UK clinical trial disaster: Five subjects sent home
A British investigation into a recent clinical trial disaster finds no apparent errors or cause for the adverse events that landed six men into critical care.
Within several weeks of falling ill during the clinical trial, five of the six patients who had participated in a London, England, clinical trial were discharged from the hospital, while the remaining patient was moved out of critical care.
TeGenero AG of Wurzburg, Germany, had been studying a humanized agonistic anti-CD28 monoclonal antibody, called TGN1412, to treat cancer and autoimmune diseases. TeGenero contracted with Parexel International of Boston, MA, to conduct a phase I clinical trial, which was conducted at the Parexel unit of Northwick Park Hospital in London.
Six young and healthy volunteers were injected with TGN1412, and two received a placebo. All six men who received the study drug became seriously ill, with inflammation, vomiting, severe pain, swollen heads, and unconsciousness. The two men who received the placebo were fine.
The sick men were transferred to critical care at Northwick Park Hospital, where they received organ support. By April 5, 2006, five of the men had been discharged from the hospital, but one remained.
Meantime, the Medicines and Healthcare products Regulatory Agency (MHRA) of Great Britain, which investigated the adverse events, issued an interim report that found no evidence of problems in the manufacturing of the product that was given to trial participants.
The MHRA report concludes, "Subject to the completion of the outstanding tests, MHRA takes the view that the adverse incidents did not involve errors in the manufacturer of TGN1412 or in its formulation, dilution or administration to trial participants."
The report further states, "The MHRA therefore concludes that an unpredicted biological action of the drug in humans is the most likely cause of the adverse reactions in the trial participants."
The MHRA also notes that the Secretary of State for Health has agreed to establish a group of leading international experts in the field to consider what changes to clinical trials may be required.
NIH launches MedlinePlus Magazine for public
Paul Rogers, former member of Congress and Chairman of The Friends of the National Library of Medicine, announced in May the launch of NIH MedlinePlus Magazine.
"The magazine sorts through the clutter of competing health claims that are out there to provide reliable information that can be used by the public," commented Donald A.B. Lindberg, MD, Director of the National Library of Medicine.
The quarterly publication will be distributed free of charge to patients and their families in the waiting rooms of selected practicing physicians across the nation. The magazine has no advertising.
Each issue of NIH MedlinePlus Magazine will link readers with celebrities and other individuals who share their own health-related experiences and discuss how these issues may affect others. The premiere issue features an in-depth MedlinePlus interview with athlete/Tour de France bicycle race winner Lance Armstrong, who talks about his own experience with life-threatening cancer.
NIH MedlinePlus Magazine is organized to help readers learn more about specific health conditions and offer the latest advice on prevention, diagnosis, treatment and research findings. Regular features will include the latest information on how to stay healthy for a lifetime and will also profile some of the most fascinating people – from laboratory scientists and public figures to patients who are making a difference in the search for medical advances.
Those interested in subscribing should write Friends of the National Library of Medicine, P.O. Box 31130, Bethesda, MD 20814. The magazine will also be available online at http://medlineplus.gov.
GAO: Improve post-approval drug oversight
A Government Accountability Office (GAO) report on drug safety released in May came as no surprise to many FDA critics who have charged that the agency lacks teeth when it comes to enforcement on pharmaceutical products after they're on the market. Others said the findings shed light on issues that the FDA already is working to improve.
The GAO concluded that the FDA "lacks clear and effective processes" on post-approval safety issues, but the government's investigational division also commended the regulatory agency for some recent organizational and policy changes, such as its new Drug Safety Oversight Board. However, the report added that "more could be done" in its oversight of post-approval safety issues to improve the dispute resolution process and to strengthen collaboration between the FDA's Office of New Drugs and its Office of Drug Safety. Both are housed within the agency's Center for Drug Evaluation and Research.
In an interview with BioWorld Today, Michael Werner, president of the Werner Group, a Washington-based life sciences consulting firm, noted that the findings could be interpreted two ways, favoring reformers who have called for drastic changes but also supporting others who believe a bit of tweaking could go a long way. He expects that the GAO report will not have a major impact on Capitol Hill. "The system is not broken," he told BioWorld Today. "But to be certain, safety issues have returned front and center in recent days, and expect more this summer when the Institute of Medicine issues another analysis on the FDA."
FDA critics warmed to the GAO's recommendation that Congress should consider giving the agency the authority to require post-approval drug safety studies, which also are referred to as Phase IV commitments or post-marketing studies. But that would require legislative change, because under current law, only accelerated approvals come with mandated Phase IV requirements.
Some regard the GAO's suggestion to better empower the agency when it comes to Phase IV requirements as a boost to those in Congress who have been pushing safety-related legislation.
Leading the charge is Sen. Charles Grassley (R-Iowa), who a year ago introduced a bill that would give the FDA's safety office independence from CDER. His measure would establish the Center for Postmarket Drug Evaluation and Research. Grassley's proposed bill is labeled S. 930, and its companion House bill is H.R. 4429.
Not everyone favors new laws, and there are many opponents of an independent safety division within the FDA. Notably, the GAO made no such recommendation. As the appropriations process moves forward, speculation continues that money could be directed toward improving the agency's existing infrastructure for pharmaco-vigilance, better funding for health care information technology that would prove useful in developing adverse event databases and matters related to the Critical Path Initiative.
In a response to the GAO report, the FDA called the findings "reasonable and consistent with" actions already under way or planned - namely additional efforts examining internal post-approval procedures.
The FDA took issue with the GAO's characterization that the safety office takes a backseat to the new drugs office. Instead, the FDA called both groups "co-equal partners" in identifying and resolving safety issues.
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