Latest Drugwonks' Blog
The inside-the-beltway crowd are speculating that two potential candidates for FDA commissioner remain in the running — Baltimore health commissioner Joshua Sharfstein and Duke University clinical trial researcher Robert Califf. On Saturday, Sharfstein, who was at an Obama rally in Baltimore, dismissed the rumor of possibly being selected for the top FDA post, telling a radio interviewer that he expects to continue as the city’s health commissioner. If so, this leaves Califf as the potential front runner. He’s no stranger to the agency and currently works with several top officials under the critical path initiative to help modernize clinical trials. The FDA/Duke co-founded Clinical Trials Transformation Initiative seeks to improve clinical trial quality and efficiency. It was formed in response to growing frustration among patients, consumers, the academic community, and industry over the difficulty of conducting high-quality clinical trials in a timely manner to produce information physicians need to define optimal patient treatments. During the firestorm after Merck withdrew Vioxx in 2004, Califf joined critics on NBC’s Today Show who questioned whether FDA should have acted sooner in requesting post-marketing safety data on the drug. At the time, Califf suggested Vioxx’s withdrawal illustrated certain regulatory shortcomings. He said “rules need to change” and FDA should require large outcome trials for drugs used to treat chronic conditions. Additionally, Califf has publicly said that the agency is starved for resources and needs a "nonpolitical scientific base for what it does,” and without these “we are going to see more catastrophes along the lines of what we saw in the past with thalidomide and even going back to the origins of the FDA, ‘the horse named Jim,’ whose illness at the time that tetanus toxin was being made led to the deaths of some children. They really got the FDA started. I think we're going to see some pretty major catastrophes if we don't repair the problem.” Califf has served on FDA’s Cardiorenal Advisory Panel and the Institute of Medicine’s (IoM) Pharmaceutical Roundtable. He served on IoM committees that recommended Medicare coverage of clinical trials as well as the removal of ephedra from the market, and its Committee on Identifying and Preventing Medication Errors. He is currently a member of the IoM Forum in Drug Discovery, Development, and Translation, and FDA’s Science Board.
Congress is calling for the establishment of a “Federal Coordinating Council for Comparative Effectiveness Research.” What does this mean? Is comparative effectiveness the same thing as cost effectiveness?
Cost effectiveness assumes an additional year of life is worth about $50,000, the average price of a fully loaded Land Rover.
(Currently, the only available treatment for metastatic renal cell cancer is immunotherapy. This halts the disease’s progress for just four months on average. But if people are unsuitable for immunotherapy, or it doesn’t work, that’s it. There’s no other treatment option.)
NICE agreed that patients tended to live longer when they were given these drugs. But when they put the data from the trials into their QALY-driven computer models, they found that the drugs cost a lot at £20,000 - £35,000 ($39,000 to $68,000) per patient per year compared to the benefit they brought patients - too much for them to recommend that the NHS prescribe these drugs.
Government sponsored studies that conduct head-to-head comparisons of drugs in "real world’" clinical settings are regarded as a valuable source of information for such coverage and reimbursement decisions -- if not for making clinical decisions. Two such studies, the Clinical Antipsychotic Trials in Intervention Effectiveness (aka CATIE), study and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study were two such “practice based” clinical trials, sponsored in part by the National Institutes of Health, to determine whether older (cheaper) medicines were as effective in achieving certain clinical outcomes as newer (more expensive) ones.
But it’s important to move beyond criticizing comparative effectiveness in its current form, and instead focus on creating a policy roadmap for integrating technologies and science that is more patient-centric into comparative effectiveness thinking.
Much the like the U.S. Food and Drug Administration created something called the Critical Path Initiative to apply 21st-century science to accelerate the development of personalized medicine, another national goal should be to create a Critical Path Initiative to apply new approaches to data analysis and clinical insights to promote patient-centric healthcare.
Why? Because comparative effectiveness should reflect and measure individual response to treatment based on the combination of genetic, clinical, and demographic factors that indicate what keep people healthy, improve their health, or prevent disease. First steps have been taken. For example, the Department of Health and Human Services has invested in electronic patient records and genomics. Encouraging the Centers for Medicare & Medicaid Services to adopt the use of data that takes into account patient needs would complement such efforts.
We need to develop proposals that modernize the information used in the evaluation of the value of treatments. Just as the key scientific insights guiding the FDA critical path program are genetic variations and biomedical informatics that predict and inform individual responses to treatment, we must establish a science-based process that incorporates the knowledge and tools of personalized medicine in reimbursement decisions: true evidence-based, patient-centric medicine.
For instance, the FDA, in cooperation with many interested parties, has developed a Critical Path opportunities list that provides 76 concrete examples of how new scientific discoveries in fields such as genomics and proteomics, imaging, and bioinformatics could be applied during medical product development to improve the accuracy of the tests used to predict the safety and efficacy of investigational medical products.
