Critical Clinical Trial Hidden From Advisory Committee

A Food and Drug Administration announced Friday that one of its advisory committees did not receive crucial clinical trial data from Bayer when it considered the safety of a blood-clotting drug last week. The trial showed Trasylol, which is usually given before heart operations to reduce bleeding, might have increased mortality. The advisory committee eventually ruled the drug's risks did not outweigh its benefits. Details of the story can be found in today's New York Times.

How could something like this happen? The government goes to great expense to hold a public meeting to discuss possible problems with a drug used during already dangerous operations. Then, a week later, a clinician who conducted a trial for the firm calls up the FDA with the additional information, which the company, according to today's Reuters account, "mistakenly" failed to tell the agency about. "Bayer said it did not share the information with the FDA immediately because there were questions about the study's methodology and the findings were preliminary," the Reuters report said.

When I first heard about this yesterday, I thought to myself, isn't this like hiding evidence in a criminal trial?

Fortunately, there's a quick and easy solution to these "oversights." Congress must step in immediately and attach an amendment to the FDA appropriations bill that says every clinical trial conducted on any approved drug or any drug up for approval must be registered with the agency prior to the enrollment of any patients. Failure to do so should lead to immediate withdrawal of the drug from the market until the newly revealed data can be properly evaluated.

With such a publicly available database, the FDA should have no problem locating all the available clinical trial data when it sits down to evaluate a drug's safety and efficacy.

Congress had the chance to pass such a bill the past two years, but it did nothing (yes, I know, this sounds like the "do nothing Congress" slogan now being used by the Democrats; but if the shoe fits . . . ).

Health Savings Accounts -- the real story

The Commonwealth Fund's Sara Collins raked health savings accounts over the coals in her excellent testimony to the Senate Finance Committee earlier this week. One fascinating tidbit: 44 percent of privately insured adults with deductibles of $1,000 or more avoid getting necessary health care or prescriptions because of the cost, compared with 25 percent of adults with deductibles under $500. To read her entire testimony, click here.

Politicking Their Way To Higher Medicare Costs

Josh Marshall's Talking Points Memo reports that the American Medical Association Political Action Committee just donated nearly $300,000 to Rep. Nancy Johnson (R-Conn.)'s campaign.

That comes as no surprise. Even if her campaign wasn't in trouble, the docs have a lot to thank her for. Johnson has been leading the charge to increase reimbursements for physicians under Medicare. She held hearings a few months back on the inadequacy of oncologist payments. If Republicans maintain control of the House, the physicians who dumped big bucks into her campaign will be expecting payback.

The physicians' lobby isn't just betting on the outcome of the election. In recent weeks, they've launched a massive lobbying blitz for higher Medicare reimbursements. Letters-to-the-editor are appearing all over the country warning that physicians will refuse to see new Medicare patients unless the payments schedule goes up.

Oncologists in particular are upset because they can no longer mark up the price of cancer drugs. Medicare has always paid for drugs administered in physicians' offices. Most cancer drugs fall into this category and physicians made a huge share of their earnings off the mark-ups. But the 2003 prescription drug act ended that system, which had been the target of Democrats and Health and Human Service Department auditors for a generation.

The past few years, the Republican Congress compensated them for their lost mark-ups by creating a phony demonstration project. But there's nothing in the hopper for next year yet. When billions are at stake, a few hundred thousand at campaign time is a small price to pay.

The End of Routine and Preventive Care?

The Wall Street Journal reports this morning that Wal-Mart in January will start offering a new health insurance plan for its 1.3 million employees and their dependents. The so-called "Value Plan" has just an $11 monthly premium, but requires families to pick up the first $1,000 of health care costs before the first dollar of coverage kicks in. Even if you end up in the hospital, the plan makes the patient pay the first $1,000 of costs. Drug coverage? Employees will pick up the first $300.

Currently, just 46 percent of Wal-Mart's workers have health insurance. Critics say the new plan will allow Wal-Mart "to cut its costs for health-care benefits and discourage unhealthy people from seeking work at its stores," the Journal reports.

Insurance scams

I let the health care insurance rate story pass yesterday without comment since I knew the press would cover most of the angles. What more can one say when health care insurance premiums, even in a "slowing" mode, grew 7.7 percent in 2005, which was more than twice the rate of inflation and workers wages. I'm reminded of Herbert Stein's famous dictum (for younger readers, he was President Nixon's chief economics adviser), "If something cannot go on forever, it will stop."

But there was one disturbing trend in the data that deserves some additional comment. The press downplayed it, following the lead of Drew Altman, the president of the Kaiser Family Foundation which conducted the survey of employer insurance premiums.

Pointing out that only four percent of Americans have so far signed up for high-deductible insurance plans linked to health savings accounts (the Bush Administration's and market enthusiasts "cure" for skyrocketing health care costs), Altman repeatedly said that talk about "consumer-driven health care is way out in front of the action in the marketplace."

Based on my own experience, I think that's going to change -- and fast. I predict uptake of these plans, especially among the well-off and relatively healthy upper middle class will take off in the next few years.

Why do I say that? This morning, my wife asked me what we should do about our health insurance next month. October is when most people with employer-based coverage have to choose their health plans for the coming year.

We're in a PPO and we both hate our primary care physicians, who seem angry as hornets who just had a broom stick stuck in their hive every time we go to see them. Is it us? The insurance companies? Their lot in life as tread-mill primary physicians who must see back-to-back patients hour-after-hour? Who knows? Who cares?

I just want a doctor who is interested in me. So does my wife. So we're looking at choosing a high-deductible "point of service" plan that will enable us to choose any doctor we want. We're already asking all of our friends. "Know somebody you like?"

