Latest Drugwonks' Blog
If you work for a pharmaceutical company, ask yourself this question: What business are you in? To the average American, you are in the business of selling. To survive and thrive you must be in the business of advancing the public health. And to do that you must be seen as both teacher and expert.
By: Marilynn Marchione, Ap Medical Writer – 2 hrs 38 mins ago
ORLANDO, Fla. – A single daily pill that combines aspirin and four blood pressure and cholesterol medicines has passed its first big test, potentially offering a cheap, simple way to prevent both heart disease and stroke.
The experimental "polypill" proved as effective as nearly all of its components taken alone, with no greater side effects, a major study found. Taking it could cut a person's risk of heart disease and stroke roughly in half, the study concludes.
This "one-size-fits-most" approach could make heart disease prevention much more common and effective, doctors say.
"Widely applied, this could have profound implications," said Dr. Robert Harrington, an American College of Cardiology spokesman and chief of Duke University's heart research institute. "President Obama is trying to offer the greatest care to the greatest number. This very much fits in with that."
The polypill also has big psychological advantages, said Dr. James Stein of the University of Wisconsin-Madison.
"If you take any medicines, you know that every pill you see in your hand makes you feel five years older. Patients really object to pill burden," and respond by skipping doses, he said.
The study was led by Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, and Dr. Prem Pais of St. John's Medical College, Bangalore, India. Results were presented Monday at the cardiology college's conference in Florida and published online by the British medical journal Lancet.
The study tested the Polycap, an experimental combo formulated by Cadila Pharmaceuticals of Ahmedabad, India. It contains low doses of three blood pressure medicines (atenolol, ramipril and the "water pill" thiazide), plus the generic version of the cholesterol-lowering statin drug Zocor, and a baby aspirin (100 milligrams).
Participants were about 2,000 people at 50 centers across India, average age 54, with at least one risk factor for heart disease — high blood pressure, high cholesterol, obesity, diabetes or smoking.
Four hundred were given the polypill. The rest were placed in eight groups of 200 and given individual components of the pill or various combinations. Treatment lasted 12 weeks.
Compared to groups given no blood pressure medicines, the polypill lowered systolic blood pressure (the top number) by more than 7 units and diastolic (bottom number) by about 6 — comparable to levels for people given the three drugs without aspirin and the cholesterol drug.
LDL, or bad cholesterol, dropped 23 percent on the polypill versus 28 percent in those taking the statin drug separately. Triglycerides dropped 10 percent on the combo pill versus 20 percent with individual statin use. Neither pill affected levels of HDL, or good cholesterol.
Anti-clotting effects seemed the same with the polypill as with aspirin alone.
Side effect rates also were the same for the polypill as for the five separate medicines.
"That was a big surprise. I would have expected five times the number of people to have side effects," said Dr. Christopher Cannon, a cardiologist at Harvard-affiliated Brigham and Women's Hospital in Boston who had no role in the study.
Collectively, the results show the polypill could cut the risk of heart disease by 62 percent and the risk of stroke by 48 percent, based on what previous studies show from lowering risk factors by these amounts, the study concludes.
Polycap's maker sponsored the study, and Yusuf has been a paid speaker for several makers of heart drugs. No price for the polypill is available, but its generic components cost only $17 a month, Cannon said.
A bigger study is now needed to see whether the polypill actually does cut heart attacks and strokes, he wrote in a commentary in the medical journal.
"It won't be for everybody," he said. Some people would be overtreated by getting medicines for conditions they don't yet have, such as high cholesterol. Others may be undertreated by too-low doses in the combo pill. Several polypills of different strengths may be needed, Cannon said.
"We have to be cautious about assuming that one size fits all," Stein said. "Treating risk factors is a lot like cooking — the ingredients count."
A polypill also would need federal Food and Drug Administration approval, even though all of its components have long been sold separately. The dosing issue could become a regulatory nightmare, Cannon warned.
"A final challenge: would the availability of a single magic bullet for the prevention of heart disease lead people to abandon exercise and appropriate diet?" he wrote in the medical journal.
That could make the risk of heart disease worse, and undo the good of the drug, Cannon said.
My mother didn't like to cook -- but she wanted her family to have "balanced" meals. (Remember "balanced" meals?) The results were predictable and adequate. (Sorry Mom.)
Similarly today, our comparative effectiveness nabobs want to field "comparative effectiveness" studies that don't make them think too hard. These studies (outlined here) will result in predictable findings based on "adequate" 20th century science that don't challenge any conventional wisdom. If we want real healthcare form -- is adequate acceptable?
No! No! No!
Literature reviews do not replace robust 21st century science.
“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.
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.
