Table of Contents 

EXECUTIVE SUMMARY ................................................................................................ 1

I. SENTINEL SYSTEM VISION............................................................................................ 3

A. Active surveillance via a distributed system....................................................................... 3 

B. Sentinel will expand FDA’s current safety surveillance capabilities ................................. 3 

II. PROGRESS BUILDING THE SENTINEL SYSTEM...................................................... 4

A. Creating a pilot Sentinel System (Mini-Sentinel)............................................................... 5 

B. The Federal Partners’ Collaboration: Leveraging CMS, DoD, and VA data ..................... 6 

C. Achieving the 25 million lives milestone ........................................................................... 7 

III. PROGRESS ENSURING SECURITY AND PRIVACY .............................................. 7

A. Inherent protections of a distributed system....................................................................... 7 

B. Focus on “minimum necessary” ......................................................................................... 7 

C. Federal law requires maintenance of system security......................................................... 7 

D. Releasing data and findings to the public ........................................................................... 8 

IV. CONCLUSION ................................................................................................................. 8
EXECUTIVE SUMMARY 

In May 2008, the U.S. Department of Health and Human Services (HHS) and the U.S. Food and 

Drug Administration (FDA) announced the launch of FDA’s Sentinel Initiative, a long-term 

program designed to build and implement a national electronic system for monitoring the safety 

of FDA-approved drugs and other medical products. Once completed, the system under 

development by the Sentinel Initiative will be called the Sentinel System. 

The announcement of the Sentinel Initiative followed passage of the Food and Drug 

Administration Amendments Act (FDAAA), which became law in September 2007. Section 905 

of FDAAA mandates FDA to develop an enhanced ability to monitor the safety of drugs after 

these products reach the market. Using a scientific approach called “active surveillance,” the 

Sentinel Initiative is designed to ensure that the Sentinel System will fulfill the mandates 

included in FDAAA. 

FDAAA set goals that FDA’s new safety monitoring system must be able to access data from 25 

million people by July 2010 and 100 million people by July 2012.1

 FDA met the July 2010 goal 

for access to patients’ electronic healthcare data and is already working towards the patient data 

access goal of 100 million patients by 2012. Having met the initial goal, FDA recognizes this 

achievement as an opportunity to provide an update to our progress in building the Sentinel 

System. 

The Sentinel System will enable FDA to monitor the safety of drugs and other medical products 

with the assistance of a wide array of collaborating institutions throughout the United States. 

Data partners in the Sentinel System will include organizations such as academic medical 

centers, healthcare systems, and health insurance companies. 

The electronic data used in this process will be accessed, maintained, and protected by the 

Sentinel System’s data partners, as part of a “distributed system.” In a distributed system, data 

remain in their existing secure environments, rather than being consolidated into one database. 

In addition to data partners, other collaborators involved in this public-private partnership will 

include, but are not limited to, patient and healthcare professional advocacy groups, academic 

institutions, and regulated industry. 

Within this distributed system, a Coordinating Center will receive and process FDA-generated 

safety questions. The Coordinating Center, with the collaborating data partners, will develop 

analytical programs so each data partner can evaluate the questions using their own local 

computer systems and provide HIPAA-compliant2

 summary information regarding the questions 

back to the Coordinating Center and FDA. 

 

1

 (Section 905(a) (3) (B) (i) – (ii) (II)). 

2

 HIPAA refers to the Health Insurance Portability and Accountability Act, which includes restrictions on the use of 

healthcare data to ensure patient privacy. 

U.S. Food and Drug Administration / The Sentinel Initiative / 1 
The Sentinel System will augment, but not replace FDA’s existing postmarket safety monitoring 

systems. For many years, various parts of FDA have gathered risk information about drugs and 

other medical products through programs that rely on external sources (such as product 

manufacturers, consumers, patients, and healthcare professionals) to report suspected medical 

product-related adverse reactions. This type of safety monitoring is known as “passive 

surveillance.” In contrast, the Sentinel System will be an “active surveillance” system, so called 

because it will enable the Agency to initiate its own safety evaluations that use available 

electronic healthcare data to investigate the safety of medical products. 

