Roche Dealt Setback in Epo Patent Wars

The U.S. District Court in Boston ruled against Roche in an erythropoietin patent dispute yesterday, dealing a temporary setback to that company's ongoing effort to bring competition to the U.S. EPO market. The full trial opens next week. Amgen holds the exclusive patents for EPO, which don't begin running out until August 2012, according to the company's filings with the Securities and Exchange Commission.

This case ought to cause some head scratching on Capitol Hill, which can't seem to get it together to pass a law allowing generic companies to make biotechnology drugs. Epogen received approval from the Food and Drug Administration in 1989. In 2012, the company will have had 23 years of post-approval market exclusivity. That's three years longer than the maximum allowable length of patent terms under U.S. law.

The Other Surge: The Uninsured

The Census Bureau reports that more than two million Americans joined the ranks of the uninsured last year, whose ranks reached nearly 47 million. There were over 8.6 million uninsured children, a 600,000 increase over 2005. All the more reason to pass S-CHIP . . . without the unnecessary earmarks.

The Most Costly Earmark in S-CHIP

Two weeks ago, a front page story in the New York Times revealed that House version of the children’s health insurance bill had secretly funneled hundreds of millions of dollars to favored hospitals – a violation of the Democrats’ pledge to remove the shroud of secrecy surrounding earmarks. The story was alarming because it provided additional ammunition to a Bush administration that was already ideologically opposed to expanding the program that provides government-run health insurance to millions of uninsured kids.

Last week, I learned that the bill contains another unheralded earmark, also unrelated to children’s health. This one, too, funnels hundreds of millions of dollars to special interests. And unlike the hospital earmarks, which were a mere raid on the treasury, this earmark, given the Orwellian name “Quality Incentive Payments in the End Stage Renal Disease Program,” will subject hundreds of thousands of Americans on dialysis to unnecessary risk, and will in all likelihood lead to premature deaths.

The legislation earmarks up to $300 million over the next three years for clinics that achieve certain quality benchmarks while treating the more than 300,000 Americans with failed or failing kidneys who receive dialysis through Medicare’s End Stage Renal Disease (ESRD) program. Chief among those benchmarks is correction of the anemia associated with failing kidneys. The payments will go to clinics that raise 92 percent of their patients to a red blood cell count that’s at least 33 percent of blood volume (or a hemoglobin count of 11 grams per deciliter).

The measure gives clinics a powerful incentive to continue using large quantities of one company’s drug – Amgen’s Epogen, which stimulates red blood cell production. The House passed the bill even though the Food and Drug Administration recently issued a black box warning cautioning against overuse and the Center for Medicare and Medicaid Services rewrote its reimbursement guidelines to limit payments for overuse of the drug.

Recent studies have shown that raising red blood cell counts over 12.5 grams per deciliter in dialysis and cancer patients increases the risk of heart attacks and premature death. Any clinic that raises 92 percent of its patients above 11 will probably have half its patients above 12 – the maximum allowable level on the FDA black box warning – and a sizable fraction above the 12.5 danger line.

It’s not as if good quality measures aren’t needed in the ESRD program. Despite rapidly expanding costs, the dismal prospects for people on dialysis has not improved over the years: there were still 230 deaths for every 1,000 patient-years of dialysis in 2004 compared to 231 deaths in 1993. No cost grew faster over those years than those for Epogen. When first approved in the late 1980s by the Food and Drug Administration, it was a godsend for dialysis patients since it eliminated the need for blood transfusions.

From the start, there was a debate over how much Epogen was enough. Should the dose be merely enough to eliminate transfusions? Or should the red blood cell or hemoglobin count be raised to near normal levels, which, of course, would require a lot more of the drug?

Amgen funded dozens of clinical trials showing that dialysis patients felt better and had more energy with higher hemoglobin levels. The company deployed a small army of lobbyists to waive that literature around on Capitol Hill and at CMS, which runs the program. They were joined by leaders of the Renal Physicians Association, many of whom had financial ties to Amgen, and patient advocacy groups like the National Kidney Foundation and the American Association of Kidney Patients, which also receive substantial funding from Amgen and the other companies that sell the products used at dialysis clinics.

And, of course, the major dialysis clinic chains, DaVita and Fresenius, joined in the clamor for higher hemoglobin levels. They receive a hefty markup – critics on Capitol Hill referred to them as kickbacks – for every dose of Epogen they administered.

The lobbying paid off. CMS twice raised the allowable hemoglobin levels until it reached 12.5 grams per deciliter. The mean level (50 percent of patients had higher levels; 50 percent had lower levels) rose from 10 grams per deciliter (30 percent of blood volume) in 1993 to 12 grams per deciliter in 2004. Medicare expenditures for Epogen shot up a staggering 115 percent to $1.8 billion between 1998 and 2004, a time period when the dialysis patient population increased by only a third.

What didn’t change, unfortunately, was the mortality rate. Despite the fact that Americans on dialysis were still dying at rates substantially higher than their European counterparts, Amgen continued to fund research that hemoglobin levels near normal (13 or 14 grams per deciliter) would improve outcomes.

The results, much to the company’s dismay, were just the opposite. Over the past year, a series of studies have been completed showing that dialysis patients with hemoglobin levels between 12.6 and 14 had significantly more heart attacks and deaths than patients within the FDA’s recommended dosing level, which is 10 to 12. The results paralleled a series of oncology studies which also showed higher mortality rates for chemotherapy patients given high doses of the drug (though sold in the cancer market as Procrit by Johnson & Johnson, the drugs are identical).

The trial results forced the FDA to act. Last March, the agency slapped a black box warning on both Epogen and Procrit. “Use the lowest dose of Epogen that will gradually increase the hemoglobin concentration to the lowest level sufficient to avoid the need for red blood cell transfusion,” the label warned. Guidelines published by the American Society of Anesthesiologists say blood transfusion are unnecessary when hemoglobin is above 10 grams per deciliter.

