Latest Drugwonks' Blog
“Comparing Drug Treatment Effectiveness in Ethnic Minority Populations. Research suggests that treatment response can vary among different minority populations due to genetic, environmental and cultural factors. Still, it is unknown which treatments work best for which ethnicities. Comparative effectiveness studies in ethnic minorities would test pharmacotherapies and behavioral treatments for substance abuse that have already shown efficacy in some populations. Results could reveal optimal treatment types for various populations, many of which are currently under-studied or under-served in terms of treatment need, including African Americans, Native Americans, and Hispanics. “
Comparative Effectiveness Research on Cancer Screening. The effectiveness of cancer screening has been established through randomized trials and other evidence for breast, colorectal and cervical cancer. However since screening for these cancers were initially introduced, there has been rapid and substantial innovation in new early detection technologies. Many of these technologies have disseminated into the practice of screening but without sufficient evidence as to their comparative effectiveness relative to earlier established technologies. In addition newer technologies may influence how the earlier technologies are most effectively used. Comparative effectiveness research in this area would augment evidence from controlled screening trials with: data from observational studies in defined populations of screening, intermediate and final outcomes; head-to-head studies of the technical performance characteristics, physician and patient acceptability and cost of alternative screening technologies, and decision models designed to project the costs and benefits of different screening technologies and strategies over the long-term at the individual, program and policy level
Comparative Effectiveness Studies of Non-Pharmacological Treatments for Chronic Low Back Pain. Observational studies or secondary data analyses to compare the effectiveness of: non-pharmacological treatments or integrative health care approaches for chronic low back pain when used in addition to and/or as an alternative to standard conventional care.
Comparative Effectiveness Research in Cancer Primary Prevention. A number of chemoprevention agents have been shown to be potentially effectiveness for the prevention of common cancers. But dissemination of chemoprevention remains low and controversy remains about the side effects associated with these agents. Comparative effectiveness research in this area would have the following aims: to document the level of dissemination of chemoprevention agents and the examine the physician, patient and health system factors that either facilitate or retard this dissemination; to conduct head to head studies of alternative chemoprevention agents and or approaches (e.g. risk stratification) to determine the relative clinical risk and benefits and economic cost of these alternatives. These studies could be conducted as adjuncts to existing controlled trials, as retrospective analysis of health system data or as prospective studies of cohorts of patients and physicians within the context of various healthcare delivery systems.
Selecting the Optimal Initial Treatment Regimen for Patients With Newly Discovered Type 2 Diabetes. The natural history of type 2 diabetes, treated by widely used current regimens, is marked by gradual increases in glucose levels, loss of insulin secretion, progressive increases in drug therapy, and frequent development of chronic complications. Clinical trial data suggests that aggressive early therapy attempting to keep glucose levels near normal is associated with a more benign long-term course. The optimal treatment regimen (effectiveness and avoidance of hypoglycemia) is not known, but current drugs provide options for multiple treatment approaches. In view of the numerous options, pilot studies are needed to assess the short-term effectiveness of common treatment strategies.
Personalized drug response and toxicity. Application of pharmacogenetics and pharmacogenomics, quantitative and systems pharmacology (this could be part of a larger grouping to include systems biology and systems genetics), ADMET pharmacology, preclinical models, and new technologies and approaches to complement pharmacogenomic studies to enhance signal-to-noise ratios and aid mechanistic studies, and consensus standards for normal and altered phenotypes in drug response and toxicity.
Imaging and Fluid Biomarkers for Early Diagnosis and Progression of Aging-related Diseases and Conditions including Neurodegenerative Diseases. Diseases and conditions of aging have a huge public health burden, and the ability to diagnose these early and follow their course would greatly help in treating and managing them.
To witness, check “The black book on hospitals” (Livre noir des hôpitaux, Calmann-Lévy 2009) which enumerates an awful range of black spots, mishaps and tragic deaths of patients who nevertheless had full faith in the French model and universal care.
That figures; what about statistics? Try this one for size: on average 40 deaths every day, in terms of “undesirable events”. Obviously this figure covers more than people dying from medical errors, negligence and other mistakes in the hospital environment. The ballpark ranges from 350,000 to 460,000 deaths annually for hospital stays, of which some 120,000 to 190,000 might have been avoided, according to the authors.
