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On several measures, the NHS came out the worst of all the systems examined. For example, it ranked worst for five-year survival rates in cervical, breast and colon cancers. It was also worst for 30-day mortality rates after admission to a hospital for either hemorrhagic or ischemic stroke. On only one clinical measure was it best: the avoidance of amputation of the foot in diabetic gangrene.
This hardly seems like a cause for national rejoicing, yet according to the report, the British were the most satisfied with their healthcare of all the populations surveyed. They were the most confident that in the event of illness, they would receive the best and most up-to-date treatment; and they were the least worried that their personal finances would prevent them from receiving proper treatment.
So, how is it that the population most confident that it will receive treatment of the highest possible standard, featuring the latest medical advances, actually has the worst survival rates in precisely those diseases that require the most up-to-date treatments?
One explanation is ignorance. The average Briton or Swede is unlikely to know that the five-year survival rate for colorectal cancer is 51.6% in Britain but 59.8% in Sweden, or that the 30-day fatality rates for myocardial infarction in those two countries are 6.3% and 2.9%, respectively. (The figures for the United States are 65.5% and 5.1%.) By contrast, the average Briton knows that if he suffers a heart attack, he will be taken to the hospital and connected to a lot of machines, from which he concludes that he is having the best possible treatment.
In my youth, I often heard the refrain that the NHS was "the envy of the world," and people in Britain are still inclined to believe that, even though they probably have never met anyone who envied the NHS and, indeed, probably know Continental Europeans residing in Britain who hurry home as soon as they require medical treatment, horrified by the prospect of subjecting themselves to a British hospital.
That said, there are some strengths the system can claim. Medical care is coordinated, for example, by means of a universal (and compulsory) system of family doctors. The lack of such coordination in the United States leads not only to a high rate of medical error but to duplication of effort.
The American rate of polypharmacy (the taking of four or more medicines daily) is twice the British rate. This difference is unlikely to reflect genuine need; the American polypharmacy rate is also 21/2 times the Swiss rate, and whatever one might think of British medical care, few would impugn the quality of care in Switzerland.
Read the full piece here.
The Pink Sheet reports, “Congress and the public should get an updated and extensive look at FDA performance over the next few years thanks to the many studies included in the FDA Safety and Innovation Act, although the additional work may tax agency personnel.” PDUFA V calls for more than 30 reports and studies.
That which gets measured gets done. But whose going to do the work? The FDA isn’t getting any additional funding or staffing to accomplish this important reportage – so what’s going to get prioritized?
That’s easy. Anything that is required by Congress gets done first – and that means PDUFA dates take a back seat.
More Congressional accountability for the FDA without additional funding?
Be careful what you wish for.
If you can’t measure it, the saying goes, it doesn’t count. But what if you’re measuring the wrong things?
The Access to Medicines Index (www.accesstomedicineindex.org) is an attempt to measure and compare the corporate social responsibility of both innovator (20) and generics (7) companies based on a number of different (and often quixotic) indicators. It was developed by Netherland's-based non-profit Access to Medicines Foundation (ATMF) with funding from the Dutch Ministry of Foreign Affairs, the UK Department for International Development and The Bill & Melinda Gates Foundation. It was launched in 2008, and comes out every two years.
The Index analyzes the following seven technical areas across four pillars:
Pillars:
1) Commitment (30% weight)
2) Transparency (30% weight)
3) Performance (30% weight)
4) Innovation (10% weight)
Technical Areas:
1) General Access to Medicine Strategy and Governance
2) Public Policy and Advocacy
3) R&D for Index Diseases
4) Patients & Licensing
5) Equitable Pricing & Registration
6) Technology Transfer (Capability Advancement)
7) Drug Donations and Philanthropic Activities
The Index concentrates on the global list of Low and Medium Development Countries based on the UN Human Development Index and World Bank Country Income level categories. The Index has historically covered 33 diseases including: WHO Neglected Tropical Diseases; the top 10 infectious diseases based on DALYs (Disability-Adjusted Life Years) from the WHO Global Burden of Diseases for the Low Development and Medium Development Countries; and the top 10 chronic diseases based on DALYs from the WHO Global Burden of Diseases for the Low Development and Medium Development Countries. The next index will likely broaden the disease scope to additional categories including NCDs, women’s health and some cancers. They also plan to place increased weighting on companies’ actual performance (vs. their commitments).
