Fantasy Pharma Economics from The Atlantic

Must medical innovation be expensive? The pharmaceutical industry flacks, lobbyists and paid academic consultants who endlessly peddle that myth were joined today in a blog post by Megan McArdle on The Atlantic magazine website. Since that magazine is one of the few journalistic outlets left in the nation where ideas are taken seriously, I thought I ought to treat her musings seriously, too. You can read them here.

To summarize briefly: The clinical trials to develop a new drug cost $500 million alone, she asserts. If you take that money from shareholders by stealing their intellectual property, innovation will dry up. And if you expect government to step in the breach, forget about it because a) government doesn't produce new drugs, it only produces molecular targets for new drugs; b) when it does come up with some basic science insights, it takes the private sector to make marketable goods out of them; and c) if you try to force innovation into the public sector, you'll wind up with one of everything -- like in the military.

This misconstrues everything we know about the pharmaceutical innovation process. First, on costs. Why does industry spend $20 billion a year on clinical trials? Is it because the cost of trials has skyrocketed? Or is it because the new drugs that industry is bringing to market are such minor innovations or no innovation at all compared to previous drugs that it takes trials with literally thousands of people in them to prove something works. Take trials for drugs that reduce heart disease by lowering cholesterol, for instance (a hot topic these days). Do you know how many people must be treated for one year to eliminate one death by heart attack with a cholesterol-lowering drug? 750. No wonder the clinical trials to approve a new medicine in this category must enroll 6,000-8,000 patients to have statistical validity. And why do we need another cholesterol-lowering drug anyway? If your previous cholesterol-lowering drug that generates billions of dollars in sales is coming off patent, you might need one. But does the public?

Now let's take a truly innovative drug to cure a rare form of leukemia that might strike 15,000 people a year. A clinical trial proving such a drug works -- like the trial that showed Gleevec worked in chronic myelogenous leukemia, for instance -- might only have to enroll a couple of hundred patients. Indeed, the better it works, the fewer people you need to enroll since the statistical significance needed to convince the FDA will be easier to reach. So from that standpoint, the more effective the new therapy, and cheaper it is to develop. (For the complete story on how a publicly-funded researcher forced Novartis to bring Gleevec through clinical trials, see my chapter on "The Failed Crusade" in "The $800 Million Pill," still available from the University of California Press if you click on the book ad to the left on my website.)

The idea that the government can't produce new drugs is a hoary myth. We have systematically undermined the government's capacity to produce new drugs in recent years. That's true. But historically, the government has produced some of the most important breakthrough drugs. Its efforts range from the Walter Reed Army Institute of Research (responsible for most new anti-malarials in the second half of the 20th century) to the National Cancer Institute (largely responsible for 50 out of 59 of the first cancer chemotherapy drugs) to the National Institute of Allergies and Infectious Diseases (the first HIV/AIDS drugs, which were actually recycled failed molecules taken from an NCI program). Indeed, the manufacturing process for penicillin, brought to U.S. shores during World War II by scientists working on the British government nickel, was developed in a U.S. Agriculture Department laboratory in Peoria, Ill.

However, McArdle is right in asserting that the locus of development of new drugs and biologics has shifted to the private sector in recent years. But as that shift has occurred, the rate of innovation has declined sharply, a point I discussed in depth in my essay "The Pharmaceutical Innovation Conundrum." Suffice it to say here that science and public health drive real innovation, while the market innovates products that satisfies a demand that may or may not have anything to do with public health. Alas, private sector innovation often does not, as in the case of useless me-too drugs or drugs for conditions that are either barely existent or have been over-dramatized through advertising. For a discussion about how a government take-over of final clinical trials that are financed by industry user fees can actually help industry improve its output of significant new therapies, see my discussion of the recent "Trials of Vytorin."

In her conclusion, it's ironic that McArdle should attack our inefficient military procurement system (no argument there) and lambast its poor record on innovating inexpensive new products ("This is how we spend four percent of our national income on something that most of the American public never sees," she writes. "Forgive me if I'm not excited about applying the same process to health care.")

Health care is now 16 percent of our national income. The drug component alone is about 2 percent of national income, and if you include all the drugs purchased by physician offices (most cancer drugs) and hospitals, which are subsumed within those categories of spending, it is probably closer to 3 percent of national income. That's nearly three-quarters of what we spend on national defense.

And what do we get? The Defense Department, under the stellar leadership of Donald Rumsfeld (who for a while was a drug industry CEO!) and his boss George W. Bush, gave us the War in Iraq. Remember Rummy's innovative hit-and-run army? Iraq was going to be the proof of that pudding. Oh well. Back to the drawing boards.

Meanwhile, our private health care system, which has put pharmaceutical innovation near the top of its priority list for a generation as a way of prolonging lives, has delivered us shorter longevity, higher infant mortality and worse general well-being (high obesity, cancer, and asthma rates, for example) than most other advanced industrial nation in the OECD.

On the innovation front, when it comes to public and private sector ineptitude, I'd say they're running neck and neck.

Few Would Argue?

Few would argue that journalists should never be allowed to invest in companies they cover.

Okay, class. True or false?

If you answered true, you have failed journalism ethics 101 and you will never get one of the shrinking number of jobs in journalism (by the way, for an important analysis of the economic woes hitting the industry and what it means for our democracy, see Eric Alterman's excellent column in this week's Nation magazine). Every newsroom I have ever worked in has had a hard and fast rule that reporters may not invest in, participate in or contribute to any organization, public or private, which they cover during their working hours.

Now, let's turn to medicine. Here's a direct statement from the New York Times's Reed Abelson in an otherwise excellent expose of conflicts of interest in one corner of the superficially regulated medical device industry. The story involves a new replacement back disk used instead of fusion therapy (neither of which are very effective):

Few would argue that doctors should never be allowed to invest in promising new technologies. But when doctors are acting as researchers, they should not have money riding on the outcome, in the view of outside experts. . .

