ICMR) have adopted international regulatory guidelines and issued Indian versions of the same.

ICMR issued the Ethical Guidelines for Biomedical Research on HumanSubjects in 2000 and Indian GCP guidelines were released by CDSCO in December 2001. The Drug Technical Advisory Board (DTAB), the highesttechnical body under the Drugs & Cosmetics Act, has endorsed adoption of GCP guidelines for streamlining clinical studies in India.The clinical protocol must be reviewed and approved by an IEC of, at minimum, seven members, including a medical scientist, a clinician, a statistician, a legal expert, a social scientist and a common person from the community.Scenario in IndiaSlide11

Ethics in clinical drug researchEthical principles

AutonomyBenficence/nonmaleficenceFidelityInformed consentDistributive justiceEthical code:The code of NurembergThe Helsinki codeEthical research questionsDrug testing in Healthy volunteers

Drug testing in pediatricsDrug testing in womenDrug testing in prisonersDrug testing in mentally disabledSlide12

Phases of clinical trials

Phase IPhase IIPhase IIIPhase IVPopulation Healthy volunteersTarget diseased patientsTarget diseased patientsMixedSample size20-80200-300100-1000>1000DurationSeveral months

Several months-yearsSeveral yearsOngoingConclusionsSafety, tolerability,PK & PDEfficacy,short term safetySafety, effectiveness and dosageLong term adverse effectsSlide13
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Design of a clinical trialStudy objective

Sample sizeRandomizationBlindingStudy designSlide15

Randomized:ControlledBlinded studies:Open:Single blindDouble blindTriple blind:

Randomized controlled double blinded studies-A method to reduce biasSlide16

Study designs1.Surveys-

--------by simple questionnaire 2.Experimental Parallel study design Simple parallel designStratified parallel design Cross over study designComplete cross over design Balanced Incomplete Block Design Latin Square Design Factorial design

3.Observational studies Case control studiesCohort studies(prospective & retrospective) Cross sectional studiesSlide17

Simple parallelSubjects assigned as two groups.

Treatment group & Control (or placebo) group.Treatment assigned to treatment group and no treatment or placebo assigned to control group.The outcome measures are compared at the end of experimentExperimental studiesSlide18

Stratified parallel

First all the subjects are divided into 2 specific groups (strata) on the basis of some predefined factor.So, 2 or more “Stratas” will be formed.Later, from the individual strata, the random samples will be taken & assigned as study groups.Slide19

Complete cross over designEach study subject receives more than one study treatment, one after the other.

Each of the time intervals in which one of the study treatments is administered is called a period. The continuation of the effect of one treatment into the following period is referred to as carry over effect.Washout period: The interval between end of a treatment and beginning of the next is called as wash out period. To eliminate the carry over effect.Slide20

Balanced Incomplete Block Design1.Each subject receives not more than two formulations.

2.Each pair of formulations occur together in the same number of subjects.3.Each formulation is administered the same number of times.SUBJECTTREATMENT ITREATMENT II1AB2BA3AC

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B

9

B

D

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D

B

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C

D

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D

CSlide21

Latin square designEach subject receives just once each formulation

Each formulation is administered just once each period.Two way cross overTreatmentGroup noSubjects in group I II 1 2 1,2,3,4,5,6 7,8,9,10,11,12 A B B AThree way cross over

I II III 1 2 31,2,3,4,5,67,8,9,10,11,1213,14,15,16,17,18 A C B B A C C B AFour way cross over I II III IV 1 2 3 4

1,2,3,4,5,6

7,8,9,10,11,12

13,14,15,16,17,18

19,20,21,22,23,24

A B C D

B

D A C

C A D B

D C B ASlide22

Factorial design Many times it is possible in one trial to evaluate two or even three treatment regimens in one study. Each drug could be compared to placebo, and any interaction of the two drugs in combination could also be evaluated.Slide23

Case control studies Investigator identifies a certain outcome in the population, then matches the diseased group to a healthy group and finally identifies differences in exposure between the two groups .

Observational studiesSlide24

Cohort studiesProspective cohort study: Cohort is identified before the appearance of the

disease.Follow a group of people who do not have the disease for a period of time and see who develop the disease.Assemble the CohortMeasure Predictor Variables and Potential ConfoundersFollow-up the Cohort and Measure OutcomesRetrospective cohort study: Designs the grouping after the data is collected.Identify a Suitable CohortCollect Data about Predictor VariablesCollect Data about Subsequent OutcomesSlide25

In cross-sectional studies, one defines and describes disease status (or outcome),exposure(s), and other characteristics at a point of time, in order to evaluate associations between them.Cross sectional studySlide26

Clinical trials in IndiaThere are numerous government funded medical and pharma institutions facilitating multi-centered trials.

India can boast of a large well trained & qualified manpower that is well versed in English.Vast availability of clinical material.Cost efficiency.Alternative systems of medicine are practiced with equal fervour as allopathy.Large patient population.Slide27

References

1.Clinical Research in Pharmaceutical Development Edited by BarryBleidt, Michael Montagne2.Clinical Trials A Practical Guide to Design, Analysis and Reporting.3.Text Book Of Clinical Trials Second Edition Edited by David Machin4.Designing Clinical Research Authors: Hulley, Stephen B.; Cummings, Steven R.; Browner, Warren S.; Grady, Deborah G.; Newman, Thomas B5.Essentials Of Clinical Trials. Edited by Stephen P.Glasser6.Fundamentals Of Clinical Research by Antonella Bacchieri ,Giovanni Della Cioppa7.Handbook Of PHASEI/II clinical Drug Trials edited by John O’Grady,Pieter H.Jobert8. Pharmaceutical Dosage Forms by Howard C.Ansel.Loyd V.Allen

, Nicholas G.PopovichSlide28

9. Pharmacology(Fifth edition) By H.P.Rang And M.M.Dale10.A Text Book Of pharmacology by Tripathi11.Biopharmaceutics and Pharmacokinetics BY V Venkateshwarlu12.www.wikipedia.org13.www. Clinical_trials.htm14. www.clinical trials/irb.htm15. www.clinical trials/Clinical-Trials-of-Drugs-and-Bio-Pharmaceuticals.htm16. http://www.fda.gov/cder/regulatory/default.html

17. www.clinical trials/understand.htmSlide29

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