FDA information systems, Sentinel Initiative seek more timely drug safety information

Key Points

Increased connectivity among healthcare entities also promises to support more efficient drug testing and development, along with more timely medical product monitoring and oversight. To take advantage of these developments, FDA is working to modernize its internal IT operations for reviewing applications for new drugs and medical products; for receiving and archiving clinical trial data and regulatory submissions; and for tracking manufacturing facilities and product supply chains.

ACTIVE SURVEILLANCE

To fulfill this mandate, FDA launched the Sentinel Initiative in 2008 and now is establishing a "Mini-Sentinel" system that will tap into medical records held by large health plans and insurers. FDA can pose queries triggered by evidence of risks seen in clinical trials or by early AE reports to databases established by CIGNA, Kaiser Permanente, and the HMO Research Network, among others. Using this distributed data model, Sentinel partners can monitor for certain events and assess evidence of health conditions associated with drug use. A second phase next year will permit direct FDA access to de-identified patient data from Medicare and other government health programs.

FDA recently signed a $72 million contract with Harvard Pilgrim Health Care to oversee a Sentinel program that can obtain near real-time signals and ensure data quality. The initiative already has access to information on 60 million patients, according to project director Richard Platt of Harvard Pilgrim and Harvard Medical School, well above the initial FDAAA requirement that FDA monitor 25 million patients by July 1 of this year. Mini-Sentinel also will work with researchers and technical experts at academic centers, private firms, and non-profit organizations to examine methods for queries that use a common data model and to establish policies and standards for validating and analyzing information from diverse information sources.

Platt and others discussed the technical, legal, and administrative issues involved in building the Sentinel System at a recent workshop organized by Mark McClellan, former FDA commissioner and now director of the Engelberg Center for Health Care Reform at the Brookings Institution. FDA Commissioner Margaret Hamburg opened the conference by emphasizing the growing importance of post-marketing surveillance of regulated products.

To have a fully functioning Sentinel System, she noted the need to design a common data model that can compare and analyze data sets, and to seek consensus on methodologies for proving and disproving causal relationships between a product and an outcome.

Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, described Sentinel as one element in a broader FDA campaign to encourage safe use of medications, to revamp the agency's pharmacovigilance system, and to explore the use of social media to publicize safety issues.

FDA also is participating in numerous worldwide collaborations that aim to better understand drug effects in different populations. Judy Racoosin, FDA scientific lead on Sentinel, emphasized that the initial system will help the agency understand the intricacies of gathering safety signals on drugs from multiple sources and closer to real time.

Sentinel is "very much a work in progress," Woodcock commented, noting that it will be very different in 5 years as the science and technology mature.

PRIVACY AND DISCLOSURE

FDA's decision to launch Sentinel based on a distributed data model reflects earlier research by healthcare experts in academia and at pharmaceutical companies that this approach can best ensure the privacy and security of patient health records.

The distributed data model avoids FDA building its own mega-database and instead leaves individual patient health information with the insurance company or health system that holds the records. That data source evaluates the information, transmits summaries to Sentinel, and confirms a specific diagnosis or report if needed.

It remains to be seen, though, how well FDA can assess safety signals through this arrangement. Even with the ability to do their own analysis on the de-identified data from Medicare, FDA staffers still may find it hard to confirm that a safety issue is real.

Another tricky issue is the timing of public disclosure of safety information. "The biggest risk to Sentinel is false positives," commented Marcus Wilson, PharmD, president of HealthCore, the data analysis subsidiary of WellPoint; too early release increases the possibility that a report may be wrong or incomplete and thus raises unnecessary alarm. But delaying communication on an emerging safety issue may result in patient harm and expose program participants to "failure to warn" liability charges. Legal experts want FDA to develop model procedures for when, how, and to whom to report drug safety findings as a way to set policies that can be applied in court.

All these issues will shape how FDA interprets and utilizes Sentinel findings in regulatory decision-making. Confirmation of safety signals could result in changes in a product's labeling, agency alerts to healthcare professionals, and public warnings about appropriate drug use.

Despite concerns about the completeness, objectivity, and timing of Sentinel safety reports, Woodcock maintains that "what we're going to get is going to be better than what we have right now."

BROADER SYSTEM

While Sentinel's prime purpose is to serve FDA's regulatory mission, the long-term vision is that it will be part of a larger health information system that also provides data for outcome studies, comparative effectiveness research (CER), and health system quality reporting.

Pharmaceutical companies support the goal of building such a multi-purpose network, said Paul Stang, PhD, of Johnson & Johnson, but this requires more investment in research methods, standards for data sources and evidence, and governance of emerging models.

Carolyn Clancy, director of the Agency for Healthcare Research and Quality (AHRQ), concluded the workshop by describing AHRQ initiatives to improve patient registries and to build distributed data research networks that can answer queries related to the effectiveness and safety of medical services and products.

These activities reflect the over-arching goal of identifying synergies between post-market surveillance and CER, and of providing incentives for healthcare providers to participate in e-health activities.

Ms Wechsler is a Washington-based reporter specializing in federal and state healthcare issues.