Why draw the line at research? Is it okay that the doctor prescribing a particular drug has a huge hunk of his or her retirement portfolio in the stock of the company that makes that drug? Isn't it possible that a physician with such a conflict of interest may ignore the signal from a new post-marketing clinical trial that suggests there are hidden dangers in the drug's long-term use (like the news this morning that Merck's Fosamax, the bone-strengthening drug that in a small number of patients also causes bone-weakening of the jaw)?

The same would be true for a start-up company -- that promising new technology. Isn't the surgeon more likely to use it once it comes on the market no matter what the evidence? In the device industry, in particular, this is a major problem since the regulatory barriers to entry for a new product are quite low (randomized, controlled clinical trials are almost non-existent in the field because sham surgery isn't possible; and loopholes in the law allow new devices considered minor variations of old devices to gain Food and Drug Administration approval with the most minimal of clinical trial testing).

Here's the description from this morning's story about the trial submitted to the FDA by the conflicted physicians:

In early 2005, when Synthes submitted the Prodisc study to the F.D.A. as part of the company’s application for approval, it used results for 162 patients who had received the device and 80 who had spinal fusion surgery.

The results did not include 50 Prodisc patients who were considered “training cases” — surgeries performed to let doctors learn how to implant the devices. Such training is fairly common in device trials.

An additional 21 patients, about 10 percent of those studied, were also excluded from the reported results.

That raised eyebrows at Medicare, which refused to pay for the surgery.

But let's assume for a moment that they approved payment for it. Now, back surgeons all over the country with investments in Prosdisc would be inserting this device in their patients and watching their investment portfolios grow.

If reporters need experts to question the "few would argue" assertion, I suggest they call Dr. Roy Poses and his colleagues at Brown University who write the Health Care Renewal blog. Or they can try Dr. Jerome Kassirer at Tufts University, author of "On The Take." They may have a second opinion.

But How Would We Put It in a Pill and Advertise It on Television?

Here's a squib from the Chicago Tribune about a study I didn't see anywhere else:

Even moderate exercise can dramatically prolong a man's life, new research on middle-age and elderly American veterans reveals. The Department of Veterans Affairs analysis found that brisk walking 30 minutes a day at least four to six days a week was enough to halve the risk of premature death from all causes. That conclusion applies more or less equally to white and black men, regardless of history of cardiovascular disease.

Anybody have the reference for the original study?

Statins Not for People at Low Risk

The journalistic bandwagon is rolling. A column in today's New York Times by Tara Parker-Pope echoes the theme blared across the cover of BusinessWeek last week: statin drugs may lower cholesterol, but for people whose only risk of a heart attack is elevated cholesterol, they have no impact on overall mortality.

The BusinessWeek story was especially provocative because the cover had the word "Lipitor" in bold red letters sitting astride a pile of pills arranged in the shape of a question mark.

Now, call me a cynic, but why does my perverted mind think to itself as I watch this coverage: "Yeah, now we hear, just when the world's best-selling drug is about to go off patent. Where were these guys three years ago?"

Why do I say three years ago? Because in September 2004 a coalition of more than 30 academic physicians and researchers inspired by John Abramson, author of "Overdosed America," and organized by yours truly at the Center for Science in the Public Interest made the same point. Indeed, we wrote a letter to the National Heart Lung and Blood Institute (NHLBI) outlining all the evidence, which was there in published clinical trials for anyone who cared to look. Statins, the letter said, may lower cholesterol in people at low risk and even many sub-groups at moderate risk of a heart attack like women and older people, but there was no evidence that the drugs actually saved lives.

The group also called for an independent panel to review the evidence, since the National Cholesterol Education Program panel of NLHBI had been dominated by physicians with ties to statin manufacturers. The letter, released to the press, drew this defensive response from Barbara Alving, then head of NHLBI. Despite the two sides being out in the open -- good reporters always love a cat fight, right? -- the mainstream of the national press ignored us.

Okay. I'm crying over spilled milk this morning. But let me renew our plea. How about it NHLBI? Now that even the national press gets it, can we get that independent panel to review the evidence?

California Shoots Down Gov's Health Care Reform Plan

A California Senate committee shot down Gov. Arnold Schwarzenegger's health care reform plan by a 7-1 vote this afternoon, thus sinking a long-shot effort to adopt universal health insurance coverage in one state. The plan relied on an individual mandate to purchase insurance as a supplement to a tax on employers who didn't provide plans. But the estimated cost of the program -- $14.5 billion -- was about equal to the projected state budget deficit, according to this AP story. Massive new spending on health care scared even the staunchest supporters of universal coverage off the bill.

As this economic downturn deepens, reformers pushing health insurance reform are going to have to elevate cost control on their agenda if they're serious about insuring the uninsured. The California legislature is probably the most liberal in the nation. Yet even they couldn't swallow a reform plan that relied on higher taxes and individual mandates.

Doctors and Counseling

Here's an interesting new study from today's Annals of Internal Medicine: Overweight diabetics offered regular counseling by their physicians become more active and lose more weight than a control group simply offered printed educational materials, the preferred option for harried physicians who are rarely reimbursed to provide regular one-on-one counseling.

The results, according to an accompanying editorial, were "modest." Yet over a year's time, more than half the counseled group reached its goals for physical activity compared to just a quarter of the group at baseline. Among those merely given printed materials, the number reaching physical activity goals went from 30 percent before the program started to 37 percent a year later.

And how about weight? One in three of the counseled group lost six pounds or more after a year in the program. But the control group saw just one in five drop that much weight.

