Latest Drugwonks' Blog
Most notable is the following excerpt -- the importance of individual differences -- which the comparative effectiveness crowd in the US blindly and blithely ignores:
"The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors."
UK, 5/5/2008 - The Lancet has been a longstanding supporter of the National Institute for Health and Clinical Excellence (NICE) in the UK. Its procedures are rigorous, scientifically driven, and publicly accountable. NICE is widely admired by many other western European nations. But consternation and disappointment characterised the reaction by patient groups and the British Society for Rheumatology to NICE's latest judgment. On April 23, NICE rejected an appeal on abatacept for patients with severe rheumatoid arthritis brought by the drug's manufacturer Bristol-Myers Squibb, the British Society for Rheumatology, the Royal College of Physicians, the National Rheumatoid Arthritis Society, and the Royal College of Nursing. The appeal committee upheld NICE's decision of October last year, and the only next possible step is an application to the High Court.
Abatacept is, with rituximab and tocilizumab, one of three new drug classes that have shown clinically significant improvement for the treatment of severe refractory rheumatoid arthritis. Abatacept acts as a selective T-cell co-stimulation modulator, designed to block a key co-stimulatory signal required for T-cell activation, a new approach to halt or reverse the inflammatory process. However, with an incremental cost-effectiveness ratio of about £37?000–£43?000, possibly even higher if different estimates are included in the model, abatacept did not provide cost-effective treatment according to NICE's threshold of £30?000 per quality-adjusted life-year (QALY) gained. Many of these estimates are no more than best guesses based on insufficient or incomplete evidence. The committee stated that “while recognising the innovative nature of the drug, the severity of the disease and the limitations around the use of the HAQ [health assessment questionnaire] in the economic modelling, …abatacept would not be a cost-effective use of NHS [National Health Service] resources for patients in whom rituximab failed or in whom rituximab is contraindicated”.
How does abatacept differ from rituximab? Rituximab, a chimeric human-mouse monoclonal antibody directed at the CD20 antigen expressed on mature B cells and pre-B cells, acts on a different pathway. Like abatacept, rituximab was shown to be effective in patients treated with methotrexate who had not responded adequately to an additional TNF a inhibitor. Again like abatacept, there are no good long-term data and no direct head-to-head trials comparing other strategies with rituximab, yet rituximab was approved in August last year. The simple difference is that rituximab is cheaper. Patients only need two infusions every 6 months compared with 14 infusions of abatacept in the first year and 13 thereafter. The incremental cost-effectiveness ratio of rituximab is estimated as somewhere between £12?000 and £30?000 per QALY gained.
Rheumatoid arthritis is common and debilitating. About 1% of the adult population in developed countries is affected, increasing to 5% for women older than 55 years. About 60% of people are unable to work and are severely restricted in daily activities 10 years after diagnosis. Although progress has been made in understanding the underlying pathogenic mechanisms, the cause of rheumatoid arthritis remains unknown. The new treatment approach is to treat early and aggressively to achieve minimum disease progression and ideally remission, a strategy that achieves the best long-term results. However, there is currently no gold standard to define remission. Progression and response to treatment are extremely variable between patients. A substantial proportion of patients (up to 30%) is not adequately controlled with currently available treatment strategies of non-biological disease-modifying antirheumatic drugs and TNF a inhibitors.
Any new and effective treatment for such a debilitating condition as rheumatoid arthritis should be welcomed with enthusiasm. But NICE is at the sharp end of husbanding NHS resources. It has to balance evidence with cost. And here there is a perilous conflict between its dual clinical and political purpose. There will be occasions when exceptions to strict cost-effectiveness guidelines must be made on clinical grounds. Abatacept is a strong candidate to be such an exception. Worse still, NICE's decision may unwittingly act as a disincentive to industry to develop new medicines in this neglected and poorly understood area. Although NICE will rightly say that it has followed the letter of its cost-effectiveness law, patients and the public may, with justification, feel that it has forgotten the spirit of those same laws—namely, that cost-effectiveness evidence needs to be interpreted with compassion as well as impartial science.