Now, I'm the first to admit that the vast majority of Americans do not have the luxury of this option. They can't afford the $100 or more out of pocket I will have to pay every time I go to see the doctor (when I find one I like). But I will get a tax deduction for the money we put into our health saving account; and we will get a smaller bi-weekly deduction from our paychecks because the premium on our high-deductible plan will be less than the plan we previously belonged to. Over the course of the year, we may even come out ahead. After all, we're still pretty healthy.

If you're upper middle class (I am), the Bush plan is for you. It reminds me of what a physician friend told me during the 1980s after Ronald Reagan got another tax cut through Congress. "I hate the bastard, but he's been very, very good to me."

Memo to Drew Altman: I predict by next year at this time, that 4 percent will be 6 percent. And within half a decade, it will be near 20 percent, virtually all of them drawn from the ranks of the upper middle class and the super rich. The plans will have successfully siphoned off the healthiest and therefore cheapest part of the insurance marketplace.

Of course, this adverse selection (this is a fancy economists' term for what happens when the least risky, healthiest people opt out of an insurance pool) will further undermine the regular insurance market. Average Americans and the shrinking number of employers who insure them will see their premiums soar ever higher. This will send additional millions into the ranks of the uninsured.

In short, high-deductible plans linked to tax-advantaged health savings accounts will win a niche in the market because when the Titanic is sinking and there aren't enough life boats, it's every person for him or herself and to hell with the folks in steerage. It's the American way. And, in case you hadn't noticed, I'm as American as anyone.

Further Thoughts on the IOM Drug Safety Report

It’s a bit frightening how little physicians really know about a new drug when it first comes on the market. Unless the drug is for a common condition like high blood pressure or mild arthritic pain, it’s probably been tested on fewer than a thousand people before the Food and Drug Administration approves it. It's quite likely a serious side effect that shows up once in every 1000 patients will escape the attention of the physicians and the company that ran the clinical trials.

That’s not what happened in the Vioxx case, of course. The clinical trials for that run-of-the-mill pain pill did show a serious side effect – heart attacks and strokes at four times the rate of a comparison drug. But the industry-funded physicians who ran the trial and the FDA reviewers who approved it ignored that clear signal. Instead, Merck's Vioxx got the rubber stamp of approval and was prescribed for millions of Americans, tens of thousands of whom died prematurely. That spectacular disaster – one of the worst drug safety fiascos in American history – led directly to last week’s blue-ribbon Institute of Medicine report calling for a complete overhaul of the way the Food and Drug Administration evaluates the safety of new drugs.

The IOM report, which received front page coverage in the national media, made a number of very good recommendations. They ranged from calls for a better surveillance system for identifying serious side effects among the patients who take new drugs to mandatory registration of all clinical trials so patients, doctors and researchers can analyze all the data companies have about their drugs.

The IOM committee, which included several well-known drug safety advocates, also wanted better warning labels on new drugs and suggested companies submit detailed surveillance and risk management plans when a drug first comes on the market. Then, the company would have to report back within five years on any surveillance data that sheds new light on the drug’s safety or efficacy.

Without saying so directly, the report also called for insulating the FDA from the political manipulation, which has been the Bush administration's singular contribution to the history of the nation's oldest consumer protection agency. The committee called for giving the FDA commissioner a 6-year term.

The committee also recognized that the drug industry, whose user fees now drive nearly half the agency's budget, has become the primary "client" for drug regulators, a classic case of industry capture. To lessen those ties, they called for greater taxpayer support for the FDA. They also demanded that a “substantial majority” of scientists who sit on the FDA's outside advisory panels be free from “significant financial involvement with companies whose interests may be affected by the committee’s deliberations.” Currently, many committees have as many as half their scientists simultaneously pulling down paychecks from industry.

If the FDA and Congress take the recommendations to heart (that’s a big if, given the pharmaceutical industry’s power over both institutions), the FDA will definitely improve its ability to spot unsafe drugs and pull them off the market. However, I still am somewhat disappointed in the report. Its authors shied away from embracing the implications of many of their recommendations.

Take direct-to-consumer advertising (“Please,” as Henny Youngman might have said). For years, the drug industry, physicians and patients did quite well, thank you, without this useless form of psychic abuse. Does the public really need to see television commercials touting toenail fungus cures and erectile dysfunction alleviators? Does a person on poisonous cancer drugs really need to see the smiling faces of fellow sufferers who are "ready for chemotherapy" because of the alleged benefits of some wonder drug? Believe me, if there is a drug out there that can relieve some of the side effects of chemotherapy, your oncologist will be aware of it and gladly prescribe it for you.

Yet, no sooner had the report suggested DTC be curbed than it cautioned that it might infringe commercial freedom of speech. Why this quibble? This was a drug safety committee. Say what’s best for public health – and then let the industry's lawyers fight it.

But the most significant flaw in the report came from the committee’s decision to ignore calls for a division of the Center for Drug Evaluation and Research, which is charged with evaluating new drug applications but also houses the FDA’s safety office. The net effect of combining the two offices is to keep FDA scientists with safety concerns under tight control (except when a stray whistleblower like David Graham wanders off the reservation).

The FDA, which used to be considered the gold standard among our science-based regulatory agencies, has fallen on hard times. Giving its scientists better tools, which the recommendations in the report would provide, would be great.

But those tools will be useless unless the agency has the will to use them. The ultimate problem at the FDA is a lack of leaders willing to stand up for the staff, who often already know when something isn’t right. Empower them to stand up to the industry when it is warranted, and we’ll once again have an FDA that can protect the public from unsafe and ineffective drugs.

Flash: IOM Issues Half-A-Loaf Drug Safety Report

The Institute of Medicine has just released its long-awaited report on the adequacy of the U.S. drug safety system. While it has some good features, it clearly avoided recommending a radical overhaul of how the Food and Drug Administration does its job.

