Drug Safety System is Broken, a Top F.D.A. Official Says
The New York Times, 6-9-05
There are several articles on drug safety this week, leading off with this one.
The FDA’s current drug safety system is a bit like the World War II era French Maginot line. Lots of very intensive, expensive, time-consuming testing before a drug is allowed on the market. But once you get past drug approval, the FDA’s voluntary MedWatch system may only capture 10% of all adverse events.
Dr. Janet Woodcock, deputy commissioner of operations at the FDA, discussed this problem at an advisory board meeting at the Institute of Medicine, which the FDA has asked to review its safety procedures.
[She told the] medical advisory board on Wednesday that the nation’s drug safety system had “pretty much broken down” and that there was room for “a lot of improvement” in the government’s approach to uncovering dangers in drugs already on the market. …
“The keystone of the current system is the prescriber, and that person is the one who decides if the benefits of a drug outweigh the risks for that patient,” Dr. Woodcock said. “This system has obviously broken down to some extent, as far as the fully informed provider and the fully informed patient.” [Ed: emphasis added]
The Maginot approach fails primarily for two reasons. First, there is no way to discover all of a drug’s potential side-effects before it is allowed on the market without bringing drug development to a halt. Second, doctors are too pressed for time to expect them to report any but the most serious adverse events.
This is not to say that doctors should have less discretion using medicines; perhaps half of all prescriptions in the U.S. are for “off-label” use, a practice that undoubtedly saves lives. We need to retain flexibility and initiative for physicians while systematically capturing more information on drug use and side effects.
Dr. Woodcock thinks that what the agency needs to do is to “improve systems for learning about problems with drugs on the market,” and “take advantage of electronic health records from managed-care organizations.” In other words, the pharmaceutical market is a vast repository of information that can be tapped if we just put the right automated systems in place and focus on disseminating that information to physicians and patients.
We don’t need a Maginot line to protect the public—we need modern information “warfare” against disease, where we send the right drug to the right place at exactly the right time.
U.S. to Develop Retrieval System for Medical Data
Wall Street Journal, 6-6-05
Drug safety, as we noted above, could be greatly improved through the advent of electronic health records. Today, for instance, doctor’s records are largely maintained with pen and paper—which greatly limits their utility in everything from detecting side effects to improving disease management strategies. Thankfully, the current administration understands the importance of bringing health care into the 21st century.
President Bush has said he wants most patients to have electronic records within the next 10 years, in an effort to reduce costs and medical errors…. Administration officials said they were wary of a plan that would have the government deciding the rules for how health-information technology will operate. They also said they wanted a gradual implementation process that would be market-sensitive.
Health and Human Services Secretary Mike Leavitt announced this week that “his department is setting up an advisory panel, with government and private-sector members, to guide national efforts to adopt health information technology,” and is “soliciting outside entities to agree on data-sharing standards and create a private certification-and inspection system for medical-records.” With any luck, other market forces, like the spread of Health Savings Accounts and growth of new “smart drugs” tailored to a patients’ genetic background will help speed the adoption of electronic records.
Some drug prices go up after rivals leave market
USA Today, 6-6-05
Some consumer groups habitually decry pharmaceutical prices at the same time that they call for more stringent FDA regulation and for fewer prescription drug approvals in general.
As any economist will tell you, however, increased regulatory costs and reduced market access for new products or competitors is a recipe for higher prices, not lower ones. For instance, New York City has rent control and rent stabilization policies that artificially control rental prices, along with some of the most convoluted zoning and building codes in the country. The result is that (outside of existing rent controlled housing) government regulations drive housing and construction costs up, which then leads housing advocates to call for more government regulation. Ironically, regulations that are meant to control prices do exactly the opposite.
The FDA’s approval process isn’t, of course, designed to control prices, but its regulations do drive up costs and limit competition. Companies that manage to bring a product to market must recoup their enormous up-front investment costs and charge accordingly. Take the following observation about current drug prices:
Wholesale prices for leading multiple sclerosis drugs Avonex and Copaxone jumped in May by 8% and 9.4%, respectively, their makers confirmed Friday. In February, sales of MS drug Tysabri were halted after several users contracted a rare brain infection.