It’s a complicated proposition—but such a body’s goal is as simple as it is essential—cost must never be allowed to trump care, and short-term savings must not be allowed to trump long-term outcomes Just as we need new and better tools for drug development, so too do we need them for comparative effectiveness measurements.
Today, comparative effectiveness is a short-term, short-sighted, politically-driven policy that results in one-size-fits-all medicine. While it may provide transitory savings in the short-term, current strategies result in a lower quality of care that result in higher healthcare costs over time.
Restrictive formularies and health care systems that deny patients access to the right medicine in the right dose at the right time but pay for more invasive and expensive procedures later on have their priorities upside down. Attention must be paid. If the devil is in the details (and it is), it’s time for a deep dive beyond simplistic and self-serving “comparative effectiveness.”
In an era of personalized medicine, one-size-fits-all treatments and reimbursement strategies are dangerously outdated. We are early in this debate, but at least we can all agree that this is not, and must not be exclusively, a debate about saving money. It must be about patient care.
NICE should think twice.
Now some facts for the likely consumer:
About seven percent of all patients who take the drug warfarin to prevent blood clots in the legs will have a major bleeding episode within one year of treatment, according to researchers who analyzed 33 studies covering 10,757 patients. About one in eight will die, 10% will bleed inside the brain, and half of these patients with an intracranial bleed will die.
Now let's administer the drugwonks comparative effectiveness test to the authors of the study: Knowing this and assuming that a family member had to take warfarin to prevent blood clots, would you refuse to pay for a genetic test or give an AHIP thumbs up to denying coverage on the grounds that at $400 a pop, society and you are better off taking the risk of intercranial bleeding and death. And that's just the leg mind you. We haven't even gotten to other warfarin uses.
I thought we were all concerned about safety.
NICE in the dock as Servier takes osteoporosis review to court
The UK’s drugs watchdog is being dragged into a legal battle over its osteoporosis ruling, which has been labelled as “unethical and short-sighted” by critics.
Drugmaker Servier is challenging the National Institute for Health and Clinical Excellence over draft guidance that recommends that doctors should prescribe cheaper drugs to women with early signs of osteoporosis, even though up to one in five patients cannot take the drugs, there are crippling side effects and in spite of more effective treatments being available.
According to the guidelines, sufferers would have to get 60% worse, based on a scoring system, before being offered the more expensive alternative treatment Servier’s Protelos (strontium ranelate).
Both Servier and the National Osteoporosis Society have criticised the guidance, labelling it unethical and claiming it will do nothing to reduce pain or prevent fractures.
In a bid to get the guidance changed, the organisations are taking NICE to the High Court, as part of a full judicial review, claiming lack of transparency and infringement of human rights by denying alternative treatment.
However, NICE denies any wrongdoing. Chief executive Andrew Dillon told The Times the recommendations had been “a complex set of guidance to produce”, but the Institute was “confident” NICE had acted lawfully.
WHY NOT 65 percent worse? I guess that would be illegal.
From the NY Times...
Drug Making’s Move Abroad Stirs Concerns
"....now experts and lawmakers are growing more and more concerned that the nation is far too reliant on medicine from abroad, and they are calling for a law that would require that certain drugs be made or stockpiled in the United States.
“The lack of regulation around outsourcing is a blind spot that leaves room for supply disruptions, counterfeit medicines, even bioterrorism,” said Senator Sherrod Brown, Democrat of Ohio, who has held hearings on the issue."
Recentlly Senator Brown went to town on by claiming the company was outsourcing production and jobs to China to save money at the expense of patient safety. Any proof? None. But, he pontificates:
"Are we supposed to believe that it’s just coincidence that China’s safety standards aren’t strong or enforced? Do we really believe that the lower manufacturing costs in Asia, depressed by slave wages, have no impact on patient safety?
“U.S. consumers are paying the highest prices in the world for prescription drugs as drug makers outsource American jobs and import tainted products. It’s safe to say that the drug industry is skating on very thin ice.”
But Sherrod and lots of other in Congress were pushing drug importation really, really hard in the past:
In 2004 Mark McClellan released a HHS task force report (that Peter Pitts helped coordinate which concluded it, "would be extraordinarily difficult to ensure that drugs personally imported by individual consumers could meet the necessary standards for a certification of safety to be made, especially if consumers continue to import prescription drugs in the same or increased numbers."
Sherrod and other pro-importation types responded:
"This one-sided report indicates no willingness to find solutions, instead dismissing importation using the same scare tactics employed by the pharmaceutical companies themselves."
In a floor speech pushing importation after the release of the report, then Congressman Sherrod said:
“Thanks to Republican leadership’s stall tactics, the only thing that’s happened on importation is we’re all a year older. The American people need to tell Senator Frist and the Republican leadership that they want an importation bill on President Bush’s desk before the November elections.”
