In the Spotlight
WHO's AIDS strategy misses the big picture
Philip Stevens, Center for Medical Progress, 2-24-05
No one can accuse the World Health Organisation of lacking ambition in its attempts to get to grips with the AIDS crisis that is currently sweeping much of sub Saharan Africa. Its "3 by 5" initiative - a plan to put 3 million people on life-extending antiretroviral treatment by the end of 2005 - is arguably the single biggest push that any multilateral body has yet undertaken to try to tackle the disease. Unfortunately, according to figures recently released by the WHO, the project looks like its going to miss its target spectacularly. Furthermore, in its emphasis on providing ARV treatment, the strategy overlooks the fundamentals that could slow down the progress of the disease: education, prevention and the development of self-sustaining health infrastructure.
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NIH Clears Most Researchers In Conflict of Interest Probe
Washington Post, 2-23-05
It’s nice to know that the principle of collective punishment is alive and well in the federal government.
“Most of the 100 or so National Institute of Health researchers who the agency has said are under investigation for allegedly engaging in secret deals with pharmaceutical companies and biotechnology companies have been cleared by NIH investigators…The unexpected finding that as many as 80 percent of the seeming improprieties were actually the result of errors by government investigators has undermined the rationale behind NIH Director Elias A. Zerhouni’s recent decision to impose severe restrictions on the personal activities and finances of all of the agency’s more than 5,000 employees.” [Ed: emphasis added]
The draconian conflict of interest rules instituted by Director Zerhouni only took effect on February 3 but are already facing withering criticism - criticism sure to increase now that the vast majority of supposed improprieties have been shown to be the result of harmless government errors.
This raises the question of why the rules were put into place even before the NIH had finished its internal investigation. The obvious answer - that the NIH was cowed by Congressional grandstanding - is hardly reassuring for an institution that is supposed to be the nation’s leading repository of scientific research. The rules should be prudently scaled back before the witch hunt for industry collusion spurs a full fledged exodus of the NIH’s best staffers.
Medicaid recipients express concern about proposed overhaul
Associated Press Newswires, 2-21-05
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 Philadelphia Inquirer, 2-21-05
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.
Rheumatologists outvote drug-safety specialists Helping patients in pain wins out over increased risks of heart attack, stroke
USA Today, 2-21-05
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.
Tricky way to fight cancer Trial vaccines use deception to alert immune system to tumors
USA Today, 2-21-05
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.
Drugs Raise Risk of Suicide; Analysis of Data Adds to Concerns On Antidepressants
Washington Post, 2-18-05
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.
Genome map offers first look at human differences.
Reuters News, 2-17-05
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.”
High-Tech Tool Planned for Physicians - GE, Partner Hope to Make Treatment, Prevention Data Available Over Internet
Wall Street Journal, 2-17-05
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.
Editorial: Too Strict at NIH
Washington Post, 2-23-05
The Post notes that under the NIH’s new conflict of interest rules “all of [its] 17,500 employees—and their spouses and minor children—would be barred from owning more than $15,000 worth of stock in a wide variety array of drugmakers, biotechnology firms, and manufacturers of medical devices. Moreover, at least one-third of the NIH workforce—scientists at a senior enough level that they have to file confidential financial disclosure forms, and those involved in dispensing grants—would be prohibited, along with their families, from holding any stock in such firms.”
The Post argues that “an across the board ban in situations in which there is no possibility of even an appearance of conflict goes too far.”
What else is there left to say?
Commentary: A safer Vioxx? Try this remedy
Joe Torg, The Philadelphia Inquirer, 2-23-05
Torg, an orthopedic surgeon in Philadelphia, says that in late 2000 he prescribed Vioxx to 8 patients, six of whom later developed high blood pressure. After asking Merck for more information on this side effect, he was notified that there was evidence that it did, indeed, have an effect on blood pressure in susceptible patients.
Nonetheless, Merck didn't acknowledge an increased risk of heart attack or stroke with Vioxx until it withdraw the drug in 2004, despite the fact that there is a “well-established correlation between high blood pressure and stroke” and heart attacks.
Torg notes that there was a very simple solution to the Vioxx problem: “Monitor the patient’s blood pressure. If hypertension develops, discontinue the drug.”
The source of the problem in this instance—and probably others—is twofold. First, the FDA’s passive reporting system used for documenting drug adverse events. Shifting to a mandatory system would allow the FDA and manufacturers to correlate drug treatments with rare but significant adverse effects like this one and adjust information to patients and doctors quickly and easily.
Second, is the FDA’s insistence on using randomized clinical trials to vet all drug safety and efficacy concerns. This leads the agency and industry to pretend that if a problem doesn’t show up in a clinical trial, it doesn’t exist. The over reliance on clinical trials when there are other faster methods available—sophisticated datamining, genetic modeling of drug toxicity—undermines public confidence in both the agency and industry.