In an editorial that appeared last April in the Journal of the American Medical Association, Daniel W. Coyne, a renal physician at Washington University School of Medicine in St. Louis, recommended maintaining hemoglobin levels for dialysis patients between 10.5 and 11.5 grams per deciliter, which meant “rarely” using Epogen when the level exceeded 10 and cutting back by 25 percent if it exceeded his target range. “This management strategy is good for patients, and would be far less expensive for society,” he wrote. “Physicians need to challenge industries that appear to be using patients as profit centers based on bad science.”

Even CMS finally recognized that its long-standing policy of reimbursing for higher hemoglobin levels had to be reversed. In July, it promised to cut payments by 50 percent if dialysis clinics report that a patient’s hemoglobin exceeded 13 grams per deciliter for three straight months.

With sales plummeting, Amgen took its cause to Capitol Hill. In the first half of 2007, Amgen spent over $9 million on lobbyists, nearly as much as it spent in all of 2006 and almost as much as the entire Pharmaceutical Research and Manufacturers Association, which is the industry’s powerful trade group.

Last February, Rep. John Lewis (D-GA) and David Camp (R-MI) introduced H.R. 1193, the Kidney Care Quality & Education Act, which called for a three-year program of additional payments to dialysis clinics for improving quality. However, no benchmarks were contained in the bill. Despite getting 100 co-signers (who’s against higher quality?), no hearings were ever held.

Instead, the House Ways and Means health subcommittee, chaired by Pete Stark (D-CA), a long-time Amgen critic, held hearings in June on anemia management in dialysis. Stark’s ultimate goal is to establish a bundled payment system for dialysis clinics, which would theoretically eliminate incentives for giving excessive amounts of any individual drug since the clinics would then have to pay for it out of their own pockets. But the speakers lineup included just one critic of high use of Amgen’s Epogen.

Alan Kliger of Yale University Medical School and president of the Renal Physicians Association led the charge for continued high use of Amgen’s Epogen. His self-contradictory testimony cited the updated guidelines published by the National Kidney Foundation (without mentioning that 10 of the 18 members of that guideline panel had financial ties to Amgen). Those guidelines called for maintaining patients at hemoglobin levels between 11 and 12 and not going over 13.

But, Kliger testified, “because every patient is unique, when it comes to ESA (erythropoietin stimulating agents like Epogen) dosing, each patient must be considered individually – not in aggregate,” he said. Then, a few moments later, he testified that “Medicare coverage policy should strive to maintain levels in all (emphasis added) patients greater than 11 grams per deciliter, given the ample data disclosing the adverse short and long-term effects to patients with persistent anemia.”

Amgen’s lobbyist army applied the finishing touches. When the children’s health insurance bill emerged on the House floor, it contained the new quality standard: 92 percent of patients should be over a hemoglobin of 11 grams per deciliter to qualify for the additional payments. Officials at CMS refused to comment on whether they had input into establishing this new benchmark. Nor has several phone calls to Amgen lobbyists turned up anyone who will take ownership of the provision.

I emailed Daniel Coyne at Washington University last week and asked him what impact the legislation will have on dialysis patients. “It would be almost impossible to get 92 percent above 11 without getting the mean to 13 or higher,” he wrote me back. “Based on older and recent studies, this would increase the risk of death in patients, have no real benefit otherwise, and probably double Epo use and costs. It also directly violates the FDA package insert which recommends target Hemoglobin to 10 to 12, which means about one-half (of patients) should be 11 or higher in well managed units.”

Increased risk of death. No benefit. Higher costs for taxpayers. The ongoing Epo saga, whose latest chapter is being written on Capitol Hill, is a perfect example of why our health care outcomes are second-rate, while our health care costs are second to none.

Stop Pushing DDT

The following lettter ran in the weekend edition of the Wall Street Journal.

To the Editor:
The Wall Street Journal's editorial position on DDT and malaria remains breathtakingly one-sided ("The Uses of DDT," Review & Outlook, Aug. 16). If you insist on scientific honesty by environmentalists, you should adhere to the same standards. Public health advocates, including environmentalists, supported the public health exception in the U.N. Convention on Persistent Organic Pollutants which allowed use of DDT for control of malaria vectors in developing countries.

Your editorial ignores a wealth of data linking exposure to DDT to human health problems. The most recent of these studies was just published in a peer-reviewed journal of the National Institutes of Health (Environmental Health Perspectives). Published in August 2007, this study is literally the first prospective research examining exposure to DDT early in life and subsequent risk to breast cancer. Women more exposed to DDT prior to puberty were five times more likely to develop breast cancer than those with lower exposure. The authors conclude that "the public health significance of DDT exposure is potentially large."

The final solution to this vexing problem won't be insisting that a pernicious chemical continue to be used. It will involve a host of experts in fields that range from vaccine development to green chemistry, offering economically realistic alternatives to a Faustian choice: death by malaria or illness from chemicals. Serious money will be necessary to make this a reality. If you would get off your pro-DDT hobbyhorse and work together with people who want to solve this problem, it might really happen.

John Peterson Myers
Chief Scientist
Environmental Health Sciences
Charlottesville, Va.

Cancer Docs' Organization Ignores Prevention

The American Society of Clinical Oncology sent out a press release today calling on the presidential candidates to articulate what they will do to further the War on Cancer when they speak at a national forum hosted by the Lance Armstrong Foundation next week. Their list of "demands" includes more money for research, better access to care, more enrollment in clinical trials, training a new generation of oncologists, and equipping the Food and Drug Administration to better evaluate new cancer drugs.

Hey, ASCO! Ever heard of prevention? Where's your call for an expanded war on smoking? How about combating obesity? Those are the two biggest causes of cancers and a sustained war on both would do far more to reduce America's cancer mortality rate than spending billions more on research.