This combination of both active and passive safety surveillance systems will provide FDA a 

more comprehensive means of monitoring drug and other medical product safety in the United 

States. 

With access to information provided from this broad array of healthcare data partners, the 

Sentinel System is being designed to enable FDA to obtain vital information to help shorten the 

time it takes to better understand new or emerging medical product safety issues. This “near 

real-time” capability is envisioned to help identify safety issues associated with drugs and other 

medical products earlier in a product’s lifecycle compared to the use of current systems. 

Because the Sentinel Initiative is a complex endeavor, FDA has launched several projects 

designed to help develop the eventual Sentinel System, including two pilot initiatives: MiniSentinel and the Federal Partners’ Collaboration. 

• Mini-Sentinel is an effort to develop a smaller working model of the distributed system 

that is envisioned for the Sentinel System. 

• The Federal Partners’ Collaboration leverages the scientific capabilities of other federal 

government agencies, including the Veterans Health Administration at the Department of 

Veterans Affairs (VA), the Department of Defense (DoD), and the Centers for Medicare 

& Medicaid Services (CMS), with the intent to use these federally-held data sources to 

develop the scientific methodologies needed for active surveillance. 

FDA has long envisioned the ability to add “active surveillance” to its wide array of tools to help 

ensure the safety and efficacy of the medical products it regulates, and was pleased that FDAAA 

legislation facilitated the launch of these efforts. 

FDA strongly believes the Sentinel System will enhance the understanding of medical product 

safety well into the 21st Century and become a national resource of value for many future 

generations of Americans. 

2 / U.S. Food and Drug Administration / The Sentinel Initiative 
The Sentinel Initiative: A Progress Report 

With the launch of the Sentinel Initiative in May 2008, FDA highlighted in broad strokes its 

vision of the Sentinel System.3 

This 2010 report provides an updated vision of the Sentinel System based on FDA’s activities 

over the past two years, and a description of progress since its launch. 

I. SENTINEL SYSTEM VISION 

A. Active surveillance via a distributed system 

The Sentinel System, as currently envisioned, will enable FDA staff to actively request 

information from Sentinel System data partners when a safety question arises about a medical 

product. This scientific approach is known as active surveillance. Data partners will include 

organizations such as academic medical centers and healthcare systems with electronic health 

record systems, and health insurance companies with administrative claims data. 

In the active surveillance environment of the Sentinel System, FDA will prioritize safety 

questions that have emerged from premarket or postmarket safety data sources (e.g., clinical trial 

data, spontaneous adverse event reports) and submit them to a Coordinating Center for 

evaluation by data partners that are part of Sentinel’s “distributed system.” Within this 

distributed system, Sentinel System data partners will securely access their databases to evaluate 

the submitted question and return HIPAA-compliant result summaries to the Coordinating 

Center. Through data checking and review activities, the Coordinating Center will assess the 

validity of the results, and then aggregate and forward them to FDA for their use in assessing the 

safety question. 

This information, together with the other benefit and risk information known about a medical 

product from its premarket development program and other postmarket safety data sources, will 

enable FDA to enhance its understanding of a postmarket safety issue and inform regulatory 

decisions and healthcare decision-making, to help protect patients from harm. 

B. Sentinel will expand FDA’s current safety surveillance capabilities 

The active surveillance vision of the Sentinel Initiative complements the largely passive 

surveillance safety systems currently in use by FDA. These passive surveillance systems include 

the Agency’s Center for Drug Evaluation and Research’s (CDER’s) Adverse Event Reporting 

System (AERS), a database that captures reports of suspected adverse drug reactions and 

 

3

 The Sentinel Report, National Strategy for Monitoring Medical Product Safety is available at 

http://www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf. 

U.S. Food and Drug Administration / The Sentinel Initiative / 3 
medication errors, FDA’s Center for Biologics Evaluation and Research’s (CBER’s) Vaccine 

Adverse Event Reporting System (VAERS), a database that captures reports of suspected 

vaccine-related adverse reactions, and FDA’s Center for Devices and Radiological Health’s 

(CDRH’s) Manufacturer and User Facility Device Experience (MAUDE) that captures reports of 

suspected medical device related adverse reactions. In addition to mandatory reporting by 

industry, FDA receives reports submitted through FDA’s MedWatch program, which enables 

healthcare professionals and consumers (i.e., patients, family members, caregivers) to voluntarily 

report suspected adverse drug reactions and medication errors. 