Anecdotal evidence attests that astonishing number of physicians in the (public) hospital environment are either alcoholics, drug addicts or afflicted by some mental disorder. For obvious reasons, no statistics on this scandal are readily available; but how come these people, albeit hopefully a minority, are still allowed to practice? (Just imagine having surgery by a psychotic doctor!)
The primary reason is simple: hospital doctors (or nurses) are government employees and thus enjoy life-time employment. Any private company would try (with difficulty but still) to fire such people, especially in view of their life-or-death responsibilities.
France retains the advantage of a relatively dynamic private sector; but although private clinics are a lot more efficient and benefit from a much lower budget, they are under constant political assault. The budget divide is roughly 80/20 in favour of state-run hospitals. Nevertheless, France is world champion of hospitals/clinics per head: one institution per 20,000 people compared to one for 40,000 people on average in Europe.
The private sector has an obligation to perform; this is where most of restructuring has taken place for economic reasons. The public sector has an obligation to ask for greater budgets despite decreasing results.
Cherchez l’erreur.
Or profit.
Because follow on biologics are no more copycats than my two children are copycats because they came from the same combinnation of DNA. You can't even say that about twins.
Needless to say, just by ignoring all the science and safety concerns and searing them into law doesn't make follow on biologics similar in structure, treatment or safety. It's just saying they do. Hell, in the Waxman bill you can even take the innovator's name. Why not just take over the company?
The propnents of a short cut to follow on products want to do testing...it's just that they want the testing to be unsuspecting doctors and patients who will not be told they are being put on an imitation until after the fact. Post market safety commitments? Why, that's just for start up biotech companies with no cash flow and only five years of market or data exclusivity... And by they way, forget about tracking safety if the killer takes on YOUR name.
Okay – so just what exactly is a Quality Adjusted Life Year (QALY)?
“A QALY scores your health on a scale from zero to one: zero if you're dead and one if you're in perfect health. You find out as a result of a treatment where a patient would move up the scale. If you do a hip replacement, the patient might start at .5 and go up to .7, improving by .2. You can assume patients live for an average of 15 years following hip replacements. And .2 times 15 equals three quality-adjusted life years. If the hip replacement costs 10,000 GBP to do [about $15,000], it's 10,000 divided by three, which equals 3,333 GBP [about $5,000]. That figure is the cost per QALY."
So, how much is a year of life worth?
"The most controversial area is where you place the dividing line between what is cost effective and what is cost ineffective. That is the "how much is life worth?" question. And there is no real empirical research to guide you. We have looked at what other government departments do. Our Department of Transport, for instance, has a cost-per-life-saved threshold for new road schemes of about about 1.5 million-pounds-per-life, or around 30,000 GBP per life year gained. The judgment of our health economists is that somewhere in the region of 20,000-30,000 GBP per Quality-Adjusted Life Year (QALY) is the [threshold], but it's not a strict limit."
That's a tough decision to make for bureaucrats, is it not?
"For many difficult questions, we capture public preferences by our citizens council, a representative sample drawn from the general public. For example we asked if should we give greater priority to children than the elderly. The group decided that a year of life was worth just as much when you are a grandparent as when you are a child. That is very culturally specific and might not apply to other countries in the world."
Thanks Sir Michael.
But, according to Dr. Frank Lichtenberg of Columbia University, for a healthcare technology assessment (HTA) scheme (such as the NICE model) to yield valid decisions in practice, it is necessary to have reliable estimates of:
ΔCOST
ΔQALY
and VSLY (Value of a Statistical Life Year)
And his main point is that the devil is in the details.
Lichtenberg believes that incorrect estimates of some or all of these key inputs are often used:
ΔCOST is frequently overestimated
ΔQALY and VSLY are frequently underestimated
And due to these estimation biases, health technologies that are truly cost-effective may often be rejected as cost-ineffective.
Per the recent debate over the utility of new cancer treatments, he makes a very interesting point -- that even though, over the past 30 years, the U.S. Mortality Age-Adjusted Rates for cancer have remained relatively constant -- (leading to such mainstream media headlines as Fortune Magazine's "Why have we made so little progress in the War on Cancer?” and NEJM articles like "The effect of new treatments for cancer on mortality has been largely disappointing” -- the often ignored reality is that 5-year relative survival rates, for all cancer sites, have increased from 50.1% in 1975 to 65.9% in 2000.