Of course the Democratic candidates should sustain America's already well-funded cancer research establishment, and improve the quality of care for those who have cancer. But if they are actually interested in winning the war, then they might consider promising a $2-a-pack tax on cigarettes to fund further research and a free YMCA membership for any American with body mass index that qualifies as overweight.

Gramsci Is Alive and Well at Yale

The latest New England Journal of Medicine contains an essay by Yale political scientist Jacob Hacker laying out his roadmap for universal health care coverage. His plan, released earlier this year by the Economic Policy Institute, would give Medicare-like coverage to everyone without insurance. He would finance the plan with a tax on employers who fail to provide their employees with private health insurance.

He frames his well-written piece as a critique of Michael Moore's film, Sicko. Moore, he says, calls for "evicting insurance companies and establishing a national health program instead."

It is an appealing vision, in many ways. We could use more populism and less caution in our health care debate. But it is also unrealistic.

Read Hacker's essay here, and see for yourself why most progressives -- even those like myself who support a single-payer national health insurance plan -- will be lining up behind some version of the Hacker plan as the health care debate unfolds. If enacted, it will not only provide universal coverage, it will create incentives for employers to gradually shift their own workers into the public plan and drop private coverage. Over time, Hacker suggests, the public plan will evolve into "Medicare for all," a single-payer system that will make the U.S. -- finally -- more or less like the rest of the civilized world.

For those who don't get the reference in the headline, Antonio Gramsci was an Italian communist, imprisoned by Fascist leader Mussolini from 1926 until his death in 1937. He believed the radicals of his day should push for reforms whose enactment would gradually move a nation toward socialism without violent revolution. The post-war Italian and French Communist parties largely embraced his vision by becoming indistinguishable from pre-war social democratic parties.

Clearly, a latter-day Gramsci is alive and well at Yale. The difference here is that Hacker wants to pull a moribund Democratic Party out of the clutches of the special interests and put it once more on the path of transformational reform.

Cancer Survival Rates Can Be Misleading

The British press is having a field day (see here and here) attacking their single-payer National Health Service in the wake of a new report showing that cancer survival rates in Great Britain are the lowest in Europe. Lancet Oncology, which published the study, editorially called for "a fundamental reassessment of the ways in which the NHS operates."

How bad is cancer care in the home of socialized medicine? The measure used in the Eurocare-4 study was survival among those diagnosed with cancer, which is defined as those diagnosed with the disease who survive five years. Cancer survival rates in England in 2003 were 52.7 per cent for women and 44.8 per cent for men. This lagged behind every other country in the European Union except Slovenia, Poland and the Czech Republic.

Guess who would sit atop the list if part of Europe? It's the U.S., where 62.9 per cent of female cancer patients and 66.3 per cent of male patients survive five years after diagnosis.

But wait a minute. I don't want to know just about survival. I also want to know what my chances are of getting cancer in the first place. It's only when we know both numbers that we get a full portrait of where the greatest risk lies.

International comparisons of incidence are not easily obtainable, but by going to Cancer Research UK and the National Cancer Institute's statistical branch, I was able to compare overall cancer incidence rates in the two countries.

Guess what. Americans contract cancer at a 27 percent higher rate! There were 470 diagnoses of cancer per 100,000 in the U.S. in 2004 compared to just 370 cases per 100,000 residents in the UK. (I also looked up those wine-sipping French with their single-payer, national health care system. They suffered just 309 cancers per 100,000 population.)

The higher rates held whether looking at women or men. Males in the U.S. suffered 556 cases per 100,000 population compared to just 408 in the UK. Females in the U.S. contracted 411 cases per 100,000 versus just 348 in he UK.

And when I looked at a different bottom line -- the annual mortality rate and not the five-year survival rate -- what I found was that the British actually do slightly better than we do with just 182 out of 100,000 Brits dying of cancer each year compared to 192 out of every 100,000 Americans.

A cancer epidemiologist would probably explain the data this way: In the U.S., we conduct far more tests, which turn up many more cancers. That in turn leads to higher survival rates because we wind up treating some cancers at an earlier stage. It probably even saves some lives that otherwise would have been lost to the disease.

But there's a downside to all those tests. They have relatively high false positive rates. In other words, they turn up minor cancers that may never have progressed to full-blown neoplasms. Yet, they are treated anyway since determining which ones will progress is impossible at that early stage.

I also suspect that different patterns of diet, exercise, stress, and toxic exposures account for some of the increased cancer rate in the U.S. But international comparisons on those indicators are even harder to come by than comparative data on cancer incidence rates.

So, yes, the British five-year survival rates from cancer are substantially lower than the U.S. But that's not the whole cancer story. This one study shouldn't be used to condemn Great Britain's National Health Service and its policy of going slow in paying for pricey, marginally effective new cancer therapies.

Health Care Reform's Bleeding Kansas

The fight over state children's health insurance plans (S-CHIP) has become the bleeding Kansas of the coming war over health insurance reform. All the papers this morning are reporting the Bush administration's Friday night "sacking of Lawrence" that severely restricted the number of poor kids that state programs can cover. As this New York Times story notes, the 1997 law creating the program specifically stated that S-CHIP programs can't be designed to substitute for private insurance. Sounds suspiciously like the 2003 drug benefit, which put insurance companies in charge of administration. The new rules sent out to state administrators late Friday would, among its crueler provisions, impose a one-year waiting period for children in near-poor families without insurance. Will the liberals in Congress who passed the S-CHIP expansion bills in July have a Pottawatomie Massacre up their sleeves when they return from their August break? . . .

Whom Do You Trust?

New York Attorney General Andrew Cuomo, acting in concert with that state's doctors, is challenging Cigna and Aetna for their physician quality rankings, an effort by the health insurance giants to steer families away from lower-ranked docs. Cuomo alleges its more about costs than quality since insurers having an obvious conflict of interest. They'd prefer patients go to low-cost providers, his spokesman says in a story in this morning's Wall Street Journal.