"An Individual Mandate Absent Comprehensive Reform Is Nuts"

Robert Kuttner, my occasional editor at The American Prospect, tackles the individual mandate issue in his column today in the Boston Globe. Here's what he has to say about the Massachusetts plan, signed into by law by former Gov. Mitt Romney, and now falling apart:

So as a middle-class Massachusetts resident not eligible for the 2006 program, here's what you get: If your employer offers lousy coverage, or sticks you with most of the premiums, you must still buy the plan, or some other plan, or the state penalizes you. The Connector's website helpfully trumpets in large type, "New Penalties for 2008."

As I've been saying on this website for several months, the individual mandate component of Hillary Clinton's health care plan, which she has championed as necessary, is the Trojan Horse of health care reform. You can no more win support by forcing people to do something than you can preserve choice by taking away people choices.

If you want employers to remain the basis for the health insurance system, then force employers to provide health insurance or pay a high enough tax to allow individuals to buy insurance at the same price as if their employers had provided it. That seems to me to be a basic, easily enforcible principle that everyone can understand. Otherwise, let's just go to a single-payer plan where employers and individuals pay in at about the same ratio as they do now (80/20) and scale an individual company's or individual worker's contributions to both profitability and wage levels. Easy. Simple. Fair.

Mandate Sinking Health Insurance Reform in Cal.

Several key Democratic legislators in the California Senate have turned against Gov. Arnold Schwarzenegger's health care reform plan, which had passed the House. A vote is expected later today. According to this morning's New York Times, they feared working people would end up paying the tab for the added costs of insurance because employer contributions were capped.

“I just came to the conclusion that the working people are going to end up paying for it,” said Senator Leland Yee, Democrat of San Francisco, who announced his opposition before a committee meeting last Wednesday. “There’s control for everybody else — the employers are protected and the insurance industry. The only group that’s vulnerable is the working people.”

Asked to surmise its odds of passage on Monday, Mr. Yee was blunt. “I wouldn’t bet 5 cents on it,” he said.

Cuomo Investigating Vytorin, Too

New York Attorney General Andrew Cuomo opened an investigation into the mass marketing of Vytorin, the Wall Street Journal reports. He'll also look into insider stock sales in the weeks leading up to the Merck/Schering-Plough's announcement that the ENHANCE trial came up empty. Congress is also investigating.

The Lessons from Vytorin

What lessons should be drawn from the trials of Vytorin?

For those not paying close attention, let’s recap the events so far (this is my reinterpretation and supplementation of the
timeline the Merck/Schering-Plough joint venture, which markets Vytorin, released yesterday):

In November 2002, the Food and Drug Administration approves the first non-statin cholesterol-lowering drug, Zetia (generic name ezetimibe). The approval is based on a single clinical trial (“Add-on”) that shows it reduces cholesterol in patients with a family history of high cholesterol who haven't reached the target level with a statin drug (Zocor or simvastatin) alone. There trial provides no evidence that the patients taking the Zetia-Zocor combination pill suffered fewer deaths from heart attacks and strokes, which is, after all, the goal of lowering cholesterol.

Shortly before the drug was approved, Merck/Schering-Plough launch an unregistered clinical trial called ENHANCE that plans to measure arterial plaque at three sites around the heart. Again, the protocol contains no plan to compare death rates in the two arms of the trial. Scheduled completion date? April 2006 with results to be released in March 2007.

Under pressure from cardiologists to show that this new class of non-statins actually improves health, the joint venture in September 2005 finally launches a large, multi-center clinical trial designed to test actual outcomes with the combo pill, now called Vytorin. Targeted completion date? 2011. This trial, at least, gets registered in the government’s clinical trials database. (The FDA reform law passed last year made it mandatory that companies register most second- and third-stage pre-approval trials and all post-marketing trials.)

During 2006, as sales of Vytorin mount into the billions, the ENHANCE trial’s data monitoring committee gets the results from ultrasound image readings. The trial sponsors deem them “biologically implausible.” They postpone the scheduled March 2007 presentation to the American College of Cardiology annual meeting while a new process for reading the images is tested and implemented. They announce new plans to release the results at the November 2007 American Heart Association meeting.

After missing that deadline, too, the joint venture convenes an “independent” panel to review the data. It concludes the image readings still have “problems.” The panel votes to change the protocol of the trial to measure just the width of plaque in the common carotid artery because it “provided the most reliable and consistent measurements.” The companies announce the change on November 19.

On November 21, the New York Times carries a front page story headlined, “After a Trial, Silence,” questioning the long delays in releasing the results of the trial and the change in its primary endpoint – a major no-no in clinical trial behavior.

Three weeks later, after several Congressional committees launch investigations, the companies flip-flop and go back to the original endpoints.

On January 15, with sales of Vytorin plunging, the companies finally release the results of the ENHANCE trial. There's no difference in any plaque measurements between the two arms of the trial, even though Vytorin (Zetia plus Zocor) did reduce cholesterol more than Zocor alone.

The American Heart Association and American College of Cardiology on the same day issue statements cautioning patients not to stop taking the drug before talking to their physicians.

A week later, the New York Times reveals that the Merck/Schering-Plough joint venture had donated $2 million to the AHA, a fact still not revealed on the press release but reported elsewhere on the non-profit’s website.

A generation ago, the drug industry accounted for about a third of clinical trials, while academic medical centers, using largely government funds, accounted for two-thirds of the tests. Today, that ratio is reversed. One estimate I’ve seen suggested industry spends over $20 billion a year on clinical trials, well over half of its collective research and development budget.

The time has come to ask whether our privatized system of clinical trial research is serving the nation’s health. The fact that a drug like Zetia can be approved and sold to millions of people for nearly a decade without any evidence that it actually saves lives is absurd. The FDA has the authority to order companies to conduct conclusive post-marketing trials. But when it does, the companies often delay complying or ignore the requests. The agency does nothing. I am not aware of a single instance where the FDA has removed a drug from the market for failing to complete a requested post-marketing trial.

