November 2012

Group Health researchers help the FDA get proactive

The U.S. Food and Drug Administration (FDA) had no doubt about the recent meningitis outbreak linked to contaminated steroids: The illness was unusual and the cause was clear. But what about subtle, complex harms such as hazardous interactions between medications or drug effects that raise the risk of disease? To catch these types of problems, Group Health Research Institute is partnering with the FDA, other health plans, and academic institutions on a new approach to routine, proactive monitoring of medical products.

Currently, the FDA monitors the safety of drugs and medical devices through retrospective studies or through spontaneous reporting by doctors, consumers, and manufacturers. With the fungal meningitis outbreak, an alert doctor suspected the cause and sounded the alarm. However, in general, only an estimated 1 to 10 percent of all adverse events, such as troublesome side effects, are reported.

Proactive, timely, and routine surveillance of medical products is the goal of the FDA Sentinel Initiative. This national system—recently recommended for expansion and sustained funding by President Obama’s science advisors—will use electronic health records (EHRs), computerized insurance claims, and health registries from dozens of organizations nationwide to monitor product safety. The FDA is starting with the Mini-Sentinel, a pilot project with a macro-sized goal of developing the framework, policies, procedures, data resources, and analytic methods for the Sentinel Initiative. This means developing methods to identify specific events in EHRs and standardize and analyze data from different health systems—while maintaining patient privacy. This is all in a day’s work for GHRI investigators.

“We’ve been involved in Mini-Sentinel from the beginning,” says GHRI Associate Investigator Jennifer Nelson, PhD, co-lead of the initiative’s Methods Core and a Steering Committee member. Associate Investigator Denise M. Boudreau, PhD, RPh, is on the Steering Committee and a Data Core Workgroup member. The Mini-Sentinel brings industry scientists and academic researchers together, potentially sparking future collaborations. Over three years, GHRI Mini-Sentinel contracts have totaled almost $1.9 million.

The experience of GHRI investigators, biostatisticians, and programmers with the Virtual Data Warehouse (VDW) of the HMO Research Network has been crucial. Dr. Boudreau says the Mini-Sentinel’s Common Data Model is “almost identical to the VDW.” GHRI researchers also brought surveillance expertise from the Centers for Disease Control and Prevention’s Vaccine Safety Datalink. As of December 2011, the Mini-Sentinel had data on 126 million people, providing the power to detect rare events that might be missed in the smaller controlled trials conducted before medical product approval.

GHRI Associate Investigator Andrea Cook, PhD, is tackling one of the major methodological challenges for Mini-Sentinel: sequential data monitoring. Most observational epidemiology studies use EHR data that are already collected and static. Data for the Mini-Sentinel is a moving target, requiring methods that accommodate multiple analyses over time, performed while new medical product users and their data arrive. Dr. Cook is also addressing confounding variables, such as medical conditions that might interfere with figuring out what caused an adverse event. “We’re also working on how often we should check for events, and what should trigger the FDA to raise a red flag and say ‘let's go study this more closely,’” says Dr. Nelson.

The Mini-Sentinel project was launched in 2009 and includes 31 health care systems, insurance companies, and universities. The first phase of the Sentinel Initiative will last until 2014 and is already yielding benefits. Dr. Boudreau says that although routine medical product surveillance has not yet started, Mini-Sentinel investigators have performed limited monitoring for the FDA, such as checking for heart problems in new users of drugs that help people quit smoking.

“The Mini-Sentinel has already advanced pharmaco-epidemiology and drug safety,” says Dr. Boudreau, “and I think Group Health researchers are being good citizens by participating in this important public health project.”

Sascha Dublin, MD, PhD, Group Health Research Institute assistant investigator, studies medication safety in older people. She led Mini-Sentinel work summarizing ways to recognize cases of atrial fibrillation (the most common kind of irregular heartbeat, which is sometimes caused by an adverse reaction to a drug) in health claims data. Now, Dr. Dublin is helping with a plan to monitor the safety of a new atrial fibrillation drug, the blood thinner dabigatran. She is also leading a group studying ways to collect more detailed and accurate data to supplement the administrative data often used in Mini-Sentinel projects.

“The goal of the Mini-Sentinel is developing methods to use real-world health care data to monitor the safety of new drugs and devices,” says Dr. Dublin. “We’re still establishing the methods, but even in the pilot phase, we might be able to identify problems with drugs or devices earlier than we could have before.”

In addition to Drs. Boudreau, Nelson, Cook, and Dublin, the GHRI Mini-Sentinel teams include Monica Fujii, Kelly Hansen, Gene Hart, Lisa Jackson, Karin Johnson, Ron Johnson, Beth Lapham, Tracey Marsh, Roy Pardee, Rob Penfold, Do Peterson, Bruce Psaty, Tyler Ross, Susan Shortreed, Greg Simon, Robert Wellman, Onchee Yu; and from the University of Washington, Patrick Heagerty and GHRI Affiliate Investigator Susan Heckbert.


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