According the Access to Medicine Foundation, the index “aims to help poor people in developing countries gain access to medicine by encouraging the pharmaceutical industry to improve its commitments and practices related to this issue.” Since it’s a comparison, the theory is that competition among companies will drive desirous “socially responsible” behaviors. That’s a noble goal, but the devil is in the details.
As Goran Tomson, professor of international health systems research at Karolinska Institute points out, the Index’s methodology cannot be reproduced, hence it cannot be considered statistically valid.
There are also troubling issues relative to the index’s metrics for success. According to the Index’s methodological designer, Afshin Mehrpouya (an assistant professor of accounting and management control at the Paris-based HEC international business school) recently said, the only current measurements are “web hits and media coverage.” That’s not very exciting, plausible, or helpful from a health policy analysis perspective.
Another metric is the opinion of patient groups. When asked why certain patient groups were chosen (they are not named in the Index), the answer was that groups were chosen based on their “credibility.” That’s code for groups who do not accept funding from the pharmaceutical industry or may share the anti-private sector bias of the party line. At minimum, it’s a dubious selection bias.
Karolinska’s Tomson also pointed out that the index’s “review committee” consisted almost entirely of “familiar faces,” thus creating an issue of normative bias.
In other words, when did you stop beating your wife?
To offer better balance and some reference, shouldn’t the Index create a parallel metric that measures the policies and political environments of low and middle-income countries to determine whether they facilitate or hinder their citizens’ access to healthcare? How about creating an index that addresses the lack of transparency in the LDC public sector and (the 800 pound gorilla in the room) corruption. These are all polite ways of saying that the design criterion stacks the deck. But, hey, doesn’t the end justify the means?
Karolinska’s Tomson put the discussion about the index—as well as the entire ICIUM enterprise—into perspective when he said the index lacked for “higher ambitions.”
“Higher ambitions” requires that the Index do more than read its own press releases and talk with its friends in NGO-Land. “Higher ambitions” requires honesty beyond one’s own cognitive mapping.
According to Index CEO and Founder Wim Leerveld, “Today all companies have teams to deliver us the requested data as they see the relevance for them.”
Maybe. Maybe not. Interviews with participating companies showed much displeasure with both the Index questionnaire, the volume and type of information being requested by the Index and the “normative bias” of the ATMi staff. In some cases, participating companies are spending hundreds of hours to collect, verify and prepare final submissions. Is it worth it?
Here are some tough questions the Indexers must ask themselves:
Q: Is the Index moving the needle? Is there evidence that this is worth the effort that companies put into it and does it justify donor funding? Have they had an impact on financial investment patterns? Web hits and press clippings don’t cut it.
Q: What work has ATMF done to validate that their metrics are in fact the right drivers to improving access? Are they selecting an agenda being pushed by activist constituents without assessing a more full-bodied picture of what is happening in the real world?
To take one glaring example, the Index operates from the assumption that the innovator pharmaceutical industry can improve access to essential medicines. But, when you examine the WHO's model Essential Drug List, very few of the 400 or so drugs deemed essential are new, or patented or were ever patented in the world's poorest countries. In category after category, from aspirin to zithromax, in almost every case and in almost every country, these medicines have always been (or have been for many years) in the public domain. That is, the medicine is fully open to legal and legitimate generic manufacture.
