PHARMACOVIGILANCE

Dr. C Mahadeo, Asc., MBBS, Dip.Surg.

WHAT IS PHARMACOVIGILANCE

Defined by WHO as: the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem Plays a key role in ensuring patient drug safety. Continuously evolving at scientific and regulatory level.

INFLUENCE

The influence and origin stems from regular negative reviews of unacceptable and dangerous side effects of drugs Multiple litigation issues and mass torts e.g. Vioxx Higher public demands and necessity for better quality product and responsibility to the client Better patient care required and necessary reduction of apprehension thus improving compliance.

CLASSIC EXAMPLES
Rofecoxib: pharmacovigilance in the APPROVe Trial showed increased incidence of sudden cardiac death vs placebo Rosiglitazone: in 2007 meta-anlaysis showed increased risk of MI and cardiac death. Thalodimide and birth defects in the 1960s This led to immediate review of pharmacovigilance guidelines in Europe with improved monitoring. (2006) Few hundred in Pakistan unregulated drug market.

WHAT IS AN ADVERSE DRUG REACTION

The Drug Regulation Authority defines this as: response to a medicine used in humans or animals, which is noxious and unintended, including lack of efficacy, and which occurs at any dosage and can also result from overdose, misuse or abuse of a medicine. The ultimate goal is to recognize ADR and improve patient safety.

HOW DO WE MONITOR AND REPORT?

Clinical trial data insufficient to make proper assessment Encourage patient reporting e.g. UK yellow card system. This is also called Spontaneous Reporting System (SRS). Remember! 94% of Adverse Drug Reactions go unreported Using Data-Mining techniques Intensive monitoring Database studies e.g. UK general practice research database

WHAT IS DATA MINING?

principle of analysing data from different perspectives and extracting the relevant information. Algorithms are often used to determine hidden patterns of associations or unexpected occurrencesi.e. signalsin large databases. Proportional reporting ratios (PPRs), compare the proportion of reports for a specific ADR reported for a drug with the proportion for that ADR in all other drugs. The calculation is analogous to that of relative risk. Using the same information, it is also possible to calculate a reporting odds ratio

The Bayesian confidence propagation neural network (BCPNN) method is used to highlight dependencies in a data set. This approach uses Bayesian statistics implemented in a neural network architecture to analyse all reported ADR combinations.

ACHIEVING THE GOAL OF PHARMACOVIGILANCE

COMMUNICATION! Erice Declaration on transparency, which was published in 1997: Drug safety information must serve the health of thepublic Education in the appropriate use of drugs, including interpretation of safety information, is essential for the Public AND health care providers All the evidence needed to assess and understand risks and benefits must be openly available Every country needs a system with independent expertise Innovation in drug safety monitoring needs to ensure that emerging problems are promptly recognised and efficiently dealt with, and that information and solutions are effectively communicated

FUTURE TRENDS
Transparency e.g. Ericie declaration Conditional approval i.e. all drug companies must have post marketing follow up and drug studies with proper data collection and analysis Risk management plans Involvement of patients in the reporting and surveys

The pharmacovigilance of tomorrow must be able to identify new safety issues without delay. If we succeed herein, patients confidence in drugs will return. Furthermore, pharacovigilance methods must also be able to describe which patients are at risk of developing an ADR and what the is course of the ADR.