"American children take anti-psychotic medicines at about six times the rate of children in the United Kingdom, according to a comparison based on a new U.K. study. Does it mean U.S. kids are being over-treated? Or that U.K. children are being under-treated? Experts say that's almost beside the point, because use is rising on both sides of the Atlantic. And with scant long-term safety data, it's likely the drugs are being over-prescribed for both U.S. and U.K. children, research suggests. "
Beside the point? I mean, it sort of matters if there is over or under treatment. But then again, Tanner has already concluded that the drugs are over-prescribed. But what does a six times the rate mean?
"In the U.K. study, anti-psychotics were prescribed for 595 children at a rate of less than four per 10,000 children in 1992. By 2005, 2,917 children were prescribed the drugs at a rate of seven per 10,000 — a near-doubling, said lead author Fariz Rani, a researcher at the University of London's pharmacy school."
Tanner seems to be talking just about kids diagnosed with ADHD and autism. And she conveniently ignores the number of kids who take the drugs for the same diseases in the US. She also ignores the fact that extensive study has gone into use of these drugs for treating of certain aspects of both disorders. In the case of anti-psychotics, risperadone has FDA approval for use in treating irritability in children with autism from ages 5-16 which most certainly explains why the study in Pediatrics found most of the increase in use overall associated with Risperdal scrips. But you don't see that information in the Tanner article...No. What you get is the implicit accusation that drug companies are promoting unsafe and off-label use of the product. Disgusting. Misleading. Damaging to parents and kids alike.
news.yahoo.com/s/ap/20080505/ap_on_he_me/psych_drugs_children
Bizzaro non sequitor paragraph in today’s New York Times article on the the Genetic Information Nondiscrimination Act:
“Ultimately unlocking all these genetic secrets will make the whole idea of private health insurance obsolete,” said Karen Pollitz, director of the Health Policy Institute at Georgetown University.
The first is that we need to redesign our healthcare system so that we reward “value rather than volume.” No argument there. It’s also very much in keeping with what Senator McCain is talking about these days.
He then turned his attention to the HHS “efficiency roadmap.” Lots of good initiatives. (I know, there are always a lot of “good initiatives.”) What was missing, however, was how to overcome one of the most significant roadblocks – state lines. Specifically, in addressing a group made up of large employers, the Secretary didn’t discuss insurance deregulation as a strategy towards more affordable, accessible, and patient-centered coverage. This must be a key strategy in the “value vs. volume” proposition.
He spent the lion’s share of his remarks (and productively so) talking about the need for inter-operability of healthcare IT platforms – where HHS has helped to both design and implement some successful programs lead the still nascent national dialogue.
One comment he made is worth repeating for both its wit and honesty. Leavitt quipped that “the wonderful thing about healthcare standards is that there are so many to choose from.”
And may we all live in interesting times.
Credit must also be given to Congressman Dingell, Congresswoman DelLauro and staff for pressing hard for more funding and hiring authority. Sometimes people can work together for the public health.
www.reuters.com/article/latestCrisis/idUSN30551443
"The Gallup-Healthways Well-Being Index asks Americans to evaluate their lives by imagining a "ladder" with steps numbered from 0 to 10, where "0" represents the worst possible life and "10" represents the best possible life. Nationally, 49% of Americans say that they presently stand on steps 7 or higher of the ladder. When asked where they will stand about five years from now, Americans report that they expect to stand on steps 8 or higher. Gallup considers this group of Americans to be "thriving." Thriving Americans' have their basic needs (such as food and shelter) met, and they have higher incomes, are less burdened by disease, report fewer sick days, and have better work environments. While nearly half of Americans fall into this category, the percentage of citizens in the thriving group is down from 60% in 2006.
On the low end of the spectrum, 4% of U.S. residents say they presently stand on steps 0 to 4 of the ladder. When asked where they will stand five years from now, Americans in this group report that they expect to stand on steps 0 to 4 of the ladder, as well. Gallup considers this group of Americans to be "suffering." Suffering Americans report that they have less access to basic needs such as food, shelter, and healthcare. They are also more likely to be burdened by disease, report more sick days, and are more likely to be divorced or widowed."
