CMS Decision on Compendia Looms

Billions of dollars in Medicare payments will be at stake this week when the Center for Medicare and Medicaid decides whether or not to add three additional drug compendia to the one that physicians already use to justify reimbursement for off-label use of cancer chemotherapy drugs. The projected decisions dates were June 2-4, according to an official I interviewed earlier this month.

Last Thursday, I sent this letter to CMS asking them to hold off on making the decision until one of the compendia -- published by the elite National Comprehensive Cancer Network -- lets the public and patients know if the physicians who wrote it have ties to manufacturers whose drugs they are evaluating.

So far, no reporter has picked up on this story (I first wrote about it here.) I find this curious. I've read a number of stories in recent months about the high cost of newer anti-cancer drugs, and how people are going broke or deep into hock trying to afford the co-pays. Newer anti-cancer biologics like Genentech's Avastin often carry price tags nearing $10,000 a month. If the use is listed in an approved compendia, Medicare and Medicaid will pay some or even most of that cost. Private insurance companies often follow Medicare's lead on payment issues.

But patients in private plans (those under 65) often have to pay a quarter or more of that price as a co-pay. They rarely have the research skills to determine if taking those drugs is the best thing to do given their dire circumstances. They usually rely on their oncologists. And their oncologists rely on these compendia to come up with off-label regimens for their desperate patients, who are often in the final stages of their ultimately fatal disease.

The evidence for including many of the off-label uses in these compendia is thin. Many, at best, add just a few months of life, often with harsh side effects. Yet they must be taken throughout the final months or even years of the diseases' progress.

It is always a close call whether or not to include these possible uses in compendia that lists both on and off-label uses. If it wasn't, the companies would have gone to the Food and Drug Administration and sought approval for that indication. Is it too much to ask on behalf of patients, doctors, and taxpayers that physicians without ties to the manufacturers make the compendia inclusion decisions? If CMS isn't willing to go that far, is it too much to ask that an agency facing long-term fiscal instability at least require that the physicians who write the compendia tell us which drug companies they work for?

Billions of dollars a year are at stake in the decisions that are slated to be made next week. Hopefully, someone on Capitol Hill is paying attention.

Conflicted Judges Give Merck Another Victory

Judging by the pattern of courtroom decisions, you'd think Vioxx was a safe drug.

A three-judge panel in Texas today overturned a jury decision awarding $26 million to the widow of a man who had died from a blood clot eight months after he began taking the drug in 2001. It was Merck's second big victory of the day. Earlier a New Jersey appeals court reversed most of a $13.9 million settlement won in a non-fatal case.

If you're into keeping score, that's 11-3 in favor of Merck in individual cases that have made their way through the court system to final jury or appeals court decisions. Does that mean that juries and judges, once they hear all the evidence, generally conclude that Vioxx is a safe drug?

Hardly. Here's one confounding variable. In Texas, the appeals court judges who ruled in the drug company's favor were elected, and in recent campaigns had received contributions from the law firms representing Merck. "Outrageous," plaintiff lawyer W. Mark Lanier told the Associated Press.

The New Jersey decision, on the other hand, gives some hope to those fighting efforts by the drug industry to use federal regulation (or the lack thereof) to preempt state product liability laws (and a tip of the hat to Ed Silverman's Pharmalot blog for pointing the errors of news accounts; he reprints the court decision here). Though the decision overturned the punitive award, the compensatory damages (about a third of the total) were left in because of a traditional product liability claim that the company had failed to adequately warn its users about potential risks.

It's unlikely this decision will affect the business-friendly Supreme Court, which recently ruled in favor of preemption in a medical device case and will hear a similar drug case next fall. The prospects for injured patients keeping their right to sue are slim.

Merck lawyers have already effectively admitted some responsibility for the Vioxx disaster. Last November the company set up a $4.85 billion pool to settle personal injury cases that involved heart attacks, strokes or death. Some 45,000 people enrolled for payments as of March 31. FDA safety expert David Graham has estimated anywhere from 40,000 to 120,000 people died from Vioxx between 1999 and 2004 before Merck voluntarily withdrew the pain reliever from the market.

Taking Chantix to Stop Smoking? Proceed with Caution

Pfizer is launching an advertising and public relations campaign to reassure the public that taking Chantix, the anti-smoking drug now approaching a billion dollars a year in sales, is safe, the Wall Street Journal reports this morning.

The drug industry giant needs to counter the recent Institute for Safe Medication Practices (ISMP) report showing a high level of adverse event reports associated with the drug. The ISMP based its report on consumer and physician complaints filed with the Food and Drug Administration.

The report included 988 serious adverse events (SAEs) during the 4th quarter of 2007, including accidents and injuries, heart rhythm disturbances, heart attacks, seizures and abnormal muscle spasms or movements, high blood glucose and new onset diabetes, aggression, psychosis, suicide, severe skin reactions, and vision disturbances.

In response to the ISMP report, the Federal Aviation Administration said it would no longer permit pilots or air traffic controllers to use Chantix, and the Federal Motor Carrier Safety Administration advised medical examiners to not qualify anyone currently using Chantix for a commercial motor vehicle license. The Chantix label includes a warning that Chantix may impair driving ability.

The FDA recently issued an alert about psychiatric symptoms linked to Chantix and requires pharmacists to distribute a medication guide with Chantix prescriptions, warning of potential psychiatric side effects.

Chantix, which was approved in May 2006, is thought to achieve its effect in smoking cessation through partially blocking and partially stimulating a type of nicotinic acetylcholine receptor. Acetylcholine receptors play many roles in the brain and body and are central to muscle contractions, including voluntary movement as well as heart muscle contractions and the tone of the smooth muscles that line blood vessels.

Chantix is thought to be most active against a particular receptor that affects the release of dopamine in the brain. Dopamine plays a major role in addiction, mood, and muscle movement. Chantix was derived from cytisine, a smoking cessation drug that has been used in Europe for decades. Of note, cytisine is contraindicated for patients with hypertension and advanced atherosclerosis. The author of a 2006 meta-analysis on cytisine stated that studies of cytisine's toxicity in humans conducted by Sopharma, the manufacturer of cytisine, were not published in scientific journals and Sopharma did not provide him with copies when he requested them.

ISMP identified the "safety signal" for Chantix through monitoring the flow of quarterly adverse event reports to detect changes in the numbers of serious events and other trends. In the 4th quarter of 2006, Chantix appeared for the first time among a small group of drugs that accounted for 100 or more reports of serious injury during the quarter. By the 2d quarter of 2007 it ranked third among all drugs in the United States. By the 4th quarter of 2007 Chantix accounted for more reports of SAEs in the United States than any other drug.

The ISMP report notes that adverse event reports do not establish causality, and the authors recommend additional research to resolve questions about the safety of Chantix. In the meantime, the authors recommend that doctors and patients exercise caution in the use of Chantix and consider alternative methods of quitting smoking.

The federal clinical practice guideline on treatment of tobacco use and dependence, adopted in 2000 and updated this month, recommends that all smokers who wish to quit be treated with drugs, unless medically contraindicated. The guideline recommends the use of Chantix, buproprion, and nicotine replacement therapy. The guideline-writing panel, chaired by Michael Fiore, has been criticized (see this February 2007 Wall Street Journal article, this post by Roy Poses at Health Care Renewal Blog, and this post by Michael Siegel on The Rest of the Story Blog) for the ties of some of its members to the makers of stop-smoking products. Fiore, a strong advocate of the use of smoking cessation drugs, is the holder of a chair endowed by GlaxoSmithKline, the manufacturer of bupropion and various nicotine replacement products.

