The Sentinel Initiative is an Ongoing Process in Which the FDA Will Mine Data from Different Databases to Help Determine the Risks of Drugs, Medical Devices, and Biologics

In a lawsuit regarding a drug or medical device, Plaintiffs’ attorneys typically argue that the manufacturer controls “all” the knowledge about post-marketing adverse events from the use of its products. They then allege that the manufacturer has missed a signal or failed to send critical information to the FDA. This scenario continues with allegations that the overworked FDA depends on that manufacturer to forward such information to them and that the manufacturer has failed in this duty. Therefore, plaintiffs conclude, a dangerous product has remained on the market without adequate warnings.

But what if a system existed in which the FDA were “in charge” and took the initiative to seek out adverse events itself? Welcome to the Sentinel Initiative. The Sentinel Initiative is an ongoing process in which the FDA will mine data from different databases to help determine the risks of drugs, medical devices, and biologics. In May 2008, Secretary Mike Leavitt of the Department of Health and Human Services described this initiative: “We are moving from reactive dependence on voluntary reporting of safety concerns — to proactive surveillance of medical products on the market.”¹

In 2005, the Secretary of Health and Human Services asked the FDA to expand its system of monitoring medical products.² The mandate for such an expanded system came in the fall of 2007 when Congress passed the FDA Amendments Act directing the FDA to create a surveillance system for monitoring drugs by using healthcare data from various existing healthcare information holders. According to that law, access to data from 25 million patients is to be achieved by July 1, 2010, and access to data from 100 million patients is to be available by 2012.³ On December 16, 2008, the FDA held a two-day workshop with representatives of the federal government, pharmaceutical and medical device industry, healthcare providers, and the public to get their input on the development of the Sentinel System.⁴ It has also entered into various contracts with private companies to research various aspects of this mammoth undertaking.⁵ The final system is not yet in place but continues to evolve over time as various stages of the system come on line.

Under the present system, the FDA relies on voluntary reporting of adverse events to help determine post-marketing risks. This system will not be abandoned. There is a recognition, though, that this system has inherent limitations which may include lack of complete information in adverse event reports. This limitation can affect the ability to assess causality of the adverse event. Under the Sentinel Initiative, the FDA will develop a query about a possible adverse event from a drug or device. It will then send this query to a variety of private and public medical data holders who will be expected to mine their data for the use of that drug or device and a certain complication or outcome. Once the data holders submit that information to the FDA, the FDA will analyze the results of the data search. This process presumably provides the FDA the information necessary to make a risk/benefit analysis; if not, the FDA may send follow-up queries for additional data mining. The FDA may then decide whether the drug or device should be withdrawn, or: “If, using methods developed in this new science, [the FDA] can determine that an adverse event is restricted to a small identifiable segment of the population, the drug, biologic, or device could remain on the market and continue to benefit those who are not subject to the [adverse] event.”⁶ In theory, this process should improve product safety knowledge, but as the FDA recognizes, there are challenges in the implementation of the Sentinel system.

Some of the challenges the FDA identifies include development of sources for the information, patient privacy and data security, scientific integrity, integrity of the data analysis, a governance structure and process — including communication of the findings to the public — and transparency.⁷

The meeting the FDA conducted with various stakeholders on December 16, 2008, discussed these issues and possible ways forward for the system. At that meeting, the FDA also made it clear that the Sentinel System would not replace the present monitoring system but would instead be “another tool in the toolbox, although perhaps as the versions would grow, this would become one of the most powerful tools we would hope.”⁸

Sources of Information:

The FDA already has in place contracts and agreements with various governmental entities, as well as private organizations, to use their data for risk evaluation under the current system. For example, in 2007, the FDA signed MOUs for sharing information with the Department of Veterans Affairs and the Department of Defense. The FDA already uses data regarding adverse events that the CDC collects from its National Electronic Injury Surveillance System emergency room database and its Transplantation Transmission Sentinel Network.⁹ Additionally, the FDA Center for Drug Evaluation and Research has contracts with four healthcare databases to perform analyses of signals received from adverse event reports.¹⁰ Presumably, these sources will be used to mine data for the Sentinel System, and additional sources of data could be added to the Sentinel System as well.¹¹

Integrity of the Data Analysis:

The system as conceived will not involve the FDA’s creating a large database for the primary data. The ownership of the data will remain with the original data holder. The network will send queries out to the data holders, and the data owners will run the query and send responsive information back to the network for analysis. Whether only the FDA will formulate the queries remains an open question. Different data sources will vary in how they code their data and how detailed that data might be, so how compatible results will be when different databases are searched and results combined is another unknown. The FDA realizes the need for methodological research to determine how data structure influences results. Additionally, there may be a need for standardization among the various data systems so that queries will have more reliability.¹² Moreover, some database information may require closer scrutiny than other information. For example, information from an insurance database is mainly input for reimbursement purposes and not for medical research. As in the present system, sometimes there may be a need to review the actual medical record.

