|Selected news articles which highlight important policy issues.||
News: Weekly Archives
News for the week of 02-14-2005
Garret FitzGerald began voicing concerns about COX-2 inhibitors shortly after Merck introduced its COX-2 drug Vioxx in 1999, and has kept up his criticisms of the drugs ever since - that is, until now. Today FitzGerald believes that the drugs should remain on market, provided that they can be modified or targeted at patients who truly need them.
“A handful of drug companies, including Merck, Ono Pharmaceutical and France’s Servier, are now working with FitzGerald…to unearth successors to the now-disgraced COX-2 class of painkillers.”
FitzGerald thinks that the problem with COX-2 inhibitors was that they were aimed at the wrong target. The COX-2 enzyme is actually the precursor for a wide ranging group of “biochemical signals” called prostaglandins that the body needs. One of the prostaglandins, called prostacylcin, actually protects the heart.
FitzGerald hopes that “If drug developers could better target their inhibitors farther down the prostaglandin chain, they might produce powerful drugs that could fight pain and avoid unknown, possibly fatal, side effects.” He hopes that further research could even lead to blood tests that would measure prostaglandin levels and allow doctors to predict which patients can take COX-2 drugs safely. “We have to find a way to use these drugs chronically in people at low cardiovascular risk but high risk of stomach problems. They’re going to be a nice case of individualized medicine.”
FitzGerald is right—and diagnostic tests like these will revolutionize drug development, patient treatment and FDA regulation. After all, current clinical models are based on the “one size fits all” dosage model that presumes that adverse drug effects are basically random and largely unpreventable. In a world of personalized medicine, drugs will increasingly be developed using biomarkers for specific patient profiles that allow doctors to maximize efficacy and eliminate the worst adverse effects.
“With great fanfare, at least nine states over the past year launched Web sites to help their residents buy inexpensive prescription drugs from Canada. But so far, the sites aren’t doing much business.”
One reason for the sputtering programs, as Sally Pipes suggested last week, is that access to affordable prescription drugs is just not a large enough problem to warrant national angst. Low income seniors and other Americans on tight budgets have many options for decreasing their prescription drug costs, meaning that state programs are likely to receive a tepid response from consumers.
“In Illinois, Gov. Rod Blagojevich predicted a ‘prairie fire’ of popular support when he defied the Food and Drug Administration in October and unveiled a Web site designed to help 18 million people in Illinois and Wisconsin buy low-price drugs from Canada and Ireland. Since then, the site…has processed only 3,200 prescriptions.”
In short, the “prairie fire” many anticipated has turned out to be a tempest in a teapot.
The real driving force behind these Web sites is the perception that prescription drugs (even when affordable) are just too expensive. Critics who accuse the drug companies of profiteering want the U.S. government to adopt Canada’s price control policies - if they have to import or implement those policies one state Web site at a time.
Since that’s the real agenda, we should have a national debate on price controls and skip the faux excitement over Web sites that Americans aren’t much interested in anyway.
Rare Strain of HIV Resists Drugs, Builds Rapidly Into AIDS
A new strain of the AIDS virus may have been discovered in an individual case in New York City (there may be other cases in California as well). The strain appears to be “highly drug resistant” and “[progresses] rapidly to [full blown] AIDS”, a process that normally takes years.
While the aggressiveness of this particular strain may be due to the genetic or physiological profile of the infected patient (who is also a drug addict), scientists have known for years that the AIDS virus mutates quickly and that drug resistant strains of the virus are becoming increasingly common.
Alarmingly, this patient’s HIV virus “didn’t respond to three of four classes of antiretroviral medications most commonly prescribed. He is now receiving a fourth ‘cocktail’ in hopes his rare HIV strain will respond.”
The potential discovery of an HIV “super virus” also comes at a time when AIDS drugs are under enormous pricing pressure in the developed and developing worlds. While it makes sense for developing nations to have access to the least expensive and most effective generic or branded drugs possible, the public should keep in mind that the next generation of AIDS medicines for drug resistant virus strains won’t come from generic companies.
They’ll come from pharmaceutical companies that are devoted to new, and expensive, innovative research. And that research is funded by the profits they make on their drugs primarily in the U.S. and Europe. Without those profits, there will be less AIDS research, fewer new AIDS drugs - and less hope for patients who contract drug resistant viruses.
Bush to Retain FDA's Acting Chief - Veteran Administrator Would Be Unlikely to Seek Broad Changes at Agency
It depends on what you mean by “broad changes.” President Bush has nominated Lester Crawford, the Acting FDA Commissioner, to formally head the Food and Drug Administration at what may be its most troubled era in decades.
Recent drug safety scares have left the agency virtually under siege, accused of becoming too deferential to the pharmaceutical industry and insufficiently concerned about patient safety.
