SEARCH

SEARCH BY CITATION

Keywords:

  • FDA;
  • mini-sentinel;
  • organizational structure;
  • principles;
  • policies

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

The US Food and Drug Administration's Mini-Sentinel pilot program is developing an organizational structure as well as principles and policies to govern its operations. These will inform the structure and function of the eventual Sentinel System. Mini-Sentinel is a collaboration that includes 25 participating institutions. We describe the program's current organizational structure and its major principles and policies. The organization includes a coordinating center with program leadership provided by a principal investigator; a planning board and subcommittees; an operations center; and data, methods, and protocol cores. Ad hoc workgroups are created as needed. A privacy panel advises about protection of individual health information. Principles and policies are intended to ensure that Mini-Sentinel conforms to the principles of fair information practices, protects the privacy of individual health information, maintains the security and integrity of data, assures the confidentiality of proprietary information, provides accurate and timely communications, prevents or manages conflicts of interest, and preserves respect for intellectual property rights. Copyright © 2012 John Wiley & Sons, Ltd.


INTRODUCTION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

Mini-Sentinel is a pilot program,i conducted under contract with the US Food and Drug Administration (FDA). Its purpose is to inform development of the Sentinel System, an active surveillance system that will monitor the safety of FDA-regulated medical products under conditions of actual use. A major objective of Mini-Sentinel is to develop a scalable and transparent organizational structure, including policies and procedures that can be adopted by the full Sentinel System. We describe here the current Mini-Sentinel organizational structure and the major attributes of the first set of principles and policies. These principles and policies are available on the Mini-Sentinel website.[1]

ORGANIZATIONAL STRUCTURE

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

Mini-Sentinel is a competitively awarded contract between the FDA and Harvard Pilgrim Health Care, a not-for-profit health plan, which sub-contracts with 24 Collaborating Institutions.ii

The structure of the Mini-Sentinel coordinating center has evolved to meet the needs of the pilot. The coordinating center, shown in Figure 1 and described below, currently encompasses the Mini-Sentinel Principal Investigator, the Planning Board and its subcommittees (Safety Science Committee, Project Operations Committee, and Privacy Panel), the Operations Center (including Management Operations and Scientific Operations), and three “Cores”: Data, Methods, and Protocol.

image

Figure 1. Mini-Sentinel Coordinating Center

Download figure to PowerPoint

The Mini-Sentinel Principal Investigator is ultimately responsible for all aspects of the pilot and reports directly to the FDA. The Planning Board and Operations Center report to the Mini-Sentinel Principal Investigator.

The Planning Board provides a regular forum for active participation by the Collaborating Institutions and the patient community. Site Principal Investigators from each participating institution serve as representatives to the Board. A member of the patient community is appointed to the Board by the Mini-Sentinel Principal Investigator. Core Leaders and the Chair of the Safety Science Committee also are on the Board, and FDA representatives participate in meetings. The Planning Board oversees Mini-Sentinel operations and activities, works with the Operations Center and the FDA to define policies and procedures, and provides a forum for communication.

The Safety Science Committee, appointed by the Planning Board, provides additional scientific guidance for the development and implementation of new data elements, statistical methods, and protocol designs. The Project Operations Committee, also appointed by the Planning Board, drafts principles and policies to govern program activities on behalf of the Planning Board. The Privacy Panel, composed of independent experts with extensive knowledge of legal and ethical issues related to the privacy and confidentiality of individual health information, provides guidance on related policies.

The Operations Center organizes the scientific, technical, analytic, and administrative infrastructure. It oversees daily operations and interacts regularly with representatives of the FDA and the Collaborating Institutions to ensure that all aspects of the pilot run smoothly. The Operation Center contains two divisions. The Management Operations Center oversees administrative matters, including budgets, contracts, communications, and delivery of work products. The Scientific Operations Center oversees scientific aspects of the pilot, including data, methods, and protocols.

