Friday, May 23, 2008

FDA's Sentinel Initiative, A Pathway To Drug Safety

In the wake of growing instances where several well known pharmaceutical drugs have turned out to be hazardous, the federal health officials have announced the launch of the Sentinel Initiative, a long term program to increase drug safety by data mining an analysis.

Drug recalls are a costly affair for patients, governments and pharmaceutical drug manufacturers alike. The case of “Vioxx” a pain relief drug, is one such glaring example that had reportedly got the manufacturer a revenue of $2.5 billion before it was voluntarily recalled by the company. Now, the company is faced with compensating the plaintiffs with millions.

The Present System Of Drug Safety

Compared to the proposed system the present system's efficacy is limited. The present system revolves around three basic sources of information.
  1. A report filed by health professionals or patients who experience serious problems and pin down their suspicion the drugs and medical devices they prescribe, dispense, or use.
  2. Case reports published in the medical literature.
  3. Results of post-approval and other clinical studies when they are performed.
Further, recently advances in information technology have opened up newer avenues for monitoring the performance of medical products. Consequently, the FDA has expanded the risk management processes by expanding data source identification and data query capabilities, improving risk identification, assessment and mitigation strategies.

Still the challenges are:
  1. That well-conducted, randomized, controlled clinical trials cannot uncover every safety problem.
  2. In a majority of cases the clinical trials aren't diverse enough, large enough and long enough in duration to extract all the information on a product's safety.
  3. Clinical trials aren't able to to reliably detect rare, serious adverse reactions that occur with long latency or in subpopulations who weren't a part of the studies.
  4. Another challenge is the rate at which new new medical products surface in the markets. As new products emerge the likelihood for their interactions with other foods, biologics, drugs (vaccine, surgical drug,etc) and medical instruments and devices also increases.

The Sentinel Initiative

The prime objective of the Sentinel Initiative is to create a nationwide, integrated, electronic system (or the Sentinel System) for monitoring medical product safety.

Such a system when developed and implemented in stages would enable the FDA to access the capabilities of multiple, existing data systems (e.g., medical claims databases, electronic health record systems) to further improve the Agency's current capability.

Moreover, this system entails the establishment of a public-private partnership, comprising myriad organizations (e.g., FDA, data owners, subject matter experts, other government agencies, etc.

This organization would, for instance develop short- and long-term project goals. It would comprise a system architecture, which would enable focused queries of a variety of data sources, located at remote sites.

The data sources are to be maintained by their owners, who would also provide consent before queries are performed on the system.

Access to and analysis of large amounts of data forms the key feature of this program. Such a facility would improve upon the already existing architecture and processes for Risk Identification, Risk Assessment and Risk Minimization.

Risk Identification: The present adverse event reporting program gets information about many medical products, alternative medicines etc, and from a variety of voluntary reporters (e.g., prescribers, dispensers, and patients). However, its limitations entail underreporting of suspected adverse events, incomplete information to enable assessment of causality, the Agency not being able to know the percentage of people that were affected.

Risk Assessment: These processes suffer, as most of the information is received voluntarily, and doesn't help in the evaluation of the rate, or the impact, of known adverse events, or even the comparative assessment of outcomes using various products.

Risk Minimization: This part entails minimizing the possible harm, at the same time continuing to facilitate the safe use of a product for those patients for whom it will be beneficial.

Some tools for risk minimization are:
  • Targeted education and outreach tools (meant to to increase knowledge and behaviors of healthcare practitioners and consumers)
  • Reminder systems (prompt, remind, double-check, practitioners and/or patients in prescribing, dispensing, receiving the products)
  • Performance-linked access tools (systems that link product access to laboratory testing results or other documentation)


The real challenge lies in the implementation of the project and specifically the challenges pertain to Privacy Protection and Data Security, Scientific Credibility of the analysis, Maintenance of integrity by insulation from undue influence, Systems Approach for effective, life-cycle, safety surveillance of medical products, Governance to provide for incorporation of a broad range of expertise and minimize conflict, Inclusiveness of stakeholders' inputs in the standards and processes of the system, Transparency of study results to public and Open Source availability of software code, standards and methods.

The project is in its initial stage and would be unfolded overtime in phases, to begin with the Medicare database would be utilized for analysis. If the program moves along as has been conceived and the obstacles are overcome, then it surely would prove to be a “quantum leap,” in F.D.A's capacity to monitor drug safety.

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