Michael Siegel, a physician with 20 years experience in tobacco control, recently stated that the guideline "overestimates the benefit of drugs in smoking cessation and overlooks population-based evidence showing that most people who quit smoking do so without pharmaceutical aids." According to this Associated Press article about the guideline, Lois Biener, a researcher on tobacco use and control at the University of Massachusetts in Boston, said there was little evidence that smoking cessation drugs are superior in the long run to quitting cold turkey, and that while a few studies have shown some benefit, it's "way less than what is claimed" by medication advocates.

-- PM

Defending Prevention

Last February, the New England Journal of Medicine ran a potentially misleading review of the cost-effectiveness of illness prevention strategies that may have led many casual readers (such as the editors of the Washington Post Health section) to conclude that most health-improving measures -- such as aggressive counseling for people who are either overweight or smoke -- cost more in the long run than they are worth. This morning, the Journal of the American Medical Association carried a proper antidote by Steven H. Woolf of Virginia Commonwealth University, who is fast becoming a leading expert on prevention techniques for improving the nation's health.

Woolf admits that personal behavior is difficult to change, and many intervention strategies for preventing disease cost more money for the health care system than they save. But he takes direct aim at the NEJM article claim that "drew similarities between the cost-effectiveness ratios of prevention and disease treatments, all but ignoring the much lower cost-effectiveness ratios of the preventive services that guidelines advocate."

But touting those physician-delivered prevention services that are cost-effective is not the core of his argument. The health care system is the improper vehicle for delivering the most cost-effective preventive services and strategies, he argues. "Behavior change occurs where people live -- at home, work and school -- but the community offers little infrastructure for modifying lifestyle."

Advertising, school lunches, restaurant menus, entertainment media, convenience technologies, and the built environment discourage physical activity and promote consumption of calorie-dense foods, large portions, tobacco, and alcohol. Social conditions (eg, inadequate education, impoverished communities) impose additional barriers.

Boosting prevention is only partially a question of how our society allocates its health care system resources. A properly defined prevention campaign requires tackling issues that lay beyond the health care system. Imagine calorie counts on every fast-food and chain restaurant menu. Imagine rejuvenated big city public health departments sending skilled nutritionists bearing dietary advice and training into low-income neighborhoods suffering from some of the nation's highest obesity rates.

Giving people the tools to help themselves lose weight is the first step in the process of reversing the nation's obesity epidemic. (A new study, also published in today's JAMA, showed the rate of childhood obesity has finally stopped growing, but about a third of all kids are still either obese or overweight, about triple what it was in the 1960s and 70s.)

Woolf's hope is that the demonstrable effect that deteriorating health is having on longevity and the economy will generate the political will to act. "Self-interest (living longer and healthier) and common interest (economic stability) may inspire the personal sacrifice of getting healthy and the collective sacrifice (by the private sector and the state) of mobilizing the resources to make it happen," he concludes.

"Trials on Trial"

My effort to call attention to the Food and Drug Administration's decision to withdraw from the Helsinki Declaration that protects people in clinical trials is finally starting to make waves. This week's Nature magazine (subscription required) editorialized that the FDA "should rethink its rejection of the Declaration of Helsinki."

The FDA argues that it should not be bound by Helsinki because of the declaration is devised by a group it does not control, and is subject to periodic revisions that could confuse trial sponsors or contradict U.S. law. But it is tempting to conclude that the FDA is dropping Helsinki not because it is changeable, but because the agency disagrees with the way it has been changing -- in particular with its constraints on the use of placebos.

And our earlier post received a trenchant comment from Abbey Meyers, the about-to-retire chief of the National Organization of Rare Disorders. She was a tremendous help to me when I was writing "The $800 Million Pill," and her thoughts on this subject deserve the wider notice that top billing for a few hours on this website gives them. So here they are:

Forget about Helsinki! What about the Common Rule? All federal government agencies that are involved in any way with clinical research signed on to the Common Rule EXCEPT THE FDA! They have not even had a bioethicist on staff until about three years ago when they hired one bioethicist. It's no wonder they approved clinical trials for the blood substitutes when human research protections were the last thing on their priority list, and it continues to be ignored not only in third world countries, but New York, Chicago, L.A., etc. And they wonder why fewer patients are volunteering for clinical trials!

Conflicted Guideline Writers Pushed Dangerous Anti-Bleeding Drug

What were they thinking?

Early last year, a task force of thoracic surgeons and cardiovascular anesthesiologists met to write new clinical practice guidelines for how to conserve blood and prevent blood transfusions during heart surgery. Just a few months earlier, the FDA had learned that Bayer, the maker of Trasylol (aprotinin), a blood-clotting drug used in surgery, had hidden results of its own study of the drug from the FDA and from an FDA advisory committee. The story made national headlines.

The hidden data showed that patients who received aprotinin were at increased risk for death, kidney failure, congestive heart failure and stroke compared to patients who received other anti-bleeding drugs. Yet here is what the guideline, published in The Annals of Thoracic Surgery in May 2007, recommended:

1. High-dose aprotinin to reduce blood transfusions, blood loss and the need for followup surgery to stop internal bleeding in high-risk heart surgery patients. (The guideline notes that the benefits of use should be balanced against the increased risk of kidney dysfunction.)

2. Low-dose aprotinin to reduce blood transfusions and blood loss in other patients having heart surgery.

3. Lysine analogues to reduce blood transfusions and blood loss in patients having heart surgery. The guideline states, however, that the safety of lysine analogues "is less well studied compared with aprotinin."

The recommendations are labeled "Class I" (the classification for treatments for which the benefit clearly outweighs the risk) and "level of evidence A" (meaning sufficient evidence is available from randomized trials or meta-analyses). The authors rejected the safety concerns with aprotinin that had been raised by Dennis Mangano and colleagues in a 2006 study published in the New England Journal of Medicine.

A subsequent study published by Mangano's group in the Journal of the American Medical Association in February 2007 was not discussed. It is unclear whether the JAMA study, which found that aprotinin raises the risk of death over five years after surgery, was available at the time the guideline was being written. If not, one wonders why such important information did not merit an update or revision.

The votes on the three recommendations were 15 to 2, 15 to 2, and 16 to 1. Eight out of 17 of the guideline authors disclosed ties to Bayer in the form of lecture and consulting fees and/or research support. Would the outcomes of these votes been different if so many of the authors had not had ties to the maker of aprotinin? If the guidelines had not endorsed continued use of aprotinin, could lives have been saved?

On November 5, 2007, the FDA requested a marketing suspension of aprotinin in response to preliminary results of a trial showing an increased risk of death in patients receiving aprotinin. A week later -- more than nine months after the JAMA study, the Society of Thoracic Surgeons finally announced that the portion of the guideline relating to use of aprotinin was under review.

--PM

BusinessWeek's Interview with FDA's Richard Pazdur

Here's some must reading this morning.

Anyone interested in the cancer drug approval process at the Food and Drug Administration should read this interview posted yesterday on the BusinessWeek website. Richard Pazdur, chief of the FDA's oncology drug division, has some interesting things to say about the differences between big and small companies that are trying to get new cancer drugs approved, and his emotional response to desperate cancer patients who want access to unproven experimental therapies.