But the chief problems facing the FDA are more scientific than they are regulatory. Controversies from antidepressants, to Vioxx, to Adderall all underscore how little the agency knows about the science underlying adverse events and how to prevent them.
As Gualberto Ruaño and Robert Goldberg argue in this week’s Spotlight, the future of drug safety lies in personalized medicine - developing targeted treatments that are tested and designed for specific subgroups of patients and have significantly increased safety and efficacy profiles.
The FDA can help accelerate the adoption of personalized medicine by embracing new science based regulations that expedite approval for drugs developed using cutting edge genetic science.
Under the current paradigm, the FDA is dependent on large scale clinical trials that might not detect adverse events until tens of thousands or even millions of patients are treated in the real world - years after a drug is first tested and approved.
New pharmacogenomics tests can allow us to spot potential adverse effects early in the drug development process, long before a single patient ever receives the drug. Moving that knowledge from the laboratory to the beside is the challenge facing the industry and the FDA now, and hopefully Commissioner Crawford will help the agency meet that challenge.
Middle-Class Families Strain Public Health-Insurance Plans
“More and more middle-class American workers are choosing to enroll their children in taxpayer-funded health insurance programs instead of the more expensive plans offered by their employers. It’s a trend that will cost publicly funded state and federal programs billions of dollars and could eventually force even consumers of private health insurance to pay higher premiums.”
This is a classic government squeeze play. As the government enlarges enrollment in public programs to higher and higher income brackets, its own costs inevitably rise. The government then squeezes health care providers by lowering reimbursement rates and throwing up burdensome regulations that drive up costs even further. Since government costs are capped, private providers pass their losses onto consumers outside of government programs in the form of higher health care costs and insurance premiums.
And then, as insurance becomes ever less affordable for employers and individuals, the government sweeps more and more people into its “safety-net” - an odd definition for a program that tends to hurt everyone who’s not in it.
Manhattan Institute Senior Fellow David Gratzer observed that "with Medicaid enrollment swelling [including the State Children’s Health Insurance Program or SCHIP], some academics have argued that the program is successful - after all, look at all the new recipients. But the reality is that governors across America have loosened eligibility requirements. In Vermont today, for instance, a family earning $51,000 is still entitled to some Medicaid benefits. Indeed, it seems that Medicaid crowds out private insurance, leaving taxpayers on the hook."
Taxpayers are actually on the hook twice: once for their taxes and again for their health insurance premiums. Getting consumers off the hook by introducing market forces into Medicaid would not only lower program costs, it would ensure better health care for low-income Americans.
The FDA has said that it intends to create a new Drug Safety Oversight Board “to review safety issues that arise in drugs already approved by the agency.”
“The board, expected to consist of FDA and other government officials, will be charged with making recommendations to the agency if it thinks action is needed, but will lack the authority to pull drugs or change labeling. It also is to recommend when the agency should alert consumers about potentially problematic drugs at an early stage, through a new Web site.”
Anything short of an independent drug safety agency will undoubtedly fail to satisfy some agency critics. Still, the real question isn’t the autonomy of the oversight board, but the quality of the information that the FDA collects - or doesn’t collect. This is a critical problem because, as Scott Gottlieb has argued, the FDA is still a veritable dinosaur when it comes to utilizing information technology.
While the jury is still out on the effectiveness of the FDA’s proposed safety board, it isn’t too early to start improving the agency’s datamining technology and creating a more effective adverse event reporting system. That structure will ultimately determine the success or failure of the FDA’s drug safety efforts, no matter what name we call it.
What Makes a Drug Too Risky? There's No Easy Answer
Pharmaceuticals can pose serious risks for a very small numbers of patients - perhaps just a handful of patients out of thousands or even millions. Does that make them unsafe?
Unlike pharmaceuticals, we have safety rules for cars, alcohol and many other consumer products that don’t necessitate product withdrawals every time there is an unfortunate accident. However, when it comes to drug safety, scientists often lack the ability to do anything other than identify a potential risk (for instance, heart attacks), let alone identify the precise cause of it. For instance, even when a given drug is only dangerous for very small numbers of people “medical science can’t definitively rule anybody in or out of danger.”
“At the same time, there are risks for not being treated. Many experts credit a rise in use of Paxil, Prozac and other antidepressants known as SSRIs for a 25% reduction in teenage suicides in the past 10 years…Failure in school and criminal behavior are among possible outcomes for kids whose attention disorders go untreated while switching pain relievers can also mean trading a risk of heart problems for one of gastro-intestinal troubles that can be just as serious.”