There’s much talk these days about identifying new biomarkers – like cholesterol – that will help industry end its drought in bringing new drugs to market. But why should the public trust the claims made on any new biomarker’s behalf when industry drags its feet in testing its validity in the only place where it matters – in a clinic trial testing whether affecting that biomarker actually improves health?

Our health care innovation system now relies on industry to finance clinical trials. But let’s not forget that the money spent on R&D is derived from patients and their insurers. It is a current cost of doing business, and accounts for about 20 percent of the price of every pill we pop. Perhaps the time has come to give patients more say over how that money gets spent.

One of the chief reforms talked about in the push for health care reform is creation of a new agency, either independent or within the government, that can conduct comparative effectiveness research on existing therapies. As the health care policy community debates that agency’s shape and scope, it should also consider giving it the authority to manage all late-stage pre-approval and post-marketing trials.

Companies would pay user fees for the trials, just as they now pay user fees to the FDA to review their results. But the new agency would design the protocols and manage the process. The goal is to ensure that data derived from the trials maximize knowledge for improving public health. And, it will be credible because direct industry influence over the conduct of the trial has been eliminated.

Dean Baker of the Center for Economic Policy and Research has suggested that all clinical trials get run through such an agency. But, in my view, early stage safety and proof-of-concept trials should stay in companies’ hands. Centralization too early-on in the process might result in frustrated innovators accusing the government or whoever ran this agency of picking winners and losers. Or, it might dampen capital markets’ willingness to invest in start-up firms if they come to believe “the agency” has become too tough in allowing experimental drugs into the pipeline.

Such an clinical trials agency would set a new gold standard for medical research: completely independent, double blind, placebo-controlled trial for truly new therapies; and completely independent double-blind, comparison-controlled trial for competing therapies.

The government has a long history of financing and managing clinical trials through the National Institutes of Health, especially the National Cancer Institute. Yet its authority and centrality has been undermined in recent years as industry-funded trials seized center stage. Companies, meanwhile, have an equally long and sordid history of refusing to fund or follow through on clinical trials that might jeopardize their bottom lines. The result? Crucial gaps in the information about new therapeutics go unaddressed.

To answer the question posed at the beginning of this post: the Vytorin episode teaches us that the time may be at hand to relocate responsibility for the nation’s sprawling clinical research enterprise.

Will the Safety Net, Flexnerian Medicine and Special Interests Trump Reform?

Flexnerian medicine, the reigning paradigm in medical research and practice, owes its name to a man who counseled against what it has come to mean over the past 60 years. In 1910, education reformer Abraham Flexner of the Carnegie Foundation issued an eponymous report calling for the reorganization of medical training. But in his report, according to this intriguing essay by Michigan State University medicine professor Howard Brody, he specifically eschewed "trying to make medical students memorize large quantities of basic science facts."

No matter, medical training has emphasized precisely that and Flexnerian medicine has come to mean the highly detailed search for the biological causes of disease so that highly specialized physician-researchers could discover and deploy targeted cures. And, as a depressing essay in today's New England Journal of Medicine by Columbia University public health professor Lawrence Brown points out, "innovation and specialization became integral to medical education and to U.S. definitions of high-quality care."

Brown offers the Flexnerian mindset as one of three reasons why he believes, despite the sturm und drang over health care in this year's election cycle, reform isn't at hand. Nothing in reformers' bag of tricks "holds much promise of disrupting these formidable medical-cultural continuities," without which, "new efficiencies and savings" are impossible.

Brown also cites the largely overlooked safety net for the uninsured, comprised of "public and voluntary hospitals, community health centers, public health clinics, free clinics and services donated by private physicians." Their very presence "drains moral urgency from the health care reform enterprise." Or, to quote President Bush, the uninsured "still get care."

The final roadblock to reform, in his view, is the lack of real concern by the special interests in the game, specifically, the business community, the insurance industry, and providers (hospitals, doctors, drug and device companies, equipment suppliers, and the rest). All fear the costs of reform will hurt their bottom lines. "The axis of opposition that has throttled reform in the past still concurs on three points: that reform should not make big government much bigger; that the costs of reform ought not to fall on them; and that other items on their agenda take precedence."

The best we should hope for, he argues, is some expansion of Medicaid and/or the states' Children's Health Insurance Programs (S-CHIP) to cover some of the uninsured. "No one knows how to infuse moral urgency into the push for universal coverage, make the system's medical style markedly less expensive, and thrust reform to the top of the agenda for powerful interest groups," he concludes.

That's not right. The moral urgency is there. Until the economy became wobbly, every poll suggested health care insecurity was the top domestic priority for most voters. The problem is that not everyone shares that agenda. Specifically, organized medicine and the special interests that influence medical practice have done quite well, thank you, as health care has soared to 16 percent of gross domestic product while health care outcomes lag other advanced industrial countries. Why should they care deeply about reform?

There are lots of tools in reformers' toolboxes for holding down the skyrocketing health care costs while delivering higher quality care. To name just a few: comparative effectiveness research, evidence-based medicine, focusing on prevention, and a strong government presence with negotiating power to hold down costs. And then there's the reforms that rarely get mentioned in the august pages of NEJM, such as reorganizing physicians into salaried group practices to remove the incentives for daisy-chain referrals that can needlessly run up costs.

The nation's premier medical journal this morning offered up its pages to a perspective that cautions reformers to aim low so that a few more people will get insured, as if getting providers a few more paying customers should be the only goal of reorganizing the insuring and delivery of health care. Correcting a dysfunctional yet stable health care system is beyond imagining and politically infeasible, in Brown's view.

Maybe. The broader business community's support for reform is only lukewarm because until recently there was plenty of cash around to support endless increases in health care insurance premiums. But if the looming economic slowdown is deep and long, with corporate profits, salaries and bonuses entering a prolonged slide, the business community's willingness to hang together with the still profitable insurance and drug companies -- not to mention high physician salaries -- may evaporate.

