In the Spotlight
Vioxx Backlash Could Derail Future of Medicine
"Personalized medicine" shows promise as alternative way of producing safer medications
Robert Goldberg, Ph.D., Paul Howard, Ph.D., Health Care News, 1-1-05
The backlash after the withdrawal of the arthritis drug Vioxx is in full swing.
Critics of the pharmaceutical industry and the Food and Drug Administration's (FDA) effort to modernize the drug development process are using the drug's link to a higher risk for heart attacks to raise questions about the FDA's safety review process and the value of new medicines overall. They say longer clinical trials should be required and newer, targeted, "smart" drugs like Vioxx should be tested against their cheaper, blunter ancestors before they are allowed on market.
Continue reading . . .
Study Suggests Way to Predict Whom Antidepressants Help
The New York Times, 12-17-04
For the first time, researchers have been able to identify a genetic variation that correlates with patient response to antidepressants. In an article published in the journal Molecular Psychiatry, “doctors from Harvard and the University of California, Los Angeles, treated with drugs 54 Mexican Americans in Los Angeles who were both depressed and highly anxious. (Limiting the study to one demographic group was a control tool.) They found that 60 percent of the group had a common genetic variant that helps govern the body’s response to stress.”
Patients with this genetic variant “were far less anxious and depressed than when they began the study” and, conversely, “depressed patients who did not have the variation got much less relief from the drugs.” Eventually, as researchers learn more about this genetic variant, it may be possible develop targeted antidepressants for patients who are resistant to traditional therapies.
Patients Weigh Pain vs. Risk : Some Former Vioxx Takers Say Alternatives Fall Short Or Carry Other Dangers
Wall Street Journal, 12-21-04
Some patients swear that Vioxx is the only drug that helped them cope with the tremendous pain from arthritis or other painful disabilities. Some researchers claim that all of the non-steroidal anti-inflammatories (from aspirin to Cox-2 inhibitors) offer basically the same pain-relief profile, and that patients who claim an additional benefit from Vioxx are just fooling themselves. Who’s right?
The answer could lie in the fact that small genetic differences between patient groups can result in large differences in how those patients metabolize drugs. This means that for small groups of patients, Vioxx really may be a miracle pain-relief drug. Should those patients have the right to take Vioxx despite other risks associated with the drug?
Those patients think so. “It is a choice no one would want to have to make. But many longtime Vioxx takers say they would have preferred to be informed of the risks involved and then decide for themselves whether to keep taking the drug. Now, they complain that they are left with few options. Some are angered and frustrated by the limited range of alternative treatments, which for them have been unsuccessful or inferior to Vioxx, and can carry significant risks of their own.”
Says one doctor: “If you live with intractable pain every day of your life, would you take a [small] chance that you would have a heart attack? A lot of my patients would.”
This is one side of the Vioxx controversy that isn’t getting the attention it deserves.
Heart Risk Seen in Naproxen
Wall Street Journal, 12-21-04
In the midst of the media frenzy surrounding Vioxx, and now Celebrex, one fact is consistently being ignored or underestimated: with the exception of aspirin, researchers generally don’t very know much about the long term risk of taking any nonsteroidal painkillers.
Take, for instance, recent data on heart attack risks with naproxen, sold over-the-counter as Aleve. An NIH study examining whether Celebrex and naproxen could prevent Alzheimer’s disease found that naproxen increased a patient’s chance of having a heart attack or stroke by 50% - and that Celebrex had about the same heart attack risk as placebo. “The Food and Drug Administration issued a statement recommending that consumers limit their use of naproxen to the amount suggested on the label, or 220 milligrams a twice a day, and not take the pills for longer than 10 days unless advised to do so by a doctor.”
Does that include the millions of U.S. arthritis sufferers who may need to take painkillers every day for the rest of their lives?
Aren’t the newer (Cox-2) drugs supposed to be bad, and the older generic drugs (like naproxen) good? Confused yet?
The problem is that, unlike Vioxx or Celebrex, older generic drugs like naproxen don’t get much media attention. It has been on the market for decades (since 1976) and sold over the counter since 1994. We take it for granted that these old drugs are safe and that it is the newer drugs that we have to watch out for. The truth is that no medicine is safe for everyone under all conceivable circumstances.
“Sandy Kweder, deputy director of the FDA’s office of new drugs, said the agency faces a ‘very confusing situation,’ partly because it lacks long-term data on the older painkillers.” In other words, it is possible that there is some (albeit low) risk with all of the NSAIDs at the high dosages and long-terms periods that older arthritis patients take them for.
That doesn’t mean that the U.S. drug supply isn’t safe – it just means that we need to focus on developing better tools for defining safety profiles for targeted patient groups. Otherwise, we’ll become too scared to use any medicines.
