Title 4. METHODS OF POST MARKETING SURVEILLANCE.pdf ✅

PHARMD GURU Page 1 INTRODUCTION:  To market a drug, the manufacturer must provide evidence of its efficacy and safety to the USFDA (Food & drugs administration) and specified regulatory authorities.  In pre-marketing testing, the number and types of patients used to demonstrate a drug`s efficacy and safety are limited compared with the number and types of patients who will eventually be prescribed by the drug after it is marketed.  Although post marketing surveillance cannot provide knowledge of the safety or efficacy of drugs, at the time of the introduction on the market.  Post marketing surveillance of drug, therefore play an important role to discover an undesirable effect that might present at risk.  It provides additional information on the benefits and risk of the drugs. ADVANTAGES:  No fixed duration/patient population.  Report all adverse drug reactions (ADR`s).  Help to detect: Rare adverse drug reactions (ADR`s) and Drug Interactions.  Starts immediately after marketing. HISTORY:  In 1960, at least two serious drug reactions were observed in many patients. Thalidomide causes limb deformities (Phocomelia).  Observed in Japan, was the optic nerve damage (sub-acute Myelo-optic neuropathy).  The PMA, Senator Edward Kennedy (D-mass) suggested that a better system was needed for monitoring the use and effects of prescription drugs, after they were marketed.  As a result, the Joint Commission on prescription drug use was established in 1976, funded largely by the drug industry, with the mandate to design a post marketing surveillance system to detect, quantify and describe the anticipated and unanticipated effects of marketed drugs. METHODS OF POST MARKETING SURVEILLANCE
PHARMD GURU Page 2  The delayed discovery of Practolol’s adverse effects spurred efforts to improve post marketing surveillance. SOURCES OF PMS INFORMATION: The following may be considered as sources of information, some sources are proactive and some are reactive.  Expert users group (focus groups)  Customer surveys  Literature reviews  Customer complaints and warranty claims  The media  User’s reactions during training programs, etc. NEED FOR POST MARKETING SURVEILLANCE:  The primary objective of post marketing studies is to develop information about drug effects under customary conditions of drug use.  Rare adverse events may not be detected in Pre-licensure studies because even large clinical trials have limitations. TYPES OF POST MARKETING SURVEILLANCE: (a) SPONTANEOUS/VOLUNTARY REPORTING OF CASES: Voluntary reporting by physicians and other health care providers, hospitals and customers may act to alert FDA and pharmaceutical firms to possible adverse effects of drugs. Voluntary reporting of cases done by:  WHO international system  National Pharmacovigilance system INDIA  local (or) regional (Joint Commission requirement)  Scientific literature publications In other countries:  US-FDA Medwatch.  UK yellow card system.  Australia blue card system.
PHARMD GURU Page 3 (b) OBSERVATIONAL STUDIES: 1) CASE REPORTS:  These are descriptions of individual patients who are exposed to a drug and who develop suspected adverse drug reactions. They can be effective in alerting the medical community to very rare adverse reactions, especially if acute, of rapid onset and uncommon in the absence of drug exposure.  However case reports do not provide an estimate of the incidence of the reaction, since, the number of exposure patients is unknown. In addition, adverse drug reactions are frequently unrecognized & clinical events may be incorrect attributed to the drug exposure. Thus case reports are mostly useful for generating rather than testing, hypothesis about drug effects. 2) CASE SERIES: These are reports of a series of patients with a particular drug exposure and their subsequent clinical course. They can be useful in quantitating the frequency of medical events after exposure to a drug. However, these studies cannot determine that the drug is the cause of any of the medical events, unless the medical event is known to be extremely uncommon in the absence of the drug exposure and much more common with other drug exposure. 3) CASE CONTROL STUDIES:  A case control study identifies a group of patients with the disease of interest and compares them with a control group of patients without the disease. Both groups are examined for antecedent drug exposure and rates of exposure are compared. This method has been used extensively in post marketing surveillance and has demonstrated many important associations.  These studies can be performed more quickly and less expensively than cohort studies. However, it can be difficult to select the appropriate control group. In addition, since these studies require questioning patients regarding prior drug exposure. 4) COHORT STUDIES:  Cohort studies compare patients exposed to a drug with a control group of unexposed patients (or) patients exposed to another drug and look forward in
PHARMD GURU Page 4 time at subsequent clinical events. The rate of events is then compared between the two groups.  Thus, they are particularly useful for studies of newly marketed drugs, looking for drug effects. In contrast to case control studies, cohort studies can measure incidence rates. These studies, however, require very large samples of patients in order to detect relatively uncommon drug effects. This results in expensive studies, which are logistically difficult to perform. 5) RANDOMIZED CONTROL TRIALS:  These are also called experimental studies, differ from cohort studies in that the investigator controls the drug exposure, one (or) more of these studies are nearly always performed prior to marketing, primarily to test the efficacy of drugs.  They're often performed on highly selected groups of patients who are free of drugs and diseases, other than those under study. Thus, the results are often not applicable to the typical patients who will be taking the drug. Although these studies are designed to include an adequate number of patients to determine the efficacy of a drug, they are usually too small to detect uncommon drug effects.  In post marketing surveillance, they are mainly used to evaluate the efficacy of drugs for new indications. They're often costly (or) impractical in specific situations. For example: when a drug`s effects are rare (or) appear only for long term use (or) a long latency period.