There are important implications for the world's poorest patients. If these patients had reliable and affordable access to these several hundred essential medicines, all available theoretically as multi-source, that is from generics companies, then global mortality and morbidity might be cut as much as 10-20% -- a huge gain for populations around the world. Strangely, the Index gives a pass to the world's largest producers of generics drugs in India and China. Those companies are not being asked to spend hundreds of hours assembling data on their contributions to medicines access. Given the potential hugely positive impact on access to medicines, any reasonable person might ask why?
Q: Is it time to reassess the Index’s bias for certain mechanisms and tools? Its fixation on the medicines patent pool, for example unfairly demoting companies that aren't in negotiations. This doesn't seem fair. The pool is only one part of a broader landscape of what's happening around access to HIV and other treatments and it's unfair to use one tool as a measure of companies' commitment when there are other things happening that are very relevant and important.
There are ideological and activist assumptions within questionnaire’s section on tech transfer question. Is the Index looking at tech transfer as a measure of access to medicines or are they promoting industrial policy? Why isn’t in-country capacity building measured? What about efforts to fight counterfeiting? If ATMi is an ideological exercise, then innovator pharmaceutical industry should question the usefulness of the proposition.
Q: How does the Index ensure each company answers the questions in the same way to allow for an apples-to-apples comparison? Is the Index able to objectively compare companies? According to one corporate participant:
“Some of the questions were just too difficult to understand and required too much interpretation. In the Pricing & Distribution section, (Q1.9) we’re asked to provide product-specific registration status. When I asked for clarification, our Index contact told us to indicate if the product is patented in the countries in which it's registered. This is not inherent in the question. Also, we think it would be useful for the Index to know where we have filed for registration but where the application may be stuck in a bottleneck since the speed of registration is highly dependent on the speed and efficiency of local countries' regulatory processes. But our contact indicated this information was not necessary.”
The concern among participating industry is that the Index is getting increasingly arbitrary and opinionated. This is exacerbated by the fact that (per ATMi staff bios on its website) – many of the Index staff has worked for NGOs such as Médecins sans Frontières and other like-minded anti-pharmaceutical industry groups.
Industry wants the Index. They value being recognized for their good work – and the competitive rankings are appreciated (and flaunted). But the agenda isn’t appreciated. Pushing TRIPS+ and penalizing intellectual property rights trivializes the nature of the program. Perhaps it’s inaccurate to say that industry wants the Index. Maybe a better statement is that industry wants an index.
Recognizing the inherent flaws and bias of the ATMi – but also the importance of measuring industry’s commitment to social responsibility and access, Business for Social Responsibility’s (http://www.bsr.org/) Healthcare Working Group has launched an effort to provide an industry-wide lens on this important issue. The Working Group’s efforts center on the group’s acknowledgement that solving this challenge is a human need, and a business priority that requires a close collaboration with other actors from industry, public and NGO sectors.
It will be interesting to see how these two programs compare – and which one survives.
First there was CATIE then, earlier this week, AHRQ reported (in the August 14th Annals of Internal Medicine) that second-generation antipsychotics are not much better than the earlier incarnations at treating positive symptoms associated with schizophrenia. That's just Son of Sham.
Now here’s some important news.
According to research published in Nature Neuroscience, scientists have discovered a molecular mechanism for resistance to antipsychotic medications. Researchers from the Mount Sinai School of Medicine in New York City found that "long-term administration of atypical antipsychotic drugs selectively upregulates expression of the enzyme histone deacetylase 2 (HDAC2) in both mouse and human frontal cortex." That "epigenetic change, which is dependent on serotonin 5-hydroxytryptamine 2A (5-HT2A) upregulation, leads to lower expression of the metabotropic glutamate 2 receptor (mGlu2), thereby limiting the therapeutic effects of atypical antipsychotic therapy, often leading to a recurrence of psychotic symptoms."
Personalized medicine anyone?
Talk about qualified health claims!
In a letter dated February 14, 2012 (published online on August 14,) the FDA warns Hershey's that its labels for "Hershey's Syrup+Calcium" and "Hershey's Syrup Sugar Free with Vitamin and Mineral Fortification" are misbranded because they don't meet the nutritional requirements to make such claims.