Lichtenberg cites two crucial studies, pointing out how health care economists must seriously reconsider the outdated estimates of a QALY:
Viscusi and Aldy: The value of a statistical life for prime-aged workers has a median value of about $7 million in the United States
Viscusi, W. Kip and Joseph E. Aldy, “The Value of a Statistical Life: A Critical Review of Market Estimates Throughout the World,” The Journal of Risk and Uncertainty, 27:1; 5–76, 2003.
and
Murphy and Topel: The value of a life year is $373,000.
Murphy, Kevin M., and Robert H. Topel, “The value of health and longevity,” Journal of Political Economy, 2006.
Attention must be paid. Hello NICE. Hello IQWiG. Hello Senators Baucus and Conrad.
If the devil is in the details (and it is) -- it's time for a deep dive beyond simplistic and self-serving "comparative effectiveness."
Praise Mitt Romney. Three years ago, the former Massachusetts Governor had the inadvertent good sense to create the "universal" health-care program that the White House and Congress now want to inflict on the entire country. It is proving to be instructive, as Mr. Romney's foresight previews what President Obama, Max Baucus, Ted Kennedy and Pete Stark are cooking up for everyone else.
![[Review & Outlook]](http://s.wsj.net/public/resources/images/OB-DJ461_oj_1ma_E_20090326193027.jpg)
APMitt Romney.
In Massachusetts's latest crisis, Governor Deval Patrick and his Democratic colleagues are starting to move down the path that government health plans always follow when spending collides with reality -- i.e., price controls. As costs continue to rise, the inevitable results are coverage restrictions and waiting periods. It was only a matter of time.
They're trying to manage the huge costs of the subsidized middle-class insurance program that is gradually swallowing the state budget. The program provides low- or no-cost coverage to about 165,000 residents, or three-fifths of the newly insured, and is budgeted at $880 million for 2010, a 7.3% single-year increase that is likely to be optimistic. The state's overall costs on health programs have increased by 42% (!) since 2006.
Like gamblers doubling down on their losses, Democrats have already hiked the fines for people who don't obtain insurance under the "individual mandate," already increased business penalties, taxed insurers and hospitals, raised premiums, and pumped up the state tobacco levy. That's still not enough money.
So earlier this year, Mr. Patrick appointed a state commission to figure out how to control costs and preserve "this grand experiment." One objective is to change the incentives for preventative care and treatments for chronic disease, but everyone says that. It sometimes results in better health but always more spending. So-called "pay for performance" financing models, on the other hand, would do away with fee for service -- but they also tend to reward process, not the better results implied.
What are the alternatives? If health planners won't accept the prices set by the marketplace -- thus putting themselves out of work -- the only other choice is limiting care via politics, much as Canada and most of Europe do today. The Patrick panel is considering one option to "exclude coverage of services of low priority/low value." Another would "limit coverage to services that produce the highest value when considering both clinical effectiveness and cost." (Guess who would determine what is high or low value? Not patients or doctors.) Yet another is "a limitation on the total amount of money available for health care services," i.e., an overall spending cap.
The Institute for America's Future -- which is providing the intellectual horsepower (we use the term loosely) for reforms like those in Massachusetts -- argues that the cost overruns prove the state must cap how much insurers are allowed to charge consumers and regulate their profits. If Mr. Patrick doesn't get there first, that is. He reportedly told insurers and hospitals at a closed meeting this month that if they didn't take steps to hold down the rate of medical inflation, he would.
Even the single-payer cheerleaders at the New York Times have caught on to this rolling catastrophe. In a page-one story this month, the paper reported on the "expedient choice" that Mr. Romney and Democrats made to defer "until another day any serious effort to control the state's runaway health costs. . . . Those who led the 2006 effort said it would not have been feasible to enact universal coverage if the legislation had required heavy cost controls. The very stakeholders who were coaxed into the tent -- doctors, hospitals, insurers and consumer groups -- would probably have been driven into opposition by efforts to reduce their revenues and constrain their medical practices, they said."