It all starts with quality, Biogen Idec CEO says ; Innovation is vital, as is learning from mistakes
USA Today, 12-20-04
This interview with Biogen Idec CEO James Mullen is a fascinating read. Mullen describes both the challenges facing the industry and the possibilities for the future growth of medical technology. Says Mullen: “The industry continues to underestimate the complexity of human biology and disease. We know 10% of what we need to know. The knowledge is accumulating at a dizzying pace, but because we know so little, we have some spectacular failures. I think its going to be some time before those statistics [on the enormous unpredictability and expense of drug development] turn around.”
On the topic of price controls and U.S. innovation, Mullen says that while U.S. consumers may be “footing the bill for innovation that is enjoyed worldwide,” the venture capital that drives the biotech industry is simply not available in Europe because the financial rewards (i.e. profits) are not there, as they are in the U.S. Consequently, the “U.S. has a huge lead in biotech jobs.”
Mullen’s description of the challenge facing biotech companies is reminiscent of an old Eastern European proverb: We know that we can turn an aquarium into fish soup, but can you turn fish soup into an aquarium?
Biotech companies have tremendous resources and a fast-growing knowledge base in systems biology and pharmacogenomics – but no one knows quite how to put all the pieces together in order to model real diseases and complete biological systems. Until we do, the industry will be in for more “catastrophic failures.”
Still, progress in biotech markets isn’t about tremendous leaps of innovation but in incremental steps where clinical knowledge and lab bench innovation work hand in glove.
Celebrex warning echoes safety failures; An analysis shows that, as the number of new drugs like Celebrex -- now linked to heart attack risks -- being given first to Americans has increased, reports of drug-induced ailments have grown.
The Miami Herald, 12-18-04
This article is pretty grim in its appraisal of the U.S. drug safety monitoring system. But just because the safety system needs fixing doesn’t mean that the approval system itself is flawed. The U.S has more new drugs approved here first than anywhere else in the world – meaning that U.S. citizens get first crack at new medicines that save lives, reduce disability, and lower other costs associated with debilitating or fatal diseases like cancer and heart disease.
Right now the FDA has a passive reporting system for drug adverse events, and that needs to change – but as part of a total reform package, which the FDA unveiled as its Critical Path initiative last year. By shifting to an “active” drug safety system, and working with health insurers to monitor adverse drug events track and off-label use of drugs, the FDA can mine a wealth of data that would’ve been impossible 10 years ago.
Funding for an active safety monitoring system is also sorely lacking. The blame for that problem lies with Congress, not the FDA. Giving the FDA the power to do better datamining and the budget to do it with should be high on Congress’ priority list in 2005.
Drug industry falling short in research and development / ANALYSIS: Firms are paying the price for faulty science
Houston Chronicle, 12-18-04
This article notes that the industry has been facing an R&D bottleneck since the late 1990s. “The decline in drug research and development has been an open secret among analysts and scientists for years. But drug company executives have insisted that their industry is fundamentally healthy and expensive research will pay off.”
For instance, “the number of new drugs approved by the Food & Drug Administration has declined sharply since the mid-1990s, falling from 53 in 1996 to 21 in 2003, even as the industry has nearly doubled its annual spending on drug development, to about $33 billion. Further complicating the process, many drugs already on the market do a reasonably good job, so the bar that new therapies – most of them expensive – must cross is very high.”
What the article doesn’t tell us is that we are still developing the tools that will allow us to integrate new advances in genetic science and computer technology into the drug development process. That is happening, and it needs to happen faster. However, industry watchers need to remember that the “critical path” from lab bench to bedside can take up to a decade: cutting edge medicines developed with genomic technology now won’t come online for another decade. In other words, keep the pessimism in check. Science never stands still.
Good Pill, Bad Pill: Science Makes it Hard to Decipher
The New York Times, 12-22-04
Does the science “make it hard to decipher”? Or is it the political climate?
The ancient Greek word for medicine is pharmakon; the same word is used for poison. This was one of the earliest insights into the drug safety issue: any substance powerful enough to have a beneficial effect on the human body is also likely to have destructive consequences when used in a different formulation, or even in a different patient.
In other words, every medicine from aspirin to morphine is simultaneously a good pill and a bad pill. Take for instance, today’s Times article on Vioxx, a drug that Merck pulled from the market back in September. Vioxx has been pilloried more than crack cocaine in recent months by industry critics and editorial boards. It turns out that the drug, in addition to being a powerful pain medicine with an additional heart attack risk for some patients, also prevents “precancerous polyps in some patients.” These polyps are sometimes the precursors for colon cancer.
