Healthy Skepticism Library item: 963
Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.
Publication type: news
Harris G.
Popular Drugs for Dementia Tied to Deaths
The New York Times 2005 Apr 12
Full text:
Older patients with dementia who are given antipsychotic medicines are far more likely to die prematurely than those given dummy pills, federal drug regulators said Monday. The warning adds to growing worries about the safety of the widely prescribed drugs.
The Food and Drug Administration said that it would now require manufacturers of the medicines to place black-box warnings – the agency’s most severe – on the labels of all the drugs. In 2003, the agency required manufacturers to add a warning about an increased risk of diabetes from antipsychotic medications.
Zyprexa and Symbyax from Eli Lilly, Risperdal from Johnson & Johnson, Seroquel from AstraZeneca, Abilify from Bristol-Myers Squibb, Clozaril from Novartis and Geodon from Pfizer are all affected by the warning.
The drugs belong to a class of medicines developed since 1989 that are supposed to be safer than the older class of medicines for psychosis, like Haldol. In high doses, Haldol and drugs like it can cause a debilitating condition called tardive dyskinesia, a lifelong affliction that can involve uncontrollable trembling, tics and jerky movements.
Doctors have become so comfortable with the safety of the newer medicines that they are now among the biggest selling in the world, with some physicians using them to treat a wide range of conditions, including schizophrenia, depression and dementia in the elderly. Indeed, some psychiatrists prescribe cocktails of antipsychotics to patients with persistent mental problems.
Zyprexa is the biggest drug expense for many state Medicaid programs, the health insurance for the poor.
But the safety of the pills has come under increasing scrutiny. Studies now suggest that the newer drugs are only slightly less likely to cause tardive dyskinesia, and worries about other side effects are mounting.
The Food and Drug Administration said that it had analyzed the results of 17 placebo-controlled trials involving the drugs, which are known as atypical antipsychotics. The agency found that elderly patients with dementia who were given the pills were 1.6 to 1.7 times as likely to die as those given placebos.
The causes of death varied, although most died of heart-related problems like heart failure or infections like pneumonia, the drug agency said.
Representatives for Eli Lilly, AstraZeneca and Johnson & Johnson said the companies were reviewing the F.D.A.‘s requirement and would work with the agency to develop new warnings.
The representatives from Eli Lilly and Johnson & Johnson noted that the companies put warnings on their labels about an increased risk of stroke more than a year ago.
The drug agency said it was considering adding the new warning to the older class of medicines “because limited data also suggest a similar increase in mortality for these drugs.”
Copyright 2005 The New York Times Company
from fdaadvisorycommittee.com
Adverse Events Definition Should Be Narrower, IRB Groups Tell FDA
The Consortium of Independent Review Boards is calling for a more restrictive definition of suspected adverse drug events observed during clinical trials.
The definition of an adverse event that needs to be reported to an IRB should be “probably or definitely” related to the study drug, CIRB President John Isidor said March 21 during an FDA public hearing on “Reporting of Adverse Events to Institutional Review Boards.”
Current regulations stipulate that adverse events must be reported to an IRB if they “at least possibly related” to use of the drug under investigation, FDA Office of Medical Policy Director Robert Temple said.
The hearing was held to address the concern that IRBs have become overwhelmed with adverse event reports due to the substantial increase in the number of large multicenter clinical trials.
Meeting participants suggested that over-reporting of adverse events may be due to the fear of litigation.
“However we craft that definition” of which adverse events must be reported, “it appears to me that people are going to push the envelope to over-report because there’s a tremendous fear in this society that if we’re going to be guilty of under-reporting, we’re going to be penalized in the worst possible way,” Isidor said.
University of Pennsylvania Associate Director of Human Research Yvonne Higgins pushed for regulation that would reduce IRB burden by shifting the responsibility for evaluating adverse events to clinical trial investigators and sponsors.
“What I want is clear guidance from a federal regulatory memo that puts the responsibility for interpreting these things back on the sponsor and the investigator and allows the IRB to do its job of protecting patients,”
Higgins said.
FDA issued a proposed rule in March 2003 (dubbed “the Tome”) that would require companies to file expedited reports of suspected adverse drug reactions unless the company is sure the product did not cause the reaction.
At the public hearing, the Association of Clinical Research Organizations suggested that the use of partially blinded analyses of study data to detect overall trends in data could also help reduce the burden on IRBs.