So how does Gallup arrive at a definition of "struggling?"
"Americans that Gallup does not classify as thriving or suffering are considered to be "struggling." The percentage of U.S. residents who are struggling has increased to 47% from 37% in 2006."Hmmm. Has anyone at Gallup read Goldilocks and The Three Bears? Or is it just that Americans are and always have been a striving culture. Or is it a function of everyone pursuing happiness? In any event, none of it explains the comment by CDC director Julie Gerbeding who equates the state with the misleading factoid that the US health care system ranks 37th in the world/....who is writing HER speeches....
Meanwhile here is the most revealing finding of the survey:
"Americans' reported level of happiness and enjoyment peaked on Easter Sunday, March 23, with New Year's Day coming in a close second. Super Bowl Sunday, Feb. 3, was also among the top 10 days that Americans reported the highest levels of happiness and enjoyment."
To me and Peter, any day the Yankees win is a great day...Looks like we will be struggling or suffering through 2008.
www.gallup.com/poll/106906/Nearly-Many-Americans-Struggling-Thriving.aspx
Many attendees support a proposal to replace drug patents with a “prize” system, wherein governments offer monetary rewards for new pharmaceuticals. A central WHO bureaucracy would decide which diseases are worth researching, establish prizes accordingly and then put the formulas into the public domain, allowing anyone to produce generics.
What could justify this overhaul? Proponents argue that patents keep drug prices artificially high and that pharmaceutical firms spend too much money on “lifestyle” drugs aimed at Westerners and too little on treatments for developing-world diseases.
Have a look at this article for further discussion of this foolishness:
www.metro.us/metro/blog/my_view/entry/Theres_a_prize_in_every_box/12382.html
The patent system doesn’t cause firms to ignore the developing world. Roughly half the research projects into Third World diseases are run by drug companies. The claim that prices keep drugs from poor patients is equally untrue. The reality? Developing countries lack the infrastructure for drug distribution. As the WHO’s HIV division director put it in 2006: “It is very obvious that the elephant in the room is not the current price of drugs. The real obstacle is the fragility of the health systems. You have health infrastructure that is dilapidated, and supply chains that don’t exist.”
Prizes might work in industries defined by “eureka” achievements like space travel. But drugs come from a long, incremental process of testing and retesting. Prizes only reward breakthroughs, not intermediate steps. Replacing pharmaceutical patents with a prize system would do untold damage to millions of poor patients.
One effect of comparative effectiveness: it locks in racial disparities in the treatment of chronic illnesses that lead to higher rates of death among African-Americans. Cost containment is achieved by letting minorities die more often.
Gene Variant Protects Black Heart Failure Patients
MONDAY, April 21 (HealthDay News) — Researchers have discovered a gene variant carried by about 40 percent of blacks that protects them after heart failure as much as widely used beta blocker drugs do.
The finding explains the puzzling results reported in trials of beta blocker therapy in black people, said Dr. Stephen B. Liggett, a professor of medicine and physiology at the University of Maryland, and co-author of a report in the April 20 online issue of Nature Medicine.
"To our knowledge, this is the first case where a genetic variant mimics the activity of a drug used to treat a disease," Liggett said.
The finding won't have an immediate effect on treatment of heart failure, the progressive loss of ability to pump blood that affects an estimated 5 million Americans, said study co-author Dr. Gerald W. Dorn II, director of the Center for Pharmacogenomics at Washington University in St. Louis. Doctors can continue to prescribe beta blockers for people with heart failure, black or white, since the drugs have little risk, he said.
But there should be an effect on future medical practice, Dorn said. "One idea in the future of drug discovery is that we will not only need to tailor therapy for individual genetic makeup but also take genetic makeup into consideration in drug testing," he explained.
Comparative effectiveness is completely ignoring such advances and the life saving benefits they bring. Remember Nitromed?
In this case people with the variant might not need a beta-blocker or as high dose. Those without will need it, Still other variations might lead to developing other regimens.