But most importantly (from a scientific point of view), here's what he had to say about efforts by some companies to salvage drug candidates that have failed in achieving their primary endpoint, which is usually prolonged survival:

One of the problems we've had is people coming to us after a drug fails because they've invested millions and millions of dollars into a drug; and then it's, "How can we salvage this?" In other words, failing your primary endpoint and then trying to salvage a trial by looking at subgroups of patients. That's akin to shooting an arrow and having it land on a wall and then drawing a target around it. It's an attempt to resurrect a trial that has failed.

Pazdur has been a frequent target of Wall Street Journal editorials, whose editors seem to have one ear permanently cocked in the direction of the cancer quackery that has always flourished on the fringes of modern medicine. It's nice to see that he hasn't lost his bearings, or his courage in standing up for scientific principles at the FDA.

The Preemption Threat

It can't come naturally for the Journal of the American Medical Association to be consistently more liberal than its rival New England Journal of Medicine. JAMA, based in Chicago, is housed within the reliably conservative physicians' guild, while NEJM is firmly nestled within Brahmin Boston's ivy-covered institutions.

A commentary in this week's JAMA (registration required) by Georgetown law professor Lawrence O. Gostin is a case in point. This non-physician properly warns physicians and the public that the Supreme Court's recent decision in Riegel v Medtronic Inc. removes the final safety net that protects consumers from unsafe medical devices: the right to sue when federal regulation has failed.

The case involved a New York man who sued after his arterial balloon catheter ruptured and almost killed him. Medtronic, the device manufacturer, claimed that since the Food and Drug Administration had approved the device, the company was no longer liable under state product liability laws. In legal parlance, federal regulation preempted state legislation. Last February, Chief Justice John Roberts' Supreme Court agreed.

According to Gostin, this misrepresented Congress' intent in passing the Medical Device Amendments in 1976, which gave the FDA the responsibility for the first time of approving medical devices for their safety and efficacy. Even its sponsors said "the legislation was to provide additional protection to consumers, not to withhold existing safeguards against defectively designed or labeled devices," he wrote. (It's interesting to note that a comparable NEJM commentary earlier this month drew similar conclusions about the negative consequences of the court's decision, but didn't buy the Congressional intent argument. "The fact that this question was answered in the affirmative by a vote of eight to one indicates that the issue was not a difficult one for the justices," its authors wrote.)

For 25 years, even the FDA held to the view that its regs didn't preempt state laws. But in 2004, after President Bush had appointed drug industry lawyer Dan Troy as FDA general counsel, the agency reversed its position and argued the preemption case.

In an era where the FDA has been systematically underfunded and its postmarket surveillance systems are clearly inadequate to identifying serious risks that emerge once the product is on the market, the courts provide a final line of defense for consumers where they can get compensation for injuries, Gostin argues. But just as importantly, it deters industry negligence and encourages a constant search for safer products. Litigation can also improve product labeling by bringing risks to light, which serves both patients and physicians.

Litigation also can uncover fraud committed against the FDA. Studies showing that companies knew about the risks of certain drugs and devices have frequently been revealed only because someone sued and their lawyers uncovered the documents during discovery. Alas, far too often that kind of information remains under seal when the cases are settled out of court. But that's a separate problem. Under this decision, that avenue of uncovering corporate wrongdoing will be shut down entirely.

Next year, the Supreme Court will hear a companion case involving drugs: Wyeth v. Levine. Dan Troy may have returned to Sidley & Austin to represent his drug industry clients. But his influence lives on at the FDA. The agency's legal office is still backing the idea that the obviously inadequate federal regulation of drugs preempts state product liability laws.

Concludes Gostin: "If the FDA's view were to prevail, patients would have no safety net in the likely event that the agency fails to detect and correct safety hazards."

In Defense of the Helsinki Declaration

Author Sonia Shah on the Nation website blasts the Food and Drug Administration for repealing U.S. adherence to the Declaration of Helsinki and substituting the agency's Good Clinical Practice guidelines to govern clinical trials run in foreign countries. I'm glad somebody picked up on our story from last week.

One reader of that earlier story suggested researchers operating in developing countries must offer local standards of care to the comparison arm of a trial, and can't get away with only offering a placebo. But what are the local standards of care? A close reading of the FDA's 1996 "E6" guidance on Good Clinical Practice (see page 39) says only that the clinical trials must comply with "applicable regulatory requirements" in the local country.

You wouldn't have to be much of a lawyer to interpret that to mean that if the local standard of care was less than what was globally available (think about an expensive anti-cancer drug, for instance), or if there was no local standard of care, then a new drug being tested in a clinical trial could be compared to either a placebo or an older ineffective medicine and still be in compliance with the E6 Good Clinical Practice guideline.

There is much room for mischief in such guidelines, especially in poor countries with inadequate regulations and lax oversight bodies. Contract research organizations are popping up all over the world to conduct clinical trials for the global pharmaceutical industry. The U.S. should be helping these countries police those groups better, not passing regulations that will make it harder for them to protect their own citizens.

Medicare Nears OK of Cancer Drug Payment Guide
That Doesn't Reveal Conflicts of Interest

Medicare's top officials as early as this morning may sign off on adding three additional drug compendia that can be used to justify reimbursement for the off-label use of anti-cancer drugs, including one that clearly violates the agency’s guidelines on conflict-of-interest disclosure.

The non-profit National Comprehensive Cancer Network’s Drugs and Biologics Compendium, drawn from its trademarked Clinical Practice Guidelines, fails to disclose the corporate ties of the 20 to 24 experts who sit on each of its 44 guideline-writing panels. Instead, it merely lists all the companies which gave money or research support to any of the committee members without reference to any specific member or the amount given.

Oncologists who administer cancer chemotherapy drugs to their patients in offices or free-standing facilities receive reimbursement for those drugs plus a small profit under Medicare's Part B program. Reimbursable drugs include those prescribed off-label as long as they are listed in compendia officially designated by the Center for Medicare and Medicaid Services, Medicare's parent agency. Most private insurers follow Medicare's lead when setting their cancer drugs reimbursement policy.

In 2006, the Medicare Evidence Development and Coverage Advisory Committee recommended that any new compendia approved by CMS carry public identification of “potential conflicts of interest of the compendia’s parent and sibling organizations, reviewers, and committee members.”

The NCCN Clinical Practice Guidelines and Compendium, published by a consortium of 21 of the nation’s leading cancer treatment centers, follow the same non-disclosure disclosure policy as the American Society of Clinical Oncology, which holds its high-profile annual meeting in Chicago starting May 30. Companies financially involved with any of the researchers behind any of the hundreds of studies released at the meeting are listed on the disclosure form. But the disclosure does not reveal which company gave money to which researcher or how much.

In addition to the NCCN drug registry, CMS early next month may approve Elsevier’s Clinical Pharmacology and Thomson Healthcare’s DrugDex and its companion DrugPoints. The Elsevier publication relies on in-house scientist-writers who are prohibited from accepting any “gifts or benefits” from the drug industry. Thomson uses outside experts supervised by its Oncology Advisory Board, many of whom have ties to industry that are disclosed on the company’s website. For instance, Thomas Marsland, a Florida community oncologist who chairs the advisory board, reports owning stock in Genentech, maker of the anti-cancer drug Avastin.