The corporate sector's first choice for reform would be some variant of the Republican plans -- put the onus on individuals and allow "consumer choice" to shrink the market. This is rationing by income and antithetical to public health, but it would be a solution to rising costs.

But if one or the other Democratic Party candidates gets in with a Democratic Congress and slashing health care costs becomes a corporate imperative, then reformers may gain the necessary ally for enacting meaningful reform.

The Mass BC/BS Proposal

Marketplace, public radio's evening business show, earlier this week covered a plan by Massachusetts Blue Cross/Blue Shield to pay a flat fee for episodes of care -- such as a heart attack -- with bonuses attached for positive outcomes. The idea is to encourage hospitals and physicians to get it right the first time and ensure that patients, once released from the hospital, follow through on taking medicine and following doctors' instructions.

I spent a half hour on the telephone with reporter Stacey Vanek-Smith supporting the concept. As this blog has noted many times, good health care is about quality, not quantity. But I also noted that flat fee schedules could be an excuse for unscrupulous providers to stint on care for difficult cases that ran over the designated amount, and that such plans needed to be carefully regulated to avoid that scenario. As I know well from my years in the business, journalistic time slots are short and one must always have "the other side." My caveats were all that made it into the report. Hear for yourself here.

Health Wonk Review -- Latest Edition

The latest Health Wonk Review is up at Vince Kuraitis' e-CareManagement Blog. Vince is a consultant for his own firm, Better Health Technologies, with a focus on better management of chronic disease. Check out his take on the most important postings from the past week on health care!

DTC Ad Reviews Halved

Lost in the outrage over useless Vytorin's overexposure on the nation's airwaves was a Food and Drug Administration notice last week that it has stopped collecting user fees from pharmaceutical companies that allowed voluntary pre-screening of direct-to-consumer drug advertising. Since Congress appropriated just $6.25 million for drug reviews, and the FDA had estimated it would collect $11.5 million in user fees for that purpose, the agency's DTC review budget has effectively been slashed in half.

According to the industry newsletter FDA Week, Rep. Rosa DeLauro (D), a drug industry critic, was behind the move. The agency's use of user fees must be appropriated by Congress. But the Connecticut Congresswoman eliminated user-fee driven DTC reviews from the recently enacted FDA appropriations bill because she is concerned that the agency has become too dependent on industry funding for its basic functions.

She's right on that score. But this seems like a case of throwing the baby out with the bathwater. Better to have industry-funded reviews of DTC ads than no reviews at all, it seems to me.

Here's an interesting take on the Vytorin commercials that's getting tens of thousands of downloads via You Tube. A product of Newstarget.com, it's not exactly from an objective source. That site's proprietor, Mike Adams, makes his living selling "natural" alternatives to prescription drugs. Still, pretty funny. Have a look:

Pharma's Number One!

Where will we get our information when all news comes online and the full-page advertisement becomes history?

Leave it to the oil and gas industry to bring the only news worth commenting on this morning. The entire back page of my Washington Post contains an ad with a bar graph comparing the profit margins of various industries during the first nine months of 2007. Guess who's number one?

Did you say pharmaceuticals at 20 percent of sales? The industry may be dogged by expiring patents, a collapsing new drug pipeline, and a steady drumbeat of bad news on its best-selling drugs like Vytorin, but none of it appears to have affected the bottom line. Only beverage and tobacco companies came close to the drug industry's profit margins. Even with $3-a-gallon gasoline, the oil and gas industry lagged far behind with profits at 8.7 percent of sales.

Perhaps the pummeling the drug companies are taking on the campaign trail from the leading Democrats signals the salad days are behind the industry. Each of the leading candidates is promising to give Medicare the right to negotiate drug pricing, which, given the larger role the government is playing in overall drug sales because of the senior drug benefit, should put a dent in those profit margins.

But a quick look at that bellwether of future performance -- the stock market -- suggests not much is going to change, at least according to investors looking for a safe haven to weather the current storm in financial markets. According to a blog post on the Wall Street Journal website yesterday after the market's close, drug stocks are down just 1.23 percent this year, compared to 10.75 percent for the S&P 500.

Full disclosure: Because this blog writes so often about health care and drug industry issues, I make it a point not to invest my shrinking retirement savings in stocks in those sectors. Damn.

NIH Nixes Knowing Outside Grantees’ Conflicts-of-Interest

After admitting it routinely fails to collect and monitor university conflict-of-interest policies, the National Institutes of Health has rejected an inspector general recommendation that it collect detailed financial information from its extramural grantees and reveal what steps institutions are taking to manage, reduce, or eliminate any conflicts of interest. Federal regulations require the 3,000 universities, medical schools and other research institutions that receive 80 percent of the agency’s $29.2 billion budget manage any financial conflict of interest that “could directly and significantly affect the design, conduct, or reporting” of government-funded research. The grantee institutions must then report those programs to NIH, although they do not have to report individual conflicts of interest. About 325,000 researchers participate in the agency’s 50,000 grants each year.

When asked, NIH could only produce 438 reports filed between 2004 and 2007, according to an investigation released last week by Health and Human Services Department Inspector General Daniel Levinson. Moreover, 89 percent of those reports did not state the nature of the conflicts or how they were managed. The 30 reports that contain that information described cases where “investigators have intellectual property associated with the grant research or financial interests in companies that are subcontractors on the research grants.” The method of managing those conflicts was disclosure in presentations and publications. Knowing such information for all institutions “could assist NIH officials in making a determination as to whether followup with the grantee institutions is necessary,” the report noted.

In the agency response, director Elias Zerhouni said requiring reporting of individual conflicts would put NIH in the business of directly managing researchers at outside institutions. However, it did agree to set up a consolidated reporting system in the Office of Extramural Research, and make the filing of annual reports mandatory as of March 1. The American Association of Medical Colleges agreed that its member institutions shouldn't have to report their faculty members' individual conflicts of interest to NIH.

