Safety Signal Dectection & Data Mining

200472114-001Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem. WHO established its Programme for International Drug Monitoring in response to the thalidomide disaster detected in 1961. Together with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, WHO promotes PV at the country level. At the end of 2010, 134 countries were part of the WHO PV Programme.

The aims of PV are to enhance patient care and patient safety in relation to the use of medicines; and to support public health programmes by providing reliable, balanced information for the effective assessment of the risk-benefit profile of medicines.

The development of new and effective medicinal products makes a positive contribution to the health and well-being of individuals. However, there is a need to improve pharmacovigilance (PV) systems to more effectively monitor and take action on safety issues associated with medicines to enhance their contribution to public health. This article looks at the current trends driving the development of PV strategies in order to achieve this aim.

Factors behind the development of current trends

  • Globalization of the pharmaceutical market.
  • Development of innovative products.
  • Increasing public awareness and changing expectation with regards to the safety of medicines.
  • Large costs associated with drug safety.

Integrated Pharmacovigilance

In the past, PV has concentrated primarily on post-marketing safety surveillance. In recent years, it has been shifted towards systematic PV throughout the product life cycle (preclinical studies to post marketing surveillance) as recommended by the CIOMS V Working Group. The effective PV system needs to integrate input from all stakeholders, both within an organization and externally.

Effective integrated PV also includes preclinical and clinical operations, clinical data management, statistics, medical writing, regulatory authorities/activities, IT and medical information, sales and marketing, and public relations.

Current Trends

The main method currently used to gather information on a drug in the pre-marketing phase is by conducting clinical trials.

Recent Developments

Data Mining Technology in Spontaneous Reporting System

  • In the past, signal detection in spontaneous reporting has mainly occurred on the basis of case-by-case analyses of reports. Recently, the reports are validated by ‘data mining’.
  • The term ‘data mining’ refers to the principle of analyzing data from different perspectives and extracting the relevant information.
  • Algorithms are often used to determine hidden patterns of associations or unexpected occurrences, i.e. signals in large databases.

Three Current Approaches in Data Mining Methods

  1. Proportional Reporting Ratios (PPRs): This method compares the proportion of reports for a specific Adverse Drug Reaction (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’.
  2. Bayesian Confidence Propagation Neural Network (BCPNN): This approach uses Bayesian statistics to analyze all reported ADR combinations. Strong relationships in the data are highlighted relative to general reporting of suspected adverse effects. The WHO Collaborating Centre for International Drug Monitoring uses this method for data mining.
  3. Multi-Item Gamma Poisson Shrinker (MGPS): It is used by the FDA for data mining of their spontaneous report’s database. The MGPS algorithm computes signal scores for pairs, and for higher-order (e.g. triplet, quadruplet). The significant more frequent combinations of drugs and events would predict.

Future Perspectives

  • Innovation in drug safety monitoring needs ensure that emerging problems are promptly recognized and dealt with, and that information and solutions are effectively communicated.
  • “Process oriented evidence” is essential to protect public health.
  • The creation of purposeful, coordinated, worldwide support amongst politicians, officials, scientists and clinicians will demonstrate benefits of PV to public health and patient safety.
  • In order to further prove PV as a science, it is essential that academia develops new methods which can strengthen the current system.
  • Furthermore, when facing an ADR, questions that patients as well as the treating physician can ask are: will this ADR disappear?; How long will it take before it does?; What treatment is needed?
  • The pharmacogenetics could play a role in identifying individual risk factors for the occurrence of certain ADRs.
  • In the future, PV has to concentrate on the patients as a source of information in addition to the more traditional groups, such as the health professionals.
  • Transparency and communication would strengthen consumer reporting, which is a positive step towards involving consumers more in PV.

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

*Also see, Programming Coding Resource for Scripts for Report Building