The report slams the agency for systematically underfunding and understaffing its safety department, and cites organizational and cultural problems that make its voice a secondary concern at FDA. The committee favors "a moratorium on direct-to-consumer advertising," at least when the product is new. But then, they immediately backtracked and cited possible legal impediments to such a stance.

While recommending increased staff and funding, mandatory registration of clinical trials with public access to drug safety information, and better labels, the IOM refused to call for creating an independent safety center outside the arm of FDA that approves new drugs. Safety advocates inside and outside the agency have long pushed for such a move.

No doubt the agency and its protectors inside the pharmaceutical and biotechnology industries will highlight this missing element in the report.

Common Sense on DDT

Today's New York Times has an op-ed from a doctor in Uganda who is on the front lines of combating malaria. Jessie Stone echoes views expressed in this space a week ago that DDT is no magic bullet in the fight against the disease. Bednets and affordable drugs are more important, Stone argues, and there are potential health effects from prolonged exposure to DDT, even in the minute doses used in household spraying.

Alas, common sense on the op-ed page after the fact doesn't undo the damage done by a major magazine article by Tina Rosenberg three years ago that was headlined, "What the World Needs Now Is DDT." That article gave a major boost to the conservative forces pushing the DDT strategy. Last week, their lobbying efforts paid off with the WHO decision to endorse wider use of the chemical, which is banned in much of the industrial world.

Need A Doc? Go To Wal-Mart

Wal-Mart announces today that it will begin rolling out a generic drugs discount strategy for its pharmacies, whose revenues have stagnated in recent years. This is a development that merits watching. Last year, the retail giant began offering clinic services for routine health care at selected stores.

Is this the coming face of health care for millions of un- and under-insured Americans? The employer-based health care system is unraveling. Virtually all Americans (all but the very well-to-do) are experienced higher co-pays, higher out-of-check premiums to make up for what their employers no longer cover, and higher deductibles when large bills (like a hospital stay) hit. Within a few years, if current trends continue, a large fraction of the American people will have nothing but a catastrophic health care plan from their employers.

This, of course, is where the Bush administration and economic conservatives would like to see health care go. In their view, making people pay for first-dollar coverage will create "market discipline." Once health care consumers (don't use the word patients; that's so 20th century) have skin in the game, their informed choices as to what they "really" need will finally bring health care spending and prices under control.

This would be a disaster for public health. For low- and moderate-income people living under already constrained household budgets, the first things eliminated would be routine check-ups and preventive care. The long-term effect would be a further downward slide in the health of the American people, which already ranks in the second tier of OECD nations (see my post here).

Wal-Mart sees a market opportunity in this evolving mess. There's good money to be made from the bottom half of the population's mad scramble to gain access to health care.

People like myself who are concerned about creating a decent health care system for all will be faced with a conundrum if we oppose, because of its inequities and its impact on overall national health, these entrepreneurial efforts to deliver routine health care services to people at affordable prices. It will be a repeat of the argument over Wal-Mart's low wages and benefits for its employees, where conservatives point out ad nauseum that the lower prices enjoyed by Wal-Mart shoppers are a far greater benefit for low- and moderate-income people than the higher wages that might go to its workers.

In health care, the same line of logic will argue that low-priced and easily accessible health care -- no matter what the quality -- is better than no health care at all. In a world where many people have no other options and there's no hope of societal change, that's a hard argument to counter.

Integrity in Science Watch -- the latest

This is a copy of the newsletter I publish weekly at the Center for Science in the Public Interest. If you'd like to get this emailed to you directly on Mondays, send a copy of your email address to science@cspinet.org.

New Study Confirms Butadiene Cancer Link, But Creates Loophole

A new study that will be released Tuesday by the Health Effects Institute (HEI), the Boston-based non-profit jointly funded by the automobile industry and the Environmental Protection Agency, confirms that 1,3 butadiene, a major air pollutant from automobiles and chemical plants, causes leukemia and other cancers, but only at high exposures. Leukemia mortality among rubber workers in the study was 170 to 270 percent higher than unexposed groups. However, the HEI researcher, Elizabeth Delzell of the University of Alabama, who has also received funding from the International Institute of Synthetic Rubber Producers and the American Chemistry Council, is about to publish a related study that will claim that the workers who got cancer were the ones who were occasionally exposed to especially high doses of butadiene. A number of industry consultants are co-authors of the paper. If accepted by regulators, this "peak exposure" theory could be interpreted to mean that butadiene is not as dangerous as previously thought. The peak exposure theory is based on sophisticated modeling that assigned exposure values to various jobs held by workers as long as 30 years ago. No measurements were ever taken.

The HEI synopsis of the report, which reflects the views of its peer reviewers, left the door open for accepting the "peak exposure" theory. While the synopsis does say that butadiene exposure estimates in the study "may be too high," and the cancer risks identified in the study "could actually be associated with lower measured concentrations of exposure," it goes on to say that if the forthcoming study from Delzell and the industry consultants "confirms that (exposure) estimates from the current investigation are accurate, this study will provide a firm basis" for assessing risk. That would eliminate the need for chemical plants to engage in further clean ups under the EPA's so-called residual risk rules; it also could affect future automobile emission rules. A residual risk rule now under consideration at the EPA has "do nothing" as one option for chemical plants that produce butadiene and routinely emit small amounts into the atmosphere.