Liggett noted: “Our idea is not to replace the physician's judgment, but to give a handle on which drugs they might want to push to higher levels and which are less likely to be helpful for specific individuals.”
Unlike population-based comparative effectiveness which ignores individual differences that – for African Americans suffering from diabetes, hypertension and breast cancer – could mean life and death.
Which is why comparative effectiveness is just Jim Crow medicine unless it’s put on a personalized path.
Doug Holz Eakin, John McCain's policy chief and Carly Fiorina, McCain campaign chair ran a conference call for the media on McCain's emerging health care vision. In essence it is this: give people money to buy coverage and seek out care anywhere that prevents disease and rewards providers and insurers that do the best job treating illnesses. Instead of an insurance system that profits from finding ways not to cover people, McCain would find ways to get insurers to compete to treat people in high quality settings and get rewarded accordingly. Consumers would have information and dollars to seek out service in this new market. How about that? Sick people being sought after by insurance companies -- much like hungry people are sought after by restaurants and grocery stores.
This is an emerging and provocative vision. More to come...
Don’t Compromise the Safety of Biotech Drugs
By Bryan A. Liang
The comparison is worth keeping in mind as the debate heats up over "follow-on" biologics. Biologics are today's most advanced medicines, fully tested biotechnology protein drugs that provide targeted therapy to victims of cancer and other diseases. Follow-on biologics are the second or subsequent versions, but they are not identical.
Congressional legislation is pending that would allow the sale of follow-on biologics without requiring extensive testing -- essentially following the same model used for approval of generic forms of traditional prescription drugs.
But most drugs we're familiar with, like the pills we get from the pharmacy, are "small-molecule" drugs -- simple chemical compounds. They can be easily manufactured and identically copied. The anti-convulsant drug valproic acid, for example, has a total of just 26 atoms.
Identical to the brand-name version, these generics can "piggyback" on a brand-name company's testing. That's reasonable. These small-molecule drugs -- which typically are made up of a total of 20 to 100 atoms -- can be copied perfectly. So they don't need independent safety testing, cost less to make and are cheaper -- allowing more patients to obtain the medical benefits.
But biologics are far more complex. The brand-name drug Herceptin, a biologic that's widely used to treat cancer, is made up of a total of roughly 25,000 atoms. Large biologics can have millions of atoms.
Biologics aren't made by combining chemicals in a flask. They're made by life forms such as cells, yeast and bacteria. Like humans, these life forms exhibit diversity in metabolism and composition, making the final product a unique, heterogeneous mix that cannot be copied exactly. So follow-on biologic forms of a drug can only be similar to the original, not identical.
Because of the complexity of biologics, there's more regulation. In comparison with common chemical drugs that can have generic versions -- such as penicillin -- which only require 50 to 60 manufacturing tests for safety and quality, biologics require at least four times that number.
So the policy challenge is to provide incentives for innovation while also ensuring that any follow-on forms of biologics that enter the market are safe.
The key lies in something called "data exclusivity," which is a legal mechanism for allowing a company to keep confidential the data associated with a drug's development. Data exclusivity usually lasts for several years and spurs innovation by protecting new inventions. This is the current rule for small-molecule drugs, and it should be applied to biologics as well. Strong data exclusivity is critical for biologics, which are about 50% more expensive to develop than small-molecule medicines.
However, the current state of science makes ensuring safety of follow-on biologics difficult. Currently, the technology to map out the exact chemical structure and function of one large biologic versus another is not available. That makes safety reviews inexact. And follow-on forms may induce unpredictable adverse reactions.
Several years ago, a fully tested biologic created in the
If even cooperative company efforts can result in unpredictable adverse reactions, any follow-on product that does not undergo full testing should be of concern. Recognizing this reality, the European Union has developed a system of assessment that requires clinical testing of follow-on products in
If chemical drugs were toy planes, biologics would be 747s, the cutting edge of medicine. Because of their complexity, any follow-on forms must be held to a higher safety standard. As we have learned in aviation, safety is no accident.
Bryan A. Liang is executive director of the
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.