But the NCCN website does not disclose that Robert J. Motzer, an investigator at Memorial Sloan-Kettering Cancer Center in New York who chairs the NCCN kidney cancer guideline writing committee committee (registration required), receives research support from Genentech. The NCCN Compendium listing for Avastin (generic name: bevacizumab) was recently updated to include its use in slowing tumor progression in kidney cancer. The Food and Drug Administration has not approved it for that indication and it has not been shown to prolong life. Avastin, which blocks blood vessel formation, can cost cost as much as $8,800 a month.

All three compendia received a scathing review from the Agency for Healthcare Research and Quality’s technology assessment program, which analyzed the compendia's reviews of 14 on- and off-label indications for commonly used anti-cancer drugs. An estimated 60 percent of anti-cancer drugs are used off-label. “Compendia claim to use evidence-based methods in their evaluation of therapeutic agents, (but) cited literature was often neither the most recent nor the most valid in terms of study design,” the reviewers noted. DrugDex was more likely than the others to list off-label indications, while the NCCN compendium was scored for failing to discuss adverse effects.

NCCN, a free-standing non-profit created by prestigious medical centers like Sloan-Kettering, M.D. Anderson Cancer Center in Houston, and the Fred Hutchinson Cancer Research Center in Seattle, acknowledged “support from many companies.” It had a $15.5 million budget in 2005. It lists 25 drug company supporters on its website, but not the amounts given.

The drug industry’s financial role in the NCCN program drew a heated response from Thomas Kaye, senior pharmacy director at Passport Health Plan, which serves 155,000 Medicare and Medicaid beneficiaries in Kentucky. “There’s an inherent bias in an organization that gets the majority of its funding from pharma,” the Louisville-based pharmacist said.

“Negative things do not get published. We deal a lot with access to care issues, and when we have limited dollars, we want to make sure we’re providing the most value for what we have," he said. "I would not like to see NCCN become an official compendium because of possible bias.”

The consulting firm IMS Health projects global sales of anti-cancer drugs will grow at an annual rate of 12 to 15 percent to $75 to $80 billion by 2012. A number of recent news stories have focused on cancer patients who are having problems affording the co-pays on their increasingly pricey chemotherapy regimens. NCCN CEO William McGivney was traveling last week and unavailable for comment.

This story first appeared in Integrity in Science Watch, a publication of the Center for Science in the Public Interest.

Is It Really the End of This Bloody Mess?

I suspect the trial lawyers will still have something to say about that.

A large clinical trial published Thursday in the New England Journal of Medicine confirmed that Trasylol (aprotinin), an anti-bleeding medication designed to reduce major bleeding during heart surgery, significantly increased the risk of death compared to two lysine analogues, which are much cheaper alternatives. The trial was stopped last October when it became apparent the drug was killing some people unnecessarily.

Patients on the slab for heart surgery were given aprotinin to reduce the need for blood transfusions. But, as this latest trial (called BART) found, they had a 50 percent higher risk of death in the first month after the operation. In an accompanying editorial, Wayne Ray and C. Michael Stein concluded that "in all likelihood, this is the end of the aprotinin story."

If so, this final chapter closes the book on a story largely written through the courageous and pioneering work of Dennis Mangano of the California-based Ischemia Research and Foundation, whose data-mining research and epidemiological review of outcomes among post-operative patients first brought the dangers of this drug to light. His story was featured on 60 Minutes earlier this year.

(And for some more background on how Bayer HealthCare, the drug's manufacturer misled the FDA, see this GoozNews post and this New York Times story.)

In the wake of this latest trial results' publication, the FDA announced that Bayer had notifed the agency that it would begin removing the remaining aprotinin stock from the U.S. market. Currently, the FDA limits access to aprotinin to investigational use according to procedures described in a special treatment protocol. The FDA also said that it is reviewing the BART data to reassess the appropriateness of this special treatment protocol.

In the editorial, Drs. Ray and Stein suggested that the aprotinin controversy lasted as long as it did because other trials of the drug tested it against a placebo instead of other available drugs. They also pointed out that although blood loss during surgery is of undisputed clinical importance, it is a surrogate endpoint.

They stated that, as with many other drugs, evaluation of anti-bleeding medications must include effects on death and other clinical endpoints, and not rely on surrogate endpoints (for more on that issue, see this GoozNews post.

Meanwhile, the results of the POISE trial, published online May 12 in The Lancet, call into question current guidelines that recommend use of beta blockers preoperatively in patients undergoing noncardiac surgery. These guidelines were based on previous studies that were small and showed conflicting results, but nonetheless adherence to the guidelines is used in quality assessments and hospital rankings.

In POISE, 8351 patients with cardiovascular disease or at high risk for cardiovascular disease were randomized to Toprol (metoprolol), a beta blocker, or matching placebo, given 2-4 hours before surgery and continued for 30 days. The patients who received metoprolol had fewer cardiovascular events but more deaths and strokes than the placebo group (all-cause mortality 3.1 percent vs. 2.3 percent, stroke rate 1 percent vs. 0.5 percent).

"What POISE says is that in the dosing we used, we see beta blockers have substantial risk in the perioperative setting," lead researcher Dr. Philip Devereaux told Heartwire, "and until someone demonstrates with a clear and large randomized controlled trial that an alternative dose is both effective and safe, it's just not rational, not in people's best interests, to be assuming -- that's how we got into this trouble in the first place."

He points out that if even 10 percent of physicians followed the guidelines, the POISE results mean that in the past decade 800,000 people have died and 500,000 have had a major stroke because they were given preoperative beta blockers.

In the cases of aprotinin and beta blockers in noncardiac surgery, many patients died or suffered injury because a drug or class of drugs were used without sufficient evidence, in the form of large randomized trials, showing that the benefits outweighed the risks that didn't show up in the limited clinical trials given to the FDA at the time of the drugs' approvals. Physicians need to weigh the strength of the available evidence carefully before adopting the latest new drug or treatment strategy.

-- by PM

Health Wonk Review

A new one is up at Jason Shafrin's Healthcare Economist website. Check it out!

CBO Wants to Play Major Role in Health Care Debate

Congressional Budget Office chief Peter Orszag told a Health Affairs forum yesterday that his office plans to play a major role in next year's health care reform debate. He now has 47 analysts working on a series of major reports that will give Congress a menu of options for holding down rising health care costs in the nation's Medicare and Medicaid programs. They will be released shortly after the fall election.

"It may be that policy makers don't want to deal with cost growth," he said. "but at least we can give them a list of 20 options."

While recognizing that government programs represent only half of health care expenditures, and that private spending is rising just as fast as public spending, Orszag said that rules adopted for Medicare in particular can determine how medicine gets practiced throughout the system. And the cost-savings potential is huge, he said.

"Thirty percent of health care services delivered do not improve health outcomes," he said. "That's $700 billion a year. There is not another area in economics that presents such an opportunity. That's five percent of GDP."

That prompted one questioner to articulate the famous nostrum that one man's waste is another man's paycheck. To which the head of the non-partisan CBO replied, "we need evidence, and we need incentives to drive patients to go for better care, not more care."

Perhaps his most interesting observation involved how to structure reform. Rather than focus on economic incentives like tax breaks that at best drive behavior at the margin, he said reformers should pay close attention to the psychological and social dynamics of how people make their personal health care choices.

