In the Spotlight
Innovative approaches to relief
Robert Goldberg, Ph.D., Washington Times, 1-12-05
Sir Harold Evans wrote that innovation is the distinguishing American quality. Nowhere is this more evident than in the American response to the tsunami tragedy. Last week the massive relief operation for tsunami-hit areas in Aceh, Indonesia, which is Ground Zero for the tragedy, was on the brink of chaos. No one was in charge of directing the distribution of aid. With tons of food rotting in storage facilities, the flow of aid came to a halt altogether when a Boeing 737 cargo plane hit a stranded water buffalo and skidded off the runway at Sultan Iskandar Muda airport, the hub of humanitarian programs for Aceh.
Continue reading . . .
No Pain, Some Gain: New drugs aimed at specific neuron targets promise relief from chronic agony
Business Week, 1-17-05
If you needed any more evidence that the current Vioxx debacle is already slowing new drug development and hurting patients, here it is: the FDA has just approved two new drugs for treating pain that work in completely novel ways, but “both Prialt and Lyrica went through a far lengthier and costlier development process than originally expected. The struggles by Elan and Pfizer to get these two pain medicines on the market highlight the immense difficulties that beset the entire field of pain research and treatment.”
For the “50 million Americans suffering from chronic pain,” news that companies may be scared away from doing new research on pain relief medications adds insult to injury. As the FDA becomes more risk averse, drugs like Prialt and Lyrica are likely to only be approved for very narrow groups of patients, making the field substantially less lucrative for pharmaceutical and biotech companies.
Why is this a problem? “The lack of a giant payoff could be a problem for future analgesics,” given the enormous costs of drug development and potential legal liabilities. Still, said one researcher, “new drugs are desperately needed…We are not covering groups of patients with very resistant pain.” Currently, “medical studies routinely find that at least 40% to 50% of patients are undertreated for chronic pain, defined as pain that lasts more than three months.”
Chemotherapy Gets Re-Engineered - Cancer Drugs Are Modified In an Effort to Cut Toxicity And Increase Effectiveness
Wall Street Journal, 1-11-05
In addition to new biotech drugs that target and kill cancer cells but leave healthy cells untouched, older chemotherapy treatments are being reformulated with new delivery methods that researchers hope will make them less toxic and more effective. “The first such drug won approval from the Food and Drug Administration Friday. Abraxane…is a version of the widely used breast-cancer chemotherapy Taxol, known generically as paclitaxel.”
Abraxane uses a “natural human protein called albumin” to deliver paclitaxel in the human body and “appears to sidestep some of Taxol’s more serious side effects.”
More research will be needed to discover if Abraxane also offers a survival benefit to cancer patients, but even if it doesn’t the reduced side effects and easier administration are a real boon for chemotherapy patients. “From an economic and convenience standpoint, [Abraxane] appears to have some advantages…If it turns out to be more efficacious [than Taxol], so much the better.”
Health Savings Accounts Off to Slow Start
The New York Times, 1-11-05
This article reports on a survey finding that “most people are wary of [Health Savings Accounts] because they do not want to risk having to spend more on their medical bills.”
“Less than a third of workers with insurance have heard about [HSAs], according to a random survey of 1,000 people by Watson Wyatt, a benefits consulting firm based in Washington. After hearing the plans described, 66 percent said the prospect of paying the full price of prescription drugs until the coverage kicked in seemed extremely undesirable, and 57 percent said that they did not want to pay higher deductibles at all. The annual deductible for family coverage is $2,000.”
Of course, without knowing how the HSAs were “described” – or who funded the survey for that matter - it is hard to evaluate how seriously to take its findings. For instance, according to the Kaiser Family Foundation, “The typical family health insurance policy now costs $9,068 per year, with employers on average paying 73 percent and employees paying 27 percent.” For the “typical” policy, this means about $2,448 in out of pocket costs, more than the annual HSA deductible.
In other words, just having a higher deductible doesn’t mean that families would be exposed to higher overall annual costs – indeed, they are more likely to be lower. And when you add in the fact that many companies subsidize employee contributions into HSAs, it is hard to believe that the high deductible would amount to much of a hurdle.