This raises an important issue. Measuring quality, not paying for errors, and rewarding doctors and hospitals that follow clinical practice guidelines are the "evidence-based" building blocks of any pay-for-performance scheme. But when insurance companies or Medicare interpret the evidence and set the quality standards, they have a conflict of interest if they also pay the bills. Great Britain has its National Institute of Clinical Effectiveness set medical practice standards for its single-payer system. It would be interesting to know what safeguards that country has set up to ensure its independence. . .

Some Seniors Still Lack Drug Coverage

The number of seniors without prescription drug coverage is down to eight percent from about a third before the 2003 drug benefit passed, according to a new survey published in Health Affairs. But one in five seniors still put off buying some drugs because of high co-pays. John Rother of the AARP tells the Los Angeles Times "that's pretty positive for most beneficiaries," but Tricia Neuman of the Kaiser Family Foundation says "there is still work to be done in making medications more affordable for seniors."

Are Diabetes Rates Really Holding Steady?

Yes, according to this article by Gina Kolata in today's New York Times. But a close review of the data contained in the study that informed the article yields a less sanguine interpretation.

The study compared the changing rate of diabetes, both diagnosed and undiagnosed, and pre-diabetes between the early 1990s and the first years of this decade. The study relied on data drawn from the well-regarded National Health and Nutrition Examination Surveys (NHANES).

While diagnosed diabetes rates increased significantly from 5.4 to 6.5 percent of the total population (12.8 to 15.8 percent for those over 65), the undiagnosed diabetes rate and ratio of people with impaired fasting glucose remained unchanged. The easy conclusion to draw -- and both the study's authors and Kolata drew it -- was that the health care system is doing a better job at identifying and treating diabetics, but the obesity epidemic hasn't really had much impact on the overall rate.

But I came away from the data with a different and more alarming conclusion. The total population with diabetes (whether diagnosed or undiagnosed) and impaired glucose tolerance reached 35.3 percent or 73.3 million Americans by 2002. While that was deemed not "statistically significantly" greater than the 33.7 percent with those conditions in the early 1990s, in crude terms, it amounted to at least 3 million more people at risk of losing eyesight, limbs, heart attacks, strokes and the other debilitating co-morbidities of diabetes.

Moreover, the lack of statistical significance was wholly an artifact of statistical manipulations to the crude data to adjust for changing demographics of the population. If one just looks at the raw numbers, the rate of diabetes, both diagnosed and undiagnosed, leaped from 7.8 percent of the total population in the earlier period to 9.3 percent in the early part of this decade. And whether we look at the raw numbers or the statistically manipulated numbers, the over-65 crowd with diabetes jumped more than three full percentage points to well over 21 percent.

Given the amount of change seen in such a short period of time (about a decade), you'd think the researchers, who hailed from the National Institute of Diabetes and Digestive and Kidney Diseases, a unit of the National Institutes of Health, would have put a different spin on the overall data, even while recognizing its lack of statistical significance. The trend certainly seems to be clear.

Indeed, if I were writing up the study, I would have noted that while the health care system is doing a better job by identifying people with diabetes, there is, alas, something about the way we live today that is fully replenishing the ranks of those who need to be diagnosed.

Is Medicare Paying for Performance? Or . . .

. . . is it simply not paying for mistakes? On its face, the forthcoming announcement that Medicare will stop paying for gross errors is long overdue (kudos to Robert Pear of the New York Times for breaking the story over the weekend). But let's not mistake this for a real pay-for-performance (P4P in the argot of health policy wonks) system. We'll know Medicare is serious about improving quality while holding down costs when the nation's single-payer health plan for seniors figures out why the elderly in their last two years of life spend twice as many days in the hospital in New York and Mississippi as they do in Oregon or Utah (for this and other eye-opening statistics on how the uneveness of care around the U.S. has nothing to do with medical outcomes, see the Dartmouth Atlas of Health website). . . Meanwhile, a new survey of 3,100 physicians shows that over 90 percent have been involved in a "near miss, minor or serious error," according to the Los Angeles Times, but less than one in five received training in how to report errors and just one in 10 said their organizations helped them cope with the stress that comes from making mistakes when peoples' lives are at stake. . .

Some interesting pushback in the Wall Street Journal today in response to the editorial page's latest blast in favor of cancer quackery. The letters in response to an op-ed calling for unrestricted access to drugs that pass early stage safety trials drew these retorts from physicians: "Asserting that because some patients get better after taking a drug it "obviously works" is a bit like asserting that because some seat-belted drivers die in car accidents, seat belts are obviously dangerous"; and "Phase 1 FDA drug trials provide ample evidence of a drug's ultimate safety(?) This is false. The scientific process is in place for a reason, and it takes through Phase 3 trials before we know if a new drug is equal to or better than the current standard of care." The one patient advocate whose letter made the paper had this to say: "As a 20-year cancer patient advocate I am forced to wonder why the Wall Street Journal continues to support this bizarre theory of a 'constitutional right' to investigational therapy." . . .

Are there ethanol pumps at your local gas station yet? A new study out of Great Britain, reported in the Guardian, says the rush to biofuels may do more harm than good in reducing carbon emissions. The reason? Researchers associated with the World Land Trust claim a major switch to biofuels will lead to deforestation in areas of the world like Brazil and Indonesia that are rushing in to feed this emerging "green" market. The authors of the study, writing in this week's Science Magazine (subscription required), conclude "policy-makers may be better advised in the short term (30 years or so) to focus on increasing the efficiency of fossil fuel use, to conserve the existing forests and savannahs, and to restore natural forest and grassland habitats on cropland that is not needed for food." Okay, help me out here. The farmers are for it. The conservationists are against it. Who's the honest broker in the ethanol debate?

Drug Marketing Unchained

Today's New England Journal of Medicine has an important article on trends in the drug industry's marketing spending. Most critics have always been hampered by the opacity of the industry's corporate reports, which subsume total marketing costs within the larger "administrative" line item. But drawing on publicly available data at the Food and Drug Administration and purchasing data from private consulting firms that serve the industry, lead author Julie Donohue of the University of Pittsburgh has been able to give us the first detailed portrait of the industry's marketing machine.