The FDA has distinct definitions of "plus" and fortified" and doesn’t “consider it appropriate" to fortify snacks or sugary foods and carbonated beverages with vitamins and minerals. The FDA also said that Hershey's Syrup Genuine product was not an appropriate reference food for the other two types of syrups, because it does not include any of the added ingredients declared on the other products.
The labels now read as Hershey's Syrup with Calcium and Hershey's Sugar Free Chocolate Syrup.
Here’s the regulatory quandary – If you pour Hershey’s Syrup with Calcium over cholesterol-lowering Cheerios, is it a combination product?
The passage of the Generating Antibiotic Incentives Now (GAIN) provisions in the latest PDUFA agreement is being applauded for adding incentives like an additional five years of market exclusivity and priority review for qualifying antibiotics – but they may not be the game-changing incentives as some in the industry hoped.
High development hurdles for antibiotics, the availability of low-cost generics and reimbursement challenges for pricey new antibiotics are likely to keep most investors on the sidelines at least until big pharma starts to show more interest in the space.
The pharmaceutical industry, particularly at the top tier, has largely abandoned the therapeutic area because of development, regulatory and commercial challenges.
GAIN, which had been a pending stand-alone bill for years, was created as a partial solution to the dilemma, driven by groups like the Infectious Diseases Society of America, the Robert Wood Johnson Foundation and the Pew Health Group’s Antibiotics and Innovation Project as well as major companies in the space – what one lobbyist called the perfect storm of academia and industry, with industry using the thought leaders’ support to make it happen on the Hill. GAIN is intended to encourage development of new antibiotics as part of an effort to combat growing antibiotic resistance by providing incentives to companies developing drugs that target resistant pathogens.
One of the key challenges facing antibiotic drug developers is uncertainty in the approval pathway for antibiotics. One of the provisions in GAIN requires FDA to review antibiotic guidelines and update them where appropriate. The agency already has been working to update guidance for industry by type of infection, as required by the previous round of PDUFA, and has turned its efforts to complicated urinary tract infections, acute bacterial skin and skin structure infections, and community- and hospital- acquired pneumonia. Nonetheless, the clinical trial requirements, statistical analyses and endpoints in some cases are considered overly burdensome by many in the industry.
A more dramatic change to FDA’s approval requirements for antibiotics could spark a sea change in antibiotic R&D. Industry had pushed Congress to consider more aggressive changes that would reduce the clinical trial requirements for new antibiotics by allowing drug makers to study new drugs by pathogen rather than by indication, or only in the most severely ill patients, which would raise the threshold for safety and create a market for antibiotics similar to that for orphan drugs, where high-priced treatments are used in only a small subset of critically ill patients. IDSA asked Congress to consider such an approach, which it calls the Limited Population Antibacterial Drug mechanism.
Beyond the regulatory hurdles, generic antibiotics are widely available, posing reimbursement challenges for expensive new brands that do reach the market. Antibiotics for resistant pathogens are mainly used in hospitals so they face the added pressure of needing to secure placement on hospital formularies. On top of all that, antibiotics are prescribed for short-course therapy, generally just a matter of days, which limits their sales potential compared to chronic treatments, and in turn, limits a company’s return on investment.
The increasing prevalence of drug resistant pathogens means there is a clear need for new agents – and a significant market opportunity for drugs that can fight resistant strains and demonstrate a compelling pharmacoeconomic value story in the process, mainly by reducing the length of time patients are required to stay in the hospital. Almost two million Americans per year develop hospital-acquired infections resulting in 99,000 deaths, according to the Centers for Disease Control and Prevention. Sepsis and pneumonia alone killed nearly 50,000 Americans in 2006 and cost the health care system more than $8 billion.
