Latest Drugwonks' Blog
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Drugmaker Servier is challenging the National Institute for Health and Clinical Excellence over draft guidance that recommends that doctors should prescribe cheaper drugs to women with early signs of osteoporosis, even though up to one in five patients cannot take the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.
This past year Dr. Troy held a series of town hall meetings throughout the country on the future of biomedical innovation. The account of his meetings were published today in a report entitled: Healthcare Innovation in the 21st Century.
He found:
"New and exciting technologies provide hope that pioneering new diagnostics, devices, drugs, and therapeutic interventions will be developed and made available to the public. However, the need to assess standards, clinical utility, safety, and cost all provide significant challenges and delays in translating scientific discovery to a marketable product. Biomedical innovation is fraught with uncertainty, risk, and a high probability of failure. Many new technologies – genomics, nanotechnology, advanced imaging, bioinformatics – offer great possibilities for the development of biomedical innovations. Yet these new technologies have also amplified the risk and uncertainty in the regulatory and payment pathways. Each of these new technologies raises questions about the safety, efficacy, and clinical use of products derived from these technologies. In many cases, the new technologies also challenge existing notions of how a biomedical innovation should be treated if it does not fall into a traditional regulatory or payment pathway, or straddles two existing pathways. In many cases, there may be a long lag between the emergence of a new technology and the issuance of regulatory guidance clarifying the pathway for product approval. Attendees noted that uncertainty can contribute to delays in the development and diffusion of new innovations, and can diminish investors’ willingness to invest in new technologies."
At a time when Congress is pouring buckets of money on failing and floundering sectors of our economy, considering legislation to force banks to issue risky loans (once again) and proposals to restrict access to new medicines while showering tax credits on green technologies some of Dr. Troy's recommendations to remedy these solutions should be adopted:
Requiring that certain funds be set aside for purely
basic research, and that other NIH grants go to basic
and translation research that has a demonstrated or
probable connection to an improved health care
outcome.
􀂾 Moving away from a binary model of safety versus
effectiveness, by having the FDA make sure
consumers have information available to them about
the spectrum of risks and benefit inherent in every
drug, biological, and device – and how these risks and
benefits may vary from person to person.
􀂾 Allowing FDA to approve applications on the basis of
inferences from known biomedical effects, rather than
always requiring clinical trial data on sizeable
populations.
􀂾 Implementing value-based purchasing across different
parts of Medicare, so that Medicare pays providers for
value or outcomes provided to a beneficiary rather
than for each service or good.
Sadly, Congress and the media marches in another direction. That's because they hate innovation...or the innovators to be more precise. And mining the innovation highway to make it riskier and more dangerous to innovate is part of the game plan. Tevi has highlighted the threats to innovation. To the extent that they are turned into policies, we will know who the enemies of progress really are.
Pfizer has just launched a commercial in British movie theaters warning about the dangers of counterfeit medicines illegally purchased online .
The commercial, slotted to be shown in 600 theaters across the UK, shows a middle-aged man spitting up a rat after swallowing a pill that arrived in the mail. (This alludes to the fact that some of the counterfeit drugs seized in the UK contained not API – but rat poison.)
According to an article in the Financial Times,
“The campaign reflects growing safety concerns – and commercial losses for the drug industry – caused by a rise in unregulated internet sales of medicines. It also marks an intriguing extension of the limits on advertising by drug companies to raise their public profile, in spite of tight restrictions on the marketing of prescription medicines to consumers. The film contains no reference to Pfizer’s medicines but shows the corporate logo alongside that of the Medicines and Healthcare Products Regulatory Agency, the UK watchdog that co-ordinates an increasing number of investigations and prosecutions of counterfeiters. It agreed to a pioneering partnership with the company.”
Well jolly good all around. Now let’s see if Pfizer will reach out to the FDA to pursue a similar program here at home. – and whether the FDA will have the courage to step up to the plate and accept the offer. That’s precisely the kind of pubic interest partnership the world’s biggest life sciences company needs in order to demonstrate that it’s heart – and pocketbook -- are in the right place. That it's in the public health business first and the selling drugs business second. And it’s just the kind of unambiguous, bold and innovative messaging the FDA needs to remind the American people – including some of our elected officials -- that drug importation is unsafe healthcare practice and unsound public policy.
To view the commercial, click here.
How big is the problem of counterfeit drugs? According to CNN:
“Many of the world's bogus drugs originate in Asia, particularly China, according to the U.S. Center for Medicine in the Public Interest. The fakes oftentimes are exported and change hands many times before reaching their unwitting consumers."These are criminal organizations that are manufacturing, distributing and selling counterfeit medicines," says Thomas Kubic, a former FBI agent and president of the Pharmaceutical Security Institute, a group funded by drugmakers. The growing trade has been fueled by the growth of Internet drug sales and the lure of lucrative profits. The Center for Medicine in the Public Interest expects global sales of fake drugs to reach $75 billion by 2010.”
The complete CNN story can be found here.
Perhaps the weakest link in the European chain of custody is parallel trade. In Europe, parallel trade (what we call “importation”) is legal between all 25 EU member states. And last year 140 million individual drug packages were parallel imported throughout the European Union — and an independent wholesaler repackaged each and every one. This means that, literally, parallel traders open 140 million packets of drugs, remove their contents and repackage them. But these parallel profiteers are in the moneymaking business, not the safety business. And mistakes happen. For example, new labels incorrectly state the dosage strength; the new label says the box contains tablets, but inside are capsules; the expiration date and batch numbers on the medicine boxes don’t match the actual batch and dates of expiration of the medicines inside; and patient information materials are often in the wrong language or are out of date. Oops.
In the EU there is no requirement to record the batch numbers of parallel imported medicines. So if a batch of medicines originally intended for sale in Greece is recalled, tracing where the entire batch has gone (for example, from Athens to London through Canada to Indianapolis) is impossible. And all the large "legitimate" Canadian internet pharmacies already admit to getting their supplies from Europe. (An interesting and important side note is that these EU-sourced drugs aren't even legal for sale in Canada. So those who say we'll be getting "the same drugs as Canadians" are just plain wrong.)
In fact, parallel traded medicines account for about 20% (one in five) of all prescriptions filled by the same British pharmacies that have had a record numbers of counterfeit recalls. In other words, drugs purchased from a British pharmacy by a Canadian internet pharmacy to fulfill an order from an American cutomer could come from European Union nations such as Greece, Latvia, Poland, Malta, Cyprus, or Estonia.
Caveat Emptor is bad health care practice and even worse health care policy. Safety cannot be compromised, even if the truth is inconvenient.
Meanwhile, I wonder how much of that settlement will go to group such as The Prescription Project, Public Citizen, The Prescription Access Litigation Project, Community Catalyst, etc and trial attorneys as opposed to state governments.. How much will actually go to Medicaid patients instead of bottom feeders and the interest groups that front for them?
$1.4 billion can buy a lot of research activity for medicines that could save the lives of kids with cancer or seniors with Alzheimers...instead most of it will go to tort lawyers.
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.