Guess what? The news ain't good.

Despite the massive hue and cry by consumer groups, critics and the more progressive corners of the medical profession, total marketing spending increased substantially in the past decade, rising to 18.2 percent of drug industry sales in 2005 from 14.2 percent in 1996, the year before direct-to-consumer advertising took off.

DTC in the most recent year cost consumers $4.2 billion or 2.6 percent of total drug sales, up from under $1 billion or 1.2 percent of sales in 1996.

But the biggest jump came from free samples, which many doctors excuse because they are sometimes handed out to poorer patients. In reality, they are a major inducement to start their patients on one particular drug. The value of those freebies rose to $18.4 billion in 2005 or 11.2 percent of total industry sales compared to just $6.1 billion or 7.6 percent of sales in 1996.

The FDA has failed miserably in monitoring the explosion of advertising. According to the survey, only one in three ads were reviewed by the agency prior to public release in 2005, down from two in three ads in 1996.

Nothing in the data suggests that the drumbeat of criticism in recent years has led the drug companies to back away from their promotional strategies. "Our data show that a mandatory waiting period on advertising for new drugs would represent a dramatic departure from current industry practices," Donohue and colleagues wrote.

Pressured by an unholy alliance between big broadcasters, publishers and the drug industry, the Democratic-controlled House and Senate eliminated restrictions on DTC from the FDA reform bills that recent passed both chambers.

Annals of Government Science

The regulatory agencies of the federal government that rely on scientific analyses to carry out their functions, whether it be protecting the environment or approving new drugs, routinely appoint outside committees to evaluate their work. The scientists on these committees are usually drawn from academia, but the specialized expertise needed to conduct these sophisticated reviews often leads agencies to pull scientists from independent research institutes and consulting firms, which often receive research funds from private firms.

To protect the process from undue influence, the government 35 years ago passed a law that said scientists who serve on these review panels could not have conflicts of interest, in other words, they couldn't have recently worked for a firm or a trade group with a direct stake in the outcome of the committee's deliberations. Nor should they come to the committee with a preconceived bias about its outcome. There were exceptions written into the law. The agency could waive a conflict of interest if the person's expertise was highly specialized, couldn't be obtained elsewhere, and needed to successfully carry out the committee's task. And scientists with perceived biases (having already written or conducted studies on the subject and come to strong conclusions, for instance) could also be appointed as long as their views with balanced by someone with a contrasting view of the subject.

There's been numerous studies, political strife and litigation over the make-up of these committees in recent years. The Bush administration's penchant for appointing religious conservatives to committees dealing with reproductive health or prominent global warming skeptics to committees contemplating climate change clearly violated the bias provisions of the law. The Food and Drug Administration has been challenged for its excessive use of conflicted advisers on its drug approval panels. The FDA reform law that goes to conference committee next month will consider limiting the number of waivers to one per committee.

The Environmental Protection Agency has received less scrutiny in this decade, but it, too, suffers from a surfit of conflicted scientists passing judgment on government studies that directly affect their employers' economic interests. This week, a coalition of consumer and environmental groups attacked the EPA for larding a proposed panel that will review its scientific evaluation of the health and cancer risks of acrylamide with scientists with close ties to companies and trade groups that either use or make the chemical. In a letter sent yesterday, the Center for Science in the Public Interest, the Environmental Law Foundation, and seven scientists pointed out that at least six of the 21 scientists being considered for slots on the panel have either worked or consulted for companies or trade groups that produce or use acrylamide.

Moreover, one nominee, a Harvard-based epidemiologist, clearly has a preconceived bias about the issue, since she has already written that acrylamide poses little or no cancer risk to humans. "The EPA needs to do a lot more work before the public will be assured that the final roster is balanced and free from conflicts of interest," the letter noted. "EPA’s failure to do so will cast a permanent cloud over the integrity and reliability of the committee's work."

Acrylamide, a commonly used industrial compound that is also produced by frying starchy food, is already listed as a neurotoxin and probable human carcinogen. The update to the EPA's risk assessment, which is due out September 15 and will be peer-reviewed by the panel, may impact a 2005 lawsuit by the California Attorney General, which is seeking cancer warning labels on acrylamide-containing foods. Food processors are looking forward to the review since they believe recent science would downgrade the chemical's danger thresholds and thus void the lawsuit, according to a May 8 Risk Policy Report published by Inside Washington Publishers (subscription required). "I suspect that the calculation of risk will be less than the existing [EPA] assessment," said Robert Fensterheim, president of RegNet Environmental Services, which provides consulting services to the chemical industry.

The EPA's decision to include Lorelie Mucci of Harvard Medical School on its list of candidates violated some basic rules of scientific conduct. She has authored several epidemiological studies in recent years that suggest there is no link between acrylamide and some cancers. Her first study was harshly criticized by experts in the field. "[Mucci's] published conclusions and public statements indicate excessive confidence in insensitive epidemiology studies to detect acrylamide's possible carcinogenicity. . . and a strong bias in favor of acrylamide’s non-carcinogenicity," the consumer and environmental groups noted in their letter.

It's likely that the EPA's draft risk assessment that will be released in September will at least make reference to her work. If it comes out the way industry expects it to come out, it is probable that it will rely on her conclusions, since she is one of the more prominent researchers in the field. That means that if the EPA puts her on the committee, it will put her in the position of evaluating her own research.

That is not an acceptable process. Yet it happens with some frequency at the EPA. When Congress gets done with their work on the FDA, the relevant committees might want to turn their attention to industry's close involvement with the advisory committees that set the nation's environmental standards.