How much antibiotic developers will benefit from the GAIN provisions depends on the molecules in development. The five years of additional market exclusivity, which comes on top of the five years of exclusivity already granted to brand manufacturers through Hatch-Waxman, is a big incentive but only in cases where patent protection doesn’t run in parallel.
My question is: so what? Has the Obama administration already raised premiums for about 1 in 15 seniors because the are wealthier? Yes. Will premiums go up over all in old style Medicare? Yes. Are co-pays in real dollars increasing across the board? Yes.
Meanwhile, here's what GAO said about Medicare advantage:
"Enrollment is up for Medicare Advantage plans, the private plan alternative to Medicare's traditional fee-for-service program, and premiums for beneficiaries are down, according to a report from the Government Accountability Office (GAO).
The GAO report, released December 1, found enrollment in Medicare Advantage plans increased by about 6%, from 7.9 million to 8.4 million beneficiaries, from April 2010 through April 2011, and the premiums seniors paid for these plans decreased 14%, saving them nearly $50 million. The average monthly premium decreased from $28 to $24 (http://tinyurl.com/7jf2cxp)."
Let's set aside the fact that most seniors in old style Medicare have supplemental insurance that pays for everything else Medicare doesn't pay for. The fact that seniors are increasingly shifting to a more competitive -- Ryan-Wyden-like -- Medicare that offers more and charges less is a good thing. Right? The proponents of single payer Medicare want to take away that existing choice and not expand it. And that's good?
Claiming that seniors would have to pick up the cost of lower priced Medicare plan is not just incorrect factually. It is the opposite of true.
Good omnibus PDUFA V article in the August issue of Nature Biotechnology.
Here’s the opening paragraph:
After months of broad discussion followed more recently by narrower negotiations among legislators, late in June the US House of Representatives and Senate passed the Food and Drug Administration Safety and Innovation Act of 2012 (FDASIA), also known as the Prescription Drug User Fee Act V (PDUFA V). With wide bipartisan majorities, President Barack Obama signed FDASIA into law on July 9, ahead of looming deadlines. Whereas some are concerned that Congress sidestepped key issues in its haste to pass the legislation, industry has generally welcomed the new law, particularly its implications for research on treatments for rare diseases.
And some selected quotes:
In terms of fostering product development for rare diseases, FDASIA encapsulates “certainly the strongest language to date, but it's not that strong,” says Peter Pitts, president of the Center for Medicine in the Public Interest in New York. Moreover, the development and review of such products “can't be expedited until the agency becomes more transparent about its risk-benefit analysis...and really explains its decisions so that they can be replicated. We need the agency to be more predictable, even if its heart is in the right place.”
More generally, Pitts says, “I give this version of PDUFA only a gentleman's B. It could have been better.” For one thing, the new law mandates only that FDA work toward developing a “risk-benefit grid” instead of setting a specific date to complete this as well as other comparably challenging projects, he says. “The agency agreed to hold meetings, and it's good to talk. But it won't get to the right place as soon as it might.”
Pitts also points out that language in the new law will not make it easy to “hold [FDA] feet to the fire.” However, on the plus side, “Congress recognized the need for more regular oversight on technical aspects of regulation,” he says. “It's one thing to have hearings on politically expedient issues, but rarely does Congress take on the sophisticated but more boring aspects of drug regulation.”
