|Selected news articles which highlight important policy issues.||
News: Weekly Archives
News for the week of 12-21-2004
Patients Weigh Pain vs. Risk : Some Former Vioxx Takers Say Alternatives Fall Short Or Carry Other Dangers
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
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.
Good Pill, Bad Pill: Science Makes it Hard to Decipher
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.
Consumers expect that over-the-counter drugs are safer than their new, prescription-only cousins – but that assumption hasn’t ever been rigorously tested. In fact, today’s drugs are only approved after much more rigorous (and longer) clinical trials than those used for decades-old generic drugs. Companies also have a financial incentive to find new uses for patented drugs, meaning that they are often screened repeatedly in different populations. For instance, studies for new drugs like Celebrex and Vioxx have focused on their potential for preventing cancer or Alzheimer’s – and involved thousands of patients who took these medicines for years on end. Trials of that size and duration are much more likely to identify rarer side-effects than those required for initial FDA approval.
This makes newer drugs look more dangerous than older ones – but for patients with chronic conditions who take generic painkillers for years, the opposite could be true. We just don’t know yet.
Because there is so much we don’t know, we need to avoid the instinct to demonize any class of drug, new or otherwise. Instead we should ensure that we are making the best use of all the tools at our disposal to match patients to the best treatments for their particular ailments.
FDA Clears Test of Patient DNA To Screen for Drug Effectiveness
For the first time, the FDA has cleared a DNA microarray test “for doctors to use in reviewing patients’ genetic information.” The test will hopefully improve doctors ability to match patients with the best medications for cancer, heart disease, and psychiatric disorders. The test analyzes DNA from a patient’s blood for “one of the genes from a group called cytochrome P450 genes, which are active in the liver to break down certain drugs and other compounds.”
Acting FDA commissioner Lester Crawford said that “physicians can use the genetic information from this test to prevent harmful drug interactions and to assure [that] drugs are used optimally, which in some cases will enable patients to avoid less effective or potentially harmful treatment choices.”
Painkillers Fall Under Sharp Review --- Health Officials to Focus On Side Effects, With Eye Toward Regulatory Action
The FDA and the NIH have launched a broad initiative to review painkiller side effects of many (at least 18) anti-inflammatory medications, “several of them household names.”
“The list of studies is potentially so broad that neither the [NIH] nor the [FDA], which are heading the initiative, could specify yesterday exactly how many such clinical trials will be intensely reviewed.”
The initiative will include all “NIH sponsored research involving all so-called nonsteroidal anti-inflammatory drugs, commonly called NSAIDS”, including “such familiar products as aspirin and ibuprofen.”
The initiative stems from the concern by some researchers that all NSAIDS (with the exception of aspirin, perhaps the most studied drug in the world) may carry with them some elevated risk of cardiovascular adverse events if used for long enough a time.
Still, consumers shouldn’t be apprehensive. Many of the drugs that we use today, and have used to decades, have well-known risks that are outweighed by their other benefits. The current furor is driven largely by how much better we have become at identifying very small risks in very large population groups. Should that mean that fewer drugs should be approved? No. As one rheumatologist from the University of Chicago noted, “aspirin has enough known dangerous side effects, such as gastrointestinal bleeding, that it probably couldn’t gain FDA approval today.”
And if we didn’t have aspirin, where would the treatment of heart disease be today?
Studies on Painkillers In Jeopardy; Researchers Assess Risk-Benefit Ratio
The risk of drug treatment always has to be weighed against its benefits – provided you know what they are. But what can we do when hysteria short circuits valuable scientific research?
Before the Vioxx withdrawal, there were literally dozens of studies testing Cox-2 drugs for the prevention of cancer or Alzheimer’s. Now, those studies have all been halted abruptly.
“The spate of bad news about painkillers has dealt a major setback to what had been a highly promising effort to use the drugs to prevent a host of leading killers, including many types of cancer, Alzheimer’s and other forms of dementia.”
