Latest Drugwonks' Blog
"Demonstration of bioequivalence (BE) between drug products can be made using blood level measurements, pharmacodynamic studies, clinical trials, and/or in
vitro studies. The US regulations deem drug products therapeutic equivalents (TE) if they are both pharmaceutically equivalent and bioequivalent."
But it became clear that current standards of BE do not add up to TE because we know more about the impact of individual variation in how we absorb and process drugs now than when the generic drug reforms were enacted in 1984. So the question is, as Kamal Midha, Ph.D. of University of Saskatchewa, who spoke about existing standards for TE of sustained release products: are current regulations for measuring BE enough?
More to the point: if the public and the FDA are demanding more evidence about the safety and reliability of new products pre and post market (including more information the pharmacodynamics and phamacokinetics of such products), why shouldn't such information be used to establish TE of generic products, particularly those where the amount of a drug released and when is essential to a drug's safety and effectiveness. While it may be true that this issue only affects a handful of drugs, it is also true that these drugs are not only widely prescribed, they are also mostly prescribed in generic form. And post market oversight of this growing market share is not a top FDA priority even as safety has become an critical (path) FDA concern,
So at the end of the day (and the conference) it became clear that better standards for tracking the impact of modified release products with new tools is not to be ignored. Rather than being a way for innovators to escape generic competition, the collection and monitoring of better measures of TE can improve the overall quality of medicines without significant costs to either part of the industry. That is the goal and essence of the Critical Path. To ignore or dismiss concerns about toxicity or adverse events of sustained release products because they are made by generic companies is to suggest that the financial interests of that industry is more important than the public health.
This issue can, as the AAPS meeting demonstrated, can be explored in a way that uses science to clarify issues and stratify risk so that the most important public health issues relative to this product class can be addressed.
The Senate Finance Committee night passed an amendment to healthcare reform legislation that would create a $1 billion temporary tax credit over two years for investments in drug R&D by companies with 250 or fewer employees.
The measure, sponsored by Sen. Robert Menendez (D-N.J.) and backed by the Biotechnology Industry Organization (BIO), would cover expenditures made in 2009 and 2010. Companies that don't have a tax liability would have the option to receive the credit in the form of a grant.
In allocating the credits and grants, the amendment instructs the U.S. Treasury to consider only projects that: "show reasonable potential" to "result in new therapies to treat areas of unmet medical need or to prevent, detect, or treat chronic or acute disease and conditions;" or to "reduce long-term health costs in the United States; or to "significantly advance the goal of curing cancer within a 30-year period."
In addition, the Treasury would consider which projects have the greatest potential to create and sustain high quality, high-paying jobs in the U.S. and to advance U.S. biomedical competitiveness.
Projects that received a credit or grant would not qualify for existing R&D or Orphan tax credits, or for bonus depreciation.
The legislation still is subject to modification as it moves through Congress. The Finance Committee is expected to approve America's Healthy Future Act early next week. It will then be merged with legislation passed by the Health, Education, Labor and Pensions (HELP) Committee and sent to the full Senate for a vote. The final Senate bill would have to be reconciled with healthcare reform legislation coming out of the House.
To date no one has kept track of the total impact on patients. In part that's because until 2007 generic companies were not require by the FDA to monitor the effect of their products in the marketplace and only then it was limited to opioid based painkillers. The increased use of generic lamotrigine is strongly associated with increased physician visits and hospitalizations. The same goes for switching patients to a generic version of other anti-convulsants, anti-depressants, etc.
The key question of the conference is what can companies do to assure that all medicines affect us in more or less the same way. As I have written before, one step in the right direction is to hold drugs that are supposed to have the same benefit and same risks to the same standards of post market evaluation. Another approach, to be discussed by Gerard Sanderink of Sanofi will be how to use biomarkers to more precisely predict dose response and absorption of products in the earliest stages of development and periodically in the post market.
The conference may seem mundane. However the fact that Bob Temple is showing up indicates just how serious the FDA is about this issue. And more generally, it underscores the fact that the public at large is unaware of the importance of how a drug is delivered. Discovering a medicine is half the battle. Making sure it is delivered safely and effectively is as important.
Accordingly, CMPI will be covering the AAPS conference "live" with bloggers and a video crew in a effort to "deliver" the modified release message in a way that it interesting and timely.
The long-awaited and much anticipated draft guidance on REMS can be found here.
Also now available (and worth a careful read or two) is the FDA's strategic plan for risk communications. Here's the press release, along with a link to the complete document.
FDA NEWS RELEASE
For Immediate Release: Sept.30, 2009
Media Inquiries: Christopher Kelly, 301-796-4676, christopher.kelly@fda.hhs.gov
Consumer Inquiries: 888-INFO-FDA
FDA Issues Strategic Plan for Risk Communication
Establishes framework for communicating with public about FDA-regulated products
The U.S. Food and Drug Administration today issued its Strategic Plan for Risk Communication, which outlines the agency’s efforts to disseminate more meaningful public health information. The plan also lays out a framework for the FDA to provide information about FDA-regulated products to health care professionals, patients and consumers in the form they need it and when they need it, and for how the agency oversees industry communications.
“We are committed to improving communications the public receives about the products we regulate,” said Commissioner of Food and Drugs Margaret A. Hamburg, M.D. “The FDA must communicate frequently and clearly about risks and benefits and inform patients and consumers about ways to minimize risk as they become increasingly involved in managing their health and well-being.”