Groups Protest Nomination of Industry Sympathizer to Top OMB Position

The Bush-appointed nominee to head the Office of Information and Regulatory Affairs, an arm of the Office of Management and Budget, has drawn sharp criticism from environmental and health advocacy groups. A report released last week by Public Citizen and OMB Watch said Susan Dudley's "ideological opposition to regulation, support for radical policies that would impair public safeguards and ties to industry" made her unfit to manage the highly influential regulations department, which has the power to weaken, delay, or eliminate public health measures. As past director of regulatory studies at the industry-funded Mercatus Center at George Mason University, Dudley opposed the EPA's attempts to strengthen policies regulating arsenic in drinking water and levels of smog. "Dudley is little more than an industry factotum," said Gary D. Bass, OMB Watch executive director. "Not since OIRA was created in 1980 has there been a less appropriate nominee."

FDA Finally Ousts Advisor Over Conflict of Interest, But Only After A Company Protests

The Food and Drug Administration booted a physician from its Anti-Infective Advisory Committee last week after receiving a complaint about his conflicts of interest from the company whose drug was about to come before the panel. Dr. Thomas Fleming, a long-time member of numerous FDA advisory panels, in 2002-3 reviewed studies on the antibiotic Factive for Oscient Pharmaceuticals' predecessor firm. He subsequently questioned the company's use of non-inferiority trials, which had been used in the initial approval of Factive. The company then protested his presence on a new committee looking into the company's request to expand the use of the drug, which also relied on a non-inferiority trial. The FDA denied him a conflict-of-interest waiver and he was not permitted to serve. (In a non-inferiority trial, the drug is compared to an already approved drug rather than a placebo. Since many antibiotics are only marginally better than placebo, critics - including several FDA examiners - believe that the statistical margins of error in antibiotic non-inferiority trials can lead to approving drugs that may not be effective.)

According to a report in the Wall Street Journal, FDA officials said their refusal to grant Fleming a waiver was unrelated to Oscient's complaint or his concerns about non-inferiority trials. The FDA let stand waivers granted to Peter Gross, a professor of medicine at the University of Medicine and Dentistry of New Jersey, and John Bradley of Children's Hospital in San Diego. Both waivers were for consulting with competitor firms. Fleming told the Journal that he is concerned that the integrity of the advisory committee process "would be significantly compromised if there is a possibility that a company could intervene in the committee-making process." The flap had no bearing on the ultimate vote, since the full panel voted 11-2 against Oscient's application to use Factive for sinusitis. The FDA usually follows the advice of its advisory committees.

NIH Passes Buck on Conflict-of-Interest Cases

The second-ranking official at the National Institutes of Health last week told a House subcommittee that only "minimal" disciplinary actions had been taken against employees who broke conflict of interest rules to consult with industry. The excuse? Technically, the high-ranking employees were members of the Public Health Service, a quasi-military corps within the Department of Health and Human Services. The "NIH concluded that the facts [warranted] referral to the corps, which has independent authority to determine the most appropriate level of discipline for its commissioned officers," said Raynard Kington, deputy director of NIH. He also revealed that Trey Sunderland, chief of the geriatric psychiatry branch at the National Institute of Mental Health, and Thomas J. Walsh, a top officer at the pediatric oncology unit of the National Cancer Institute, had not yet been punished for receiving hundreds of thousands of dollars as consultants for drug companies while on the government payroll. John Agwunobi, Assistant Secretary for Health for the Department of Health and Human Services for the Public Health Service, refused to discuss displinary cases that were still underway. The HHS Office of the Inspector General also came in for criticism during the hearing for failing to investigate conflicts of interest at NIH.

Harvard Prof Cleared of Ethics Violations Gave Major Gift to Dental School

It turns out that Dr. Chester Douglass, who last month was cleared of violating Harvard Medical School ethics rules after misrepresenting a graduate student's research linking water fluoridation to cancer in young boys, gave $1 million to the university in 2001 for its new $22 million dental research facility, which was completed in 2004, the Harvard Crimson reports. According to the Environmental Working Group, a number of Harvard alums involved in public health have asked interim president Derek Bok, who recently authored University in the Marketplace: the Commercialization of Higher Education,to release the details of its investigation into Douglass, who consults for Colgate-Palmolive Co. and edits its publication, "The Oral Care Report." A Harvard spokesman said the university has turned the results over to the federal Office of Research Integrity, which found no further cause to investigate.

Who Wrote The Medicare Formulary?

I've seen lots of articles lamenting the doughnut hole in Medicare's drug benefit, but nary a one complaining that seniors can't get the drugs their doctors prescribe. Amazing, isn't it? No one seems to have a single complaint that the drug plans, generously reimbursed by the federal government, are seeking to hold down costs by prohibiting people from buying pricey me-too drugs.

What's up? Have physicians and their patients suddenly wised up and said, no thanks, now that the government is paying the tab, I'll go for the generic?

A small clue as to what is going on is contained in the Annals of Internal Medicine that hits physicians' desks tomorrow morning. Physicians who wrote the Medicare drug purchasing guidelines (the so-called formulary) review how they went about their business.

In 2003, Congress told the Center for Medicare and Medicaid Services (CMS) that it should contract with the U.S. Pharmacopeia to draw up model guidelines for Medicare Part D formularies. The U.S. Pharmacopeia, for those not familiar with the organization, is a freestanding non-profit outfit headquartered across the street from the Food and Drug Administration in Rockville, Md. It sets standards for all prescription and over-the-counter medicines, dietary supplements, and other healthcare products manufactured and sold in the U.S. Like many standards-setting groups, it derives most of its revenue from industry, which has an interest in having an objective, outside party create a level playing field for their competition.

But as a go-between government and industry, especially when government is now ponying up somewhere around $60 billion a year for drugs, one has to wonder just how objective they might be. Do they have the interests of taxpayers at heart, the patients or their major clients?

I don't have access to the Annals, so I'd be curious to learn how they made their decisions. But the abstract distributed on the Internet had a most intriguing conflict of interest disclosure. The guidelines, the disclosure assured readers, were written "according to USP's strict rules regarding conflict of interest."