One researcher said the current media frenzy has “created a situation of mass hysteria that’s completely unwarranted.... I don’t think we have all the data yet and we may be drawing premature conclusions.”
Hopefully, as more information emerges on the utility of this class of drugs, public fears will recede and the studies can be completed. Until then, patients with a family history of cancer or at high risk of developing dementia will just have to wait patiently until our politicians and trial lawyers have sorted out all the issues in the court of public opinion.
FDA Approves First in a New Class of Pain Drugs
The FDA has recently approved a new class of painkilling drugs based on a “synthetic version of a sea snail venom.” The drug is intended for use by AIDS and cancer patients who are unable to achieve pain relief from other powerful painkillers like morphine.
The drug, called Prialt, “offers an important new option for patients,” who have terminal illnesses and are suffering from “intractable pain.” Some benefits of the new drug compared to older ones: the drug doesn’t generate resistance after repeated use and is not addictive. However, like all drugs, this one has side effects, including the potential to cause dizziness, confusion, difficulty walking, and hallucinations.
The approval of Prialt offers a timely reminder that painkillers are vital tools in the battle against suffering and disease, and that increasing the number of therapeutic alternatives available to physicians and patients means that fewer patients have to suffer needlessly.
Doctors, Too, Ask: Is This Drug Right?
A better question to ask is “Is this drug right for this patient?” The rush to embrace “evidence based medicine” looks good or bad depending exactly what is being used to constitute “evidence”, and what you do with it. Take for instance, the following: “for at least the last two years, doctors at the Mayo Clinic, the Veterans Affairs Department and the Kaiser Permanente health plan have been sharply limiting their use of Vioxx and Celebrex. That is because those three institutions, after undertaking separate reviews of test data available on various painkillers, reached the same conclusion: For most patients, Vioxx, Celebrex, and a related drug, Bextra, did not work any better than older pain relievers or provide any safety benefits beyond them.”
If this is to say that this constitutes “evidence” that drugs should be given to patients who get the greatest benefit from them, or at the lowest risk of side-effects, few people would quibble with it. But if insurers instead mandate that doctors prescribe a one-size-fits all regimen where every patient de facto gets one drug or treatment until it proves ineffective or harmful, stretches the definition of evidence into something that looks suspiciously like cost-control. After all, the right treatment for this patient, may not be the treatment that works for the average patient.
The answer then, is not to design a health care system that can only generate average observations and then declare it evidence that one treatment is the best for everyone. Instead, we need to improve our datamining systems to look for rare adverse events, improve genetic screening that correlates for disease states and specific treatment regimens and, last but not least, make sure that doctors get state of the art diagnostic training that allows them to offer each patient the most effective care possible.
This will give clinicians the discretion and tools to make sure that each patient is treated like an individual – not a datapoint.
India's new patent law to shake up drug industry.
India is preparing to enter a bold new world in 2005, “when laws recognizing foreign patents take effect, ending a copycat trade [in pharmaceuticals] that has fostered local pharma firms for three decades and helped bring cheaper medicines to the poor.”
Indian policymakers hope that joining the global rules protecting pharmaceutical patents will lead to an influx of foreign investment in Indian companies that are shifting to R&D based pharmaceutical and biotech projects. In the long run, India hopes that these former copycat companies will be able to compete successfully with European and American companies in global health care markets.
However, the new regime will not impede access to older generic drugs, nor drugs aimed at helping the world’s poorest nations. “The new rules to not apply to drugs patented before 1995, so [companies like Cipla, a generic manufacturer] can continue selling its widely distributed version of the HIV treatment AZT. Even copies of drugs patented between 1995 and the introduction of the new law are unlikely to be withdrawn.”
India’s new commitment to patent protection is more evidence that the path out of poverty leads through free markets, property rights, democratic elections, and a judicial system devoted to protecting the rule of law.
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