Latest Drugwonks' Blog
It’s got to be more than just “sign here.” And it’s about time.
The IOM report on ethical and scientific issues in post-marketing drug safety studies could very easily get lost in the frenzy over you-know-what. That would be a shame because its real value lies in an intelligent and thoughtful outline of how to restructure informed consent. And in our age of the digitally empowered healthcare consumer, this is welcome news
"When a substantial amount of information indicating that a drug to be studied may involve serious safety risks has already accumulated, there are heightened obligations to ensure that potential participants understand the risks posed by study enrollment," the IOM Committee on Ethical and Scientific Issues in Studying the Safety of Approved Drugs says in a letter report.
The IOM says the emphasis given to risk information in the informed consent process should increase with the severity of risk and the level of certainty about the causal connection between a drug and the adverse outcome. "At a minimum, risks that should be disclosed should include any black box warnings, the 'major statement' currently listed in television advertisements, any adverse event findings of an FDA advisory committee, and a summary of evidence from published peer-reviewed studies."
The committee notes that in addition to verbal disclosures and written consent documents, there is a growing set of additional tools, such as videos and interactive electronic presentations that can enhance potential study participants' understanding of risks they may face.
Bravo.
"Whatever efforts are employed to communicate with potential participants, it is key that they include information that is useful to participants about where the weight of the evidence falls with regard to serious risks and the level of confidence that experts have in drawing conclusions about the risks," IOM says.
Potential study subjects should understand how treatment they will receive in the study differs from the current standard of care. "This is particularly crucial in cases in which medical practice has shifted away from prescribing the study drug because accumulating evidence from passive surveillance, observational studies and small trials or meta-analyses suggests that another therapy is as effective and has a more favorable safety profile," IOM says.
And, of course, FDA must assure that the post-marketing study is appropriately designed to answer the public health questions at issue and minimize risk to participants. Risks should be judged acceptable by FDA, data safety monitoring boards and institutional review boards and the study and subjects should be continuously monitored. As always – but it’s certainly worth repeating.
“Ignorance is never better than knowledge”
-- Enrico Fermi
As a commentary in this week's Biocentury suggests, the FDA's public hearing on Avandia being held this week is stacked in favor of Steve Nissen and David Graham, the two most public and vociferous critics of the drug. Something tells me that forces within and outside the FDA are seeking to force FDA commissioner's Peggy Hamburg's hand.
If the advisory committee votes to pull Avandia it will be hard for the FDA not to concur. And that will be the beginning of the end of the FDA's science-based regulatory authority, at least under this administration. It will mean that that marauders who react to any safety signal can run to the media and members of Congress to slow down or delay a product's approval or kill it's sales. It's means that meta-analysis, which has become a powerful data dredging tool for generating risks and diverting attention from benefits by producing spurious statistical association will triumph over biologically based outcomes.
Fearmongering requires new and unexpected risks. It must eliminate efforts to individualize treatment based on risks and benefits.
Nissen and Graham along with their fellow travelers on the one side. Dr. Hamburg and the FDA's future is on the other.
The decision on Avandia will decision which way regulatory science and the FDA will go for years to come.
One of the more interesting subtexts surrounding King James’ move to Miami is the negative economic impact it will have on the economy of Cleveland specifically and the Ohio in general.
A similar subtext (albeit one that has been entirely ignored) is the negative economic impact the State of Michigan will experience following the University of Michigan’s recent announcement that it will ban any industry-sponsored CME.
The Fighting Wolverines currently receive about $1,000,000 in such services. And in cash-strapped Michigan that ain’t chump change when libraries are being shuttered and teachers are losing their jobs.
And for what larger purpose? The U-M's intent in banning industry funding for CME is "to dispel the risk or appearance of conflict of interest.”
It will also result in less CME for the university systems physicians. The school expects the number of CME courses to decline "somewhat" as a result of the new policy.
(According to the ACCME, the university produced 499 separate CME activities last year, reaching more than 130,000 physicians.)
"Somewhat less" CME is not acceptable. Does the university system expect the taxpayes of Michigan to make up the difference -- so that they can exult in their political correctness?