And Sherrod just pushed Peter Rost (our fellow blogger) for FDA Commissioner who made a name for himself by pushing drug importation. At the time Sherrod was still for allowing drugs made by slave labor and cheaper ingredients into the US, albeit through Canada, Europe and other areas and from FDA inspected facilities in India, China, etc. only and with pedigree, chain of custody and tamper resistant packaging all in place (all of which counterfeiters will be happy to comply with). And at the time Peter (Rost) not Pitts was a vice president of marketing at Pfizer and "the first" pharmaceutical industry executive to say publicly that reimportation "can be safe, rejected the administration's arguments about minimal cost savings," the Free Press reports. He said, "If importation didn't work, you wouldn't have had it in Europe for 20 years. This is so wrong" (Detroit Free Press, 12/22/04).
Well, I think Peter was wrong and still is. But at least he is not a hypocrite.
Currently, applicants submit studies demonstrating that the rate and extent of absorption of a generic drug meets bioequivalence limits, but additional bioequivalence studies conducted on the same formulation typically are not submitted. These include studies that failed to meet passing criteria, as well as multiple successful studies. The agency infrequently sees this additional data and is generally unaware of the existence of such studies.
Applicants also must submit data in an annual report on all post-marketing bioequivalence studies for an approved drug product formulation during the annual reporting period.
SCRIP World Pharmaceutical News reports that, “The agency notes that if it receives failed bioequivalence studies for a given application, it might make a different decision about whether to approve the generic than if it had received only the pivotal passing study.”
The FDA is limiting the additional studies to those conducted for the "same drug product formulation,” rather than requiring submission of all studies conducted with developmental formulations. "Same drug product" is defined as the formulation of the product submitted for approval, and any formulations that have minor differences in composition or manufacturing method but are similar enough to be relevant to the agency's bioequivalence determination. The FDA intends to issue draft guidelines giving specific examples of formulations it considers to be the same drug product.
Attention must be paid to the issue of bioequivalence -- particularly by those at the WHO and elsewhere who are toying with the idea of "clinical equivilence" for follow-on biologics.
I regard the incoming administration with trepidation. Not because of it's agenda because on first, second and third glance it seems to have none. But rather, it seems to worship at the altar of being perceived as effective. What did Nick Carraway say about Tom Buchanan in The Great Gatsby being a "series of successful gestures." Exactly.
No permanent allies. No permanent friendships. Just permanent interests.
And to maintain it's interests the administration will toss biomedical innovation to the wolves. Not because they want to but because the way it is done, in bits and pieces and in the dark of night and couched in cost containment and consumer protection it will be really easy to make it harder and harder to produce and bring to market any innovation. Want your votes on the stimulus bill it will cost you a change to allow an override of pre-emption. Want expanded SCHIP coverage? Allow CMS to establish reference pricing for breakthrough drugs or special rebates. Want more NIH funding? Be prepared to require that anyone receiving NIH funding be allowed to collaborate with industry. More funding for the FDA? Be prepared to saddle the agency with regulation of tobacco, TV ads and drug importation.
Can we expect the media to analyze the impact of all this? Not at all. The journalists who believe that "science should not be for sale" and who work at newspapers that can't be given away have led the way in making people believe that the commercialization of medical discoveries is essentially a criminal enterprise no different than the one Madoff concocted.
Sadly, many of those in the crosshairs appear oblivious or believe they can survive by engaging in accomodation or seeking what is known as a "seat at the table."
Ask the biotech industry in the UK and Europe if that's a recipe for success and prosperity.
The Executive Board of the World Health Organization meets next week with significant discussion expected on a new secretariat report on counterfeit medical products
The counterfeit drugs report will be the “big IP item” on the agenda next week, a developed country source predicted. A developing country source predicted a “very difficult discussion” on the document.
Several nongovernmental sources have expressed concern over the use of the term “counterfeit” in general - saying that legally speaking it is associated with violations of trademark law, a legal association which is confirmed in international law by its definition in the World Trade Organization Trade-Related Aspects of Intellectual Property Rights (TRIPS) Agreement relating it specifically to trademark violations. They also say that even statements within the report itself that “legal instruments related to intellectual property rights have a broad scope and are not focused on the protection of public health,” cannot take away the fact that the terminology is focussed on IP and not on healthcare.
A Brazilian delegate agreed with this assessment, saying “we do not want to see WHO as an agency of enforcement related to trademark,” and the use of the word “counterfeit” automatically brings in discussion of IP, especially given its presence in TRIPS. Further, the delegate added, the work of IMPACT was done outside the WHO and therefore “and we cannot simply import IMPACT recommendations without discussion.” It should not be legitimized as though it were an intergovernmental process, the delegate explained.
