New Tools Track Safety, Value in Medicine - Pharmaceutical Executive


New Tools Track Safety, Value in Medicine

Pharmaceutical Executive


As a prelude to a fully operational real-time Sentinel System, FDA has established a mini Sentinel pilot to test scientific methodologies for investigating drug use issues, explained Judy Racoosin, CDER's scientific lead for Sentinel. A main goal set by FDAAA is to access data on at least 100 million individuals by July 1, 2012, building on its success in tapping into drug use information on more than 25 million patients seen last July (see Pharm Exec, March 2010). FDA also has formed a drug surveillance collaboration with other federal agencies, including the Centers for Medicaid and Medicare Services, the Veterans Administration, and the Department of Defense, to query these health data banks on safety issues of mutual interest.

Over the past three years, Sentinel has established basic principles and policies, including a Common Data Model, core safety surveillance methods, and Health Outcomes of Interest (HOIs) that deserve evaluation. A Sentinel Coordinating Center operated by Richard Platt of the Harvard Pilgrim Healthcare Institute can send out queries to databases operated by Kaiser Permanente, WellPoint, and the HMO Research Network, among others, and then evaluate resulting responses. Because the Sentinel Initiative involves public health operations, as opposed to research, its query-and-analysis process can proceed without waiting for institutional review board approval.

Benchmarking REMS

Sentinel will test several key protocols this year. One project will assess whether certain postmarketing regulatory initiatives such as REMS (risk evaluation and mitigation strategies) enhance the safe use of medicines. An active surveillance project is monitoring certain outcomes associated with rotavirus and human papillomavirus vaccines. An important study will examine cardio events in users of diabetes drugs by comparing the incidence of myocardial infarction in patients prescribed saxagliptin (Bristol-Myers Squibb's Onglyza) to those taking other diabetes treatments.

The importance of building a solid methodological foundation for interpreting results also was discussed at a symposium sponsored by the Observational Medical Outcomes Partnership (OMOP), a collaboration of industry, FDA, and the Foundation for the NIH (FNIH). OMOP is examining how well different methods and data sources can identify valid safety signals and whether meaningful information can be gleaned from disparate observational data sources that use varying terminologies. The program has identified ways to assess the strength of associations between drug exposure and specific adverse events, such as liver failure or bleeding, and is examining the impact of missing patient information and how well alternative study designs can deal with variations in patient demographics, comorbidities, and drug exposures.

OMOP's success in identifying methods and tools through an open, collaborative process has prompted the participants to extend the partnership beyond its initial two-year time frame. The group also plans to expand into methods that could apply to medical devices and biologics, in addition to drugs, and to assess approaches for CER and healthcare quality measures.

Going Public

As Sentinel moves forward, sponsors and researchers are looking at the broader implications of dealing with early drug safety signals in ways to avoid alarming the public. The mini Sentinel study on diabetes treatments and cardiac events, for example, raises questions about when and how FDA will make public any findings, noted GlaxoSmithKline general counsel Daniel Troy at the Sentinel workshop. Even if FDA says it won't release early results prior to full analysis, outside lawyers and policymakers may try to compel disclosure, which could lead to liability for failure to warn. This applies not just to pharma companies, but also to data partners that hold safety information in their systems, Troy pointed out.

Behrman acknowledged that liability is very much on the agency's mind because it could drive companies away from the Sentinel project. Realistic expectations about what an active drug surveillance system can do is important, said Troy. Sentinel is not the "be-all and end-all" information system, and FDA needs to make it clear to the public that Sentinel signals are based on observational data, which has limitations in making informed judgments about medical safety issues.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at


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