Since an important aspect of healthcare reform is about lowering costs, how will similar moves by other large public universities (motivated not by public health but by "perceived conflicts") be justified?
Speaking of Cleveland, in the January 2010 issue of Academic Medicine (Adad. med. 2010; 85:80-84), four researchers from the Cleveland Clinic published a paper entitled, "The Effect of Industry Support on Participants of Bias in Continuing Medical Education." The purpose of the study: "To obtain prospective evidence of whether industry support of continuing medical education affects perceptions of commercial bias in CME."
The method: "The authors analyzed information from the CME activity database (346 CME activities of numerous types; 95,429 participants in 2007) of a large, multi-specialty academic medical center to determine whether a relationship existed among the degree of perceived bias, the type of CME activity, and the presence or absence of commercial support."
The study's conclusion? "This large prospective analysis found no evidence that commercial support results in perceived bias in CME activities. Bias level seem quite low for all types of CME activities and is not significantly higher when commercial support is present."
The American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) have adopted a new policy regarding the disclosure of conflicts of interest. Here's the key paragraph:
"There is no inherent conflict of interest in the working relationships of physicians with industry and government. Rather, there is a commonality of interest that is healthy, desirable, and beneficial. The collaborative relationship among physicians, government, and industry has resulted in many medical advances and improved health outcomes."
What a unique perspective -- a "commonality" rather than a "conflict" of interest.
We should all pay attention to our nomenclature. It's not about "conflict of interest" -- it's about (as Secretary Sebelius correctly says) "interest." And having an "interest" is not necessarily a bad thing -- as long as you're transparent about it.
When it comes to CME and "interest," we need to weigh it against benefit. And, as with drugs and devices, we must consider the "safe use" of industry-sponsored CME.
"The best interest of the patient is the only interest to be considered."
William Mayo, MD
Congressman Jeff Flake (R,AZ) from CMPI on Vimeo.
Hamburg opposes separate safety reviews
FDA Commissioner Margaret Hamburg told BioCentury she opposes separating postmarket safety oversight from new drug reviews, a policy Rep. Rosa DeLauro (D-Conn.) and Sen. Chuck Grassley (R-Iowa) are promoting. DeLauro recently announced plans to attach a report instructing FDA to create an independent postmarket drug safety office to an appropriations bill.
"We need to strengthen the integration of safety and efficacy throughout the lifecycle of medical products," Hamburg said. "It would be a mistake to further separate and stovepipe safety and efficacy." Hamburg said she is considering organizational changes to better integrate safety and efficacy oversight. In addition, she said FDA needs to "strengthen safety science, and that's why I've asked the Institute of Medicine to do a report [on postmarket safety studies], and our Science Board will be undertaking a study about safety science at FDA"
Hamburg supports releasing complete response letters
Releasing information about negative decisions on drug applications could benefit drug developers and advance scientific progress, FDA Commissioner Margaret Hamburg said Tuesday at a conference on drug development. An FDA transparency working group's draft proposals include publicizing redacted versions of complete response and refuse to file letter.
"We don't publish information when we don't approve a drug as to why we don't approve it, but that information clearly could have broad value," Hamburg said at the meeting, sponsored by Friends of Cancer Research, Ewing Marion Kauffman Foundation, Council for American Medical Innovation and others. Companies might oppose public release of information about rejection of their application, but "those same companies can recognize there are benefits if everyone opens up and does the same,” she said.
Hamburg told BioCentury that disclosures would describe the reasons for a rejection. They also "would obviously speak to the adequacy of data in certain instances, but more significantly, that certain approaches might not be effective or certain kinds of molecular entities have certain toxicities, and that could have relevance beyond a particular application." FDA would not release commercial confidential information "without industry's explicit permission," she said.
Robert Butler MD died this week of leukemia at the age of 83, full of projects and brimming with new constructs for future research. I was a junior at SUNY Buffalo when I read "Why Survive? Being Old in America.” What I found striking about the book what Butler’s ability to deconstruct aging as a product of disease, not of getting old, which he argued was society’s convenient way of not investing time and money into understanding the biological processes that characterized “getting old.”
An excellent tribute to Dr. Butler can be found here: tinyurl.com/26ph5s9
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