The same study that found a potential cancer benefit for Vioxx resulted in Merck yanking it off the market. How's that for irony? One oncologist who worked on the study says that “it was clear that markedly fewer patients developed precancerous polyps while taking Vioxx and that no other study had shown such pronounced effects in patients, who previously had such polyps and were at risk for developing more.” The article goes on to note that this (and other recent concerns about other drugs) “points to troubling realities in the calculus of risk versus benefits.”
What makes this reality “troubling” is apparently the fact that no drug is entirely safe, and that FDA regulators cannot reassure the public that approved drugs are safe all the time, for everyone. Another researcher observed that in long clinical trials with large populations of relatively healthy patients (like the cancer trial mentioned previously), “it is almost impossible to be sure that in some relatively small fraction of patients, there won’t be side effects, even severe side effects.”
Bottom line: the current media frenzy obscures, even hides, unavoidable medical trade-offs from the public. If both of these findings had come out at the same time, Vioxx might still be on the market, with fewer prescriptions as a pain reliever and more research forthcoming on its potential use as a cancer drug. Doctors and patients could determine for themselves whether Vioxx was worth the risks. Now it’s gone altogether.
That’s a troubling reality.
REVIEW & OUTLOOK (Editorial) Pazdur's Revenge
Wall Street Journal, 12-20-04
The Wall Street Journal notes that recent revelations about Vioxx and Celebrex have created a perfect storm where avaricious trial lawyers “have launched a campaign of unprecedented size and scope that threatens the R&D budgets not just of Merck but of the entire pharmaceutical industry.” Says one trial lawyer: “It’s not as big as asbestos and it’s not as big as tobacco but it’s number three.”
Meanwhile, “Congressional opportunists” and some bureaucrats at the FDA are using the controversy to “make it even harder for innovative therapies to get to market.” One of those bureaucrats is Richard Pazdur, “the FDA’s oncology (cancer) drugs chief,” who wants to slow down the fast-track approval process for new cancer drugs. “The faster approval concept was a response to protests from AIDS activists in the 1980s and was later extended to cover therapies for other terminal diseases.” The Journal says that the “Pazdur interpretation of the rule would effectively kill the accelerated approval process, since there are off-label therapies for just about everything.”
Punishing drugmakers for doing good
Doug Bandow, The San Diego Union-Tribune, 12-16-04
Doug Bandow has written a gem of a business plan for aspiring MBA’s: “Create a company. Spend billions of dollars. Develop life-saving products. Be vilified.”
Sounds good, except for the “be vilified” part. Unfortunately, this is the reality in the pharmaceutical industry right now, where companies are routinely pilloried for not being perfect – rather than lauded for being good.
In no other sector of the market economy are the incentives for enhancing human well-being more closely linked to the profit motive than they are in the pharmaceutical and biotech sectors. Nonetheless, the very same mechanisms that drive medical innovation – profits, patents, and advertising – are the forces that “a gaggle of activists and politicians” denigrate, and then clamor for turning “drugmakers into public utilities” and allowing the government to set price controls for drugs.
Bandow reminds his readers that “medicines lengthen lives, improve the quality of life, and reduce hospitalization and surgery. Americans might prefer to pay less for their medicine. But they will be the biggest losers if they myopically kill the golden pharmaceutical goose.”
Pharmaceutical Group Chiefs March to Individual Beats
Greg Critser, Los Angeles Times, 12-20-04
This is an interesting article on the history of leadership at the Pharmaceutical Research and Manufacturers of America (PhRMA), the trade group for the drug industry. Critser notes that the PhRMA leadership has often taken stands that had pro-consumer results (and cut against the industry’s own interests). “[The PhRMA leaders approach to issues] often flows from individual political beliefs as much as from political connections and industry obligations.”
Perhaps this will help to slow the media rush to demonize the industry, and force pundits take a closer look at the nuances in how companies actually conduct themselves – as opposed the reigning caricature of greedy drug barons who are oblivious to their public obligations.
The Price of Too Much Caution
Dr. Scott Gottlieb, New York Sun, 12-22-04
This is another winner from Dr. Gottlieb, who reminds us that the current furor over pharmaceutical safety has, ironically, grown out of the real safety gains made by industry in recent decades. Comparing the pharmaceutical industry to the airline sector, Gottlieb notes that both of them are very heavily regulated and have excellent safety records; nonetheless, the better and more successful they are at safety, the worse every individual failure appears in the public eye.
Gottlieb writes that safety is always a trade-off between risks and benefits, and that “today we have the safest [drug] system in the world, but few glaring gaps to easily improve on. When it comes to making new drugs safer, most of the obvious solutions are already accounted for and we have reached the flat part of the curve that measures incremental safety against the additional cost. We can make our drug development system a little safer, but only at a very big cost.”