These spontaneous reporting systems are categorized as “passive surveillance” systems because 

they must wait for industry, consumers, patients, and healthcare professionals to recognize and 

report suspected adverse events for FDA to become aware of potential medical product related 

problems. 

Unlike passive surveillance, Sentinel’s active surveillance system will enable the FDA to use 

existing electronic healthcare data in near real-time, a key advantage to more quickly evaluating 

and understanding a safety issue. Additional advantages of an active surveillance system include 

the ability of FDA staff to evaluate safety issues in targeted subgroups of patients (e.g., the 

elderly) and also to have the capability to evaluate adverse events occurring commonly in the 

general population (e.g., myocardial infarction, fracture) that tend not to get reported to FDA 

through its passive reporting systems. 

II. PROGRESS BUILDING THE SENTINEL SYSTEM 

In anticipation of the Sentinel Initiative launch in May 2008, FDA had already begun working 

with the public and private sectors to establish goals, identify concerns, and initiate activities and 

pilot programs to lay the ground work for building an active surveillance system for medical 

product safety. An Attachment to the 2008 Sentinel Initiative Report lists dozens of initiatives 

that were in progress in 2008 in the public and private sectors.4

 Those collaborations have 

continued and new ones have been initiated. Two critical pilot programs that are shaping the 

development of the Sentinel System are the Mini-Sentinel pilot and the Federal Partners’ 

Collaboration. 

• Mini-Sentinel, launched at the end of 2009, will enable FDA to query privately-held 

electronic healthcare data (including administrative claims and clinical data) representing 

approximately 60 million patients. 

• The Federal Partners’ Collaboration, which includes the Centers for Medicare & Medicaid 

Services (CMS), the Veterans Health Administration at the Department of Veterans Affairs 

(VA), and the Department of Defense (DoD), will enable FDA to query federally-held 

electronic healthcare data, including administrative and claims data, and data from electronic 

health record systems. 

 

4

 The Sentinel Report, National Strategy for Monitoring Medical Product Safety is available at 

http://www.fda.gov/downloads/Safety/FDAsSentinelInitiative/UCM124701.pdf. 

4 / U.S. Food and Drug Administration / The Sentinel Initiative 
A. Creating a pilot Sentinel System (Mini-Sentinel) 

In September 2009, FDA awarded a contract to Harvard Pilgrim Health Care, Inc. (Harvard 

Pilgrim) to develop a smaller working version of the future Sentinel System. The pilot has been 

dubbed “Mini-Sentinel.” Harvard Pilgrim is establishing the Mini-Sentinel Coordinating Center 

(MSCC) that will operate as a scaled down version of the Sentinel System and enable the 

Agency to test scientific methods and develop new activities to help create the Sentinel System. 

The MSCC will lead a consortium of more than 20 collaborating institutions.5 As described in 

Figure 1 below, the MSCC will be able to take FDA-identified safety questions and submit them 

to participating data partners for evaluation. Data partners will evaluate the safety questions in 

their database, behind established firewalls, and return HIPAA-compliant summaries of results to 

the MSCC. 

2

FDA

Coordinating 

Center 

reviews and 

aggregates 

findings, and 

sends 

summary 

results B 

Data 

partners 

provide 

summary 

results B 

Coordinating Center

Figure 1: Overview of the Mini-Sentinel Safety Question Evaluation Process 

A. Only those academic institutions with electronic healthcare data will receive safety questions for evaluation. 

B. Data partners will provide summary results from analyses conducted within their secure data environments. Those summary 

results will not include directly identifiable health information. 