A meeting of the International Medical Products Anti-Counterfeiting Taskforce (IMPACT) – a taskforce of anti-counterfeiting stakeholders, including pharmaceutical industry associations and drug regulatory authorities, international agencies and non-governmental agencies, and enforcement bodies, launched by the WHO in 2006 – in Tunisia in December 2008, for instance, defined counterfeits in such a way that “disputes about patents” would not be accidentally equated with counterfeits. However, the new report contains the broader statement “recognizing that disputes about IP rights are not to be confused with counterfeiting.” A developed nation delegate said that the patent definition is preferable, but expected disagreement on the issue.
The definition IMPACT agreed on is: “a product with a false representation of its identity and/or source. This applies to the product, its container or other packaging or labeling information. Counterfeiting can apply to both branded and generic products. Counterfeits may include products with correct ingredients/components, with wrong ingredients/components, without active ingredients, with incorrect amounts of active ingredients, or with fake packaging.”
The definition by IMPACT adds that “violations or disputes concerning patents must not be confused with counterfeiting of medical products,” yet there is much concern – particularly on the part of developing countries and non-governmental agencies – that disputes concerning trademarks could still be conflated with counterfeiting.
The International Federation of Pharmaceutical Manufacturers and Associations (IFPMA)’s director general Alicia Greenidge approved of the report, saying it “touches on some key issues concerning the fight against counterfeits, including the appropriate definition of a counterfeit medicine,” and endorsed the IMPACT definition. She added that “generic medicines play an important role in ensuring global health and are unfortunately themselves widely counterfeited, [therefore] it is important to have a definition which provides guidance that authorized generic medicines are not counterfeits and which also assures that patent actions are not confused with counterfeit actions … this will help authorities in both developing and developed countries to identify and address counterfeits of trademarked products, including the many authorized branded generics.”
APPROPRIATION OF $1.1 BILLION FOR CER RESEARCH
Subtitle B-Health and Human Services, AHRQ (pg. 141)
• $700 million is appropriated to carry out titles III, IX of the Public Health Service Act( establishes NIH, and AHRQ), title XI of the Social Security Act (CERTs program, peer review), and section 1013 of MMA to conduct or support CER. $400 million will be transferred to NIH (leaving $300 million to AHRQ).
• In addition, $400 million will be allocated at the discretion of Secretary of HHS for efforts that:
o Compares the clinical outcomes, effectiveness, and appropriateness of items, services, and procedures that are used to prevent, diagnose, or treat disease
o Encourage development of networks that can generate outcomes data
o $1.5 million will go to the IOM for a report recommending national priorities for CER
• Public Accountability:
o Secretary shall publish information on grants and contracts awarded with the funds
o Shall disseminate research findings from grants and contracts to clinicians, patients, and the general public
o Recipients of funds shall ensure an opportunity for public comment on the research
• Secretary will provide congressional committees an annual report research being conducted/supported and an operating plan for FY 2009 and FY 2010
ESTABLISHMENT OF ‘FEDERAL COORDINATING COUNCIL FOR COMPARATIVE EFFECTIVENESS RESEARCH
• Council shall coordinate and assist government agencies with conducting CER
• Council will advise Congress and President on CER infrastructure, CER funding, and other opportunities
• Council is composed of 15 members all of whom are federal officials/employees with responsibility for health-related programs, appointed by the president. Includes CMS, AHRQ, FDA, VA, DOD
• At least half the members will be physicians (working in government)
• By June 2009, the council will submit a report to the President and Congress detailing recommendations.
What does all this mean?
1. It is, if not a clone of the UK National Institute for Clinical Excellence (NICE), a kissin' cousin.
2. Absolutely nothing in the current legislative language would stimulate the development of measures and studies to advance personalized medicine.
3. There will be inevitable bias towards large randomized trials a la CATIE and ALLHAT.
4. And who will ARHQ rely on for its research? Most likely entities funded by HMOs and other payers with a goal towards cost containment.
5. The underlying assumption is that comparative effectiveness research will deliver improved outcomes via better quality evidence concerning the best treatment, prevention, and management of any given health condition. It assumes that comparative effectiveness research helps patients, providers, and payers of health care to make more informed decisions. But is there any evidence that these assumptions are true?
How about a study to determine whether comparative effectiveness research, compared to other types of research, actually delivers on these lofty goals? How about a meta-analysis to examine how comparatively effective comparative effectiveness research is?
6. And what if such a body swiftly morphs into a New World version of NICE, dictating de facto guidelines for reimbursement and coverage. Doesn't it become an obstacle to access, just like in the UK -- denying patients coverage to innovative uses of new mediccal technologies?
Yes we can ... what? Embrace a healthcare system that is cost-based rather than patient-centric?
No thank you.
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.