However, doctors and patients can navigate this tangled web of costs and benefits if they have access to the right information. Increasingly, personalized medicine will allow patients and doctors to chose therapies from exercise to drug therapy with confidence that they really work based on reliable DNA tests - as opposed to trusting the conclusions of a randomized and highly artificial clinical trial.
Safety is, in the final analysis, defined in a personal context, patient by patient. Anything short of that is just a lucky guess.
Genome map offers first look at human differences.
The genome map will help researchers identify combinations of genes that lead to disease, better predict how different patient groups will respond to drug treatments, and eventually even help doctors and patients avoid drugs that might cause devastating adverse effects.
This is “the first published map of human genetic differences [which will offer researchers] a major step toward truly personalized medicine, from predicting who will get what disease to finding ways of choosing the best drug for an individual patients…The map..looks at more than 1.5 million tiny genetic differences among 71 people..enough to find some of the most common genetic variations involved in diseases such as Alzheimer’s, cancer and multiple sclerosis.”
The development of better health information technologies, including portable electronic health records, are critical for making personalized medicine a success, since they will give doctors access to a patient’s entire medical history, the most up-to-date medical guidelines, and help them avoid wasteful and ineffective treatments that cost U.S. consumers and taxpayers billions of dollars every year.
Now, two groups, General Electric and Intermountain, “a nonprofit health-care network based in Salt Lake City” have announced “an agreement to develop a comprehensive software system that provides physicians with Internet-type access to clinical protocols and relevant information at the moment of treatment.”
The partners are hoping to fuse “Intermountain’s clinical-decision database and systems created during the past few decades with GE’s new information technology that it will sell to the health-care network. The result, they say, will be a system that gives physicians the latest information for treating and preventing a range of medical care [issues] from bed sores to cardiac arrest.”
Will the plan serve as a prototype for national adoption? That depends. Health care providers are generally paid in a fee-for-service paradigm, which means that they are reimbursed if they do their jobs well or badly. Investing heavily in IT infrastructure might lower overall costs, increase efficiency and improve health care—but hospitals and doctors might not benefit directly—if at all.
The missing link is a true market for consumer driven health care, where individuals with Health Savings Accounts could target their spending at the most efficient providers with most effective IT, rather than being trapped in networks that focus on transient cost-savings rather than true effectiveness. As long as third party payors dominate American health care, IT improvement will face a long uphill battle.
Drugs Raise Risk of Suicide; Analysis of Data Adds to Concerns On Antidepressants
The same forces that split drug safety advocates and clinicians over COX-2 drugs are forming around the popular class of relatively new antidepressant drugs are called SSRIs.
A large “meta-analysis” of 702 controlled clinical trials involving 87,650 patients has shown that “[a]dults taking poplar [SSRI] antidepressants such as Prozac, Paxil, and Zoloft are more than twice as likely to attempt suicide as patients given sugar pills, according to an analysis released yesterday of hundreds of clinical trials involving tens of thousands of patients.”
SSRIs have become hugely popular—some would say over prescribed—because they have a track record of efficacy (in adults) and fewer side effects than older antidepressants known as “tricyclics.” Fewer side effects leads to better patient compliance, i.e. patients who take them will stay on them longer and have better control over their disease and its symptoms. Still, the rise in popularity has led some experts to be concerned that doctors are treating the drugs too cavalierly, and are prescribing them for minor ailments that might be better be treated with other tools.
Some drug safety experts are touting the latest data as confirming increased suicide risks for the drugs, while clinicians argue that the data is being interpreted out of context. For instance, if the drugs are so risky, why have suicide rates been declining?
Weighing in on the debate, one trustee of the American Psychiatric Association said that “If these medications were really increasing the incidence of suicide attempts, you would think we would be seeing more completed suicides…In fact, we are seeing exactly the opposite.”
In particular, adolescent suicide rates “have dropped 25 percent” since SSRIs have come on the market, “even as more than a million children were put on the drugs.” In fact, patients on SSRIs might feel better and ironically are more likely to admit to a suicide attempt than patients who remain gripped by depression. Consequently, statistical analysis like the one quoted above may overstate the risks of using the drugs because they are based on “muddied data.”
In any event, we should focus our concern on real issues—like possible over prescription of effective drugs—instead of inventing risks that will scare patients who really need the drugs away from them.
Medicaid recipients express concern about proposed overhaul
Governor Jeb Bush’s plan to overhaul Florida’s Medicaid system by moving recipients from the current fee-for-service model into managed care is already drawing criticism—and praise. Bush’s proposal “in large part calls for paying private managed care providers to take on Medicaid patients instead of reimbursing individual care givers for treatment.”
Most of the criticism has been generated by anxiety over potential benefit cuts or declining standards of care as Medicaid patients are transferred into privately administered programs.
