PHARMACOEPIDEMIOLOGY Epidemic: An epidemic is a classification of a disease that appears in a given human population, during a given period. Ex: Bubonic plague, Great Influenza. It can be Endemic or Pandemic. Infectious diseases that occur at a constant but relatively high rate in the population are said to be ‘Endemic’. Ex: Malaria, Chickenpox, etc. Infectious diseases that spread through human populations across a large region or worldwide are said to be ‘Pandemic’. Clinical Pharmacology: It is the study of Pharmacological effects of drugs in human beings. It provides knowledge important for the effective and safe use of drugs in human population. Epidemiology: It can be defined as the study of the distribution and determinants of diseases in populations. Pharmacoepidemiology: The study of the use and effects/ side effects of drugs in large numbers of people with the purpose of supporting the rational and cost-effective use of drugs in the population thereby improving health outcomes. Pharmacoepidemiological studies are carried out in 2 ways as follows: 1. Case-control studies & 2. Cohort studies. Case- control studies: Case-control studies are one type of epidemiological study designs used to identify factors that may contribute to a medical condition by comparing a group of patients who have that condition with a group of patients that do not. They are the most frequently epidemiological studies. undertaken analytical They are the only practical approach for identifying risk factors for rare diseases. They use patients who already have a disease or other condition to see if the characteristics of these patients differ from those who don’t have the disease. Advantages: Quick and easy to complete, cost-effective. Most efficient design for rare diseases. Usually require a smaller study population. Can study multiple potential causes of disease. Permit study of diseases with long latency between exposure and manifestation. Disadvantages: Uncertainty of exposure-disease time relationship. Inability to provide a direct estimate of risk. Not efficient for studying rare exposures. Subject to biases. Concerned with one disease only. Cohort Studies: Cohort studies are the other type of epidemiological study designs which include larger number of subjects and proceed from cause to effect. It is a type of analytical study. Also called as follow- up studies, incidence studies, panel studies, longitudinal studies or prospective studies. They are of the following 3 types: 1.Prospective 2.Retrospective 3.Historical retrospective Advantages: May be used to study multiple outcomes. Allow complete information on the subject’s exposure, including quality control of data and experience thereafter. Methodology and results are clearly understood by non-epidemiologists. Disadvantages: Expensive and time consuming. Inefficient to study rare diseases. Exposure patterns may change during the course of the study and make results irrelevant. Loss to follow-up. What led to the need for Pharmacoepidemiology in India? ‘Over the counter’ usage of freely available drugs which leads to its misuse and various consequences. Utilization of various systems of medicine like Allopathy, Homeopathy, Ayurveda, etc. by the people. Adverse Drug Reactions. Inadequacies of Clinical Trials. Ex: Models not possible for investigation of certain drug events e.g. pregnancy, very young, very old. RCTs often inadequate to answer questions on safety. RALES Study: RALES (Randomized Aldosterone Evaluation Study). The Cardiac Heart Failure patients were initially treated with Diuretic, Digoxin and ACE inhibitor. But addition of Spironolactone improved survival by 30%. Thus prescription of Spironolactone increased by 150%. Later Post Marketing Surveillance showed 30% decrease in survival. Reason: In reality patients with Renal Failures also consumed the above combination with Spironolactone which was not tested during clinical trials in such subjects. Thalidomide Disaster: Elixir Sulfanilamide Disaster(1937): Diethylene Glycol was used as a diluent for liquid preparation of Sulfanilamide. Lethal agent was not Sulfanilamide but rather its diluent Diethylene Glycol. Approximately 105 patients died due to its therapeutic use. Drug Utilization Studies: Drug utilization research is defined by WHO as ‘the marketing, distribution, prescription and use of drugs in a society with special emphasis on the resulting, medical, social and economic consequences.’ Drug utilization studies are done to facilitate rational use of drugs in populations. Allow comparisons between regions, countries. Help continuous quality improvement, etc. Drug Utilization studies contribute to rational drug use in three important ways: 1. Description of drug use patterns. 2. Early signals of irrational use of drugs. 3. Interventions to improve drug use – follow-up. Drug Utilization Metrics: Drug Utilization metrics include the following: 1. Defined Daily Dose & 2. Prescribed Daily Dose. Defined Daily Dose: It is defined as the estimated average maintenance dose per day of a drug when used for its major indication. It is expressed as DDDs/1000 inhabitants/day. In hospitals drug use is considered as DDDs/100 bed days adjusted for occupancy. Prescribed Daily Dose: It is defined as the average dose prescribed according to a representative sample of prescriptions. It can be determined from prescription studies and medical or pharmacy records. It gives the average amount of a drug that is actually prescribed. Study of Drug Effects: Pharmacoepidemiological studies are carried out to study the effect of drugs. These studies include Signal Generation. Signal Generation: Definition Of Signal: It is a reported information on a possible causal relationship between an adverse event and a drug. The relationship may be unknown or must have been incompletely documented previously. Methods of Signal Generation: Signal Generation includes the following methods: 1. Spontaneous Reporting. 2. Prescription Event Monitoring. 3. Record Linkage. 4. Post Marketing Surveillance. Spontaneous Reporting Spontaneous Reporting: A system by which practicing clinicians are encouraged to report any and all adverse events with a drug is said to be ‘Spontaneous Reporting’. The reports have to first reach the National Centre. The reports from the National Centers are then sent to Uppsala Monitoring Centre (Sweden). Reporting varies with: Severity of the reaction. Time from market introduction. Promotional claims. Promotion of reporting system. Publicity of specific association. When to Report? As soon as you suspect that drug therapy has resulted in a negative, unintended effect. Speed is essential. What to report? Adverse reactions of Type A and Type B. Poisoning. Quality problem. Medical Error. Dependence and abuse. Lack of Effect. Advantages: Covers all medicines. Easy to implement. Rare reactions identifiable. Inexpensive. Do not interfere with clinical practice. Disadvantages: Under reporting. Markedly subject to biases. Delayed effects unnoticed. Information inadequate, incomplete, not verifiable. Cause-effect relation difficult to establish. Prescription Event Monitoring: It is a non-interventional observational cohort technique. It is used to study large cohorts. It is done to check that nothing interferes with the doctor’s decision regarding which drug to prescribe for each individual patient. It is also used for signal generation. Provides information regarding: * All adverse events. * Death from any cause. * Hospitalization. * Fetal abnormalities. Record Linkage: It refers to the task of finding entries that refer to the same entity in two or more files. It is simply the integration of information from two independent sources. It is an appropriate technique to join data sets that do not have a unique database key in common. Each patient in the database has a unique identifier. Helps in monitoring drug use and effect via database research. Has enabled health care administrators and researchers to: * Maintain a comprehensive database. * Link to local statistical files. * Link to survey data. * Link to clinical data. * Link to social data. Post-Marketing Surveillance: It is a practice of monitoring a pharmaceutical drug or device after it has been released in the market. Post-marketing surveillance can confirm or deny the safety of a drug after it is used in the general population by large number of people who have a wide variety of medical conditions. It is carried out by the pharmaceutical industry. A single cohort of 5,000-10,000 patients are studied. Follow up is done in months or years. Finally data is submitted to regulatory authorities. Aim of Pharmacoepidemiology: Patient Counseling. Formulations of public health/ policy decisions. Formulations of therapeutic guidelines and discovery of new indications. Pharmacoeconomic decision making. Conclusion: A great deal of work needs to be done in the areas of drug toxicity, drug interactions, indigenous drugs and pharmacogenetics among others. Studies regarding cost-effective alternatives have to be done.