This document provides an introduction to pharmacoepidemiology. It defines pharmacoepidemiology as the study of drug use and effects in large populations. It discusses study designs used in pharmacoepidemiology including randomized trials, cohort studies, case-control studies, and case reports. Reasons for performing pharmacoepidemiology studies include fulfilling regulatory and legal obligations, assessing drug safety, and generating or testing hypotheses. Common data sources are spontaneous adverse event reporting, prescription databases, and medical records. Issues like adherence, molecular factors, ethics, and economics are also discussed.
12. (B) New types of information not available from premarketing studies (1) Discovery of previously undetected adverse and beneficial effects (a) Uncommon effects (b) Delayed effects (2) Patterns of drug utilization (3) The effects of drug overdoses (4) The economic implications of drug use
13. (C) General contributions of pharmacoepidemiology (1) Reassurances about drug safety (2) Fulfillment of ethical and legal obligations
14. Study designs available for PE studies In hierarchical order of progressively harder to perform but more convincing Randomized clinical trials Prospective cohort studies Retrospective cohort studies Case-control studies Analysis of secular trends Case series Case reports
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16. First put forth by Sir Austin Bradford Hill in 1965Coherence with existing information (biological plausibility) Consistency of association Time sequence Specificity of association Strength of association Quantitative strength Dose-response relationship Study design
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18. Analysis of secular trends and case-control studies- useful to explore these associations
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20. (B) Marketing (1) To assist market penetration by documenting the safety of the drug (2) To increase name recognition (3) To assist in repositioning the drug (a) Different outcomes, e.g., quality-of-life and economic (b) Different types of patients, e.g., the elderly (c) New indications (d) Less restrictive labeling (4) To protect the drug from accusations about adverse effects (C) Legal (1) In anticipation of future product liability litigation
21. (D) Clinical (1) Hypothesis testing (a) Problem hypothesized on the basis of drug structure (b) Problem suspected on the basis of preclinical or premarketing human data (c) Problem suspected on the basis of spontaneous reports (d) Need to better quantitate the frequency of adverse reactions (2)Hypothesis generating—need depends on: (a) whether it is a new chemical entity (b) the safety profile of the class (c) the relative safety of the drug within its class (d) the formulation (e) the disease to be treated, including (i) its duration (ii) its prevalence (iii) its severity (iv) whether alternative therapies are available
22. Thus, the decision to conduct a PE study can be viewed as similar to the regulatory decision about whether to approve a drug for marketing or the clinical decision about whether to prescribe a drug. In both cases, decision making involves weighing the costs and risks of a therapy against its benefits.
33. Individual spontaneous reports of ADRs, medication errors, & product quality problems, sent to FDA directly or indirectly, combined with data from formal clinical studies and from medical and scientific literature, comprise the primary data source upon which postmarketing surveillance depends.
53. In CCS, multiple case-control studies are conducted simultaneously in order to monitor the effects of prescription and OTC medications and dietary supplements (e.g. herbals) on risk of various illnesses.
54. CCS relies on self-reports of medication and dietary supplement use
61. The limited contribution of spontaneous ADR reporting system in detecting hazards such as oculomucocutaneous syndrome with practolol, led Inmanto establish the system of PEM at the Drug Safety Research Unit (DSRU) at Southampton in 1981
62. It is one form of pharmacovigilance and is complementary to spontaneous reporting of suspected ADRs
74. Pharmacogenomics- Studies of genetic variability on drug exposure + encompasses approaches simultaneously considering data about thousands of genotypes in drug discovery and development, as well as responses in gene expression to existing medication (genome-wide approach)
75. Molecular PE- focuses on effects of genetics on clinical outcomes from medication use
80. Cost-effectiveness of such approaches must be justifiable given the additional costs of genetic testing in clinical care
81. Ethical, legal and social implications of genetic testing must be considered and addressed
82. Another concern, that medicines will be developed only for the most common, commercially attractive genotypes, leading to ORPHAN GENOTYPES.
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85. Cost of drugs is not limited to their purchase price
86. Includes the cost of preparation, administration, monitoring for and treating side effects,etc…
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88. Economic data from Phase III studies are used to support initial pricing of new therapies and are used in professional educational activities by pharmaceutical firms
89. Post marketing economic studies are used to compare new therapies with existing ones and also to confirm the initial Phase III economic assessments of the product.
90. 3 types of economic analysis- cost-benefit - cost-effectiveness (mc used in medical care) - cost-identification
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92. HRQOL has become an established outcome measure in clinical research
93. Encompasses - ability to function normally - to be free of pain - free of physical, psychological and social limitations or dysfunction - free from iatrogenic problems associated with treatment
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97. Patient may commence taking the medicine but, execute the prescribed dose regimen poorly
98. They may discontinue taking the medicine altogether at anytimeThe high incidence of early discontinuation gave rise to the term “persistence” which is defined for each patient as the time between the first-taken and the last-taken doses
104. Essence of eMEM is to imbed into the drug package microcircuitry that is connected to one or more micro-switches which detect when the maneuvers occur that are needed to remove a dose of drug from the package
105. These maneuvers which vary from one type of package to another, are referred to as “medication events”.
109. A prominent feature with patients’ dosing histories is – -the higher occurrence of dose omissions with evening doses than with morning doses -higher omissions on weekends than on weekdays -gradual ↑ in frequency of dose omissions as duration of t/t increases. -white coat compliance
110. There is a simple pragmatic reason for wanting to know what impact these deviations from the recommended dosing regimen have on the effectiveness and safety of the drug in question Case example: “How much adherence is enough?” Background- Doxycyclinehyclate 100mg , orally BD for 7 days, is generally accepted std of care for chlamydial infections of male urethra or lower genital tract of females. Question- How much does adherence alter responsiveness to doxycycline Approach- Study carried out by Public Health Dept of State of Alabama(USA) to examine the impact of poor compliance with prescribed dosing regimen of doxycycline on outcome of chlamydial treatment.
114. It is preferable from the consumers’ perspective, to make such a discovery early rather than late in a pharmaceutical product’s commercial lifetime
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