Ch 1 what is pharmacoepidemiology lec bmeskel for uo g sop pscm yi jan 30 2021

Phar 7041 Fundamentals of Pharmacoepidemiology

1. Fundamentals of Pharmacoepidemiology ( Phar 7041) Department of Pharmaceutics School of Pharmacy College of Medicine and Health Sciences University of Gondar [email protected] Tel: [phone] Berhanemeskel W.Gerima Atsbeha

2. Course Objectives Enabling Objectives: To meet the course objective, at the end of the course, learners will: Describe the scope and applications of pharmacoepidemiology Discuss common study designs and methods used in pharmacoepidemiological studies Assess the relevance and limitations of various pharmacoepidemiological research designs Describe qualitative research concepts in pharmacoepidemiology Compute measures of association or risk Identify errors in pharmacoepidemiologic studies Explain sampling issues in pharmacoepidemiology Explain data sources and data collection techniques in pharmacoepidemiology Discuss drug utilization research Describe systems for the reporting of adverse effects and their use for pharmacoepidemiology. Discuss Pharmacovigilance Differentiate systematic review and meta-analysis Practice stages of systematic review and meta-analysis Assess heterogeneity in meta-analysis and handle it Assess reporting bias in systematic review and meta-analysis Apply pharmacoepidemiologic principles in practice 2

3. Reference Materials Pharmacoepidemiology , 4 th edition, Storm B. L. (Ed), John Wiley and Sons Ltd, England, 2005 . Textbook of Pharmacoepidemiology , Storm B. L. And Kimmel S.E. ( Eds ), 2007, John Wiley, New Jersey. Pharmacoepidemiology – An Introduction , 3rd edition, Hartzema A.G., Porta M., Tilson H.H., ( Eds ), 1998, Cincinnati OH, Harvey Witney Books Company . Remington’s : The Science and Practice of Pharmacy , 21st edition, University of The Sciences in Philadelphia, 2005, USA . 3

4. 1. Introduction (2 hrs ) 1.1. What is Pharmacoepidemiology? 1.2. Potential Contributions of Pharmacoepidemiology 1.3. Reasons to Perform Pharmacoepidemiology Studies 4

5. 5 Public Health Pharmacy Pharmacoepidemiology BRIDGE

6. 1.1. What is Pharmacoepidemiology? Outline 1.1.1. Definition 1.1.2. Historical Background 1.1.3. Pharmacoepidemiology Scope and relationship with other fields 1.1.4 . Current drug approval process 6

7. 1.1.1. Definitions of P harmacoepidemiology Study of drugs as determinants of health and disease in the general unselected population Science of measuring drug mediated health events in well defined large number of populations Study of the utilization and effects of drugs in large numbers of people Application of epidemiological methods to pharmacological issues 7

8. Definitions It links EXPOSURE and OUTCOME for any appropriate sub-groups in any selected medicines in terms of Therapeutic gain Length of life Quality of life Adverse events Pharmacoepidemiology borrows from both pharmacology and epidemiology A BRIDGE SCIENCE - spanning both pharmacology and epidemiology 8

9. 1.1.2. Historical Background US law, Pure Food and Drug Act, passed in 1906 followed by FD and cosmetic Act in 1938 . Preclinical toxicity testing and clinical data about drug safety required before drug marketed . ‘ Thalidomide disaster’ in 1961 led to establishment of committee of safety of medicines in 1968 in UK and changes elsewhere . ‘ Pharmacoepidemiology ’ first appeared in medical literature in British Medical Journal (BMJ ) in 1984 .* 9 *Lawson D. H. (1984). Pharmacoepidemiology: a new discipline. British medical journal (Clinical research ed.), 289(6450), 940–941. https ://doi.org/10.1136/bmj.289.6450.940

10. Drug Toxicity Thalidomide Chloramphenicol and Grey Baby Syndrome Gynecological cancer in offspring of women receiving Diethyl Stilboestrol Oculomucocutaneous syndrome with Practolol Liver disease from Benoxaprofen Valvular heart disease from Dexfenfluramine Cardiac arrhythmias with T erfenadine Multiple drug interactions with M ibefradil 10

11. What papers have shaped Pharmacoepidemiology? 11

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15. Controversies 15

16. 1.1.3 . Pharmacoepidemiology Scope and Relationship with Other Fields Pharmacoepidemiology Scope Pharmacoepidemiology is the application of epidemiological principles and methods to the study of drug effects in human populations . The goals are to characterize , control and predict the effects and uses of pharmacological treatment regimens in a defined population. Pharmacoepidemiology is also concerned with the economic impact and health benefits of unintended drug effects . 16

17. Pharmacoepidemiology Clinical pharmacology Epidemiology Pharmacoepidemiology vs Other fields Study of the effects of drugs in humans Attempt to optimize the use of drugs tried to individualize the therapy and tailor to the needs of specific patient Individualization of therapy requires determination of risk/benefit ratio specific to the patient Useful in providing information about the beneficial and harmful effects of any drugs Permitting a better assessment of the risk/benefit balance 17