FDA Waives Off Obvious Conflict of Interest on Avandia Panel

The chairman of the Food and Drug Administration advisory panel that voted last month to allow Avandia (rosiglitazone) to stay on the market with stricter heart risk warnings did not receive a conflict-of-interest waiver despite having recently earned a $2,000 speaking fee from the drug’s manufacturer, GlaxoSmithKline.

Clifford Rosen, an endocrinologist and professor of nutrition at the University of Maine, told the agency about that relationship as well as his clinical trial work for Glaxo competitors Eli Lilly, Merck and Novartis. He also revealed it on the New England Journal of Medicine website last week at the tail end of his essay entitled “The Rosiglitazone Story – Lessons from an FDA Advisory Committee Meeting.”

“I listed it all on the FDA sheet, and they never saw it,” Rosen told Integrity in Science Watch, a newsletter published by the Center for Science in the Public Interest. “They told me, ‘I’m sorry. We missed it.’”

An FDA spokeswoman claimed that “Dr. Rosen did not have any interests relevant to the meeting topic that rose to the level that would require a waiver.”

Is the Worst Yet to Come?

Okay. So the Fed bailed out the hedge funds holding subprime debt, which is going south due to rising foreclosure rates among low- and moderate-income folks who bought overpriced homes with teaser-rate mortgages. But is the worst yet to come? This from the morning Wall Street Journal:

Today we do not have only a liquidity crisis like in 1998; we also have a insolvency/debt crisis among a variety of borrowers that overborrowed excessively during the boom phase of the latest Minsky credit bubble. First, you have hundreds of thousands of U.S. households who are insolvent on their mortgages. And this is not just a subprime problem: the same reckless lending practices used in subprime – no downpayment, no verification of income and assets, interest rate only loans, negative amortization, teaser rates – were used for near prime, Alt-A loans, hybrid prime ARMs, home equity loans, piggyback loans. More than 50% of all mortgage originations in 2005 and 2006 had this toxic waste characteristics. That is why you will have hundreds of thousands – perhaps over a million - of subprime, near prime and prime borrowers who will end up in delinquency, default and foreclosure. Lots of insolvent borrowers. – Nouriel Roubini, Roubini Global Economics

Curious about what he meant by the "Minsky credit bubble"? You can find out, and get a fully explanation of why he believes this credit crunch crisis is far from over, from this blogpost on his website.

Hospital-Acquired Infections

The American Medical Association is using its political clout to get states to crack down on sanitary conditions at storefront health care clinics, like those launched by Wal-Mart, CVS and other large retailers. Whlie their real purpose is to eliminate competition, it's important that health departments responsible for maintaining standards keep a close watch over these facilities, which are popping up like mushrooms around the country.

That said, I'm wondering if the AMA has joined forces with Consumers Union in its war against the carnage caused by infections contracted in the nation's hospitals. Again, unsanitary conditions are largely to blame. This latest survey from the Association for Professionals in Infection Control and Epidemiology, Inc. found that 46 out of 1,000 hospital patients or nearly one in 20 who checked in came down with antibiotic-resistant staphylococcus aureus (MRSA). This parallels an earlier Centers for Disease Control study that estimated hospital-acquired infections kill 99,000 Americans every year -- twice the number killed in car wrecks.

Boogah. Boogah.

Prevention Is Good for Our Economic Health

New York Times’ economics columnist David Leonhardt either didn’t do his homework or willfully ignored evidence that contradicted his thesis. Either way, the result was an ill-informed, misguided column in today’s New York Times that pooh-poohs Democratic candidate campaign pledges to make prevention a centerpiece of health care reform.

The argument, propounded by a handful of health care economists, is that prevention costs more money in the short-run than it will save in the long-run by reducing chronic diseases like diabetes or by eliminating or postponing expensive heart attacks and strokes. “Preventive care saves real money only when it replaces existing care that is expensive and doesn’t do much, if any, good,” he writes.

There’s two things wrong with this argument. First, it is simply wrong. There are many short-term, prevention strategies that provide immediate payback to society in the form of lower health care costs.

Jeanne M. Lambrew of the Brookings Institution’s Hamilton Project, in her paper calling for “A Wellness Trust to Prioritize Disease Prevention,” lists a number of health care or public health interventions that would save or extend lives at either no cost or at an overall savings for the health care system. They include prophylactic aspirin use to prevent heart attacks; universalizing childhood immunization; adult vision screening; and brief intervention programs for habitual tobacco users.

Even the one example Leonhardt gave – diabetes prevention – is contradicted by recent studies that have appeared in the academic literature. Leonhardt wrote:

Any effort to promote health has its own costs. Doctors and nurses need to spend time with patients to persuade them to change their behavior. (Ever tried to get someone to stop smoking or drinking?) For a new program to work, it has to reach people who are not being helped by whatever exists now – and who thus will be among the most difficult and expensive patients to treat.

He then quotes physician/economist Jay Bhattacharya of Stanford, who claims an antiobesity program must treat five people – “not cheaply” – to prevent one case of diabetes.

I presume his one-in-five response rate refers to the Diabetes Prevention Program, which was run by the National Institutes of Health in the late 1990s and earlier part of this decade. It compared a rigorous intervention program for obese people with elevated blood sugar levels (pre-diabetic) to giving them drugs (metformin) and a placebo. The intervention included a “16-lesson core curriculum covering diet, exercise and behavior modification that was taught by case managers on a one-on-one basis, followed by individual session (usually monthly) and group sessions.”

Doesn’t get more expensive than that, does it?

Here’s what their cost-benefit analysis found (Annals of Internal Medicine, March 2005, p. 323-332): The prevention program postponed the onset of diabetes by 11 years on average, compared to a three-year delay for people on drugs. The absolute reduction in incidence of diabetes, a debilitating and costly disease, was 20 percent and 8 percent, respectively, compared to placebo. And the cost? Just $1,100 per quality-adjusted life year (QALY) for the counselor-driven intervention compared to $31,300 for the drugs.