The plan defines three key areas–FDA’s science base, its operational capacity and its policy and processes – in which strategic actions can help improve the FDA’s communication about the risks and benefits of regulated products. The plan also identifies over 70 specific actions for the FDA to take over the next five years, including 14 that the agency commits to accomplishing over the next year. They include:
- Designing a series of surveys to assess the public’s understanding of, and satisfaction with, FDA communications about medical products
- Producing a research agenda for public dissemination
- Creating and maintaining a useful, easily accessible internal database of FDA and other relevant risk communication research
- Developing an expert model to characterize tobacco-use related consumer decision-making and better understand the likely impact of FDA oversight of tobacco products
- Developing a “library” of multi-media communications on safe food practices for general education purposes and for use with crisis communications concerning food contamination episodes
- Posting pictures of FDA- regulated products affected by Class I or high-priority Class II recalls as part of recall notices/information
- Developing detailed action plans at the agency and center levels for implementing and achieving the proposed action steps, including timelines, responsibilities and resource needs
The plan reflects the FDA’s belief that risk communications must be adapted to the needs of different audiences and should be evaluated to ensure effectiveness. The plan also focuses on improving two-way communication through enhanced partnerships with government and non-government organizations, and focuses on policies that affect areas of high public health impact.
For more information:
FDA’s Strategic Plan for Risk Communication
“The leading proposal in the Finance Committee would apply to family insurance plans that cost roughly $21,000 and up starting in 2013. For the sake of fairness, the threshold would vary based on geography and the average age of a company’s work force. In all, something like 10 percent of plans would be subject to the tax in 2013, according to the Center on Budget and Policy Priorities, a research group."
(The complete New York Times story can be found here.)
60% of the American public gets their health benefits through their jobs -- and they’re not “free.” According to the Kaiser Family Foundation, the average American worker with “employer-provided” healthcare pays about 41% of the cost.
So – will benefits be taxed before or after the 41%? Clearly the answer is – before.
And as everyone’s favorite economist, Robert Reich, opines, "According to the Congressional Budget Office, taxing all employee health benefits would yield a whopping $246 billion every year. Even limiting the tax to higher-income employees would go a long way to funding universal health care. Employer-provided health insurance is the biggest tax break in the whole federal income tax system.”
The AFL-CIO’s Gerald Shea, the union’s top healthcare lobbyist, sees the definition of “Cadillac” shifting with time, “People are going to see this as a huge middle-class tax hit.”
The New York Times agrees:
“ … the number of affected plans would grow over time. The Senate has been talking about having the threshold rise each year by the inflation rate plus one percentage point. Since medical spending has been rising much faster than inflation, more and more plans would probably cross the threshold in the years after 2013. Over the next decade, the Congressional Budget Office has estimated that the tax would pay as much as 25 percent of the cost of extending coverage to the uninsured.”
And so does Robert Reich. “So a sensible and politically feasible alternative is to limit tax-free employer-provided health benefits to workers whose incomes are under, say, $100,000 a year, and subject those with higher incomes to progressively higher taxes on them."
Can you say, “mission creep?”
"...recently, the Yaz line’s image has been clouded by concerns from some researchers, health advocates and plaintiffs’ lawyers. They say that the drugs put women at higher risk for blood clots, strokes and other health problems than some other birth control pills do. Those critics, though, are up against a large European health study, sponsored by Bayer, the German pharmaceutical giant, that reported the opposite conclusion. The Bayer-financed study said that cardiovascular risks in women taking Bayer products were comparable to those taking an older formula of birth control pills."
www.nytimes.com/2009/09/26/health/26contracept.html
Hmm...
Here's a blog from a law firm leading the litigation against Bayer, the company that makes Yaz:
"The risks associated with this popular birth control pill are severe; many women who took Yaz or Yasmin have died or been seriously injured because of the serious health risks associated with the drug. In fact, the FDA received over fifty reports of Yaz and Yasmin-related deaths between 2004 and 2008, most involving increased levels of potassium and occurring in women as young as 17 years old. Imagine how many went unreported! A growing number of lawsuits have been filed by or on behalf of these women, charging the drug manufacturer with inadequately warning them of the increased risks Yaz and Yasmin pose to those women who use the oral contraceptive.
While the public-at-large and many physicians may not recognize an adverse reaction to drospirenone, the health risks have been known for longer than many realize. In 2002, the British Medical Journal reported some practitioners’ concern about the drug as a result of 40 cases of venous thrombosis among women taking it. Also, in 2003, the Journal published a paper that detailed reports of thromboembolism deaths and injuries thought to be caused by Yaz and Yasmin.
www.nolan-law.com/yasmin-yaz-ocella-birth-control-injuries/#side%20effects
The FDA has been reprimanding Yaz and Yasmin manufacturers for misleading and inadequate television advertising for the drug for quite some time."
Here's Singer again... stoking the fires, fanning the flames, leading the witness...
"The health questions and the lawsuits may rattle consumer confidence, but the warnings from federal health authorities about advertising and quality control raise larger questions about Bayer’s approach to complying with government rules, said Michael A. Santoro, an associate professor at the Rutgers Business School who has studied ethics in the pharmaceutical industry. "
False Claims Act anyone? That's the fulcrum which the trial lawyers use to leverage meager findings about safety into a conspiracy of silence and misrepresentation.
I see another Avandia in the making.