The survey also notes that HSAs allow workers to “keep any unspent balance from year to year and take it along if they change jobs,” which 84% of the people polled said “were important features.”
Overall, the outlook for HSAs is bright, especially if additional reforms are added – such as making a national market for health insurance, requiring mandatory purchase of health insurance, and creating risk adjusted subsidies for low-income citizens.
Painkillers: The Misadventure Continues
Washington Post, 1-11-05
“A new study shows that regular use of…traditional nonsteroidal anti-inflammatories drugs (NSAIDs) [like aspirin, ibuprofen, or naproxen] substantially increases risk of ulcers and bleeding in the small intestine.”
Although the study is very small, it lends weight to what we already know about older NSAIDs and the associated health risks. “David Graham, a gastroenterologist at the Michael E. DeBakey VA Medical Center in Houston, had 21 regular NSAID users and 20 people who used either [Tylenol] or nothing to treat their arthritis pain swallow endoscopic cameras. Resulting pictures showed that 71 percent of NSAID users suffered small intestine injury. Only 10 percent of the control group had such injuries, and theirs were comparatively minor. None of the participants in the study…showed or felt outward symptoms of the intestinal problems.”
The study’s findings underscore the reality that no drug – even the ones sitting in your medicine counter at home – is totally safe. It is, however, possible to maker safer drugs if we continue to invest in medical innovation. Unfortunately, we have become so inured to the risks from older medicines, and so outraged at companies producing new medicines, that we are undermining the discovery of better, safer drugs.
Company of the Year Biotech Behemoth Long a two-hit wonder, Amgen is on the brink of a research renaissance that will target cancer, diabetes and more.
Amgen is one of America’s first biotech companies, and a case study in the power of market competition to drive innovation and medical progress. Forbes recognizes that at first glance Amgen is an unusual choice for Company of the Year. The biotech giant “hasn’t produced a big seller in a new category since 1991,” and remained focused for many years on only two categories of treatments, anemia and cancer care.
However, as a result of persistent competition and market pressures the company has diversified and restructured its development pipeline in recent years and now has “40 drugs in preclinical or patient trials, more than at any time in the company’s history and up from only 22 during the entire 1990s.”
The genius of the market is that inefficient or lazy companies are eventually driven out of business. In order to remain successful, biotech firms have to continuously joust for the best scientific talent and scarce investment dollars – ensuring that America’s pipeline for innovative new medicines never runs dry.
After all, there will always be another biotech start-up looking to become Forbes’ next Company of the Year.
New Test May Detect Parkinson's Early, Aid Search for Drugs
Wall Street Journal, 1-7-05
A new speech test may enable doctors to identify Parkinson’s patients years before the disease has killed enough brain cells to express its classic symptoms: “trembling in the limbs, difficulty controlling movement, and…paralysis.”
The test, developed by Pfizer, “[analyzes] how people speak”, since areas of the brain controlling small muscles, like vocal chords, are affected before those controlling larger muscle groups involved in walking. If additional studies validate the speech analysis test, physicians will have access to a simple, relatively inexpensive method of diagnosing Parkinson’s patients before irreparable harm is done, and can use the test as a screen to measure the efficacy of new potential treatments.
“As things stand now, the lack of a standard test for Parkinson’s, like blood sugar for diabetes, stymies efforts to gauge the effect of experimental drugs.”
A Quandary in Good News
The New York Times, 1-7-05
The revelation that C-reactive protein [CRP] is a biomarker for heart disease has thrown another strand into the already tangled web of data on Cox-2 inhibitors like Vioxx and Celebrex. This is because while some Cox-2 drugs are under suspicion for possibly raising heart attack and stroke risk for some patients, they are also anti-inflammatory drugs that have been shown to lower CRP levels.
“For example, Vioxx, which was pulled from the market in late September because of those risks, had been found in a study just a month earlier to cut CRP levels in half, from the danger zone to a level considered excellent. Celebrex, still on the market but linked to an increased risk of heart attack, has also been found to lower CRP levels.”