Did those "strict rules" limit who sat on the 17-member committee? Turns out one physician on the committee worked for Caremark, which offers a Medicare Part D prescription drug plan; another provided health economic consulting to pharmaceutical companies and received an educational grant from Merck; there was a Pfizer employee on the list, who, it was dutifully disclosed, also owned stock in J&J; a Pfizer consultant who provided advice to pharmacy benefit managers also wangled his way onto the committee; while another industry consultant reported he received grants from Wyeth, AstraZeneca, Merck, and Pfizer.

And we're supposed to feel reassured that this was a group looking to hold down costs?

DDT Makes a Comeback

The World Health Organization today announced it will officially encourage the use of the insecticide DDT, which has been banned in many parts of the world, to help combat mosquitoes that spread malaria. The move is part of WHO malaria chief Arata Kochi’s effort to reinvigorate the global movement to “roll back malaria,” which, when announced in 1998, was supposed to cut the incidence of the disease in half by 2012. More than half way there, there is, if anything, more malaria in the world today – an estimated 500 million cases a year. One to two million people die annually from the disease, most of them children in sub-Saharan Africa and South and Southeast Asia.

The WHO strategy for rolling back malaria has three parts: massive deployment of artemisinin-based combination therapy (ACT), which is effective against the most deadly form of the parasite, Plasmodium falciparum, which has grown resistant to most older drugs; deployment and use of insecticide-treated bednets in homes open to the elements, a common condition in much of the underdeveloped world; and indoor residual spraying, which can be effective in holding down nighttime mosquito feeding in homes that have standard walls, doors and windows.

The move to encourage the use of DDT for indoor spraying represents a major victory for conservative politicians and advocacy groups, who have been pushing the “use DDT” campaign for the past five years. Sen. Tom Coburn (R-OK), a physician, has been a major champion in the Senate, demanding that the U.S. Agency for International Development pour more of its anti-malaria effort into DDT purchases.

Beyond the politics of sticking a needle in the eye of anti-pesticide activists in the environmentalist community (for more on this aspect, see my post here), what’s behind this effort? I’ve spoken to numerous malaria experts in the past year. There is no doubt that DDT, which is extremely cheap to make, can play an important role in malaria control in some parts of the world. But how big a role? Are there any potential side effects from its use? And are there alternatives?

Last fall, I spoke with Prof. Janet Hemingway of the Liverpool School of Tropical Medicine shortly after the Bill and Melinda Gates Foundation awarded the school $50 million to develop new insecticides. Here’s her assessment:

Q. What role do you see DDT playing in the global anti-malaria campaign?

Hemingway: When you use DDT for indoor residual spraying, it has quite a lot going for it. It lasts longer. It still works in many countries, but not all. The idea that we should be using it everywhere, though, is blatant nonsense. There are countries where there are high levels of resistance.

Q. Since we know there are environmental issues, why not use alternatives?

Hemingway: Various environmental lobbies have other insecticides in their sites. Organo-phosphates like malathion are nerve poisons and there’s a big push to get rid of them altogether. The same is true for carbamates. Plus they’re relatively expensive to make, so if you take away agricultural uses, it doesn’t make sense to produce them for indoor residual spraying in the developing world. DDT is cheap to make.

Q. How about the chemical used on the bednets? That must be pretty safe.

Hemingway: Pyrethroids are the only ones used on bednets because of their rapid kill action. But we have a lot of pyrethroid resistance coming through now in Asia and Latin America and Africa. We’re going to lose them to resistance. So all we’ll have is DDT.

Q. But you said earlier that DDT resistance was emerging, too.

Hemingway: There is a lot of resistance to DDT in India, Zanzibar and parts of Tanzania. Down in South Africa (where many of the conservative groups pushing DDT use have outposts), there is no sign of resistance.

Q. So like the parasites that have become resistant to most drugs except artemisinin, the mosquitoes that spread malaria are growing resistant to most insecticides. What can you do about that?

Hemingway: It's clear we need new compounds. We just got a $50 million grant from the Gates Foundation to look for alternatives. The time frame is five years. We’re looking at better formulations of some of the insecticides we’ve already got. DDT lasts six months if you spray it on a wall, the others are 3-4 months, which is another advantage for DDT.

So we’re looking for something that lasts just as long, can be used on walls as well as bednets, and doesn’t have the potential health effects of DDT. We’re working closely with industrial partners (like Bayer Crop Science). Industry has some chemicals they’ve developed for the agricultural industry that may be modified to be used against public health pests.

EPO -- Again

Medicare spends more money on Amgen's Epogen than any other drug in its medicine chest -- $1.75 billion in 2005. Virtually all of it went to patients on dialysis. (The agency also pays for the same protein for cancer treatments, but those are sold under the brand names Aranesp by Amgen and Procrit by Johnson & Johnson.)

Given that level of spending, you'd think there would be pretty good evidence that this drug, which raises the red blood cell count, is delivering positive results for the unfortunates suffering from what the government and physicians euphemistically call "End Stage Renal Disease" (ESRD). The euphemism refers to the fact that the average life expectancy of a person who enters dialysis after their kidneys fail is about five years.

You'd think that but you'd be wrong. In fact, the evidence suggests just the opposite. Of course, treating the anemia associated with kidney failure was a godsend when Epogen first came on the market in 1987. It ended the need for blood transfusions, and allowed dialysis patients to have red blood cell counts (hematocrits) near normal.

However, the Food and Drug Administration's initial approval for Epogen called for raising hematocrits to about 15 percent below normal. While most patients don't notice the difference, Amgen, through a series of studies it funded, attempted to show that higher hematocrits were better for patients. Their measuring sticks? "More energy" and "greater alertness." Through intense lobbying, they used those studies to browbeat Medicare into reimbursing dialysis clinics to raise hematocrits to slightly below normal. Not surprisingly, in the wake of that 1997 decision, Medicare spending on Epogen soared.

