Title 14. ADHOC DATA SOURCES.pdf ✅

PHARMD GURU Page 1  In Pharmaco-epidemiological studies, the data sources available as Ad hoc sources are those that are collected during Post-marketing surveillance studies.  Ad hoc concerns with providing data regarding drug safety in long term use or It concerns about the drug aspects in a large population which is seen in post marketing studies compared to pre-marketing studies. DIFFERENT AD HOC DATA SOURCES: 1) Spontaneous reporting 2) Global drug Surveillance 3) Case-Control Surveillance 4) Prescription-Event Monitoring 1)SPONTANEOUS REPORTING OF ADVERSE EVENTS:  Spontaneous reporting systems are the most common method used in Pharmacovigilance to generate signals on new or rare adverse events, which is not discovered during clinical trials.  Very useful in generating hypothesis, and to find out possible explanations for the adverse event in question.  In order to ensure that safe and effective pharmaceuticals are available, FDA relies on:  Voluntary reporting by health care professionals or consumers.  Mandatory reporting of Adverse Events by manufacturers as required by law and regulation.  Individual spontaneous reports of ADRs, medication errors, & product quality problems, are 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 post marketing surveillance depends.  FDA also employs data mining techniques to identify 'signals' (previously unrecognized or unidentified serious AE).  After confirmation of a 'signal', FDA can initiate various regulatory actions like:  Labeling change such as a 'boxed warning'.  Restricted use or distribution of the drug.  Name or packaging changes. ADHOC DATA SOURCES
PHARMD GURU Page 2  A "Dear Health Care Professional" letter.  Withdrawal of a medical product from the market. EXAMPLE: Signal identified via spontaneous reporting confirmed by a formal Pharmaco- epidemiology study. BACKGROUND:  Phenylpropanolamine (PPA) is the ingredient used in OTC, as a decongestant, and in OTC weight loss products.  In 1984, FDA received reports of Hemorrhagic stroke (bleeding into brain or into tissue surrounding brain) in association with PPA.  In addition, there were published reports in literature. QUESTION:  Is the use of PPA-containing products associated with hemorrhagic stroke? APPROACH:  To confirm this signal, an ad-hoc case-control study was conducted. RESULTS:  The study demonstrated a statistically significant increased risk c hemorrhagic stroke among both appetite suppressant users and first-time users of PPA as cough/cold remedy. OUTCOME:  FDA Advisory Committee meeting discussed the case-control study and recommended that PPA be considered not safe for OTC use.  FDA then took steps to remove PPA from all drug products and requested all drug companies to discontinue or reformulate PPA-containing products.  Thus, a formal epidemiological study is usually needed to confirm a signal identified through spontaneous reports.  In spite of its limitations (underreporting, incomplete reports, etc) spontaneous reports of AEs provide an important cornerstone for Pharmacovigilance in the US. In UK, spontaneous ADR reporting scheme is done with the help of Yellow card scheme.
PHARMD GURU Page 3 2. GLOBAL DRUG SURVEILLANCE:  Global reporting of concerns about suspected adverse drug reactions is a vital alerting tool.  The WHO Collaborating Centre for International Drug Monitoring in Uppsala (now known as the Uppsala Monitoring Centre, UMC).  Today, 73 countries — Full official members, 12 countries — associate members  National centers should report monthly frequency.  Recently, there has been an international effort to:  Harmonize the terms used to describe the adverse events.  To set criteria and definitions for at least the major serious types of reactions.  To harmonize the way data are stored and communicated internationally.  Main agencies involved in this are WHO, CIOMS, ICH and the EU.  The Medical Dictionary for Regulatory Activities (MedDRA) is being used worldwide.  ICH E2B format, which is a guideline for the transmission format for information to be included on an ADR case report, is being used. 3. CASE-CONTROL SURVEILLANCE (CCS):  Like prescription drugs, non-prescription drugs can also have serious adverse effects and unintended benefits.  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.  CCS relies on self-reports of medication and dietary supplement use. STRENGTHS:  CCS has the capacity to monitor: 1) Prescription drugs. 2) Potentially important confounders. 3) Over-the-counter drugs. 4) Dietary supplements.  Can have high statistical power because of large number of cases accrued  As CCS obtains data on many exposures and many outcomes, it has capacity to discover unsuspected associations.
PHARMD GURU Page 4 EXAMPLE:  Assessment of effects after long intervals or duration of use. Ex: Adverse effect of estrogen supplements on risk of endometrial cancer persisted for 15-19 yrs after cessation of use.  Allows for assessment of whether genetic polymorphisms modify the effect of a medication or supplement on the risk of the illness.(buccal cell samples) LIMITATIONS:  Potential for selection bias and  Potential for recall bias. 4. PRESCRIPTION EVENT MONITORING:  PEM is a pharmaco-epidemiological study in which a cohort of users of a medicine is defined from prescriptions and followed-up for a defined period (often 6- 12months) so as to identify all adverse events occurring in the early post- treatment period.  The limited contribution of spontaneous ADR reporting system in detecting hazards such as oculomuco-cutaneous syndrome with Practolol, led Inman to establish the system of PEM at the Drug Safety Research Unit (DSRU) at Southampton in 1981.  It is one form of Pharmacovigilance and is complementary to spontaneous reporting of suspected ADRs.  Method of both hypothesis generation and testing. Publication provoked many subsequent studies which confirmed the association. Inverse association between aspirin and risk of colorectal cancer was documented in CCS.