FDA 

sends 

safety 

question 

4 

Coordinating 

Center 

sends 

analysis 

3

1 

Health 

 Insurance 

Companies 

Academic 

Institutions A 

Healthcare 

Systems 

Data Partners 

FDA 

communicates 

findings to 

inform health 

care decisions 

5 

 

5

 The collaborating institutions in the consortium include the following organizations: CIGNA Healthcare; 

Cincinnati Children's Hospital Medical Center; Brigham and Women's Hospital; Duke University School of 

Medicine; HMO Research Network sites (includes Group Health Cooperative, Harvard Pilgrim Health Care 

Institute, HealthPartners, Henry Ford, Lovelace Clinic Foundation, Marshfield Clinic Research Foundation, Meyers 

Primary Care Institute (Fallon)); HealthCore; Humana-Miami Health Services Research Center; Kaiser Permanente 

(includes: KPNC, KPSC, KPCO, KPNW, KPG, KPHI, KPOhio, KPmidatlantic); Outcome Sciences, Inc,; 

University of Illinois at Chicago; University of Iowa, College of Public Health; University of Pennsylvania School 

of Medicine; Vanderbilt University School of Medicine; Weill Cornell Medical College. 

U.S. Food and Drug Administration / The Sentinel Initiative / 5 
The Mini-Sentinel pilot will create a kind of laboratory, giving FDA the opportunity to test 

epidemiological and statistical methodologies in the evaluation of postmarket safety issues and 

learn more about some of the barriers and challenges, both internal and external, to establishing a 

Sentinel System for medical product safety monitoring. 

The MSCC and participating data partners will use a common data model as the basis for their 

analytic approach. The approach requires the data partners to transform their data into a 

standardized format. Data converted to the standardized format are included as a part of the 

Mini-Sentinel Distributed Database. Utilizing this standardized data format, the MSCC is able to 

write a single analytical software program for a given safety question and provide it to each of 

the data partners. This allows for each data partner to run the program on its standardized data. 

Data partners will conduct analyses behind their existing, secure firewalls and send HIPAAcompliant summary results to the MSCC for aggregation and further evaluation. 

The MSCC results evaluation process will include checking of the data and analytic program to 

ensure it ran correctly. MSCC will conduct additional analyses of the results to assess their 

validity and provide FDA with both the aggregated results and the summary results from each 

data partner. The use of a common analytic program will minimize the potential for differences 

in results across data holders resulting from differences in the implementation of an active 

surveillance protocol. 

As part of its contract, Harvard Pilgrim is responsible for ensuring that data use complies with 

HIPAA. FDA will not require patient-, provider-, or health plan-specific identifiers. Any results 

provided to FDA will either be aggregated from all data partners or presented as summary results 

from individual data partners, and supplied in a standard predetermined format. As currently 

envisioned, all analyses of data will be performed by the data partners in their secure 

environments without transfer of directly identifiable information. 

B. The Federal Partners’ Collaboration: Leveraging CMS, DoD, and VA data 

FDA is furthering the science of medical product safety surveillance by broadening existing pilot 

programs that use federally-held data sources. The effort, known as the Federal Partners’ 

Collaboration (FPC), which involves the Federal Partners CMS, VA, and DoD, expands the 

SafeRx project, a collaboration between FDA and CMS that utilizes Medicare and Medicaid data 

for medical product safety surveillance. The FPC is similar to the Mini-Sentinel pilot in that it 

utilizes an active surveillance approach and involves a distributed system. However, unlike 

Mini-Sentinel, the FPC does not use a common data model. Rather, the FPC develops a common 

active surveillance protocol, and then each data partner writes analytic code to run the protocol in 

their database. 

Lessons learned from this pilot will be compared to lessons learned using a common data model 

where centralized analytics are employed (e.g., Mini-Sentinel). In this way, FDA can compare 

the potential benefits and drawbacks of every data partner running a single analytic program 

based on a common data model versus each data partner developing its own analytic program 

based on a common protocol. 

6 / U.S. Food and Drug Administration / The Sentinel Initiative 
C. Achieving the 25 million lives milestone 

FDAAA set goals that FDA’s new active safety monitoring system must be able to access data 

from 25 million people by July 2010 and 100 million people by July 2012. Although the 

Sentinel System is still under development, FDA has established partnerships with multiple data 

partners that would enable access to healthcare information for more than 60 million lives. 

Those sources include information from the Federal Partners’ Collaboration, including CMS, 

VA, and DoD, and the data partners comprising the current Mini-Sentinel Distributed Database. 