Moreover, health care costs actually declined for people under 45 who were given the intervention program. In other words, there was a greater and immediate payback if you intervened early.

Want a comparison? The estimated cost per QALY for cholesterol-lowering statin pills is $35,000 to $165,000. Presumably, we’ll be getting the $35,000 cost when Lipitor goes generic.

There’s real excitement about the potential for these lifestyle intervention programs. Today’s Journal of the American Medical Association, for instance, reports on a North Carolina experiment that implemented a version of the Diabetes Prevention Program over several years and got similar results. It also quotes from a Finnish study that followed up with individuals after the intensive counseling ceased. It showed that the benefits were long-lasting.

Not only was Leonhardt wrong on the facts, but he unwittingly applied a double standard. Health care economists who do cost-benefit analyses for the drug industry or other providers routinely use the net-present value of long-term health care expenditures to justify the short-term purchase of whatever it is they are selling. In other words, if a million people take our pills starting today for the next 30 years, the health care system will get overall reduced costs that adjusted for inflation justify the increased expenditures now.

But when it comes to prevention, the payoff has to be immediate. As I said earlier, there are some interventions where the paybacks are immediate – like aspirin use to prevent heart attacks. But the real savings from prevention programs are long-term, and well worth the expenditure.

It would be a crying shame if this misleading column dissuades any of the Democratic candidates from including a vigorous prevention strategy as part of their overall health care reform platforms. Americans understand we have a growing crisis in our overall well-being, fed by high-salt, high-sugar, high-fat diets, lack of exercise, high levels of stress, and inadequate and uninvigorating leisure. They also understand that the entire medical system is making a bundle by selling ineffective and sometimes unnecessary treatments for the consequences of our unhealthy lifestyles.

Even if the economics weren’t attractive – and I’m saying they are – putting health into the health care debate is a message Americans are dying to hear.

Signposts That the Health Care Debate Is Shifting

The drumbeat of bad news for Big Pharma continues. First, a federal appeals court rejected the Abigail Alliance's efforts to force the Food and Drug Administration to approve new drugs for dying patients before they've been proven safe and effective. And the front page of today's New York Times has a story showing that the long-predicted shift to generic drugs -- an inevitable by-product of the pharmaceutical industry's failure to generate new drugs that represent a significant medical advance when their blockbuster drugs lose patent protection -- is finally taking hold in the marketplace.

To me, these stories suggest that the era where drugs, drug safety, and drug pricing dominated public concerns about the direction of our health care system is drawing to a close. Last week's battle over state health insurance programs for children (S-CHIP) was the forerunner over the coming debate over health insurance reform, and the health insurance reform debate will inevitably turn to the broader issue of societal affordability. Drug spending, which represents just one-tenth of overall health care costs, is just one part of that larger problem.

When it comes to that issue, New Mexico Gov. Bill Richardson's comments in Iowa yesterday are worth highlighting. Alone among all the candidates, he is claiming that health insurance can be expanded to cover all Americans without raising taxes on the general public. Of course, that's a bit disengenuous. He would get there by requiring employers who don't provide coverage to contribute to a fund for insuring the uninsured. But his broader message is a welcome antidote to the liberal platitudes offered by the other candidates. "By streamlining the system, increasing efficiency, and asking everyone to pay their fair share, we can make accessible, affordable health care a reality for everyone," he said.

But his "increasing efficiency" is so far an empty vessel. Will he go the final mile and begin talking about reorganizing how health care is delivered in this country, which inevitably takes on the individual practioner/specialist model that undergirds many physicians' incomes? Will he outline some proposals for saving money while transforming the quality of care in the nation's hospitals, which are the largest component of health care costs? And will he talk about ways to eliminate useless procedures, tests and drugs that needlessly inflate costs without commensurate benefit?

Indeed, when will he or any of the candidates begin putting health into the health care debate? Along those lines, today's Journal of the American Medical Association has a short news article on an innovative North Carolina test program that showed that public health lifestyle intervention programs (blood sugar screening; nutrition and diabetes management courses; organizing walking classes) can significantly reduce the incidence of diabetes. If implemented on a nationwide basis, that could have a significant impact on obesity, the rising tide of diabetes and, ultimately, lower overall health care costs.

Here's an interesting question someone might want to ask the candidates at the next presidential debate (either party):

If you had an extra $5 billion to spend on health, would you put it into more research for a cure for diabetes or into public health programs to reduce the incidence of the disease?

India Disallows 'Obvious' Patents

India's Supreme Court voided Novartis' application for a patent on a variation of Gleevec, the company's miracle cure for one form of leukemia. The ruling is being hailed by groups like Doctors Without Borders as a major victory for charitable organizations that are trying to get inexpensive medicines to the developing world.

I was struck by the similarities between this case and recent fallout from the KSR v. Teleflex Supreme Court case in the U.S., which involved gas pedals but may have broad implications for many pharmaceutical industry patents. At issue is whether a small change in an existing product qualifies as a new invention, or whether it fails one essential quality of anything considered innovative: it must not be obvious.

What's obvious? When a drug company makes a minor changes in a small molecule drug so it can extend its patent life, that's obvious.

The news coverage this morning of the Novartis case in India left me wondering, though. Is Gleevec off patent? I don't think so. So has Novartis patented this variation as a replacement for later in the drug's life cycle? Is it possible that the Indian company came up with the obvious change in the Gleevec molecule as a way of getting around the original patent, and that variation was already patented by Novartis? And if the Indian company did that, did it also conduct new clinical trials to ensure the new drug works?

This is one case where a barebones story from ten thousand miles away didn't give us the whole picture. Perhaps some of my readers know the answers to these questions.

Drug Marketing Exposed -- Again and Again

The Los Angeles Times devotes its health section today to exposing drug industry marketing to physicians. Last week, Sen. Charles Grassley (R-IA) proposed legislation that would require that drug companies list all their payments to physicians (when they're hired as "consultants" and "speakers" for peddling drugs to their fellow docs at professional meetings). One can only hope this constant drumbeat of criticism is having an effect on corporate boardrooms.