For instance, insurance programs should be structured so that people default into the lowest cost option that delivers the best care. Most people, he said, do not choose their health care plans, they default into them. "Inertia is an incredibly powerful force in human behavior and ignoring that is just not an option," he said.

On a down note, he added his voice to the growing conventional wisdom that prevention measures will not generate savings for the health care system. All candidates for president have made prevention promotion a central motif in their health care plans, claiming that it will save the health care system money in the long run by promoting healthier lifestyles and arresting ill-health before it progresses to chronic disease.

In the candidates representatives' panel that followed, Harvard University's David Blumenthal, who is advising Sen. Barack Obama, said the key to determining which prevention steps make sense (those most often cited by prevention advocates are direct interventions to help smokers quit and to help obese people adopt better eating and exercise lifestyles to prevent diabetes) is cost effectiveness research that accurately measures the benefits of such programs.

"We know much secondary prevention is within the range of what makes sense in terms of cost effectiveness," he said.

George Washington University's Jeanne Lambrew, an informal adviser to the Clinton campaign, emphasized the need for the nation to create a "best practices institute," which could encourage physicians and public health agencies to adopt such cost-effective prevention measures.

Former CBO chief Douglas Holtz-Eakin, who is advising Sen. John McCain, signaled the Republicans, if elected, will fight against creation of new agencies to generate cost-effectiveness studies and develop authoritative best practices guidelines. These new agencies will be able to identify not just cost-effective prevention measures, but should help lower costs by highlighting those technologies that are both pricey and less effective and therefore shouldn't be reimbursed by payers.

"We need decentralized information sharing," the Republican presumptive nominee's adviser said. "We need to build a system that seeks out information about profitable prevention measures, one that is decentralized, not government run."

FTC Wants to Waylay 'Pay to Delay' Deals

A few months back, the Federal Trade Commission sued Cephalon for paying four generic drug makers to refrain from selling generic versions of the anti-sleepiness drug Provigil until 2012. Each of the four companies had challenged the only remaining patent covering Provigil (modafinil), which is taken by people with sleep apnea, narcolepsy, and shift-work sleep disorder.

U.S. sales of Provigil totaled $800 million in 2007, and accounted for more than 40 percent of Cephalon's total revenue. The prospect of generic versions of Provigil entering the market posed a major threat to the company.

The saga began in 2002 when the four generic companies submitted applications with the Food and Drug Administration to begin marketing generic versions of Provigil. Each company had either designed around, or challenged the validity of, the only remaining patent on Provigil. Cephalon sued them all. In late 2005, with the companies nearing FDA approval, Cephalon agreed to pay the companies more than $200 million to stay out of the market.

Despite its losing streak in such cases, the FTC filed suit, accusing Cephalon of engaging in anticompetitive practices and abusing its monopoly power.

Two federal appeals courts recently upheld similar "pay for delay" settlements. Not surprisingly, these favorable rulings caused the frequency of such settlements to increase. In fiscal 2006, half of all pharmaceutical patent settlements (14 of 28) contained such payments. Such deals cost consumers millions of dollars by keeping lower-cost generic drugs off the market.

So what's behind the current case? It's clear that many FTC officials are tired of seeing their authority eviscerated by the courts (see this Washington Post op-ed by FTC commissioner Jon Leibowitz). By bringing the action against Cephalon, it appears the FTC is hoping to create a "circuit split" that could lead eventually to Supreme Court review. Of course, it's not likely the super-business-friendly Roberts court would side with consumers, either.

That's why the FTC is also supporting legislation pending in both houses of Congress that would ban the payoffs. Alas, that faces tough sledding, too. An Associated Press analysis of lobbying reports for fiscal year 2007 showed that about 12 generic and brand-name drug makers and industry trade groups spent $38.8 million on lobbying Congress.

"Lobbyists have a lot of influence in Washington," said Sen. Herb Kohl (D-WI), who sponsored the Senate bill. "If we can just get this to a vote, it will be pretty hard for people to vote against it. A vote against this is a vote against consumers."

-- by PM

Who Stopped the FDA Effort to Curb Procrit Ads?

The Food and Drug Administration held off ordering Johnson & Johnson to pull controversial Procrit ads in 2002 after the Office of the Chief Counsel, then headed by attorney Dan Troy, intervened. Five years later, Troy, now representing J&J from the corporate law firm of Sidley & Austin, emailed former colleagues at the OCC while the agency was considering slapping a black box warning on the drug to "make sure that people understand the limits of their authority."

The email revelations were contained in documents released last week during a House Government Oversight subcommittee hearing on the negative effects of direct-to-consumer (DTC) advertising. They were republished on The Cancer Letter website over the weekend.

It's not clear from the emails if Troy was directly involved in getting the FDA to retreat from pulling the Procrit ads in 2002. Nor is it clear that Troy's efforts to influence the agency in 2007 involved DTC, since the ads had already stopped running.

Still, Scott Amey, general counsel for the watchdog group Project on Government Oversight, called for the FDA to "investigate whether any employee involved in formulating the advertising policy is now working for the other side." Federal revolving door rules prohibit former officials from lobbying on "particular matters" on which they participated "personally and substantially."

In the intervening years, studies have concluded that high doses of Procrit and the other red blood-cell promoting drugs (Aranesp and Epogen by Amgen) may make cancers worse. The FDA last year slapped a black box warning on the drugs.

The Procrit ads, which ran from 1998 to 2005, promoted the idea that taking the drug would give cancer chemotherapy patients "strength for living." The FDA staff that reviewed the DTC ads in 2001 and 2002 called that claim "misleading." The claims "have not been demonstrated by adequate and well-controlled clinical trials," the agency said.

Those protests were overruled by the Office of the Chief Counsel, according to notes from a May 29, 2002 meeting.

During the hearing, investigations subcommittee chairman Bart Stupak (D-MI) grilled J&J's Kim Taylor, who heads its Ortho Biotech division, about the ad campaign's misleading claims. While the drug was approved for treating anemia associated with chemotherapy, it had never been proven to reduce chemo-related fatigue.

FDA staff letters as early as 1998 sought to get the company to modify its ads. "Procrit is intended, among other things, to treat anemia associated with certain chemotherapeutic regimens, not 'tiredness' in general," the agency wrote. In December 2001, it escalated its concerns, branding the advertising slogan "strength for living" as "misleading."

Taylor told Stupak that "we had a reassurance that during the period concerned, the FDA was satisfied that we complied with regulations." That reassurance appears to have come from the Office of the Chief Counsel, not the office that regulates DTC ads.

FDA Scraps Helsinki Declaration on Protecting Human Subjects

In the mid-1990s, the National Institutes of Health ran a clinical trial in Africa testing whether a new antiretroviral drug to combat AIDS worked to prevent mother-child transmission. The trial created an ethical uproar because the control group received a placebo instead of an older anti-AIDS drug called AZT, which had already been proven successful in reducing the number of babies who contracted HIV from their mothers.

To critics, failure to provide a proven therapy to participants in this and similar trials was a basic violation of standards outlined in the Helsinki Declaration on protecting human subjects in research, originally adopted by the World Medical Association in 1964. But to the U.S. Food and Drug Administration and the drug industry, to which it had grown increasingly close over the course of the 1990s, it contradicted its longstanding policy of only requiring trials showing that a new drug was "better than nothing," i.e., better than placebo, to win regulatory approval. If the drug industry were to closely adhere to the Helsinki Declaration, it would always have to run comparison trials if an effective drug were already available.