Three clusters of subject matter experts work together in what are called “Cores” devoted to data, methods, and protocols. The Data Core leads the development and implementation of data infrastructure, including the Mini-Sentinel common data model,[2] the distributed data approach, and related data standards and quality measures. The Methods Core leads development and implementation of analytical methods, focusing on epidemiological and biostatistical concerns. The Protocol Core leads engagement with the FDA regarding active surveillance topics as well as development and implementation of surveillance protocols and validation of exposures and health outcomes.

Mini-Sentinel Collaborating Institutions include both Data and Academic Partners that provide access to healthcare data and scientific, technical, methodologic, and organizational expertise, as needed to meet the requirements of the project. Representatives of the Collaborating Institutions participate in various capacities, including as members of the Planning Board, the Safety Science Committee, the Project Operations Committee, the Cores (Data, Methods and Protocol), and workgroups engaged in task order and other Mini-Sentinel activities.

Ad hoc project workgroups are created to perform specific activities, such as building and maintenance of infrastructure or designing and leading evaluations of particular regulated medical products and health outcomes of interest. For each activity, workgroup members: (i) develop a project plan, including detailed specifications for its implementation; (ii) collaborate with the Operations Center, Core Leaders, and the FDA to ensure that workgroup activities correspond to FDA needs and expectations; (iii) design and implement appropriate data collection strategies and analytic methods; and (iv) prepare reports and other deliverables.

PRINCIPLES AND POLICIES

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

Mini-Sentinel principles and policies are intended to do the following: (i) ensure that Mini-Sentinel conforms to the principles of fair information practices; (ii) protect the privacy of individual health information; (iii) maintain the security and integrity of data; (iv) assure the confidentiality of proprietary information provided by either the FDA or Collaborating Institutions; (v) provide accurate and timely communications regarding the work of the pilot and its findings; (vi) prevent or manage actual or apparent conflicts of interest; and (vii) preserve respect for intellectual property rights. Additional policies will be developed as warranted.

Fair information practices

Mini-Sentinel's policies are informed by the Fair Information Practices[3] and adhere to the greatest extent possible to the following principles derived from them: (i) openness and transparency; (ii) purpose specification and minimization; (iii) collection limitation; (iv) use limitation; (v) data integrity and quality; (vi) security safeguards and controls; and (vii) accountability and oversight. Because Mini-Sentinel is a public health activity, as discussed below, its policies do not specifically incorporate provisions for individual control or remedies.[4]

Privacy

Mini-Sentinel policies conform to the US privacy requirements that apply to public health practice. The determination that Mini-Sentinel's activities are public health practice in support of FDA's public health mandate was made by the FDA, in consultation with the US HHS Office for Human Research Protections (OHRP). A consequence of the determination that Mini-Sentinel activities are public health activities is that Institutional Review Boards (IRBs) that oversee research involving human subjects do not review these activities. As described elsewhere,[5] the US Health Insurance Portability and Accountability Act of 1966 (HIPAA) Privacy Rule[6] permits covered entities to disclose protected health information (PHI)[7] to public health authorities without patient authorization.

It is not necessary for the FDA or the Mini-Sentinel Coordinating Center to receive personally identifiable information (PII)[8] as defined by the US Privacy Act of 1974[9] to perform Mini-Sentinel's surveillance activities. Collaborating Institutions and investigators adhere to the minimum necessary standard[10] of the HIPAA Privacy Rule. Data requests are limited to the minimum amount of data necessary to respond to the FDA's needs. Unless essential to the validity of a particular activity, as dates of service might be, PHI is retained by Data Partners. Direct identifiers such as name, address, and medical record or social security numbers are not shared.

In addition to federal regulations governing the use of individually identifiable health information, there also are numerous state laws, which must be observed in the conduct of Mini-Sentinel activities.[11] Data Partners are responsible for adherence to state laws.