Here's my advice to drug industry execs: Why don't you come up with something innovative? Docs will beat a path to your door. Marketing costs? Minimal.

Monument to the Bush Years

Over the past several months, craftsmen on scaffolds hanging from the semi-circular wall surrounding the cavernous stairwell at the DuPont Metro station near downtown Washington, DC have been diligently carving a poem, which, if you crane your neck, you have just about enough time to read before the escalators descend into the darkness. They completed the project last week by carving "Walt Whitman, 1865" into the curving, gray, granite wall. President George W. Bush hasn't even left office yet, but in Washington, it's never too early to start building monuments:

"Thus in silence,
in dreams projections;
returning, resuming,
I thread my way
through the hospitals;
the hurt and the wounded
I pacify with soothing hand;
I sit by restless
all the dark night --
some are so young,
some suffer so much --
I recall the experience
sweet and sad. . ."

-- Walt Whitman, 1865

Bancroft Family Folds

Murdoch Wins Bid For
Biggest Business
Broadsheet
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Remembering
'Rabbi Caught in
Sex-Slavery Ring'
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Editorial Page
Vows to Stay
Right Wing

The editorial pages are still the first thing I read in my morning Wall Street Journal. It gives us lesser mortals a portal for viewing the unvarnished id of America's ownership class.

For those of us who follow the drug and biotech industries, it's crucial. Those industries' executives and their think tank toadies have an unfettered pathway onto its pages. Today, for instance, an oncologist who made millions with one successful anti-cancer drug complains that the Food and Drug Administration has gotten too tough on new ones because it didn't give fast-track approval to a traditional chemo agent for prostate cancer -- a drug that couldn't win a single vote from a panel of independent outside experts last week.

Is there actually someone out there who thinks the 76-year-old Rupert Murdoch, creator and owner of Fox News and employer of Roger Ailes, would try to change that outlook? L. Gordon Crovitz, the Dow Jones publisher, assures us this morning that their readers and contributors can count on the paper remaining a bastion of anti-regulatory zealotry:

The nastiest attacks have come from our friends on the political left. They can't decide whose views they hate most -- ours, or Mr. Murdoch's. We're especially amused by those who say Mr. Murdoch might tug us to the political left. Don't count on it.

Contrary to the fears of many journalists in the paper's newsroom, I also don't think you'll see many changes in news coverage. If anything, he'll beef up political coverage in Washington, which, given the Journal's business focus, should increase the amount of news flowing from the nation's woefully undercovered regulatory agencies. That's a good thing.

Murdoch has learned a few things since he briefly owned the Chicago Sun-Times in the mid-1980s, which was his first foray into U.S. publishing. Columnist Mike Royko immediately quit and joined the Tribune, giving that newspaper, with its long history of right-wing conservatism and anti-unionism, an undeserved centrist image.

A few weeks into Murdoch's Sun-Times proprietorship, an ambitious editor inserted a wire story headlined "Rabbi caught in sex-slavery ring" deep inside the paper. Thousands of subscribers in the heavily Jewish north shore suburbs cancelled their subscriptions, starting that once great newspaper's long-term slide into irrelevance. Conrad Black merely finished what Murdoch started.

A few years later, Murdoch bought the struggling New York Post and transformed it into a right-wing rag. But it was a shell of a newspaper at the time, and his willingness to pour money into the project kept tabloid journalism alive in the one city in America that appears to have the stomach for it. I've always liked tabloid journalism myself -- in the 1950s we had two papers come into the house; my dad read the New York Times and my mom read the Daily News. Great sports. Great cheesecake. And Dick Tracy. What else could a young boy want?

But don't look for any tabloid-like transformations at the Journal, or even political meddling. The man is spending $5 billion. This is the journalistic equivalent of buying a trophy wife. Screw around too much with the merchandise and she'll leave you broke and broken-hearted.

He may end up broke anyway. This deal reminds me of the Tribune Co.'s decision to purchase Times-Mirror in 2000 -- also at the peak of a business cycle and at a hefty premium to then already-inflated stock market price. The only ones who made out on the deal were the ones who got out. The Tribune has taken a lot of heat for journalistic mismanagement, but that is merely a proxy complaint for the company's loyalty to the bottom line, which dictates layoffs and shrinkage to cope with declining advertising revenue.

Will Murdoch's Journal be able to escape a similar fate? Today's New York Times leads with a story suggesting that the advertising sales people who work for Murdoch are among the most aggressive in the business. The story had the smell of fear about it. Yet, while a broadsheet newspaper war would be fun to watch, the sad fact is that the two papers are fighting over a shrinking market. Ultimately, no one wins such a battle.

For me, the most interesting business question is whether Murdoch will follow through on his public musing about making the paper's website freely available. Right now, it is the most successful pay news site on the web. I am one of 900,000 people ponying up nearly $100 a year for the right to get web access to Journal coverage. Do the math: that's nearly $100 million. It's making money. Yet Murdoch thinks he can do better by getting "more eyeballs" via free circulation and selling advertising.

I think that would be a big mistake. Advertisers have always placed a higher value on paid circulation over freebies thrown up on peoples' lawns. It shows that readers place a value on the product. Why is the web any different?

The biggest strategic mistake newspapers made a decade ago was giving away their content for free. Now, aggregators like Google and Yahoo reap the advertising revenue by repackaging a product produced by someone else. What's going to happen when newspapers can no longer afford to produce that product? The aggregators will either have to repackage undigested public relations or get into the news business themselves. And, as was always true with freely-circulated papers, the incentives are all toward choosing the p.r. model.

As long as the Journal keeps its website a part of paid circulation, it is living proof that serious news journalism (as distinct from opinion) will survive the transition to the era of internet information distribution. Serious journalists needn't fear Murdoch's politics or his opinions. They should fear his business model.