III. PROGRESS ENSURING SECURITY AND PRIVACY 

Safeguarding the privacy and security of all information FDA processes is of paramount concern 

to the Agency. It is a fundamental part of FDA’s ongoing responsibilities as it fulfills its mission 

to protect public health. Since the launch of the Sentinel Initiative, FDA has engaged thought 

leaders in the privacy and security field. One of the first contracts awarded under the Sentinel 

Initiative involved the identification and analysis of potential privacy issues. 

A. Inherent protections of a distributed system 

Within the Sentinel System’s distributed system, directly identifiable data will not be transferred 

to FDA. Instead, directly identifiable data will remain under the local control of participating 

data partners, behind existing firewalls, and protected by established privacy and security 

safeguards. Those data partners who participate in the Sentinel System will perform analyses of 

their own data upon request and provide HIPAA-compliant summary results. 

B. Focus on “minimum necessary” 

FDA recognizes that there may be infrequent occurrences when de-identified data may not be 

sufficient for medical product surveillance. There may be instances that require the sharing of 

more specific information between data partners and the Coordinating Center. For example, in 

some cases, individual medical record review is required to confirm that a patient had an adverse 

event of interest. Therefore, FDA is actively exploring approaches that will ensure that only the 

minimum amount of directly identifiable information necessary leaves its local environment to 

meet the needs of the specific active surveillance evaluations. FDA is also engaging with 

privacy experts to explore other avenues of consumer protection that should be developed or 

expanded. 

C. Federal law requires maintenance of system security 

The Sentinel System, like all systems that process, publish, transmit, or store FDA information or 

information on behalf of FDA, must be protected in accordance with the Federal Information 

Security Management Act (FISMA) of 2002. The Sentinel System must be fully assessed as part 

of the FDA Certification and Accreditation process as required by FISMA and the Office of 

Management and Budget before being put into production. 

U.S. Food and Drug Administration / The Sentinel Initiative / 7 
D. Releasing data and findings to the public 

FDA has in place a number of mechanisms for communicating safety information to the public, 

including product labeling and a range of safety communications that are posted on FDA's Web 

site and disseminated through FDA’s MedWatch program. The Agency will follow similarly 

transparent methods of publicly communicating relevant and timely safety information obtained 

through Sentinel System evaluations. 

IV. CONCLUSION 

FDA welcomes this opportunity to report the status of the Sentinel Initiative. We have made 

significant progress and are committed to continuing this ambitious pace. Attachment 1 shows 

the many milestones FDA has already achieved in developing the Sentinel System. The 

requirements laid out by Congress in section 905 of FDAAA will be met and even exceeded. 

Attachment 2 highlights contracts and cooperative agreements instrumental in the development 

of the Sentinel Initiative. 

Since the launch of the Sentinel Initiative in May 2008, FDA has built upon the work that had 

already been initiated to expand the Agency’s postmarket safety monitoring capabilities to 

include active surveillance approaches. 

Over the coming years, lessons learned from efforts such as Mini-Sentinel and the Federal 

Partners’ Collaboration, will allow us to further refine plans for the implementation of the 

Sentinel System. These pilots, along with other ongoing activities, will enable us to design the 

Sentinel System in a way that addresses the complex needs of an active surveillance system, 

including technological, methodological, legal, and operational challenges. 

Importantly, FDA is working to ensure that the privacy and security of directly identifiable 

information are strictly maintained in accordance with federal and state laws and regulations. 

As FDA develops the Sentinel System as a tool to conduct active surveillance on the medical 

products it regulates, we are careful not to lose sight of its potential value to other public and 

private entities. FDA envisions that the Sentinel System will become part of a larger national 

partnership that will meet the needs of regulators as well as others including healthcare systems, 

academicians, and the regulated industry. Such a partnership would be of interest, not only to 

those evaluating the safety of medical products, but also to those aiming to improve the quality 

of healthcare. 

We are working to ensure that the Sentinel System’s distributed system of electronic healthcare 

data is developed in such a way that it becomes a national resource of value for future 

generations, providing the maximal value to the public health. 

