BETHESDA, MD 11 March 2011—By the end of March, the first data analysis based on FDA’s fledgling electronic active surveillance system for medical products should be complete, a workgroup leader recently announced.
And, if the subsequent nine quarterly data analyses proceed as planned, the surveillance system will estimate the relative risk of myocardial infarction (MI) in saxagliptin users ahead of the company-sponsored Phase IV study.
Bruce Fireman, a workgroup leader for the FDA-sponsored program known as Mini-Sentinel, described its first medical product evaluation during a virtual roundtable held by the Brookings Institute on January 31.
This first evaluation, he said, focuses on MI and oral hypoglycemics because "heart attack is a serious outcome of great interest in the diabetes population, and it’s an outcome that can be ascertained well by Sentinel data partners."
Fireman’s employer, Kaiser Permanente, is one of several health systems, academic medical centers, and health insurance companies that have volunteered to participate in Mini-Sentinel, a pilot project in the Sentinel Initiative. The groups analyze their firewall-protected databases to answer FDA-submitted safety questions.
The purpose of the nearly three-year-old initiative, according to FDA, is to provide the agency a "proactive" system—the Sentinel System—for identifying and evaluating safety issues in the nation’s medical products.
While FDA was evaluating Bristol-Myers Squibb’s new drug application for saxagliptin, the agency decided that it needs to know the cardiovascular risk of new antidiabetic therapies that treat type 2 diabetes.
The decision, contained in "Guidance for Industry: Diabetes Mellitus—Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes," was announced in December 2008.
The agency’s recommendations apply to clinical studies that are planned or completed before a company submits its new drug application or biologics license application. Bristol-Myers Squibb submitted its new drug application for saxagliptin half a year before those recommendations came out.
FDA approved the new drug application in mid-2009 but required five postmarketing studies.
One of those studies is a randomized, double-blind, controlled trial that evaluates the effect of saxagliptin on the occurrence of major adverse cardiovascular events, including MI, in patients with type 2 diabetes.
The company, according to FDA, plans to complete the study by mid-2015 and submit the final report by January 31, 2016.
At ClinicalTrials.gov, the Web page for the study states an estimated enrollment of 12,000 patients age 40 years or older. These patients will receive saxagliptin alone or with other medications that treat type 2 diabetes.
Fireman said the Mini-Sentinel study will end in June 2013, having begun in July 2009 and using baseline data back to July 2007.
"This study population will have at least 1.3 million people with type 2 diabetes," he said. "We’re anticipating about 47,000 heart attacks in this study population."
According to the study’s protocol, the patients are new users of saxagliptin or similar users of the four following antidiabetic therapies: sitagliptin, long-acting insulin, pioglitazone, or the second-generation sulfonylureas glimepiride, glipizide, and glyburide.
Fireman said the research team expects to have data from 23,000 person-years of saxagliptin use by adults and similar experience for each of the other therapies. The team expects the incidence of MI to be about nine cases per 1,000 person-years.
If those expectations hold, he said, the study will have 81% power to detect a 33% increase in the relative risk of MI among saxagliptin users.
Richard Platt, with Harvard Pilgrim Health Care Institute, said Mini-Sentinel also plans this year to evaluate safety issues that have arisen with older drugs, rotavirus vaccines, and human papillomavirus vaccines.
The institute is affiliated with Harvard Pilgrim Health Care, which received the contract from FDA to develop Mini-Sentinel, including its coordinating center.
Mini-Sentinel’s coordinating center, according to FDA’s schematic, acts as the go-between, shielding the "data partners" and the agency from each other. No identifiable health information is supposed to leave the data partners.
The Sentinel System is FDA’s response to a 2007 mandate to develop a postmarket risk identification and analysis system.