Now they tell us. What really whipped along RomneyCare were claims that health care would be less expensive if everyone were covered. But reducing costs while increasing access are irreconcilable issues. Mr. Romney should have known better before signing on to this not-so-grand experiment, especially since the state's "free market" reforms that he boasts about have proven to be irrelevant when not fictional. Only 21,000 people have used the "connector" that was supposed to link individuals to private insurers.
Which brings us to Washington, where Mr. Obama and Congressional Democrats are about to try their own Bay State bait and switch: First create vast new entitlements that can never be repealed, then later take the less popular step of rationing care when it's their last hope to save the federal fisc.
The consequences of that deception will be far worse than those in Massachusetts, however, given that prior to 2006 the state already had a far smaller percentage of its population uninsured than the national average. The real lesson of Massachusetts is that reform proponents won't tell Americans the truth about what "universal" coverage really means: Runaway costs followed by price controls and bureaucratic rationing.
That physician is named Dr. John Muney.
With all the brouhaha over the relative efficacy of prostate cancer screenings, you'd think the media would be watching for some really important news -- like a biomarker that could change the whole paradigm. Alas, the MSM seems to have missed the story entirely. Not shocking, but nevertheless disappointing considering the play they gave to the cost-effectiveness angle just last week.
But drugwonks won't let that happen
According to researchers from the
The
The study shows "that galectin-3 is cleaved during the progression of prostate cancer and might be associated with metastasis, cell growth and tumorigenicity. Expression of intact versus cleaved galectin-3 thus might be used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer," wrote study author Avraham Raz and colleagues.
Go Wolverines!
The study appears in the April issue of The American Journal of Pathology.
Meanwhile in the UK, the government seems to be finding a way to keep it's biotech industry and the patients who depend on it alive before it's too late:
Click Here to Read More
Grim Outlook For UK Biotech Industry
Mar 11, 2009
By: Sarah Houlton
One-third of publicly owned UK biotechs have less than six months’ money left in the bank, and just 0.2 percent of the London Stock Exchange is now made up of biotech companies. “A new approach to funding is needed to fill the gaps left by investors,” claims Aisling Burnand, chief executive of the BioIndustry Association.
“We are faced with a very different world than we were a few years ago,” says Bioscience Innovation and Growth Team chairman Sir David Cooksey. The BIGT just released Bioscience 2015, an industry report designed to map out the market for the next six years.
First released in 2003, the report had been written to look forward 12 years and forecast where industry would be. In this revised and refined report BIGT has have lowered its sights.
The main problem, Cooksey claimed, is that investors simply do not see enough reward to justify the risk in putting their money into the sector. “There are hurdles in the way such as NICE and the EU clinical trials directive, which has been more stringently applied in the UK than in other countries,” he says. “We have to change the balance.”
This drying up of finance for biotechs is a real problem. “Biotech companies have not given good enough returns to investors to make them want to come back. Private sector angels, venture capitalists, and public markets have all turned away. We need to make it more attractive, and then I have no doubt that as the extra funding is rolled out we will get the situation where there is more participation in terms of the public sector.”
However, Cooksey does not believe that a large investment by government is the right way ahead, in contrast to the demands made by Sir Chris Evans and a group of his fellow venture capitalists at the end of last year. “We’ve not said, ‘Let’s have $1 billion in [government] funding,’” he claims. “If you look at history, governments putting a lot of money into technology development with civil servants picking the winners has not had much success.” Rather, they are looking for regulatory help and enhancements to the existing R&D tax credit scheme to encourage pharma companies to invest in biotech.
He believes that if Big Pharma were given more confidence in the biotech sector and had a more collaborative involvement at an earlier stage, it should give investors more confidence, too. “We are looking for real support from government to put a regulatory environment in place that will be effective in the longer term,” he adds. “We need to look at how to change the drug development pathway, use modern techniques to make it cheaper, faster and safer—it’s currently unnecessarily expensive. We are in danger of it no longer being worth a company’s while [to get into drug discovery] as they will never get to be able to sell a product at the price they need and which is also acceptable [to the payers].”