But what were the medical results of that policy? In a paper published in 2004 in the Journal of Clinical Epidemiology, Dennis Cotter of the Medical Technology and Practice Patterns Institute and his colleagues at Johns Hopkins and the Boston VA showed that attempts to reach normal hematocrits, which required LOTS more Epogen, did not correlate with increased longevity for people on dialysis. In fact, they showed that raising ESRD patients' hematocrits to normal levels actually resulted in shorter lifespans because it increases the incidence of heart attacks, strokes and other cardiovascular events.

Gee. You mean thickening the blood in people who have severe microvascular distress from a lifetime of untreated hypertension and diabetes (which are the primary causes of kidney failure) causes heart attacks? To quote that famous line in Casablanca, I'm shocked.

Now, Cotter and colleagues are back in the latest issue of Health Affairs (subscription required), bringing us up to date on the Bush administration's policy on Medicare spending for Epogen. In a move that NO ONE in the mainstream press covered (Hey, another half billion dollars in drug spending? Who cares?), CMS this past April gave dialysis clinics the okay to raise patients' hematocrits to 39, which is normal for women and a shade under normal for men.

If Cotter's earlier paper is correct, the end result of this policy will be shorter lifespans for many dialysis patients, but greater sales and higher profits for Amgen. To use the dry language of the Health Affairs study, "CMS has tacitly implemented a policy that does not appear to confer additional proven benefit to its beneficiaries."

What would Cotter do about it? First, improve the evidence for drugs Medicare buys. Payment decisions should no longer be based on surrogate markers like the relationship between higher hematocrits and a subjective measure like "more energy."

Second, the agency should require randomized clinical trials, systematic reviews and meta-analyses to prove that a drug it pays for results in better outcomes for patients. In addition, since the companies selling the drugs have a stake in the outcome, those trials, reviews and analyses should be conducted by physicians without conflicts of interest.

Finally, if CMS doesn't have that kind of evidence generated in independent studies, it shouldn't pay for any drug that has not been prescribed for an FDA-approved use and at an FDA-recommended dosage.

This past week, Bernadine Healey, the former head of the National Institutes of Health, launched a wrong-headed attack against evidence-based medicine in U.S. News and World Report. (For a good blog entry attacking her article, see Gavin Yamey's latest posting on the PLoS Medicine website.) The Amgen-Epogen-dialysis saga is a perfect example of how ignoring the evidence is costing taxpayers a bundle.

Meanwhile, economic pundits like Robert Samuelson (see today's Washington Post) rail against increased Medicare spending (even though its costs are rising at a much lower rate than overall health care spending, a fact I wish he had mentioned in today's column).

But I agreed with his larger point, which is that uncontrolled health care spending (not just Medicare) will bankrupt the rest of the economy if left unchecked. But how should we rein it in? But cutting benefits and raising first-dollar coverage so people will simply stop going to the doctor for minor ailments and preventive care?

That would be a tragedy. What we need now are reporters in the mainstream media willing to go after companies like Amgen that rip off Medicare. Of course, we also need courageous editors willing to ignore the fact that the drug industry's full page ads are a major prop in their shrinking bottom lines.

But that's another story.

FDA's Graham Pleads for Common Sense

David Graham, the Food and Drug Administration safety officer who blew the whistle on Vioxx, has concise and damning review of the clinical trial history for the Cox-2 inhibitor class of painrelievers in this week's Journal of the American Medical Association. If the lessons of recent history are learned, he concludes, "the FDA's concerns will now be squarely focused on patient safety rather than corporate profitability, and, ultimately, common sense will prevail." You got to love the optimism.

What If It Were Docs Versus Drugs?

The latest Therapeutics Letter out of Canada points out that Canadians now spend 25 percent more on drugs than on physicians. Why? Drug spending more than doubled between 1996 and 2003, while physician payments lagged. I suspect a similar study in the U.S. would find the same trend.

Moreover, the study showed that fully 80 percent of the increased spending on drugs went for so-called "me-toos," which are drugs that are no different therapeutically from other drugs already on the market. Companies bring them through the expensive clinical trial process so they, too, can have an entry in lucrative markets like pain relief or gastric distress -- hence the name, me-too.

Their conclusions? "Since most new me-too drugs are much more expensive than equally effective older drugs, they represent a waste of health care resources. Physicians collectively have the power to prevent this waste and thus free up money for other sectors of the health care system," the report said.

That suggests a powerful argument that could be addressed to those doctors whose offices still accept pens, mugs and lunchtime pizzas (today's New York Times reports on a new rule at Stanford University Medical School prohibiting these forms of marketing): If you start prescribing equally effective generics instead of the pricey me-toos, you'll lose the mugs and pens. But you might get a raise.

9/11 Five Years Later

This is a day of remembrances and I had to smile this morning as I listened to historians Doris Kearns Goodwin and David Kennedy on the radio asking an interesting series of "what if" questions. High on their list: What if President had actually united the country by taking some concrete steps to reduce our oil consumption, which remains the primary financial prop for Middle Eastern terror?

Their comments reminded me of my own first reactions to the terrible events of five years ago. Sitting in my home office, cut off from my students in lower Manhattan (I was teaching at New York University at the time), I penned these words for Marketplace Radio. The commentary aired on September 18, 2001:

America is in a war against terrorism and people on the home front want to help. But what should they do? Progressives like myself wring our hands about defending civil liberties and stemming hatred during these perilous times. But that’s not enough.

If we want to catch the hearts and minds of the American people, we have to say more. I propose that we use this moment of national grief and unified purpose to advance a positive agenda.