What are we to make of these findings? Nothing, yet. The problem physicians, regulators and patients face is that clinical trials usually only focus on a very narrow range of clinical data and outcomes. Untangling the full relationship between anti-inflammatories and heart disease won’t happen until we design better clinical trials that collect baseline genetic data at the individual level and correlate it with biomarkers like CRP and cholesterol. Then we can track responses to different treatment regimens, including Cox-2 inhibitors or statins, and pinpoint the mechanisms behind different adverse drug events or health improvements.
This will allow us to build a bottom-up picture of heart disease and drug treatment, as opposed to the confusing hodge-podge of isolated facts bombarding us now.
Two Studies Suggest a Protein Has a Big Role in Heart Disease
The New York Times, 1-6-05
Scientists have discovered a new biomarker that may play a critical role in the development of heart disease – perhaps an even more central role than that currently attributed to cholesterol. “Reducing the levels of [C-reactive protein or CRP] secreted by the body may be as powerful a tool in slowing heart disease and preventing heart attacks and cardiac-related deaths as lowering cholesterol, two teams of researchers are reporting today.”
The studies, published in The New England Journal of Medicine, followed “patients with severe heart disease who were taking high doses of statin drugs, which reduce both cholesterol and CRP. Lower CRP levels, the researchers found, were linked to a slower progression of atherosclerosis and fewer heart attacks and deaths.” Most notably, “this effect was independent of the effect of lowering cholesterol.”
While more research is needed to understand the direct role, if any, CRP plays in heart disease, some cardiologists are already recommending that CRP levels be measured in addition to cholesterol. Said one researcher: “There is a huge payoff if doctors understand that they need to test not just for cholesterol but also for CRP. . . . That alone will save tens of thousands of lives right there.”
Richard A. Epstein, Legal Affairs, 2-1-05
Richard Epstein, a senior fellow at the Hoover Institution, reviews two books on the pharmaceutical industry, both by former editors in chief of The New England Journal of Medicine, Marcia Angell and Jerome P. Kassirer. Both authors are ardent critics of the pharmaceutical industry and the FDA, and advocate much more extensive regulation of how drugs are developed and marketed in the U.S. Epstein, however, takes them to task for straying beyond their true expertise.
“Angell, a pathologist, and Kassirer, an internist, aren’t writing about medicine. They are writing about complex social institutions in which it is not possible to have all good things simultaneously. You can’t get new drugs to market if you make them freely available. And you have to absorb some risk of injury to push needed drugs through the FDA process.”
Concludes Epstein: “Their inability to grasp fundamental economic principles about market incentives, gains from trade, the time-value of money, and the importance of innovation leave the authors open to easy attack.”
The New Heart Disease Threat
The New York Times, 1-11-05
The New York Times acknowledges that “[t]he evidence has gotten much stronger that a substance known as C-reactive protein [CRP] may be every bit as important as cholesterol in the diagnosis and treatment of heart disease” in light of two studies recently published in the The New England Journal of Medicine. The studies have also “shown that drugs that reduce the levels of that protein in patients with severe heart disease can slow the progression of atherosclerosis and prevent heart attacks and cardiac related deaths.”
We would also add that the flurry of studies on different statins, and new discoveries on the underlying biology of heart disease are being funded by pharmaceutical companies eager to prove the utility of their medicines – and profit by it.
A perfect match between the market and medical progress.
No Black and White Answers
James K. Glassman, Tech Central Station, 1-10-05
In the struggle against AIDS in Africa, there is a growing dispute over whether or not generic copies of AIDS medicines are as safe and effective as the original brand name drugs on which they are based. On the one hand, there is the World Health Organization (WHO), the Global Fund to Fight AIDS, Tuberculosis, and Malaria, and groups like Doctors Without Borders, which claim that the WHO approved generics are as safe and effective as any branded drugs used in wealthy countries.
On the other hand, there is a growing chorus of skepticism from groups like the Hudson Institute, the American Enterprise Institute, and others who note that, as James Glassman does here, “the WHO list [of approved drugs, including generic AIDS drugs] is maintained by a tiny staff with no facilities for testing, and the WHO does not warrant safety or effectiveness. Drugs that do not meet even these standards are now floating all over Africa, with no means of recall.”