18. Pharmacoepidemiology Pharmacology Epidemiology Therapeutics Statistics Study of the effects of drugs 18

19. Health services research Clinical epidemiology Health economics Outcomes research Pharmaco - Epidemiology Epidemiology Economics Conceptualization by Harry Guess 19

20. 1.1.4 . Current Drug Approval Process The current drug approval process includes: Preclinical phase- animal testing Clinical Phase I- metabolism of the drug, safe dosage range in humans, on Healthy subjects Phase II- pharmacokinetics of the drug, common ADRs on the possible efficacy of the drug, daily dosage and regimen, on patient subjects Phase III - evaluate a drug’s efficacy, more information on toxicity, on patient subjects (500-3000 ) Phase IV – POST MARKETING SURVEILLANCE 20

21. 1.1.4 . Current Drug Approval Process (2) 21 Human study subjects Pre-marketing Phase Post-marketing Phase Drug approval    

22. Limitations of Pre-marketing Trials Carefully selected subjects may not reflect real-life patients in whom drug will be used Study subjects may receive better care than real-life patients Short duration of treatment Study sample size Studies with 3000 patients cannot reliably detect adverse events with an incidence of < 1 per 1000 , even if severe Studies with 500 patients cannot reliably detect adverse events with an incidence of < 1 per 166 , even if severe 22

23. About 20% of drugs get new “black box” warnings after marketing About 4% of drugs are ultimately withdrawn for safety reasons Consequences of Limitations of Pre-marketing Trials 23

24. 1.2. Potential Contributions of Pharmacoepidemiology A. Information which supplements to the information available from premarketing studies —better quantitation of the incidence of known adverse and beneficial effects Higher precision ( eg . Prazosin ) In patients not studied prior to marketing , (e.g . the elderly , children, pregnant women) As modified by other drugs and other illnesses ( eg . Timolol ) Relative to other drugs used for the same indication 24

25. 1.2. Potential Contributions of Pharmacoepidemiology B. New types of information not available from premarketing studies Discovery of previously undetected adverse and beneficial effects (a) Uncommon effects (b) Delayed effects Patterns of drug utilization The effects of drug overdoses The economic implications of drug use C. General contributions of pharmacoepidemiology Reassurances about drug safety Fulfillment of ethical and legal obligations 25

26. 1.3. Reasons to Perform Pharmacoepidemiology Studies? Common reasons to perform pharmacoepidemiology studies are for Regulatory decision about whether to approve a drug for marketing or Marketing purpose Legal issue Clinical decision about whether to prescribe a drug 26

27. 1.3. Reasons to Perform Pharmacoepidemiology Studies? A. Regulatory A1. Requirement : a plan for post marketing pharmacoepidemiology study is required before the drug that will be approved for marketing. This is designed to clarify residual questions about drug’s efficacy and toxicity . A2. To obtain earlier approval for marketing : if the drug regulatory agency believed that serious problems could reliably and rapidly detected after marketing , it could feel more comfortable releasing the drug sooner . A3. As a response to questions by regulatory agency : some post marketing studies of drugs arise in response to case reports of adverse reactions reported to the regulatory agency. A4. To Assist Application for Approval for marketing elsewhere 27

28. 1.3. Reasons to Perform Pharmacoepidemiology Studies? B. Marketing B1. To assist market penetration by documenting the safety of the drug B2. To increase name recognition : the fact that a study is underway will often be known to prescribers as well its results once it is publicly presented and published increased name recognition 28

29. 1.3. Reasons to Perform Pharmacoepidemiology Studies? B3. To assist in repositioning the drug Different outcomes: one can explore different outcomes resulting from the use of drugs for approved indication Different types of patients: one could also explore the use of drugs for the approved indication in types of patients other than those included in premarketing studies. Example: children and elderly New indications: by exploring unintended beneficial effects, or even drug efficacy, one could obtain clues to and supporting information for new indications for drug use Less restrictive labeling: because of questions about efficacy or about toxicity, drugs are sometimes approved for initial marketing with restrictive labeling. Additional data may be obtained from pharmacoepidemiology studies that help to make the labeling less restrictive 29

30. 1.3. Reasons to Perform Pharmacoepidemiology Studies? B4. To protect the drug from accusations about adverse effects: when a question about drug toxicity arises, it often needs an immediate answer or else the drug may lose market share or even be removed from market 30

31. 1.3. Reasons to Perform Pharmacoepidemiology Studies? C. Legal C1. Post marketing surveillance studies can theoretically be useful as legal prophylaxis to defend against product liability suits. 31

32. 1.3. Reasons to Perform Pharmacoepidemiology Studies? D. Clinical D1. Hypothesis generating- need depend on Whether it is a new chemical entity The safety profile of the class The relative safety of the drug within its class The formulation The disease to be treated including its duration , its prevalence , its severity , whether alternative therapies are available D2. Hypothesis testing Problem hypothesized on the basis of drug structure Problem suspected on the basis of preclinical or premarketing human data Problem suspected on the basis of spontaneous reports Need to better quantitate the frequency of adverse reactions 32