Retail prices for painkiller Mobic rose 7% to 11%, depending on the dose, from September through early March, says Consumer Reports. Last September, rival Vioxx was withdrawn from the market because of cardiovascular risks. Other painkiller prices also rose. Prescription-strength Motrin was up 3.9% to 13.3%, depending on the dose, says Consumer Reports. It analyzed retail sales data from market researcher NDCHealth.
Al Heaton, pharmacy director at Blue Cross and Blue Shield of Minnesota, said that “I have never seen a price decrease for other (drugs) when one rival comes off the market.”
The solution to this problem is not to cap prices, but to bring more rivals into the market by streamlining FDA regulations. After all, prices are signals to producers to bring new products to market. Higher prices in one sector will lead companies to shift their investments to those indications (e.g., for multiple sclerosis, cancer, etc), producing more options for patients and physicians. Insurers can also leverage product competition to bargain for lower prices. Even in pharmaceutical markets, competition is still the best solution for improving consumer welfare.
Casting a new light on healing; Low-level laser therapy shows potential in repairing damaged organs and tissues
Los Angeles Times, 6-6-05
Star Trek style medicine may be closer than you think. Researchers are investigating the possibility that certain wavelengths of laser light can promote healing in many types of injuries, perhaps even for nerve and spinal cord damage. One researcher, Juanita Anders, has been studying the process for nearly a decade.
She has found that in rats, laser therapy can repair severed spinal cords, allowing once-injured animals to walk again. "It's remarkable," said Georgetown University researcher Kimberly Byrnes, who collaborated with Anders on the research. It was conducted in Bethesda, Md., at Anders' lab at the Uniformed Services University, the U.S. military's medical school. "We got significant growth across the injury," Byrnes adds.
Anders and Byrnes aren't the only ones coming up with promising laser results. Small groups of researchers scattered across the globe are testing the lasers on a range of ailments, including heart attacks, nerve injuries and internal wounds.
"This has the potential to change medicine," said Dr. Harry Whelan, a neurology professor at the Medical College of Wisconsin who experiments with lasers in treating serious eye injuries.
Medicare’s Will May Be FDA’s Way
Los Angeles Times, 6-5-05
The FDA is currently in discussion with Medicare to use its enormous database of prescription drug records to spot rare side effects.
…the FDA's current system of voluntary reporting picks up no more than 10% of serious drug reactions. To help shrink the knowledge gap, Medicare head Mark McClellan, a doctor and an economist who once ran the FDA, has proposed a Medicare-based system to track the safety and effectiveness of medications.
McClellan proposes taking billing data from the prescription program, which will begin in January, and combining it with healthcare information already collected when Medicare users submit claims for hospital and doctors' care. By cross-referencing the information, a computer system could spot signs of trouble.
Patients' personal information would be protected, but the data pool would be so large that problems could be much easier to detect than they are now, he said.
The real challenge will be ensure that the Medicare information is detailed enough that the FDA can separate drug safety issues from the random noise in the Medicare population—for instance, when a 75 year old smoker has a heart attack, was it from the smoking or from the four prescription drugs he was taking? If they can surmount this hurdle, the system will quickly become valuable resource.
Study Suggests Gene Tests Could Ease Use of Anti-Clotting Drug
The New York Times, 6-2-05
Researchers announced this week the discovery of a gene that influences how patients metabolize the blood thinning drug Coumadin (warfarin), “which an estimated two million Americans take each day to help prevent blood clots because of problems like a heart attack, an abnormal heart rhythm, a stroke or major surgery.”
Establishing a proper dose of warfarin as patients start taking the drug is one of the peskiest problems in medical practice. In picking a first dose, doctors consider factors like the patient's age, sex and medical history. Then the doctors rely on costly blood tests that must be repeated frequently over a period of months to adjust the dose to ensure that the drug will work safely. Misjudgments in doses can critically affect the clotting mechanism, leading to potentially fatal bleeding.