First, let’s immediately wean America from its depends on foreign oil. As Daniel Yergen wrote in “The Prize,” oil has fueled both economic growth and great conflicts in the 20th century. But in the 21st century, it has become albatross around the advanced industrial world’s neck.

It is the primary source of not only air pollution and global warming, but of geopolitical instability. Isn’t it shocking that so many of the terrorists came from Saudi Arabia, the world’s largest oil producing state? The technology is there today to end our oil dependency. If it wanted to, the automobile industry could within five years have every vehicle rolling off assembly lines using clean technologies like fuel cells or battery-powered hybrid engines.

Second, America is now faced with a crisis in the airline industry. Let’s build a high speed rail system. That would solve two problems. It would reduce our appetite for oil, and take the pressure off the airlines by eliminating most flights under 300 miles. We’re dreading that airport gridlock and long lines for security checks. We could entangle that mess by shifting government investment into high speed trains. And by building a high speed rail system, it would create tens of thousands of jobs, just what the economy needs right now. And don’t forget: the Interstate Highway System was built in the name of national defense.

Ending our dependence from foreign oil; a high speed rail system; jobs from a major public works project – these home front programs are practical, they are progressive, and they would give the economy a boost. And most importantly, it would unite the nation in the home front war on terrorism in a way that doesn’t sacrifice our basic freedoms.

In Washington, this is Merrill Goozner for Marketplace.

What can we say about the Bush administration's response to 9/11 five years later? It still hasn't begun work on this crucial agenda. Instead:

By every objective measure on the one issue that even the President says he should ultimately be judged, George W. Bush has been a total failure.

J&J Seeks Objectivity, But Does It Seek All Truths?

The Wall Street Journal reports this morning that Johnson & Johnson's Scios unit "named" Duke University and the Cleveland Clinic to run a $100 million trial testing the safety and efficacy of Natrecor, a heart-failure drug widely promoted for off-label uses that may cause kidney failure among other unwanted side effects. For background on this story, see my op-ed, posted here, from a year ago.

While I'm sure that the two institutions will do all in their power to insure the independence of this high-profile study, the key word in the story is highlighted in quotes above: J&J NAMED the institutions. The writer could have used the word "chose" or "selected." Whatever. The point is that industry-funded studies will always bear the taint of conflict of interest as long as the sponsor, who has the most at stake, plays a role in organizing the study.

This is as much true in the world of environmental science as it is in pharmaceutical science. Every study that has ever been done on the subject shows a correlation between outcomes and sponsors. In other words, a study funded by a particular source is likely to come up with an outcome that reflects the self-interest of that source.

How to avoid this taint? Simple. If J&J needs a study done, it should be able to pay a fee -- the cost of the study -- to an independent agency, which then selects the clinicians and statisticians who will conceptualize the protocols of the trial. If J&J wants to spend $100 million on a clinical trial involving Natrecor, there are probably many more questions of interest to learn besides whether this particular drug is safe.

For instance, how does it compare to every other drug out there for the same condition? How useful is it when given off-label (the greatest expense associated with use of the drug)? How does it stack up in a cost-benefit analysis compared to other drugs for the same condition.

Memo to the Duke and Cleveland Clinic investigators involved in this trial: Curious minds would want to know.

Governator Vetoes Single-Payer Bill

I learned from Harold Meyerson's op-ed in today's Washington Post that Gov. Arnold Schwartzenegger is transforming himself into a pseudo-liberal (a girlie-man?) to resuscitate his comatose poll ratings. Alas, he didn't report the big news out of California yesterday, which would have contradicted that image. The governator vetoed the single-payer health insurance bill passed by the Democratically-controlled Sacramento legislature last month.

The text of the veto message was instructive because it uses every Big Lie that will be thrown against progressives who unite around a national single-payer plan as the only real solution to the U.S. health care financing crisis. Here's just one paragraph:

Socialized medicine is not the solution to our state's health care problems. This bill would require an extraordinary redirection of public and private funding by creating a vast new bureaucracy to take over health insurance and medical care for Californians - a serious and expensive mistake. Such a program would cost the state billions and lead to significant new taxes on individuals and businesses, without solving the critical issue of affordability.

Nearly every phrase in that paragraph is untrue. Let's go over them one by one.

Socialized medicine? Every time my elderly, ill mother visits a doctor at her nursing home, the private physicians, hospitals and the nursing homes that bill Medicare for her care are a mix of for-profit and not-for-profit health care providers who definitely are not employed by the government. The provision of health care under Medicare is a private affair. When Medicare was passed in 1965, the American Medical Association attacked it as socialized medicine. It wasn't then. It isn't now. Another way to describe single-payer health insurance is Medicare for all. As in the current Medicare, as in Canada, the provision of most health care will be by private sector actors.

Create a vast new bureaucracy? Every time I go to the doctor, the dentist or my eye doctor, I fill out a separate set of forms reflecting the different insurance companies that pay for those services. My various doctors maintain huge staffs simply to manage the dozens of insurance systems they must bill in order to get reimbursed for services.
Analyses of single-payer health care plans estimate the one-time cost savings from eliminating the vast bureaucracies that dominate our current health care system at 10 to 20 percent of total costs -- a potential $200 billion one-time windfall.

Cost billions and lead to significant new taxes? One private analysis of the California bill, conducted by the respected Lewin Group, estimated the state's single-payer plan would reduce total health care payments in the first year while insuring everyone who is currently uninsured.

The only half-truth in that veto message was the statement that single-payer health insurance would involve an extraordinary redirection of public and private funding. The original bill, later stripped of its financing provisions (which turned it into a mere symbolic measure), called for substituting payroll taxes on employers and individuals for the current system of employer-provided health insurance coupled with individual co-pays and deductibles.