Meanwhile, The Cancer Letter (subscription required) reports that two leaders of the International Early Lung Cancer Action Project from Weill Medical College of Cornell University in New York failed to disclose patents and patent applications in their published reports claiming success for using CT scans for early detection of lung cancer. The controversial clinical trial reports and related articles have appeared in the New England Journal of Medicine, Journal of the American Medical Association, Archives of Internal Medicine, The Lancet, Chest, Clinical Cancer Research, Natural Clinical Practice Oncology, and Cancer Cytopathology without disclosure. Claudia Henschke and David Yenkelevitz have both received NIH grants in recent years to conduct research involving lung cancer screening, according to the agency’s grants database. The one awarded patent has been licensed by Weill to General Electric, which manufactures CT scanning machinery. The journals are investigating the failures to disclose the patents.

Last October, Congress launched an investigation into a rival NIH-funded group exploring the use of CT scans for early detection of lung cancer after a group called the Lung Cancer Alliance alleged two of its lead investigators took money from the tobacco industry. The Lung Cancer Alliance, a pateitn advocacy group formed to push for lung cancer screening, is funded in part by GE.

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

Strings Tied to Industry-Academic Collaborations at "Big Oil U"

American universities may be jeopardizing their academic integrity by giving oil, gas, and other polluting industries unprecedented influence over the research those companies fund on campus, according to a report released yesterday by the Center for Science in the Public Interest.

A CSPI survey of nine schools with industry-funded research programs aimed at studying and abating global warming found six of nine let corporate executives sit on boards overseeing grants; five of nine gave companies first rights to intellectual property; and five of nine let companies review and possibly delay publication of studies. The report revealed that industry investment in energy research plunged over the past several decades, and that the university-based programs fall well short of making up the difference.

"It's a cheap subterfuge for carbon-emitting companies," said Merrill Goozner, director of the Integrity in Science project at CSPI and co-author of the report. "They get the prestige of associating themselves with major respected universities, yet can control the direction of research, get first rights to intellectual property, and can delay any finding that doesn't help the bottom line."

According to CSPI, the industry-academic partnerships highlighted in Big Oil U. represent a strategic shift for carbon-emitting industries. Instead of discrediting the science behind global warming, companies increasingly want to be seen as part of the solution. Between 1998 and 2005, Exxon gave more than $19 million to groups that promoted the idea that global warming was a hoax. Yet beginning in 2006, ExxonMobil ads proudly touted its contribution to a program at Stanford, a 10-year $225 million program: "Today an energy company and a leading university share a common goal. The common good." Another ExxonMobil ad bore the Stanford University seal. Stanford gave its industry collaborators special rights in eight of the nine areas measured by the survey. The other energy industry-sponsored programs surveyed were at UC-Berkeley, UC-Davis, Princeton, MIT, Rice, Caltech, Georgia Tech, and Carnegie Mellon.

The report recommended that universities accepting corporate funding adopt policies to protect their autonomy and preserve researchers academic freedoms. They included prohibiting representatives of corporate donors from sitting on research programs governing boards; prohibiting industry donors from
controlling the content and direction of research programs; eliminating first rights intellectual property clauses from donor agreements; and ensuring that company representatives cannot make substantive editorial changes in manuscripts or delay their publication.

This story appeared first in Integrity in Science Watch, a weekly newsletter from the Center for Science in the Public Interest.

The Iraqi Death Toll Revisited

The controversy continues over how many Iraqis have died as a result of the U.S. invasion and subsequent occupation. Yesterday, Sheldon Rampton, who runs the indispensable PR Watch from Madison, Wisc., wrote this analysis in a comment to my earlier post. I thought his insight into what may have accounted for the differences in the two studies in question worth bringing to the fore, so here it is:

The Lancet study's figure of 600,000 cannot be directly compared to the 150,000 figure just reported in the study conducted by the WHO and the Iraqi government. The Lancet study used a different methodology and attempted to calculate the TOTAL number of people -- including both civilians and combatants -- killed as a result of the war, whereas the WHO/Iraqi study came up with an estimate just of the number of CIVILIANS killed by VIOLENCE.

As the WHO/Iraqi researchers stated in a Q&A summary accompanying their study, "The non-violent mortality rate increased by about 60%, from 3.07 deaths per 1000 people per year before the invasion to 4.92 deaths per 1000 people per year in the post-invasion period. This was not further addressed in this analysis, which focused on mortality due to violent deaths."

Since Iraq has an estimated population of 27 million people, an increase of 1.85 deaths per 1,000 people per year from non-violent causes would add another 50,000 deaths per year, or another 150,000 deaths during the three-year period of the study. That's a very crude estimate, and someone with a more careful look at the data could probably refine it further, but it suggests that if we really want to compare the two studies, the difference is between the Lancet's 600,000 deaths vs. about 300,000 deaths according to the WHO/Iraqi study. That's still a significant difference, but not as large a difference as the popular press is making it out to be.

In addition, there are also some methodological differences between the studies which may account for some of the difference in results. First, the WHO/Iraqi study didn't visit some areas of the country due to concerns for the safety of their field researchers, and instead instead relied statistical extrapolations for those areas based on numbers compiled by Iraq Body Count, an organization that tallies deaths reported in newspapers and other public sources. If the areas most dangerous to field researchers also happen to be the areas where journalists are least likely to report, this extrapolation from IBC's data may have produced an undercount.

A second methodological difference is that the WHO/Iraqi study was conducted later than the Lancet study. In the interim, I believe something on the order of 2 million people fled the country to escape violence. Of course, if a family flees the country after a member of the household has been killed, there will be no one home to report that person's death to the field researchers when they come knocking, thus producing an undercount (which would be exaggerated further if people who had family members killed were more likely to flee the country than people who stayed).

I don't have any way of quantifying the possible effect that these two factors may have had on the study's results, but I think it's jumping the gun to assume that the two studies are in huge contradiction with each other.