Researchers “[analyzed] the genetic makeup of patients taking warfarin in clinics at the University of Washington in Seattle and Washington University in St. Louis and found that they fell into three dosing groups - low, intermediate and high.” The “genetic variations identified in the study correlated with the grouping, suggesting the findings hold promise for simplifying warfarin therapy” if a new genetic test could be developed that would help doctors prescribe the best possible dose quickly and easily.
Follow-up safety testing lags for FDA "fast-track" drugs, study finds
The Seattle Times, 6-1-05
U.S. Representative Edward Markey (D-Massachusetts) claims that the FDA’s accelerated approval program is “broken and failing to ensure patient safety.” Accelerated approval is an FDA initiative designed to give drugs suffering from serious and life-threatening diseases quick access to promising drugs. In return for accelerated approval and market access, companies must agree to complete studies confirming the medicines’ safety and efficacy. Markey, however, has issued a report challenging the FDA’s management of the program.
The government's “fast track” system that makes new medications quickly available to treat the deadliest illnesses has become a route for companies to market drugs without fully proving their effectiveness or safety, either before or after they go on the market…companies have completed slightly more than half of the post-market clinical studies they pledged to conduct, the report found.
Dr. Scott Gottlieb, a former FDA official, took a dim view of Markey’s report on his website, www.FDAinsider.com:
…Rep Markey’s model is off. He includes in his analysis studies unrelated to the accelerated approval program, which overstates the findings of his paper.
The larger problem here is also one of math – not only Rep Markey’s analysis but also the FDA’s own statistical methods.
The biggest reason why companies are unable to complete post-market studies after drugs are approved through the accelerated pathway, is that all of these drugs treat life-threatening disorders (they have to in order to qualify for accelerated approval) and dying patients are unwilling to roll the dice on a placebo controlled trial – taking a chance they may get little more than a sugar pill – when the drugs are readily available on the market.
For these reasons, companies have a hard time enrolling these studies, or often need to conduct them overseas, in countries where the new drugs aren’t available yet.
Autoimmune Diseases: Trying to Shut Off the Body’s Friendly Fire
The New York Times, 5-5-05
As we mentioned above, physician autonomy in how they prescribe drugs often saves lives and contributes to the progress of medical knowledge.
Take, for instance, autoimmune diseases like lupus. Lupus is a frightening disorder where the body is torn apart by in a biological civil war that can cripple or kill those it afflicts. According to the NIH, there are 80 known autoimmune diseases that afflict between 14 and 22 million Americans. Unfortunately,
Little is definitively known about the causes of autoimmune diseases or how to treat them. It has been more than 30 years since a new drug was approved for lupus, for instance, and the existing drugs have severe side effects. But scientists are now using genetics and biotechnology to gradually unravel the mind-boggling complexity of the immune system.
In the meantime, patients and physicians struggling with lupus often must make due with medicines used “off-label”—i.e. drugs that are used to treat other illnesses and that are not specifically FDA-approved for that disease. This strategy buys time for researchers to expand their understanding of the disease and develop more targeted therapies.
The Wall Tumbles
Grace-Marie Turner, Galen Institute, 6-9-05
The Supreme Court of Canada has overturned a Quebec law denying patients the right to purchase private health insurance. Turner recounts the context of the decision and predicts that it will have a ripple effect throughout Canada.
The equivalent of the Berlin Wall came tumbling down in Montreal today as the Supreme Court of Canada struck down a Quebec law that had banned private health insurance for services covered under medicare, Canada's socialized health care program.
"This is indeed a historic ruling that could substantially change the very foundations of medicare as we know it," Canadian Medical Association president Dr. Albert Schumacher said after the ruling. …
Liberals in the U.S. that admire the Canadian health care model should take note of the Canadian court’s ruling that Canada’s “right” to health care amounts to a right to wait in line.
FDA Disappoints Lung Transplant Patients
Dr. Scott Gottlieb, Forbes, 6-8-05
Gottlieb notes that criticism of the FDA is expected by the FDA’s internal reviewers, who have some insulation from political pressure. The FDA’s outside advisory committees, on the other hand, are much more likely to hedge their recommendations to protect themselves from public criticism.