Rather than accede to international norms, the FDA and the U.S. government in the succeeding years lobbied hard to get the WMA to amend its rules. And it has, several times. For instance, it now allows use of placebo-controlled trials for less serious illnesses. But the basic guidelines protecting human trial subjects' access to best available therapies remained intact.

Why is any of this relevant today? Last week, the FDA formally declared that it will no longer require that clinical trials submitted to the agency to get regulatory approval for a new drug adhere to the Helsinki Declaration. The new rule, which goes into effect next October, was supported by the drug industry but opposed by numerous public interest, patient advocacy, and consumer groups. The new rule requires only that trials conducted abroad by drug manufacturers follow good clinical practices (GCP) and include a review and approval by an independent ethics committee. There's nothing in GCP guidelines that requires patients in the control arm of a trial get access to already proven therapies. They only need receive the standard of care in that country.

What will this mean for the concept of "informed consent" in a poor country? Imagine for a moment that you live on $2 a day in, say, Zimbabwe, and have high blood pressure. Since the disease isn't life-threatening, you skip buying the available anti-hypertensives being sold in the village pharmacy because you can't afford them and none are on the national formulary. Hence, there is no local standard of care.

Now say you learn while visiting the village clinic that an international pharmaceutical company is recruiting patients for a clinical trial testing a new anti-hypertensive drug. If you join the trial, you may only get the placebo. But there's a 50-50 chance you will get the new drug, which hasn't been proven yet, but might work.

Are there risks associated with taking this new drug? Well, so far, none that the doctors think are serious enough to cancel the trial. But it says right on the form that something may turn up in the clinical trial in which you are being asked to participate. You sign up. After all, a 50-50 chance of getting a drug that has a good chance of working (the drug industry wouldn't be here testing it if it didn't, right?) is better than no drug at all. And how much risk could there be, anyway?

Is that really non-coerced, informed consent?

It's getting tougher and tougher to recruit patients in the U.S. to participate in clinical trials. It's also getting a lot more expensive for drug companies to run them here. The result is that 35 percent of all trials submitted to the FDA in new drug applications now take place abroad. This new rule will only make that number grow.

Moreover, many of those trials conducted abroad (or about 15 percent of all trials) aren't even be registered with the FDA. Unlike trials conducted in the U.S., companies do not have to submit an investigative new drug application (IND) to the FDA before beginning research in foreign countries. The FDA estimates about 575 of the foreign trials submitted to the agency each year as part of new drug applications do not go through the IND process. In other words, the FDA has no record that they even exist.

The FDA is required by law to monitor clinical trials conducted under INDs to protect their human subjects. But an Inspector General's report released last September found that the FDA had no registry of trials (which was rectified by passage of the FDA reform law last October); no registry of the Institutional Review Boards that were supposed to be monitoring trials conducted under its auspices; and independently monitored fewer than one percent of the trials it knew about.

And now it has passed a rule that increases the likelihood that more trials will go abroad and that more of them will not even be registered with the FDA, which makes them all but impossible to monitor.

In the final rule published in the Federal Register, the FDA rejected the notion that adopting the self-regulating GCP standard and eliminating references to the Helsinki Declaration "will hurt subjects in developing countries or result in less protection for subjects in foreign studies." The agency noted that GCP requires trial sponsors closely monitor trial behavior and report adverse events. If I were a headline writer at the New York Daily News, the headline on that story would have been: FDA to Global Poor: Drop Dead.

What I can't understand is why no one in the U.S. press, including in the medical literature, paid attention to this story in the past year as this change was underway. Has the U.S. become entirely callous about the impact its ill-conceived policies are having on the rest of the world? Or am I off-base and this stuff really doesn't matter.

Two New Books Well Worth Reading . . .

The New England Journal of Medicine asked Steffie Woolhandler and David U. Himmelstein, long-time advocates of single-payer national health insurance, to review two new books that offer radical prescriptions on two issues that are central to meaningful health care reform: the corporate takeover of modern medicine and the perverse incentives that encourage physicians to overtreat the worried well. You need a subscription to read the review, but needless to say, it was quite positive. Here are the titles, available in finer bookstores or from your favorite online seller:

The Corrosion of Medicine: Can the Profession Reclaim Its Moral Legacy? By John Geyman. 344 pp. Monroe, ME, Common Courage Press, 2008. $24.95.

Worried Sick: A Prescription for Health in an Overtreated America. By Nortin M. Hadler. 353 pp. Chapel Hill, University of North Carolina Press, 2008. $28.

I'll know this blog has made the big time when publishers start sending me review copies in the mail. Ditto to editors looking for reviewers.

Northwest Indiana

As I awaited the results from Indiana last night, I was stunned by the lack of curiosity about Lake County, Indiana shown by the commentators on CNN. I spent a year of my life reporting for the Hammond Times, now the Northwest Indiana Times, so I know a bit about that turf.

The area, fondly known as "the region" to its inhabitants, is a microcosm of American society. Gary, its largest town, is a predominantly poor black city. But the predominantly white counterparts along the southern tip of Lake Michigan to the west -- Hammond and East Chicago -- are also very poor and working class, dilapidated communities that surround downsized steel mills.

But there are about 25 other towns in the county, and the further south you go (Crown Point, the county seat, and my favorite, Merrillville), the whiter and more middle class it gets. In the far south of the county, it is farm country.

I mention this because while awaiting the results, the on air commentators asked no questions about how the "white" areas of the county were voting. When Hammond mayor Tom McDermott was given national air time, all they could ask him about was the delay in reporting the vote. He repeatedly said that he had sent in his vote totals to the county board of elections, and he was upset as anyone that they hadn't been reported to the nation.

But he let slip that Clinton won by 600 votes in Hammond. No one followed up on that comment. 600 votes? There were probably 20,000 votes or so out of Hammond. That means that Obama did very well there. Perhaps the growing black and Hispanic population in that small city accounted for his showing.

Ultimately, Clinton did well enough to hold onto her slim victory in the state. But I suspect it was the more upper middle class areas of Lake County that preserved her margin. Last night's vote in Indiana, and especially in a town like Hammond, suggested to me that white working class Democrats, who have been one of the pillars of the Clinton candidacy, will, in these tough economic times, ultimately support an Obama candidacy.

Steals on Wheels

Medicare recently launched a durable medical equipment competitive bidding program that could save taxpayers and patients $1 billion a year through lower prices on motorized wheel chairs, oxygen tanks and inhalers -- three major Medicare cost centers often associated with aging or disabled smokers and ex-smokers with chronic obstructive pulmonary disease.

Lower prices and lower co-pays through competition? What a radical concept. It was supposed to roll out nationwide next year.

But according to this story in The Hill, which circulates on Capitol Hill, wheelchair and oxygen tank suppliers have launched a furious campaign to get Medicare to drop the program. In traditional inside-the-beltway fashion, they've hired a lobbying/public relations firm, Quinn Gillespie & Associates, to create an astroturf patient group called the National Coalition for Assistive and Rehab Technology to lobby against the program.

If you're a corporation lobbying against competitive bidding, it's probably best if you have people in wheel chairs with oxygen tanks do it.