The March toward Marginal Medicine

Is there no room for discussion of cost-effective health care in the pages of our leading daily newspapers? Nearly 50 million people are uninsured in this country largely because health insurance is unaffordable. Medicare faces a financial crisis as the Baby Boom heads into its retirement years. Yet the New York Times today managed to splash across the top of its front page word of a new $300 prostate cancer screening test that purports to measure a man's risk decades beforehand. This is, don't forget, a disease already overdiagnosed and overtreated with horrendous side effects for thousands of late middle-aged men.

The story was sprinkled with a few comments questioning the need for this new test. But the last word -- usually reserved for a source who best sums up the attitude of the author (the ever enthusiastic Gina Kolata) -- was given to one of the test's co-inventors, William B. Isaacs, a urologist at Johns Hopkins University. As usual, Ms. Kolata failed to disclose that his university is a co-owner of the patent on the new test.

"We have worked with enough families that have a positive family history to know that people are anxious to know their risk of prostate cancer,” Isaacs said.

Why do I find myself cupping my hands over my privates as I read what these people have to say? Full disclosure: my father was diagnosed with prostate cancer around age 70, when he was already several years into his Alzheimer's decline. His urologist operated, leaving my mom with the added duties of cleaning up after an incontinent in addition to looking after her increasingly vacant husband.

The genetic variants measured by the new prostate cancer test are known as biomarkers. A biomarker is something you measure to indicate the presence of disease, but isn't a disease itself. The king of biomarkers (in a commercial sense) is cholesterol, whose measurement and resulting treatment has spawned a $40 billion-a-year industry. In the wake of a trial showing that Vytorin, a pill combining two cholesterol-lowering drugs, did not reduce heart disease, some doctors are now questioning the entire theory, according to this story buried in the business section.

Of course, a number of well-designed trials have shown that lowering "bad" cholesterol with statin drugs in patients seriously at risk of heart disease reduces heart attacks and strokes. And, as the story pointed out, "doctors generally believe that the amount by which cholesterol is lowered, not the method of lowering it, is what matters."

But there's always been an alternative theory percolating on the fringes of cardiology: that statins have anti-inflammatory effects -- sort of like aspirin -- and that may account for some of its cardio-protective properties. The Zetia component of Vytorin lowered cholesterol, but wasn't a statin. One possible explanation for the ENHANCE trial's failure is that the combination of the two drugs didn't have the same anti-inflammatory effects of a single large dose of a statin drug.

Hmmm. Has anybody ever conducted a comparative trial testing Lipitor versus aspirin for people at risk of heart disease? Just a thought.

Anyway, the story quotes Scott M. Grundy of Texas Southwestern Medical Center to defend the status quo. Grundy chaired the industry-influenced National Heart Lung and Blood Institute panel that issued controversial guidelines for cholesterol management in 2004. What the story failed to disclose is that Grundy has financial ties to virtually every statin manufacturer.

The final piece of depressing news this morning is a study in the New England Journal of Medicine reporting that a trials showing that anti-depressants are ineffective rarely appear in the medical literature. The Wall Street Journal has a good synopsis. The recently enacted Food and Drug Administration reform law now requires that the results of all clinical trials get posted in a government database, so this study, which only looked at trials prior to 2004, may be out of date. But the reality is that billions of dollars are being spent for drugs that are marginal or, in some cases, no effect on depression and other mental disorders.

That depressing.

Al Franken's First TV Ad

Thank you Ezra Klein for posting this YouTube link to Al Franken's first television ad, now running in Minnesota. I liked it, and thought you might, too.

Judah Folkman

For most of his career, Judah Folkman, the pioneering cancer researcher who died late Monday at 74 of an apparent heart attack, was scorned by everyone but the government.

As a young naval surgeon in Bethesda, Maryland, he and a fellow researcher noticed that mice tumors stopped growing when removed from the body, but resumed their explosive growth when reattached. As his biographer Robert Cooke described that mid-1960s incident to the Associated Press, "that was the clue that set him off. He reasoned there was some barrier that stopped those tumors from growing. And after years of banging his head against the wall he realized that it was the blood supply."

Folkman hypothesized that inhibiting the regulatory protein that triggered the production of new blood vessels would slow tumor growth. It wouldn't be a cure for cancer. He was always cautious about his claims. His hope was to develop a mechanism for controlling tumors, and perhaps turning the dread disease from a death sentence into a chronic condition.

Today, there's nearly a dozen anti-angiogensis drugs either on or approaching the market and dozens more in development. Every one of them owe their existence to Folkman's discoveries, which would not have been possible without the almost uninterrupted financial support of the National Cancer Institute over four decades.

Son of a Columbus rabbi and a social worker, he saw medicine as a way to emulate his parents' dedication to community service. Yet he was no altruist. In the last decade of his life, he worked closely with numerous pharmaceutical companies as his insights moved from bench to bedside. He recently joined the board, took stock options and consulting fees from start-up Synta Pharmaceuticals, which is investigating new cancer drugs.

But for most of his career, he was on the NCI grants treadmill. Most cancer researchers never accepted his theory that blocking blood vessel growth could control cancer. Folkman ignored them as he doggedly pursued his search for the proteins that stimulated and stopped blood vessel growth. Like so many physician-researchers of his generation, he had been inspired as a young man by Sinclair Lewis' Arrowsmith and Paul DeKruif's The Microbe Hunters, whose core message was that failure was an inescapable part of scientific life.

The fact that he was brilliant as well as stubborn didn't hurt. A graduate of Ohio State, he became a full professor at Harvard Medical School by the time he was 33. They placed his lab at Children's Hospital in Boston next to John Enders, who had won the Nobel Prize for his work on polio. At one point, when NCI was about to turn him down for a grant (which didn't happen because Mary Lasker intervened with the National Institutes of Health scientific advisory board), Enders told him not to worry.

