Eli Lilly and Company - Comment

July 17, 2009 Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852. Re: FDA-2009-N-0192 Via Internet to: http://www.regulations gov Dear Sir(s)/Madame(s), We are pleased to submit comments on the Sentinel Initiative contractual report entitled “An Analysis of Legal Issues Related to Structuring FDA Sentinel Initiatives Activities” [Document ID: FDA-2009-N-0192-0003.2]. We support the Food and Drug Administration (FDA) in their efforts to develop the Sentinel Initiative as required by Section 905 of the Food and Drug Administration Amendments Act (FDAAA) of 2007. We also applaud FDA in soliciting input and comments from stakeholders and making this information available to the public. We look forward to the continued development of the plans for implementing the Sentinel Initiative. We also look forward to providing additional comments and insights once more specific information regarding the implementation of the Sentinel Initiative is outlined. As the Sentinel Initiative is envisioned to strengthen FDA’s ability to monitor the performance of marketed products, there are a number of elements that will need to be addressed in order to have a successful and sustainable Sentinel system. These include topics such as governance, operations, database models, data sources, scientific methods, communications, privacy, and legal considerations. We would like to commend the eHealth Initiative in their efforts to summarize the various legal issues that will need to be considered as part of the development of the Sentinel Initiative. Overall, we found the report to be very informative and a good summary of the possible legal issues. We agree with the author’s recommendations describing the phases of the Sentinel Initiative, need to provide guidance on the distinction between public health surveillance and research, and the establishment of a comprehensive communication plan. Listed below are more specific comments regarding the report. Specific Comments on Sentinel – Analysis of Legal Issues 1) Important Data Fields in De-identified Data: The authors review the standards for de-identification of data (page 12-13). Currently, this standard includes the option of utilizing a qualified statistician to review a database to determine whether the likelihood that an individual could be re-identified is extremely small. For researchers, this statistical standard enables researchers to utilize databases that are considered de-identified even though they may contain dates of service. In pharmacovigilance research, the inclusion of dates of service can be very important to researchers who must determine the relationship between the time that a medication was initiated and the occurrence of a potential adverse event. While the standards for de-identification of databases are being re- evaluated, we would suggest that this document include a discussion of this topic, specifically highlighting the importance of the issue of dates of service in this type of research. 2) Communication Plans: On page 77 of the document, the authors write, "In Part I, we conclude that, because phase 1 of the Sentinel Initiative will only involve data source response to FDA queries, rather than data source analysis of drug safety findings, phase 1 of the Sentinel Initiative should not pose a risk of tort liability to the data sources. In other words, where the data source is reporting events but is not evaluating the risks represented by those events, the data sources would not acquire any knowledge that would justify reporting to patients or physicians. Once details of subsequent phases of the Sentinel Initiative are known, the participants will need to evaluate their risk of liability. If subsequent phases involve transmission of identifiable information to the FDA (rather than completely de-identified information as contemplated in Phase 1 of the Initiative), that reporting of more detailed information should not pose any additional risk to the data sources for failure to warn. However, if the data sources are involved in the analysis or research of drug safety in response to safety signals, participants should carefully evaluate their potential liability." In these statements, the authors appear to be attempting to make a distinction between each entity simply sending data to the FDA for the FDA’s analysis vs. each entity actually performing an analysis and sending that analysis to the FDA. In addition to this distinction being important from a legal standpoint, it also leads us to reflect on the importance of gaining greater clarity on the analytic model that will be utilized in the Sentinel Initiative. Are entities expected to send de-identified patient level data (with all of the data elements that are deemed to be important in the analysis) to a central analytic group that combines the patient-level data and performs the analysis? Alternatively, are analysts at each entity being asked to perform a centrally- specified analysis based on their entity’s database? In the latter case, each entity is not simply a data provider, but rather an analytic group that contributes a result that they recognize will be aggregated with the results contributed by other entities. 3) Internal Review Boards: The authors recommend that a central IRB be used for Sentinel Initiative projects vs. using IRBs at multiple institutions (page 76). While this may be a good policy for having consistent approaches to the Sentinel Initiative research studies, some of the data environments that would like to participate in Sentinel may, as a matter of policy at their institutions, have to take the additional step of getting approval from their institutional IRBs. The possibility of involvement of both central IRBs and IRBs at multiple institutions underscores the importance of the government taking steps to provide appropriate guidance to institutional IRBs considering how to consistently apply existing privacy rules (including the recently enacted privacy changes in the HITECH Act) to projects involving the retrospective analysis of administrative claims and electronic medical record data. This effort might be considered a component of Sentinel Initiative planning and implementation, but it could also benefit retrospective research that occurs outside the Sentinel Initiative. The recent Institute of Medicine Report (Beyond the HIPAA Privacy Rule: Enhancing Privacy, Improving Health through Research) speaks to the variability of interpretations by individual IRBs as a potential barrier to research. We appreciate the opportunity to comment on the current report on possible legal issues for the Sentinel Initiative. Please let us know if you have questions or need additional clarification. We would also welcome the chance to provide additional comments and insights as more detailed information is released on the Sentinel Initiative. Sincerely, Donald G. Therasse, M.D. Vice President, Global Patient Safety Lilly Research Laboratories Eli Lilly and Company