However, he says, this cannot be done by the UK on its own—it will have to involve the EU and the FDA, too. “Changes in the global regulatory system will take time and effort,” says serial entrepreneur and former BIA chairman Simon Best. “In the past four or five years, the sector has fallen out of favour. If we can do more work using modern tools such as genetics and genomics, and run smaller, better focused trials, it will be a reduced ask for investors.”
There is also the suggestion of allowing patients to receive drugs for life-threatening diseases after Phase II trials on a conditional licensing basis. “Hopefully safety issues would be flagged up more quickly, and the poor uptake of innovative drugs could be addressed,” Best said. “We want to see more pivotal trials carried out in the EU, maybe allowing conditional licenses while still doing Phase III trials in the US. This would allow us to address safety issues much earlier, and identify which patient populations could most benefit—or would most likely to have problems. I’m not convinced that post-marketing surveillance is the way ahead.
We’re all used to state AGs suing drug companies for inappropriate promotion of off-label indications (Neurontin comes to mind – among others). Now there’s an interesting new wrinkle.
16 state Attorneys General (Oklahoma, Alaska, Utah, Iowa, Colorado, Kansas, Maine, Missouri, Nebraska, New Mexico, North Carolina, Rhode Island, South Dakota, Texas, West Virginia, and Wyoming) have written to Abby Black (Director, Center for Drug and Health Plan Choice at CMS) to complain that Part D participating insurance companies are requiring that their customers fail on a variety of off-label therapies before they will be reimbursed for medicines that have the more appropriate, on-label indication relevant to their particular conditions.
The AGs write, “Just as it is inappropriate for pharmaceutical companies to market drugs for off-label uses, it is equally inappropriate for health insurance companies to refuse to reimburse for physician-prescribed medications unless a patient first undergoes treatment with drugs that are off-label. … This practice of requiring treatment with an off-label drug before reimbursing a patient for using a drug
Many issues here – particularly the validity of the FDA label for anything post Wyeth v. Levine – but an equally important question is when is off-label not off-label? At present, the answer seems to be; when it's on-formulary and off-patent.
Case in point, pregabalin (Lyrica) and Iowa (coincidentally, the state represented in the United States Senate by Charles Grassley).
Iowa Medicaid requires preauthorization for pregabalin -- which is FDA-approved for (among other indications) fibromyalgia. In Iowa a patient with a diagnosis of fibromyalgia must first fail on at least two of the State's "preferred" agents -- trycyclic anti-depressants, topical lidocaine, or gabapentin. None of these three agents are approved by the FDA for the treatment of fibromyalgia.
But they are less expensive than the on-patent, on-indication product. So what we've got here is step-therapy based on off-label usage. Not unheard of, certainly, but it does start sending some interesting policy messages about the appropriateness of off-label use in various circumstances. (And it's more than a little bizarre when you consider that Pfizer, the manufacturer of pregabalin, had to pay a $430 million fine for off-label promotion of gabapentin.)
The actions of the Hawkeye State Department of Human Services are even more peculiar considering that Senator Grassley (R, IA) asked the U.S. Government Accounting Office (GAO) to investigate off-label prescribing -- and not because he thought it was a valuable tool for patient care.
So here's where we stand: Off-label use of on-patent medications is bad, but off-label use for generics is good. Translation: off-label use is good when it saves the payer money.
Here’s how the Sweet 16 end their letter to CMS:
“Insurance company requirements that patients utilize off-label treatments before being reimbursed for FDA-approved treatments are dangerous and should not be permitted. The same policy considerations that support a ban on off-label marketing by pharmaceutical companies support the prohibition of this insurance company practice.”
Here is the complete letter to CMS.
Are you paying attention Mr. Waxman?
Benefit Design Index
By Melinda C. Haren, RN; Kirk McConnell
The cost of employee health coverage continues to grow faster than inflation,1 putting additional economic pressure on employers ...
American Health and Drug Benefits
Cost sharing of Rx is climbing faster than premiums AND inflation....drug spending is falling. We know that compliance falls and disease burdern increases as a result.
Meanwhile insurers diddle about reimbursing for personalized medicine which is very cost effective and product ...
The Economic Impact of Personalized Medicine: Genetic Testing in Metastatic Colon Cancer May Save $604 Million Annually
By Caroline Helwick
So much for controlling health care costs.
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.