8 / U.S. Food and Drug Administration / The Sentinel Initiative 
ATTACHMENT 1. SENTINEL INITIATIVE MILESTONES 

 

Sept. 2007 Congress passes FDA Amendments Act (FDAAA) requiring FDA to collaborate with federal, 

academic and private entities to develop methods to obtain access to disparate data sources and 

validated means to link and analyze safety data. FDAAA establishes goals of including 

25,000,000 patients by July 1, 2010; and at least 100,000,000 patients by July 1, 2012.

March – Sept 

2008 

Sentinel Team kicks off its series of Stakeholder meetings, including meetings with other 

Federal agencies and outside stakeholders (patients, consumers, academics and other experts, 

potential data partners, vendors, regulated industry).

May 2008 FDA launches Sentinel Initiative and issues a report outlining the program and its goals.

June 2008 Sentinel Team establishes Federal Partners Working Group, which meets quarterly to explore 

issues related to the Sentinel Initiative and other related federal initiatives.

Aug-Sept. 2008 Sentinel Team awards eight contracts to inform the Agency on the development of the Sentinel 

System by addressing issues related to governance, privacy, data and infrastructure, scientific 

operations, and outreach (see Attachment 2).

December 2008 Sentinel Team and eHealth Initiative Foundation cosponsor the public workshop Sentinel 

Initiative: Structure, Function and Scope, in cooperation with Brookings Institution. 

Stakeholders participating include academia, potential data partners, vendors, consumers, patient 

representatives, Federal partners and industry.

Sept 2009 Sentinel Team awards a cooperative agreement to The Brookings Institution to convene 

discussions on topics related to active medical product surveillance.

Sept 2009 Sentinel Team awards two contracts to inform the Agency on the development of the Sentinel 

System addressing issues related to privacy regulations at the state level and data sources for 

veterinary medicine safety surveillance (see Attachment 2).

Sept 2009 Sentinel Team awards a contract to Harvard Pilgrim Health Care, Inc. to create a Coordinating 

Center to support the development of the scientific operations for the Sentinel Initiative (“MiniSentinel). 

Jan 2010 2nd Annual Sentinel Initiative Public Workshop is convened by the Brookings Institution’s 

Engelberg Center for Health Care Reform and supported by a grant from the FDA. 

Jul 2010 FDA access to 25 million patients achieves a FDAAA mandate. 

U.S. Food and Drug Administration / The Sentinel Initiative / 9 
10 / U.S. Food and Drug Administration / The Sentinel Initiative 

ATTACHMENT 2. CONTRACTS AND COOPERATIVE AGREEMENTS TO INFORM 

THE AGENCY ON THE DEVELOPMENT OF THE FDA SENTINEL SYSTEM 

The following documents are now available in the FDA docket and on the Sentinel Web site

http://www.fda.gov/Safety/FDAsSentinelInitiative/default.htm. 

• Developing a Governance and Operations Structure for the Sentinel Initiative, an eHealth 

Initiative Foundation report. 

• Engagement of Patients, Consumers and Healthcare Professionals in the Sentinel 

Initiative, an eHealth Initiative Foundation report. 

• Defining and Evaluating Possible Database Models, a Harvard Pilgrim Health Care, Inc. 

report. 

• Evaluation of Existing Methods for Safety Signal Identification, a Group Health 

Cooperative Center for Healthcare Studies report. 

• Evaluation of Potential Data Sources for a National Network of Orthopedic Device 

Implant Registries, an Outcome Sciences, Inc. report. 

• Evaluation of Timeliness of Medical Update for Surveillance in Health Care Databasesand IMS Government Solutions report. 

• Evaluating Potential Network Data Sources for Blood and Tissue Product Safety 

Surveillance and Studies, a Pragmatic Data report. 

• Evaluation of State Privacy Regulations and Relation to the Sentinel Initiative, a Qual-Rx 

report.

Work on the following projects is still ongoing. 

• Evaluation of Potential Data Sources, a Booz Allen Hamilton report. 

• Evaluation of Potential Data Sources for Animal Drugs used in Veterinary medicine, an 

Insight Policy Research, Inc. report.

• Detection and Analysis of Adverse Events to Regulated Products in Automated 

Healthcare Data: Efforts to Develop the Sentinel Initiative, Harvard Pilgrim Health 

Care, Inc. 

• Convener of Active Medical Product Surveillance Discussions, The Brookings 

Institution.