S eminar on CLINICAL TRIALS

1. Seminar on CLINICAL TRIALS Presented by Y.SRUTHI M.Pharmacy –II sem DEPARTMENT OF INDUSTRIAL PHARMACY UNIVERSITY COLLEGE OF PHARAMACEUTICAL SCIENCES KAKATIYA UNIVERSITY WARANGAL-506009

2. Contents • Introduction on Drug Development Process • Understanding Clinical Trials • Types of clinical trials • Clinical trial protocol • Regulatory bodies governing clinical trials • Ethics in Clinical Drug Research • Phases of clinical trials • Study Designs • Clinical Trials in India • References

3. Schematic representation of new drug development process New chemical Entity Preclinical studies Investigational New Drug Application Clinical trials Phase I Phase II Phase III Preclinical studies plus Product formulation Mfg & controls Package & label design LT animal toxicity 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

4. CLINICAL TRIALS These are biomedical or health related research studies in human beings that follow a predetermined protocol.

5. Understanding Clinical trials • Why 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?

6. Types of clinical trials: • Treatment trials • Prevention trials • Diagnostic trials • Screening trials • Quality of life trials

7. The clinical protocol • Contents: • Statement of purpose and objective of the study • Outline 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 criteria • Description of dosing plan, including dose levels, route of administration and duration of patient exposure.

8. …contd • Description of the patients observations, measurements and tests to be used • Clinical 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 IRB

9. Regulatory bodies governing clinical trials FDA-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 important Institutional 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.

10. Scenario in India • 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 allocated • to 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 Human • Subjects in 2000 and Indian GCP guidelines were released by CDSCO in December 2001. The Drug Technical Advisory Board (DTAB), the highest • technical 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.

11. Ethics in clinical drug research • Ethical principles • Autonomy • Benficence/nonmaleficence • Fidelity • Informed consent • Distributive justice • Ethical code: • The code of Nuremberg • The Helsinki code • Ethical research questions • Drug testing in Healthy volunteers • Drug testing in pediatrics • Drug testing in women • Drug testing in prisoners • Drug testing in mentally disabled

12. Phases of clinical trials

14. Design of a clinical trial • Study objective • Sample size • Randomization • Blinding • Study design

15. Randomized controlled double blinded studies -A method to reduce bias • Randomized: • Controlled • Blinded studies: • Open: • Single blind • Double blind • Triple blind:

16. Study designs • 1.Surveys---------by simple questionnaire • 2.Experimental • Parallel study design • Simple parallel design • Stratified parallel design • Cross over study design • Complete cross over design • Balanced Incomplete Block Design • Latin Square Design • Factorial design • 3.Observational studies • Case control studies • Cohort studies(prospective & retrospective) • Cross sectional studies

17. Experimental studies • Simple parallel • Subjects 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 experiment

18. 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.

19. Complete cross over design • Each 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.

20. Balanced Incomplete Block Design 1.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.

21. Latin square design Each subject receives just once each formulation Each formulation is administered just once each period.

22. 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.

23. Observational studies • 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 .

24. Cohort studies • Prospective 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 Cohort • Measure Predictor Variables and Potential Confounders • Follow-up the Cohort and Measure Outcomes • Retrospective cohort study: Designs the grouping after the data is collected. • Identify a Suitable Cohort • Collect Data about Predictor Variables • Collect Data about Subsequent Outcomes

25. Cross sectional study 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.

26. Clinical trials in India • There 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.

27. References 1.Clinical Research in Pharmaceutical Development Edited by BarryBleidt, Michael Montagne 2.Clinical Trials A Practical Guide to Design, Analysis and Reporting. 3.Text Book Of Clinical Trials Second Edition Edited by David Machin 4.Designing Clinical Research Authors: Hulley, Stephen B.; Cummings, Steven R.; Browner, Warren S.; Grady, Deborah G.; Newman, Thomas B 5.Essentials Of Clinical Trials. Edited by Stephen P.Glasser 6.Fundamentals Of Clinical Research by AntonellaBacchieri ,Giovanni Della Cioppa 7.Handbook Of PHASEI/II clinical Drug Trials edited by John O’Grady,PieterH.Jobert 8. Pharmaceutical Dosage Forms by Howard C.Ansel.LoydV.Allen, Nicholas G.Popovich

28. 9. Pharmacology(Fifth edition) By H.P.Rang And M.M.Dale 10.A Text Book Of pharmacology by Tripathi 11.Biopharmaceutics and Pharmacokinetics BY V Venkateshwarlu 12.www.wikipedia.org 13.www. Clinical_trials.htm 14. www.clinical trials/irb.htm 15. www.clinical trials/Clinical-Trials-of-Drugs-and-Bio-Pharmaceuticals.htm 16. http://www.fda.gov/cder/regulatory/default.html 17. www.clinical trials/understand.htm

29. THANKYOU