Data integrity and security

Development of a valid and reliable system for active surveillance of the safety of FDA-regulated medical products depends upon access to accurate, precise, and timely data from a large and varied array of sources. The majority of Mini-Sentinel's data activities rely on the use of a distributed data approach. Data Partners transform data already in their possession as a result of the normal course of providing or paying for clinical care into a standard format specified by the Mini-Sentinel common data model.[12] This enables many analyses that rely on individual level data to be performed by means of analytical programs distributed to Data Partners by the Scientific Operations Center for local implementation. Data Partners return summary results of these analyses to the Scientific Operations Center. A key advantage of this approach is that individually identifiable health information can be removed before data are released by the Data Partner to the Scientific Operations Center for further analysis. This simplifies compliance with federal and state regulations regarding the privacy of individual health information. The distributed dataset approach also ensures that individuals familiar with the characteristics of the source data are active participants in analyses based on that data.

When it is necessary to verify that electronic health data accurately identify exposures or outcomes of interest, Data Partners may share information concerning individuals with other health service organizations that have provided services to those individuals. This may involve an insurer identifying relevant plan members and then obtaining medical records (stripped of direct identifiers) from clinics or hospitals to facilitate validation of an exposure or health outcome of interest to the FDA.[13] Data Partners must clearly identify and segregate data received from these outside sources and refrain from using that outside source data for any other purposes. Further, Data Partners must limit access to outside source data collected for Mini-Sentinel purposes to authorized individuals engaged in related Mini-Sentinel activities.

Data Partners may use their own original source data transformed into the Mini-Sentinel common data model format for other purposes, including research, as long as they comply with applicable state and federal laws and regulations, including HIPAA and the Common Rule.[14] Use of the data for non-Mini-Sentinel purposes may require IRB oversight.

Mini-Sentinel data are managed in accordance with national standards established by the HIPAA Security Rule.[15] Data transfer between Data Partners and the Operations Center and between the Operations Center and the FDA is performed by means of a secure file sharing server. Data in the possession of the Operations Center also are managed in accordance with the US Federal Information Security Management Act of 2002 (FISMA).[16] Administrative, physical, and technical safeguards are employed to ensure the confidentiality, integrity, and security of electronic health information.

Confidentiality

Confidentiality provisions apply to the following: (i) PII and PHI concerning individuals; (ii) information that is proprietary to and maintained as confidential by Collaborating Institutions; and (iii) data and communications concerning queries and evaluations not yet made public by the FDA.

Each individual who receives confidential information from the FDA must sign a non-disclosure agreement stipulating that he or she will not disclose confidential information provided by the Agency to any unauthorized person. Non-public information shared between the FDA and Collaborators may not be used to solicit or otherwise encourage funding by industry or other organizations or agencies.

Proprietary or commercial confidential information, including but not limited to formulary data and rates of medical product utilization and disease incidence, is shared only with Data Partners' explicit authorization, unless required by law. Collaborators may not use confidential or proprietary information obtained from other Collaborating Institutions in the conduct of Mini-Sentinel activities for different purposes unless approved in writing by the original source of the information.

Communications

Descriptions and reports of Mini-Sentinel activities are placed in the public domain, typically on the Mini-Sentinel website, within 30 days of completion and verification. Additionally, the FDA uses its regular communications mechanisms as warranted. The FDA has the right to release results at any time if it deems such action is in the best interest of the public.

Collaborators who are not federal employees have the right to present and publish Mini-Sentinel findings and their interpretation of these results. The FDA has the right to review and comment for up to 30 days but has no control over the content of presentations or publications.

Conflict of interest

Both individuals and institutions must avoid conflicts of interest, including activities or relationships with other persons or organizations that: (i) affect a Collaborator's ability, or potential ability, to render impartial assistance or advice, or give the appearance of doing so; (ii) impair or might impair the Collaborator's objectivity; or (iii) allow or might allow the Collaborator to acquire an unfair competitive advantage.