The article also offers a nice table of PDUFA V highlights:
FDASIA reforms to FDA
* Accelerated Approval: Fast Track designation and accelerated approval for “a broad range of serious or life-threatening diseases or conditions”
* Advisory Committee Conflicts: No cap on conflict-of-interest waivers for advisory committee members
* Breakthrough Therapies: Expedited development and review of drugs for serious and/or life-threatening diseases that show major improvement over the standard of care in phase 1/2 trials
* Biosimilars Performance Goals: Commitment to process 70% of original biosimilar biological product application submissions within 10 months of the receipt date in 2013 (up to 90% in 2017)
* Communication Training: Staff at CDER and CBER to better communicate with drug development teams and manufacturing. Independent auditors to evaluate interactions between sponsors and FDA in discussions on labeling, REMS and other potential issues before submission and during review. FDA to consult with patients during product development and review and to host four meetings with patient groups per year in different diseases
* Critical Path Appropriation: $6 million annually for FY13–FY17 to promote public-private partnerships
* Drug Review Timelines: Extends by two months the PDUFA deadlines for Standard and Priority Review of NMEs and original BLAs
* Foreign Clinical Trials: Encourages collaboration with European and Asian regulators to prevent duplicative trials
* Guidances: FDA to issue guidance on development of abuse-deterrent drugs and on online promotion of regulated products, including social media. Sixty days before issuing any draft or final guidance on laboratory-developed tests, FDA must notify Congress
* Pediatrics: Formalizes the Best Pharmaceuticals for Children Act and Pediatric Research Equity Act and extends Priority Review voucher program to rare pediatric diseases
* Qualified Infectious Disease Products: Priority review and additional five years of exclusivity for novel anti-infective drugs against pathogens with “potential to pose a serious threat to public health”
* Rare Disease Experts: FDA to establish list of rare disease experts whom FDA may consult
The complete Nature Biotechnology article can be found here.
And speaking of fast track authority, Representative Brian Bilbray (R, CA) has drafted “The Patient Choice Act,” which would amend PDUFA V and provide a must swifter fast tract for critical and life-saving medicines.
Under “PROVISIONAL APPROVAL FOR ADEQUATELY SAFE FAST TRACK PRODUCTS” the draft bill reads:
Subject to the requirements of this subsection, if the Secretary determines that a drug that is designated as a fast track product under this section is adequately safe, the Secretary shall grant provisional approval and the drug may be introduced into interstate commerce on or after the date such provisional approval is granted.
Interestingly, all the power (per the draft language) rests with “the Secretary,” not the FDA. Considering the highly disturbing recent Plan B precedent – do we really want fast track approval authority residing with the Secretary of Health and Human Services?
Mr. Bilbray’s draft bill can be found here.
It is likely the last place you will ever see it.
Interesting article in the Lancet (Volume 380, Issue 9841, Pages 611 - 619, 11 August 2012 doi:10.1016/S0140-6736(12)60861-7), Hypertension in developing countries.
Here’s the summary:
Data from different national and regional surveys show that hypertension is common in developing countries, particularly in urban areas, and that rates of awareness, treatment, and control are low. Several hypertension risk factors seem to be more common in developing countries than in developed regions. Findings from serial surveys show an increasing prevalence of hypertension in developing countries, possibly caused by urbanisation, ageing of population, changes to dietary habits, and social stress. High illiteracy rates, poor access to health facilities, bad dietary habits, poverty, and high costs of drugs contribute to poor blood pressure control. The health system in many developing countries is inadequate because of low funds, poor infrastructure, and inexperience. Priority is given to acute disorders, child and maternal health care, and control of communicable diseases. Governments, together with medical societies and non-governmental organisations, should support and promote preventive programmes aiming to increase public awareness, educate physicians, and reduce salt intake. Regulations for the food industry and the production and availability of generic drugs should be reinforced.
Common sense? Not to everyone. It seems that members of uncivil society are somewhat perturbed since they prefer to focus on evil multinational corporations (MNCs) and patents as the key public enemies of public health in the developing world. They become defensive whenever issues like governments buying poor quality generics comes up, or the use of counterfeits, or the inconvenient fact that in Africa, 99% of all essential drugs are off patent or were never patented, but millions of patients don't have reliable access to them -- which puts the spotlight back on generics companies, kleptocratic governments and the failures of their health systems.
Uncivil society groupies appear reluctant to delve into the factors behind why millions of people in Africa and other LDCs don't have access to non patented, off patented, legally generic (and reliably high quality) essential drugs in Africa --but they'll devote gallons of ink to their claims about the predations of patents and MNCs.
Love, so to speak, among the ruins.
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.