I don't know if payroll taxes are the best way to go. But for the sake argument, let's look at what the impact of such a shift might be on individual businesses and households. Would they be worse off or better off from a financial standpoint?

The short answer is that it all depends. If you own a business that currently provides your employees with very good health insurance with very low co-pays and deductibles (a shrinking share of the U.S. business community), then a single-payer plan financed through payroll taxes would probably make your business slightly better off and your employees slightly worse off. You'd get a huge break by not having to buy health insurance anymore, which would be largely, but not entirely, offset by a payroll tax. (Example: it might cost you 10 percent of the average employee's pay to provide him or her with health insurance; the employer payroll tax might be 8 or 9 percent.)

But what if you owned a business that didn't provide health insurance for many or any of its employees (the Wal-Marts of the world). You wouldn't save much by eliminating your insurance bill. But you would be stuck with the new employer payroll tax. In other words, all businesses would now be on a level playing field, no longer competing through the benefits they provide.

How about individuals? If your employer provides you with a Lexus plan with very low co-pays and deductibles or you are a high income worker, the individual health care payroll tax of 2 or 3 percent would probably increase your health care payments (assuming you're relatively healthy).

But if you are like most employees today with employer-provided health insurance, your out-of-check co-payments for health insurance are approaching $100 or more a month. On top of that, you're paying $10 or $20 for every doctor's visit, ditto for prescriptions and face a large deductible if you wind up in the hospital. Most families easily pay $1,500 a year or more in health care bills. A person would have to earn over $75,000 a year before their payroll tax equalled that amount. And you could rest assured that, in the case of a medical emergency, you would never be faced with a bankruptcy-inducing hospital co-pay.

As I said, I'm not sure that a payroll tax is the best way to go. Eliminating health insurance payments for businesses and all employers is like handing out a $600 billion-a-year tax break -- by far the largest in U.S. history. If the nation could ever have an honest discussion about "redirecting" the way we pay for health care that was fair for everyone concerned, we certainly would want to consider making income taxes and possibly even a value-added tax a part of the mix.

But the governator's rhetoric yesterday suggests honest discussions about health care reform is not on anyone's agenda -- especially if you are a Republican governor with rapidly sinking poll numbers looking to burnish his liberal credentials in all the wrong places.

Blank Verse

Dr. Arnold Blank of Forest Hills, NY has an enlightening essay in this week's Journal of the American Medical Association. You can read it by clicking on the above link. It's worth five minutes of your time.

Paying for an Aston-Martin, Getting A Ford

Whenever I see a cost-benefit analysis for a new medical technology, I grab onto my wallet. It has long been known that the outcomes of clinical trials funded by drug and device companies tend to favor their sponsors. But cost-benefit analyses take this tendency to a whole new level. Indeed, if there’s ever been a cost-benefit analysis sponsored by industry that didn’t favor the new technology, I’ve yet to see it.

That’s why I was fairly surprised by the widespread attention given this week to a Harvard University study by David Cutler in the New England Journal of Medicine suggesting that the U.S.’s massive investment in health care over the past four decades has been money well spent. When I first saw it, I shrugged. “Another C-B analysis. No one can take this stuff too seriously.”

But I was mistaken. Defenders of a health care system that is threatening to bankrupt the rest of the economy have a new mantra. Yes, we spend more than any other country on earth on health. But look what we’re getting for our money!

The average cost per year of life gained between 1960 and 2000 was just $19,900, the study concluded. Even for those over aged 65 in the past decade – when health inflation was at its highest – the cost per added year was $145,000. While that may seem high by some measures, is it too much for a wealthy society like ours? “The national focus on the rise in medical spending should be balanced by attention to the health benefits of this increased spending,” the report soberly concluded.

Why do I feel like the guy who just paid $125,000 for an Aston-Martin only to discover he had a Ford engine under the hood?

In 1960, the United States health care system consumed just 5.1 percent of our gross domestic product, not very different from most other advanced industrial nations. We didn’t have Medicare or Medicaid. Millions of people went without health insurance.

Yet it was an age of middle class prosperity and upward mobility. U.S. life expectancy hit a respectable 69.9 years that year, up nearly a decade from 20 years earlier. Among the 30 nations that today belong to the Organization of Economic Cooperation and Development (the OECD is the club for “advanced” industrial nations), the U.S. ranked in the middle of the pack at 16th. But it was a fairly clustered top. The U.S. was only 3.7 years off leading Norway’s 73.6 pace.

Fast forward 40 years and where are we? By 2000, the U.S. life expectancy had risen to 76.8 years. But our rate of increase has lagged badly behind the rest of the world. Japan had emerged as the leader, a full 4.4 years ahead of the U.S. We’d slipped five notches in the ranking to 21st, and if it weren’t for newcomers to the ranks of the OECD like Turkey, Korea, the nations of Eastern Europe and Portugal, we’d be dead last.

But what’s happened to spending in that period? Our health care system by 2000 was consuming 13.3 percent of GDP (it’s now up to 16 percent). No country on earth spends anywhere near as much. Take Canada, for instance, that hellhole of long lines and frustrated patients, if we’re to believe some reports. Their life expectancy exceeds ours by 2.5 years and they spend 4 percent less of GDP on health.

Indeed, if we compare our rate of increase to other nations, it cost U.S. businesses and consumers 1.19 percentage points of increased economic output for every year of additional longevity over the past 40 years. It cost most other countries about half that.

Improved and therefore more expensive health care has been responsible for some of the increase in longevity of the past 40 years. Half – Cutler’s estimate – seems reasonable. But studies like his can only serve to distract attention from the fact that our fractured and inefficient health care system, plagued by high administrative overhead, delivers worse outcomes that most other advanced industrial nations despite imposing far higher costs.

Where are the NEJM studies that explain that?