Detailed conflict of interest policies for both individuals and institutions are under development at the time of this writing. Meanwhile, with respect to individuals, Collaborating Institutions must have written policies on conflicts of interest, which comply with US 42 CFR, Subpart F, Section 50.601 et seq and 45 CFR Part 94. The institutions must certify that, if conflicts of interest exist for individuals participating in Mini-Sentinel activities, such conflicts will be reported to the Operations Center and the Collaborating Institution will provide written assurance that the conflicts have been managed or eliminated in accordance with the policies of the Collaborating Institution and 42 CFR, Subpart F, Section 50.601 et seq and 45 CFR Part 94. Mini-Sentinel will be attentive to the evolving individual conflict of interest policies of the National Institutes of Health.

As noted above, development of criteria for recognizing and reporting conflicts of interest with respect to institutions also is under way. Until a more formal Mini-Sentinel policy is developed, Collaborating Institutions are required to use their best efforts to identify potential institutional conflicts of interest and bring them to the attention of the Mini-Sentinel Principal Investigator, who establishes a course of action in consultation with the FDA, Mini-Sentinel legal counsel, and the Collaborating Institution.

Intellectual property

Intellectual property developed under the auspices of Mini-Sentinel is placed in the public domain. These products may include policies, protocols, reports, data models, and computer programs. Individual collaborators and their institutions retain all rights and privileges pertaining to property developed with other resources. Collaborators are allowed to assert copyright in technical or scientific articles based on or containing such data that are published in academic, technical, or professional journals, symposia proceedings, and similar works.[17]

CONCLUSION

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

Mini-Sentinel is a work in progress. The structure, principles, and policies described here have allowed the program to operate effectively during its start-up phase. Lessons learned from the process of creating and implementing these will further inform the FDA concerning ways of appropriately managing the eventual Sentinel System that are not only feasible and transparent but also consistent with the highest standards of scientific rigor and imbued with respect for the privacy of individuals and their PHI.

CONFLICT OF INTEREST

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

The authors declare no conflicts of interest.

KEY POINTS

  • The FDA's Mini-Sentinel pilot, a collaboration of 25 institutions, is developing governing principles and policies which will inform the Sentinel System.
  • Mini-Sentinel includes a Principal Investigator; Coordinating Center; Planning Board and subcommittees; Operations Center; Data, Methods, and Protocol Cores; and ad hoc workgroups.
  • The principles and policies ensure that Mini-Sentinel observes fair information practices, protects individual privacy, maintains data security and integrity, assures confidentiality of proprietary information, provides accurate and timely communications, manages conflicts of interest, and respects intellectual property.

ACKNOWLEDGEMENT

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES

FDA contract number: Mini-Sentinel is funded by the Food and Drug Administration through the Department of Health and Human Services Contract Number HHSF223200910006I.

  • i

    The views expressed in this document do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices, or organizations imply endorsement by the US government.

  • ii

    Aetna; America's Health Insurance Plans; Brigham and Women's Hospital Division of Pharmacoepidemiology & Pharmacoeconomics in the Department of Medicine; The Center for Health Care Quality at Cincinnati Children's Hospital Medical Center; Columbia University Department of Statistics; Critical Path Institute; Duke Clinical Research Institute; HealthCore, Inc.; HMO Research Network, including: Group Health Research Institute, Harvard Pilgrim Health Care Institute, HealthPartners Research Foundation, Henry Ford Health System, Lovelace Clinic Foundation, Marshfield Clinic Research Foundation; and Meyers Primary Care Institute; Humana; Kaiser Permanente Center for Effectiveness and Safety Research; Outcome Sciences, Inc.; Rutgers University Center for Health Services Research on Pharmacotherapy, Chronic Disease Management, and Outcomes at the Institute for Health, Health Care Policy, and Aging Research; University of Alabama at Birmingham - Deep South Musculoskeletal Center for Education and Research on Therapeutics; University of Illinois at Chicago; University of Iowa, College of Public Health, Department of Epidemiology; University of Pennsylvania School of Medicine; Vanderbilt University School of Medicine; Weill Cornell Medical College.

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. INTRODUCTION
  4. ORGANIZATIONAL STRUCTURE
  5. PRINCIPLES AND POLICIES
  6. CONCLUSION
  7. CONFLICT OF INTEREST
  8. ACKNOWLEDGEMENT
  9. REFERENCES