Folks on the Hill under pressure from these "lobbyists" might want to take a look at this new report, out today from Inspector General Daniel Levinson's office. He found that Medicare's Part B program, which reimburses physicians and some durable equipment manufacturers for drugs administered in their offices or through devices like inhalers, is getting ripped off by certain users of the program.

Three years ago, Medicare switched to a new pricing system that only paid a five percent margin over the drug manufacturer's price for drugs sold under Medicare Part B. It was called the Average Sales Price system, and it pretty much knocked the profit out of drugs administered in doctors' offices.

But the equipment makers apparently are a different story. The OIG looked at all the drugs purchased by Medicare under Part B, and found that 44 were sold to the agency at greater than the five percent margin required by law. In just one quarter, it cost the agency $16 million in excess charges. But just one drug, generic albuterol contained in inhalers, accounted for fully $9 million of those excess charges. That's a cool $36 million a year, or 14 percent of the quarter billion that Medicare spent last year on the drug.

Hill staffers should print out copies of the OIG report. And when those wheelchair-bound ex-smokers on oxygen hit their offices, they should tell them to take it back to Quinn Gillespie. The "lobbyists" should also be instructed to tell the durable equipment makers that it's time to get used to competitive bidding, and to start charging "us" a fair pass along price for drugs.

Huffington's Post

I went to hear Arianna Huffington speak Monday evening, shortly before she made news by claiming in an online column that presumptive Republican nominee John McCain told her shortly after the 2000 election that he hadn't voted for George W. Bush. McCain promptly denied the charge. Given his obvious taste for good looking women twenty years his junior, it isn't hard for me to believe both of them are telling the truth.

But I digress. My real purpose in attending a signing event for her new book, "Right Is Wrong," was to talk about journalism. Her three-year-old online site, The Huffington Post, now has over a half million unique visitors daily. It recently surpassed the Drudge Report in traffic, is chock full of ads (and profitable), and recently began hiring real, full-time journalists.

All well and good. I'm all for entrepreneurial success in journalism, especially when the proprietor isn't Rupert Murdoch.

In her talk, Huffington lashed out at the mainstream press, who "act as if there is no such thing as truth and are more interested in cozying up to those in power than in holding them accountable." Though a frequent guest on talking-head TV, she dismissed the limited reach of cable television's endless chatter. "We have our own platform now," she said, pointing to the success of her own site, Talking Points Memo, Daily Kos and other stars of the leftwing blogosphere firmament.

But add it all up and what do you get? There's maybe 200 jobs that have been created by all the online political ferment on the left. Most of her site is made up of blogs like this one, created by people who have other, full-time jobs who get nothing for their effort. She herself is independently wealthy.

Meanwhile, in the real world of MSM (mainstream media), the Bureau of Labor Statistics will report on its annual job survey later this week. It measures the number of people in each job category. The number out Friday will be for May 2007.

Before going over to hear Huffington speak, I looked up the number of "reporters, correspondents and editors" in the U.S. in May 2006. The total came to a shade under 160,000. In May 2001, the total was a shade under 170,000. Given the accelerating job losses of the past two years, I suspect the total reported later this week will be around 150,000 and the actual number now well below that.

The point is: What will happen when there's no one left in the hated MSM to write the primary dispatches (like that wire copy) that tell us news consumers what's actually happening in the world and gives the endless army of pundits fodder for their commentary? It's great that a tabloid-style news outlet like the Huffington Post can blast away day after day about the Bush administration seeding television news shows with former military men still on the Pentagon payroll. But it took a team of investigative reporters at the New York Times a year to unearth and document that story.

Her response was somewhat heartening. A new round of venture capital financing will allow the Huffington Post to expand its reporting staff. They are forging deals with non-profit investigative outlets like the American News Project and angel-investor-funded start-ups like The Washington Independent, a feisty new voice in the nation's capital edited by Los Angeles Times veteran Allison Silver. The non-profit Center for Public Integrity, started by Chuck Lewis and run now by NPR veteran Bill Buzenberg, is still doing its thing and ProPublica run by former Wall Street Journal editor Paul Steiger has been on a hiring spree. It plans to grow to, gulp, 25 full-time journalists. The Kaiser Family Foundation is about to launch its own primary news service to cover health care issues.

What is most notable about all this activity is that it is non-profit and primarily funded by foundations. Many of these benefactors have agendas. There's nothing wrong with that in and of itself. Most of these new non-profit outlets have gone to great lengths to ensure that there is the same separation between funders and news managers that the MSM always claimed to have between advertisers and its news managers (I say "claimed" because I could tell some hair-raising stories about stories I had spiked because they would have alienated advertisers.)

But will benefactors lose interest? The economics of that model ultimately creates an environment where the primary audience for reporters and editors is their funder, not the public. I have seen this dynamic at work in the non-profit world.

I hope Huffington is economically successful with her online venture and hires a thousand journalists. It will prove that there really is an economy behind the New Economy.

I spent most of my work life in the private sector. In the end, I believe there really is something to be said for creating a product that meets a marketplace test, and that includes the written, broadcast and online word. I suspect the general public will always be somewhat skeptical about journalism that depends on the kindness of strangers.

Doc Pay: Salaries v. Fee-for-Service

Health care reform entails more than health insurance reform, although you wouldn't know it by listening to the candidates of both political parties. Achieving affordable universal coverage will depend on holding down the relentless rise in health care costs, and that will depend on changing the way health care is delivered. Reform must include changing the way physicians are reimbursed.

The current system relies on fee-for-service medicine, which encourages doctors and hospitals to do more services to increase revenue. And its primary beneficiaries are high-paid specialists, who rely on the 21st century equivalent of the time-and-motion studies used by factory engineers in the early 20th century to create compensation schemes for skilled workers.

Under such schemes, the amount of time needed to perform each task in a complicated project (like a tool-and-die maker cutting a new mold for a machine tool) is multiplied by a rating of the skill needed to perform each task. That's then multiplied by the pay scale to come up with the relative value of each worker's time. So in the steel foundry where I worked in the late 1960s, the tool-and-die makers earned 50 percent more than the molders, and twice as much as the laborers.

Medicine uses the same system to determine physician compensation. An American Medical Association committee dominated by high-paid specialists determines the "relative value" of the skills needed to perform, say, eye surgery compared to analyzing a rare eye disease that might be easily treatable with a drug, or shouldn't be treated at all.

The result is wide variability in physician income, and a huge incentive for doctors to enter specialties that not only get high rates for each procedure but can game the system by doing far more procedures than the original time-and-motion studies suggested they could. Sometimes that is a result of improved technology. More often, it is simply the result of ramming more patients through the procedure mill. Today's Wall Street Journal had an enlightening chart showing the resulting disparities in physician income:

Alas, the story offered an inadequate analysis of what needs to be done. Instead of discussing the relative value system and giving voice to critics who suggest scrapping it entirely, the story talked about a looming shortage in sub-specialties that are paid like general practitioners (non-surgical eye specialists in the story). The implication was that insurers need to raise these sub-specialties' relative pay to attract young doctors to the field.

Arnold Relman, the former editor of the New England Journal of Medicine, in his new book "A Second Opinion" offered a different approach. Yes, different physicians have different skill sets and some take longer training than others. That should be recognized in pay scales.

But, he suggests, the more important reform is that physicians be organized into group practices that encompassed all the necessary specialties. And they should be paid not by the number of patients they see or can run through their individual offices, but by skill, experience and their relative importance to improving patients' overall health.