A Prescription for Health
David Gratzer, National Review Online, 12-21-04
“Republicans haven’t had much luck with health care,” David Gratzer observes, but he chronicles two new books from noted free-market health care experts (Sally Pipes, The Pacific Research Institute; John Goodman, The National Center for Policy Analysis) that should give politicians on both sides of the aisle plenty of good ideas to build on.
“Both Pipes and Goodman find an alternative in the concept of greater individual choice and control. Rather than leave important decisions up to others” policymakers should put consumers “in the drivers’ seat” for their own health care spending. Both authors agree that Health Savings Accounts are a vital first step in this direction and “marry real insurance (that is, coverage for high and unpredictable costs) with contributions to a savings account that can be used to pay for smaller health expenses and rolled over from year to year.”
We look forward to more powerful health care research from both of these scholars – and perhaps another book from Dr. Gratzer himself.
If you are interested in learning more about these two books you can find them here:
Miracle Cure: How to Solve America's Health-Care Crisis and Why Canada Isn't the Answer
, by Sally C. Pipes
Lives at Risk: Single-Payer National Health Insurance Around the World
, by John C. Goodman, Gerald L. Musgrave, Devon M. Herrick
Don’t Blame Canada
Robert Goldberg, Ph.D., National Review Online, 12-23-04
Manhattan Institute senior fellow Robert Goldberg weighs in on the recently released HHS Task Force report on drug importation and describes it as “a welcome breath of fresh air in the increasingly stale debate over drug importation.”
While advocates of importation will undoubtedly spin the report into a moral victory, Goldberg focuses on the report’s central findings: “The fact is, there is only a limited amount of drugs that can be supplied at price-controlled levels worldwide. No degree of safety and surveillance can change the laws of supply and demand. Europeans and Canadians are able to get quality drugs at lower prices only because Americans pay free-market prices that fuel research and development.”
The Painkiller Panic
Wall Street Journal, 12-23-04
The Journal editorial today is a clarion call for sanity in the midst of what is shaping up to be a very irresponsible debate on drug safety: “One of the most frustrating things about the latest news on painkillers is that almost none of the people reporting it understand the concept of relative risk – i.e. that a doubling of adverse events like heart attacks still doesn’t mean that event is very likely. A doubled risk might well be a chance worth taking, especially if the baseline risk is low to begin with and the drug’s benefits are significant for the patient in question.”
The key phrase is “patient in question.” Regulators (and certainly not industry critics) are in no position to substitute their judgments for that of physicians and their patients, who can best determine for themselves the relative benefits and risks of a given treatment.
Public hysteria over small incremental risks will, in the long run, create a very large threat to public safety if the FDA retrenches and makes it even harder than it already is for industry to create vital new medicines.
Report on Prescription Drug Importation
HHS Task Force on Drug Importation , 12-21-04
The Department of Health and Human Services Task Force on Drug Importation has released its much anticipated report on prescription drug importation. It concludes that individual importation of prescription drugs over the internet, the favored route today, carries with it significant risks. Any commercial program to import prescription drugs safely and in bulk (i.e., enough to meet a significant portion of U.S. demand) would be an enormously complex and costly endeavor.
In fact, the U.S. would have to make enormous outlays for very little overall savings – perhaps 1% or 2% at the margins. Over the long run, importation would probably increase pressure to impose price controls in the U.S., especially once it turned out that importation wasn’t the panacea its supporters have claimed.
Data on the effects of drug price controls imposed in other developed nations can be found in another document released yesterday, this time by the U.S. Department of Commerce: Pharmaceutical Price Controls in OECD Countries: Implications for U.S. Consumers, Pricing, Research and Development, and Innovation
For more background on U.S. government attempts to control drug prices in the U.S., please see the Manhattan Institute report, Are Price Controls Good for Your Health?
The Interaction of Public and Private Insurance: Medicaid and the Long Term Care Insurance Market
Jeffrey R. Brown, Amy Finkelstein, NBER Working Paper No. w10989, 12-1-04
As many researchers have long argued, these authors find that “the provision of even incomplete public insurance can substantially crowd out private insurance demand.” This means that, over time, private insurance providers will exit the long-term care market and leave government to (increasingly) foot the bill. This is because “Medicaid's large crowd out effect stems from the very large implicit tax (on the order of 60 to 75 percent for a median wealth individual) that Medicaid imposes on the benefits paid from private insurance policies.” Public policies designed to lure insurers back into this important sector will be ineffective “as long as Medicaid continues to impose this large implicit tax.”
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