Revising the clinical trial model—for instance, increasing the use of biomarkers as suggested in the FDA’s Critical Path project—would go a long way towards improving drug safety.
Commentary: Good Drug, Bad Customers - II
Holman W. Jenkins Jr., Wall Street Journal, 2-23-05
When it comes to Vioxx there is plenty of blame to go around—and not all of it for the FDA and industry. Doctors and insurers should also come in for some well deserved criticism.
Holman Jenkins has been arguing this case for months and points out that if Vioxx returns to the markets “big winners will be patients” who will have another option for managing serious chronic pain, and doctors who “have reason to be gratified as well”, since no one has taken them to task for peddling a $2 pill when a 15 cent one would have done as well for the vast majority of patients.
In Jenkins opinion, “the big loser would be the insurance industry. It’s attitude toward prescription drugs is ‘we don’t want to pay for them’ unless they save money by reducing the need for expensive hospital visits. Prescription drugs for mild chronic pain don’t readily fit this description…So how come insurers spent $5.6 billion on Cox-2s in 2003”? [Ed: emphasis added]
In fact, studies have shown that the better a patient’s insurance coverage, the more likely they were to be placed on Vioxx. “Insurance companies have been forced to become America’s primary purchasers of health services but are vilified if they ever say ‘no’ to a patient. No wonder they did a characteristically inept job of making sure we got our money’s worth from Cox-2 spending.”
The problem is that the main people spending on health care—employers—get a tax write-off for their expense, allowing them to shift more benefits to workers without bearing the full cost. “The sad truth is that neither doctors nor insurers nor GM are prepared to sacrifice a huge tax benefit for ‘health insurance’ even while they whimper about the consequences and beg the government to do something about it.”
Wall Street Journal, 2-22-05
Last week the FDA advisory committee on Cox-2 drugs ruled that Vioxx should be allowed back on the market, albeit that all drugs in the same class should receive powerful label warnings about potential cardiovascular side-effects.
The Journal says that “[t]his is great news for anyone who might ever have a need for chronic pain management, or indeed an interest in a rational regulatory environment for all future drug development. And it’s a well-deserved rebuke to the nexus of trial lawyers and journalists who whipped up such disproportionate hysteria about the Cox-2s last fall.”
They also praise acting FDA Commissioner Lester Crawford, who allowed 3 days of open hearings on the issue, where everyone, including Cox-2 critics, were given a fair hearing. Ultimately, however, “decisions about the risks and benefits of Cox-2s and other drugs should almost always rest with doctors and patients, not Washington bureaucrats.”
F.D.A. Moves Toward More Openness With the Public
Gardner Harris, The New York Times, 2-20-05
The FDA advisory committee meeting on COX-2 inhibitors and other older painkillers was not, perhaps, as explosive as some had expected. Harris praises the agency for adopting a culture of openness, and allowing disagreements within the agency—particularly between staffers who guide the drug approval process and those who monitor patient safety, to be aired in public.
“These changes were not voluntary. The F.D.A. has been forced by a series of embarrassing scandals over the past year to transform its “Daddy knows best” culture. An unrelenting investigation by Senator Charles E. Grassley, Republican of Iowa, has made creating a new agency culture a matter of political survival. The new secretary of health and human services, Michael O. Leavitt, has championed the changes, promising to bring “transparency” to the agency, a vow echoed by Dr. Lester M. Crawford, the agency’s longtime acting chief who was nominated this week as permanent commissioner.”
Transparency is important for other reasons as well—namely a patient’s right to control their own health care decisions. As patients learn more about prescription drugs, they will increasingly understand that no drug is completely safe, and that they need to become more active participants in their own health care.
As they become more comfortable with that control, they will be less prone to panic whenever a rare drug interaction or adverse effect surfaces. More transparency at FDA is more than welcome in an age of consumer driven health care, and FDA regulation should adapt accordingly to ensure that more power and control—along with better information—is passed along to patients and their doctors.
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer
Yixin Wang, The Lancet, 2-23-05
Researchers in this study hoped to use “genome-wide measures of gene expression” to “identify patterns of gene activity that [can] subclassify tumours” and hopefully provide clinicians with better ability to target specific treatments in patients with lymph-node-negative breast cancer. The researchers used Affymetrix Human U133a GeneChips, to analyze “the expression of 22,000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment.
They found that “in a training set of 115 tumours” they were able to identify “a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years…even when corrected for traditional prognostic factors in multivariate analysis. The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients..87 postmenopausal patients…and 79 patients with tumours of 10-20 mm…a group of patients for whom prediction of prognosis is especially difficult.”
They conclude that “the identified [gene] signature provides a powerful tool for identification of patients at high risk of distant [tumor] recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.”
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