Privacy of the Data:

Data generated by the Sentinel Initiative will have to be protected. Various privacy laws already protect patient information: Federal HIPPA regulations, the Federal Privacy Act, and various state laws, to name a few. HIPAA balances the privacy needs of the patient with the need for public health research and should allow de-identified data to be shared with the FDA if other HIPAA requirements are met. Successful implementation of the Sentinel system will require appropriate privacy policies and technology to protect data, including determination of who has access to that data and the purposes for which it can be used.¹³

Communication with the Public:

The Sentinel System has been described as a “real time” system. The idea is that queries will be sent, data will come in and be analyzed, and an assessment of the risk/benefit of the medical product will be done by the FDA, all in a rather short time frame. When and by what means that analysis should be communicated to the manufacturer, the physician, and the public are two important issues facing the FDA in designing this system. Should the FDA communicate to physicians immediately that there is an identified risk and a query is being sent out, or should the physician be told only when the risk is confirmed? If a query is leaked to a media source before the FDA has completed its risk assessment, will patients be scared into stopping a drug they need to treat a medical condition based on an allegation or suspicion about a risk that may turn out to be non-existent or extremely rare?¹⁴ How will manufacturers be kept in the loop so that they continue to have the ability to monitor their products effectively? These, and questions like them, must be answered over time as the Sentinel Initiative refines its policies and procedure.

What should your company do?

It would seem prudent for pharmaceutical, biologic, and medical device companies to avail themselves of appropriate opportunities for input into the process for the Sentinel Initiative. The system can have a significant impact on how companies evaluate product risks. By appropriate involvement, a company may demonstrate its commitment to improving safety of its products by supporting a system that will retrieve information about possible risks as soon as possible. The FDA is actively looking for input on the Sentinel Initiative. It has held two conferences on it and may hold others in the future. Additionally, a plethora of information about the Initiative resides on the FDA website.¹⁵ The website includes reports from completed projects dealing with various aspects of the Sentinel process, offering greater detail about how the process is being formulated.¹⁶ Companies also have the ability to comment on these reports using FDA docket number FDA-2009-N- 0192.¹⁷ While such comments can indicate a company’s commitment to improving the post-marketing system, only a few companies have taken advantage of the opportunity to comment on these reports. Moreover, since this is a system that likely will impact the pharmaceutical and medical device industry for years to come, having some voice in shaping its final form would seem wise. At the very least, a company should assign someone in its medical safety section to keep up with developments by signing up on the Sentinel homepage for e-mail updates.

No one can say with certainty what the Sentinel system ultimately will look like or how it will evolve over time. One thing is certain, though: Sentinel will change how the safety of medical products is evaluated in the future.

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[1] See <http://www.hhs.gov/news>, news release dated May 22, 2008. Last accessed Nov. 24, 2009.

[2] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm089474.htm#summary>. Last accessed Nov. 24, 2009.

[3] The Food and Drug Administration Amendment Act of 2007, Section 905.

[4] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm149341.htm>. An earlier meeting of such groups was held in 2007. Last accessed Nov. 24, 2009.

[5] For example, the FDA has entered into a contract with Harvard Pilgrim to define and evaluate possible database models and with the group Health Cooperative Center for evaluation of timeliness of medical update for surveillance and healthcare databases. See The Food and Drug Administration and eHealth Foundation in Cooperation with the Brookings Institute Sentinel Initiative: Structure, Function, and Scope (PDF). Dec. 16, 2008. <http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/CriticalPathInitiative/PastEventsonCPI/UCM113469.pdf>. Last accessed Nov. 24, 2009. (From Dec. 16, 2008 Transcript p. 18 located at http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm149341.htm). Last accessed Nov. 24, 2009.

[6] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm089474.htm#science>. Last accessed Nov. 24, 2009.

[7] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm089474.htm#challenge>. Last accessed Nov. 24, 2009.

[8] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm149341.htm>, Dec. 6, 2008 Transcript, p.13. Last ac­cessed Nov. 24, 2009.

[9] See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm089474.htm#attachment>. Last accessed Nov. 24, 2009.

[10] Id. The four entities were Ingenix Inc. (United Healthcare Group), Vanderbilt University, Kaiser Foundation Research Institute, and Harvard Pilgrim Healthcare Inc.

[11] The FDA has entered into a contract with IMS Gov­ernment Solutions for evaluation of potential data sources for the Sentinel Initiative. See <http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm149341.htm>, Transcript, pp.12, 17-18. Last accessed Nov. 24, 2009.

[12] Id. pp. 23, 31.

[13] Id. pp. 57-63.

[14] Id. pp. 72-73.

[15] By going to the website and clicking on the “S” in the A to Z Index on the home page of the website, you are directed to a list that includes “Sentinel.” Clicking on this link will direct you to the page regarding the Sentinel Initiative. See <http://www.fda.gov>.

[16] One can find these reports by going to the Sentinel home page and clicking on “Deliverables from completed contracts.” See <http://www.fda.gov/Safety/FDAsSentinel Initiative/ucm149343.htm>. Last accessed Nov. 24, 2009.

[17] Click on a link with this docket number on the “Deliverables from Completed Contracts” page to read these comments.

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