…a series of lopsided votes from the agency's outside advisory committees to turn down otherwise promising new drugs leaves the overwhelming impression that the criticism has cast a darker shadow of caution over these outside advisors than even over rank-and-file FDA staff.
The latest came on Monday with a stunning split decision on an effective new medicine called Pulminiq to prevent rejection in lung transplant recipients, a condition that is fatal in more than half of all cases once the malady sets in.
That the advisory panels would be the first to grow skittish seems to make sense. It is one thing when the media and Congress go after rank-and-file FDA reviewers and agency hands. Most people who work at the FDA expect the criticism, and there are many institutional protections built into the agency that shield its professional staff from gratuitous attacks.
But members of the FDA's outside advisory committees, who are drawn from the ranks of academic medicine, are rewarded for serving only by the enhancement to their reputation, and don't have similar protections or expectations.
Unequal care troubles CEO
Tom Walsh, Detroit Free Press, 6-7-05
Walsh recounts an interview with Pfizer CEO Hank McKinnell, the author of the new book “A Call to Action: Taking Back Healthcare for Future Generations.” Walsh notes that,
One of McKinnell’s more provocative arguments is that too many Americans are over-insured. That's right, over-insured -- not uninsured or under-insured. ‘We need to approach health insurance just as we approach other insurance in our lives. It's not for everyday expenses. Nobody has automobile insurance that pays for oil changes,’ he said.”
The WHO: A Time for Reconstitution
Richard E. Wagner, Campaign for Fighting Diseases, 6-1-05
Wagner criticizes the WHO for spending much of its budget on politically correct but medically dubious causes that have little, if any, impact on health in developing countries.
In a world in which life-expectancy is increasing as a result of rising personal prosperity, one would expect the WHO to devote its limited budget to the trans-boundary diseases which pose the greatest threat to global health.
While this should include threats such as avian flu, it must also include diseases like AIDS and malaria, which disproportionately affect the poor.
Instead, the WHO is throwing money at the modish obsessions of western health bureaucracies, ranging from road safety to blood pressure. Its self-appointed remit is so broad that it is surprising they don't yet have a global initiative to stop children from running with scissors.
[Wagner’s analysis] of the WHO's budget for 2006-7 reveals that the agency focuses far too much on non-communicable diseases - such as high blood-pressure and psychiatric health - and not enough on AIDS, malaria and other communicable diseases of the poor. Unsurprisingly, most of this money is swallowed up by bureaucracy, bloated salaries and public relations.
Effect of VKORC1 Haplotypes on Transcriptional Regulation and Warfarin Dose
Mark J. Rieder, Ph.D., Alexander P. Reiner, New England Journal of Medicine, 6-2-05
This study documents how the researchers (mentioned above) identified the genetic variation that appears to be responsible for how warfarin is metabolized differently in different patients (and even different ethnic groups). Researchers
…conducted a retrospective study of European-American patients receiving long-term warfarin maintenance therapy. Multiple linear-regression analysis was used to determine the effect of VKORC1 haplotypes on the warfarin dose. We determined VKORC1 haplotype frequencies in African-American, European-American, and Asian-American populations and VKORC1 messenger RNA (mRNA) expression in human liver samples.
We identified 10 common noncoding VKORC1 single-nucleotide polymorphisms and inferred five major haplotypes. We identified a low-dose haplotype group (A) and a high-dose haplotype group (B). The mean (±SE) maintenance dose of warfarin differed significantly among the three haplotype group combinations…
VKORC1 haplotype groups A and B explained approximately 25 percent of the variance in dose. Asian Americans had a higher proportion of group A haplotypes and African Americans a higher proportion of group B haplotypes. VKORC1 mRNA levels varied according to the haplotype combination.
The management of warfarin therapy is complicated by a wide variation among patients in drug response. Variants in the gene encoding vitamin K epoxide reductase complex 1 (VKORC1) may affect the response to warfarin…. VKORC1 haplotypes can be used to stratify patients into low-, intermediate-, and high-dose warfarin groups and may explain differences in dose requirements among patients of different ancestries.
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