The U.S has established a process at the FDA for fast tracking approval of combination generic AIDS drugs (in as little as six weeks) but to date “none of the copy drugs has been approved, and the FDA will not say if any have been submitted.” At the same time, “since June, 18 Indian-made ARVs that were once listed by WHO as pre-qualified for use in relief programs were removed by the United Nations agency or voluntarily by the manufacturers—Ranbaxy, Cipla and Hetero.”
This is not just an ivory tower dispute between academics over whose authorization counts: “a flood of untested generics…could lead to widespread misuse and eventually to drug resistance [in strains of the AIDS virus], eradicating years of progress.”
There is some additional reason for concern as well, since the UN is under tremendous pressure to fulfill its commitment to treat 3 million AIDS patients by 2005 – a goal that it will almost certainly miss. UN officials are also desperately eager to salvage its reputation after the massive oil-for-food scandal.
The underlying question is whether the UN is approving untested, and possibly dangerous generic drugs to salvage its own reputation. Perhaps it isn’t and these drugs will turn out to be every bit as safe and effective as claimed.
But it is disturbing that no one is asking hard questions and demanding clear answers.
After all, we can be sure that if an American company and the FDA had approved these drugs for use in Africa, and then suddenly withdrew them, there would be an international hue and cry.
An Overdose of Ads
The Boston Globe, 1-6-05
This editorial notes that the Vioxx debacle was fueled by the popularity of the drug, i.e. it was certainly prescribed and used by a larger population than was necessarily appropriate given its safety profile and indications. “Vioxx became such a big seller even though it was designed for a specific group of mostly older patients with a risk of gastro intestinal problems because Merck peddled it in a highly successful mass-media campaign using skater Dorothy Hamill.” While there are no indications that Merck knowingly exposed patients to a drug it thought was dangerous, the business model Merck pursued – the blockbuster model – created the tsunami that is now threatening to destroy it.
In the future, companies will have to pay much closer attention to how they market drugs, and use genetic screening, datamining and physician education to match drugs more precisely with patient profiles.
In the short run this may that fewer drugs are used by tens of millions of people, but in the long run it will also allow companies to demonstrate efficacy and cost-effectiveness and develop a safety track record that will reassure patients, physicians, and regulators that America’s drug supply is every bit as safe and effective as advertised.
How Technocrats are Taking Over the Practice of Medicine: A Wake-Up Call to the American People
Twila Brase, Citizens Council on Health Care, 1-1-05
This report criticizes the development of “evidenced based medicine” (EBM) as an initiative that “involves a technocratic takeover of the practice of medicine through health data collection, guideline creation, intrusive clinical surveillance, pay-for-performance strategies, and centralized medical decision making.”
Brase is concerned that, once implemented, EBM “will lead to a limited list of approved health care services…as determined by the agendas and values of a small cadre of politically motivated, personally biased individuals sitting around a table making treatment decisions far from the patient’s bedside.”
C-Reactive Protein Levels and Outcomes after Statin Therapy
Paul M. Ridker, M.D., New England Journal of Medicine , 1-6-05
This study “evaluated relationships between the LDL cholesterol and [CRP or C-reactive protein] levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infarction or death from coronary causes among 3,745 patients with acute coronary syndromes.”
The study found that patients in whom “statin therapy resulted in LDL cholesterol levels of less than 70 mg per deciliter (1.8 mmol per liter) had lower event rates than those with higher levels. . . . However, a virtually identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels (2.8 vs. 3.9 events per 100 person-years, P=0.006),” regardless of the overall level of LDL cholesterol.
The study concluded that patients “who have low CRP levels after statin therapy have better clinical outcomes than those with higher CRP levels, regardless of the resultant level of LDL cholesterol. Strategies to lower cardiovascular risk with statins should include monitoring CRP as well as cholesterol.”
Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease
Steven E. Nissen, M.D., New England Journal of Medicine , 1-6-05
Researchers in this study “performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up.”
Overall, the study found that “the mean LDL cholesterol level was reduced from 150.2 mg per deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at 18 months…and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole…but not in either treatment group alone.”
The researchers concluded that “for patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP."
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