“If you take my prescriptions away from me, I’ll die within two weeks because I’ll go into rejection, said Lynda Gehring, 61, of Ocala, who received a heart transplant seven years ago. ‘I have two grandchildren and I’d like to live seven more years to seen them grow a little bit more. I intend on doing that and I want you people to help me.”
However, the reality is that Medicaid’s reliance on the fee-for-service model already under-treats many patients with chronic diseases who require coordinated or long term care management. These patients are often under-treated and find themselves bottoming out in expensive hospital or emergency room settings as manageable ailments spiral out of control.
Some experts and managed care providers think that managed care will improve the health of these patients. “If anything, their needs are going to be met more…With the fee-for-service program, you don’t have that kind of coordination [between health care providers]….We can take care of the whole person—not a fragmented outsourced kind of thing where the psychiatrist doesn’t talk to the general practitioner.”
When Medicaid was enacted in 1965 the fee for service model made sense in an era when there were few program recipients and medical care was generally very limited. As medical care grew more sophisticated and expensive, Medicaid enrollments mushroomed.
Today, state Medicaid programs operate a fragmented system that is cumbersome, expensive, and outdated. Introducing market forces, Health Savings Accounts, and managed care into Medicaid may very well be its best hope for survival.
Drugs to break addiction's hold; Tests of a number of new medications have researchers hopeful.
The personalized medicine revolution may soon impact how physicians treat and manage drug and alcohol addictions.
While no drug is a silver bullet for addiction, new brain imaging techniques and advances in the understanding of how genes affect addiction are giving researchers new targets for potential drug therapies that will target “specific drugs to specific addicts.”
“For example, preliminary research suggests that Antabuse, a medicine that makes drinkers sick, may help nondrinking cocaine addicts. Naltrexone may work best in another subset of hereditary alcoholics who feel high when they drink, rather than sedated…”
While personalized medicine is often touted as benefiting only wealthy or sophisticated patients, the fruits of our increased understanding of human biology will pay dividends across many diseases—like addiction—where there are currently few effective therapies.
When it comes to deciding whether a drug with known risks is worth keeping on the market, who should have the final word? Clinicians who use the drugs in patients day in and day out, and are intimately familiar with the disease they are treating—or statisticians and drug safety experts who use complex but abstract statistical models for calculating benefit to risk ratios?
The contrast between a clinical versus a statistical approach came to a head during last week’s FDA advisory committee meetings on COX-2 drugs where the rheumatologists who treat arthritis patients outvoted the FDA’s drug safety experts and led the charge to keep COX-2 drugs on the market despite their link to an increased risk of heart disease and stroke in some patients.
“[R]heumatologists on the panel and in comments to the panel argued that in their practices, COX-2 inhibitors appear to be the only drugs that work in certain patients. Patients who testified before the panel echoed the doctors’ comments, saying that they thought an increased risk of heart attacks and strokes was a fair trade-off for what they considered to be unparalleled pain relief. ‘Vioxx saved my life,’ said patient Robert Thibadeau, who told panelists he was diagnosed with rheumatoid arthritis more than 30 years ago.”
Statisticians who rely on clinical trials and datamining are apt to dismiss the idea of patient variance as anecdotal or due to chance; clinicians argue that their patient populations are too diverse to allow an all-or-nothing approach to drug treatment. While statistical modeling is often a very useful “big picture” tool, there is a growing body of evidence that individuals can respond very differently to the same drugs, or even closely related drugs in the same class.
As the science of pharmacogenomics advances, doctors will be increasingly able to validate “anecdotal” patient responses by matching them with individual physiological and genetic factors—validating drug efficacy and safety.
Eventually, the migration of personalized medicine into doctor’s offices will make FDA advisory panels like this one—who weigh in on drug safety issues years after a drug is first released—largely obsolete.
In ways that researchers are only beginning to understand, cancer cells mask themselves from the immune system, allowing them to grow and multiply unimpeded by the body’s normal defenses.
To get around this cancer “blind spot,” researchers are focusing on ways to train the immune system to recognize cancer and attack it as if it was a foreign invader, in much the same way that flu or chickenpox vaccines work by inoculating the body with a harmless virus or viral particles that stimulate a powerful immune response. While cancer vaccines may never be powerful enough to cure cancer, “they may shrink smaller masses or eliminate traces of cancer that linger after surgery.”
No cancer vaccine has been approved by the FDA, but several are in late stage testing, including Provenge, a prostate cancer vaccine that just last week reported that it “helped men with advanced disease who are no longer benefiting from standard hormone therapy live 4 months longer than patients who got placebos.”
Ultimately, cancer vaccines may become part of “cocktail” cancer therapies that utilize several targeted treatments and transform cancer from a feared killer to a manageable chronic condition.
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