This would give a huge boost to general practitioners and docs who coordinate care. And it would eliminate the perverse incentive that encourages specialists like radiologists and invasive cardiologists to overprescribe many diagnostic tests and surgical interventions.

The Hazards of Secret Science

The development of a blood substitute -- a liquid that has a long shelf life, does not need refrigeration and does not cause infection -- would provide a potentially lifesaving option for surgical and trauma patients with shock from loss of blood. Such a product would be especially in rural areas and military settings.

Most blood substitutes developed to date have been hemoglobin-based products (hemoglobin is the oxygen-carrying protein in red blood cells). Past studies of these blood substitutes suggested that they may be more dangerous than real blood, although the differences have not always been statistically significant.

Charles Natanson and colleagues at the National Institutes of Health teamed up with health advocates from Public Citizen to conduct a meta-analysis of existing trial data on blood substitutes, which was published on-line in JAMA on April 28. By combining the results of 16 trials, they found a 30 percent increased risk of death and an almost threefold increase in risk of heart attack in patients who received blood substitutes, as compared with patients receiving usual care.

The authors call for existing and future blood substitutes to be tested in animals before further clinical trials in humans are allowed to proceed. They point out that if the FDA had conducted a meta-analysis of blood substitute trials by 2000, the increased risks would have become known, and further harm to patients could have been prevented.

Because much of this data was nonpublic, it was impossible for scientists outside the FDA to fully assess the risks. "When 'secret science' is allowed, scientists are unable to build on the successes or failures of other researchers testing similar products, and patients can be repeatedly exposed to risks unnecessarily," the authors wrote.

The authors call for Congress to enact three major changes to the availability of information on clinical trials:

* Reverse the FDA's policy of treating as confidential all corporate materials submitted to it during the product development process, including the investigational new drug application.

* Amend Exemption 4 to the Freedom of Information Act to allow the public interest to be considered when the material sought is considered confidential commercial information.

* Require the results of all clinical trials to be publicly reported, including trials of drugs that have not been approved by the FDA.

-- PM

The Rise of the Uninsured Insured

Today's New York Times leads with a story documenting inadequacies in a growing number of health insurance policies. Rising co-pays, deductibles and caps on coverage are leaving many families with huge and unpayable bills despite thinking they were insured for serious or sudden illnesses. Here's a major anecdote worth highlighting:

Shirley Giarde of Walla Walla, Wash., was not prepared when her husband, Raymond, suddenly developed congestive heart failure last year and needed a pacemaker and defibrillator. Because his job did not provide health benefits, she has covered them both through a policy for the self-employed, which she obtained as the proprietor of a bridal and formal-wear store, the Purple Parasol.

But when Raymond had his medical problems, Ms. Giarde discovered that her insurance would cover only $22,000, leaving them with about $100,000 in unpaid hospital bills.

Even though the hospital agreed to reduce that debt to about $50,000, Ms. Giarde is still struggling to pay it — in part because the poor economy has meant slumping sales at the Purple Parasol. Her husband, now disabled and unable to work, will not qualify for Medicare for another year, and she cannot afford the $758 a month it would cost to enroll him in a state-run insurance plan for individuals who cannot find private insurance.

Here, writ small, is a description of everything wrong with today's insurance market and the conservative approach to health care reform.

* The individual insurance market is notorious for selling inadequate policies that do not cover the true cost of serious illness. Policies that cover just $22,000 of a $122,000 hospital bill aren't insurance in any meaningful sense of that word. They are more properly categorized as a "bait and switch" scheme to defraud the unwary. The Federal Trade Commission should take note.

* Individual "health savings accounts" can never generate enough savings to cover such shortfalls. Moreover, while the newspaper account doesn't reveal how or why Raymond Giarde "suddenly" developed congestive heart failure, HSAs also make it less likely that he would have sought out preventive care long before he developed the disease.

* State programs for the uninsured are far too expensive to provide a meaningful alternative for the uninsured. At $758 a month or $9096 a year, Washington's plan appears to be charging the full cost of family insurance.

Now let's turn to the health care plan of presumptive Republican nominee John McCain annnounced last week and see how it would help this family.

* The $5,000 tax credit for families would not have covered the cost of even the state-run pool for the uninsured, much less a decent family plan. Indeed, it was $250 a month short.

* McCain would expand HSAs, which would be no help to a family like the Giarde's facing a $50,000 hospital bill not covered by inadequate insurance. Given their inability to afford the state plan and the fact their faltering business was already struggling to afford their existing plan, how likely is it that they would have also put aside a few hundred dollars a month for first-dollar coverage decisions like preventive care? Isn't it more likely that, if they had the money, they would have used it to buy adequate coverage for serious illnesses like Mr. Giarde's?

Would McCain's promised Guaranteed Access Plan to make state programs to cover the uninsured affordable have made the difference for this family? His proposal lacks any details. But as I said earlier this week, his advisers' claim that it would cost a maximum of $10 billion nationwide lacks any credibility. That's just $200 per uninsured person in the pool. For every Giarde (someone who suffers from a serious or chronic illness), there would need to be over 600 people who didn't cost the system a dime. How likely is that?

Health Wonk Review

A new one is up at the Medical Humanities blog. Check it out!

HSAs -- Another Wasted Subsidy for the Well-Off

No one should be surprised by the Government Acccountability Office report out yesterday showing that the six million Americans who opened Health Savings Accounts have an average household income two-and-a-half times the national average ($139,000 versus $57,000). The economics of tax breaks compels it.

In theory, HSAs were designed for people with high-deductible insurance plans to cover unanticipated but large medical expenses. But they work like Individual Retirement Accounts (IRAs). The government allows a household to deduct a dollar from income for every dollar it deposits in an HSA.

But high income families benefit much more than low income families from such schemes. Why? Because high income families pay at a higher tax rate. So, if that family with $139,000 in income is in the 31 percent tax bracket, every dollar deposited in an HSA saves it 31 cents in taxes. But if that family with $57,000 in income is in the 15 percent tax bracket, every dollar deposited in an HSA only saves it 15 cents. In that sense, it is like the home mortgage deduction, whose benefits also go disproportionately to people who have the largest mortgages and pay the highest amount of interest on their homes.

Reps. Pete Stark (D-CA) and Henry Waxman (D-CA) are pushing legislation that would require proof that withdrawals from HSAs are actually going for health care. But that wouldn't change the fact that 40 percent of people with high-deductible plans haven't opened these accounts, and won't. For people in the lower middle class or the poor who have to buy a high deductible plan because they work for a lousy employer who either doesn't provide health insurance or only offers high-deductible or high co-pay plans, how likely is it that there will be room in their budgets to also sock away a couple hundred dollars a month for a rainy day health care fund?

HSAs are another gimmick based on the illusion that consumer choice is the best way to rein in rising health care costs. Make patients have "skin in the game," and they will make wiser choices, the theory goes.

Yet as many studies have shown, consumers don't make wise choices when forced to spend their own money on health care. In the short run, they skimp on routine and preventive care, which only makes it more likely that they will develop chronic conditions. And when either chronic disease or a medical crisis occurs, HSAs are quickly exhausted and become irrelevant in determining what kind of care people choose.

HSAs are nothing but another health care plan for the well-off that undermines preventive care. The next Congress should repeal this wasteful subsidy, not tinker with its rules.