"This just proves that there are no experts of the future," he said. "There are only experts of the past, and they sit on the study section."

It took nearly three decades to isolate the proteins that turned blood vessel growth on and off -- endostat and angiostat. The crucial paper was published in 1993. After that it was only a matter of time before drug companies found inhibitors that blocked vascular endothelial growth factor (VEGF). Folkman himself is listed as an inventor on 49 patents, many of them licensed through Children's Hospital to private firms. The first to market with its own molecule was Genentech, which won approval for Avastin (bevacizumab) from the Food and Drug Administration in February 2004.

As predictable as sundown, the press turned his emergence from obscurity into a storm-filled night. In May 1998, Gina Kolata splashed a sensational story across the front page of the New York Times headlined, "Hope in the Lab: A Cautious Awe Greets Drugs That Eradicate Tumors in Mice." The story proclaimed a cure for cancer was on the horizon, and featured DNA co-discover James Watson claiming Folkman was going to cure cancer in two years. A day later Kolata had a multi-million dollar book deal and the stock of the company that Folkman was working with soared.

Within days, the inevitable caveats and cautionary statements emerged. The Times told Kolata to reject her book deal. Folkman had never wanted his work to be sensationalized in that way. "I don't think angiogenesis inhibitors will be the cure for cancer," he wrote a few months later in Scientific American. "But I do think that they will make cancer more survivable and controllable, especially in conjunction with radiation, chemotherapy, and other treatments."

Anti-angiogenesis drugs must be ranked as one of the great advances in the long-running war on cancer. They are a novel way of extending life for months and even years in some cases. They have far fewer side effects than traditional chemotherapy drugs, which are indiscriminate cell killers and therefore highly toxic.

And, they owe their existence to a government-financed system of basic medical research that sustains unpopular ideas over the arc of a long career. Folkman dedicated his life to science, not making money. The result is medical progress, and a lot of companies making a lot of money.

Bad News Day for Big Pharma

Big news, all bad, for Big Pharma today.

The Supreme Court this morning turned down the Abigail Alliance's claim that dying patients have a constitutional right to investigational drugs. The ruling upholds a core regulatory authority of the Food and Drug Administration, which, if undermined, would have opened the floodgates to reimbursed quackery.

Also, Merck and Schering-Plough released the data from the long-delayed Vytorin trial (the pill combines a drug from an unproven class of cholesterol lowering agents with a generic statin) that showed the pricey combo pill was no better than the generic alone. The companies have been under fire for delaying the results of the ENHANCE trial and changing its endpoints midstream.

The House Energy and Commerce Committee, chaired by Rep. John Dingell (D-MI) vowed to pursue its investigation into the companies' management of the trial. “Heart disease is a serious and growing national problem. American consumers and their doctors should not have had to wait nearly two years for this information. Why did Merck and Schering-Plough go to great lengths to delay the study results? Why did they attempt to manipulate the data?," Dingell said. "We will continue our investigation until these questions are answered.”

Yes, heart disease is a serious problem, and perhaps it's time for Congress to investigate just how much benefit the population at risk is getting from the $20 billion a year that is spent on statin drugs to lower cholesterol, which is, after all, only a surrogate marker for the disease. In an elegantly brief commentary in last week's British Medical Journal, a Scottish physician named Des Spence reviewed the seminal 1995 study of his fellow countrymen that led to widespread use of the drugs:

Whether it’s worth treating high cholesterol is a common enough question. No one who sees the charts and listens to the sales pitch would doubt it—but numbers are open to being spun. Let’s consider the trial known as WOSCOPS—the west of Scotland coronary prevention study (New England Journal of Medicine 1995;333:1301-8). It wasn’t by chance that the west of Scotland was chosen. The participants were men aged between 45 and 64 in the most socially deprived area in western Europe. More than three quarters (78%) were current or former smokers, and their average cholesterol concentration was 7 mmol/l. If lowering of cholesterol concentration was going to work anywhere it was going to work here. The study ran for five years, and the researchers reported a 32% reduction in cardiovascular mortality in the group of men who took statins. (Similar reductions were seen in all vascular events, but death is the irrefutable end point whose delay is most of interest to patients.) Other studies have replicated similar results, and so the pandemic of "cholesterol" swept the world.

But the numbers can be presented in another way. Converting the 32% relative risk reduction into an absolute reduction gives a derisory 0.7% reduction in cardiovascular mortality and a number needed to treat of 143 over the study period. Although it may be cheating, this figure can be annualised to give 715 to prevent one vascular death. So, putting it crudely, some 714 patients a year gain no benefit from treatment, even in the highest risk population in the world.

You can look at that number another way. If a prescription for Vytorin or Lipitor (the world's best-selling statin) costs $85 a month, that's $1,000 a year. So the cost of saving one life via anti-cholesterol drug therapy is $714,000. Or, if it were your money (and not the insurance company's), you'd be paying $1,000 for a one in 714 chance of avoiding a heart attack. Worth it?

Organized Medicine Warned on "Entrepreneurial” Guidelines

Professional medical societies should actively oppose legislative health care mandates that rely on clinical practice guidelines produced by “entrepreneurial activity,” a commentary in last week’s Journal of the American Medical Association argued. The article was triggered by the Screening for Heart Attack Prevention and Education (SHAPE) Task Force Report, which appeared in a Pfizer-funded supplement to the July 2006 American Journal of Cardiology.

The SHAPE guideline called for non-invasive screening for “subclinical atherosclerosis” through tests such as ultrasound or CT scans for all men 45 to 75 and all women 55 to 75 who are considered more than minimally at risk for a heart attack or stroke. Legislation has been introduced in Texas that would require insurance companies to cover the tests.

The SHAPE task force was created by the Houston-based Society for Heart Attack Prevention and Eradication, which was created in 2001 by Morteza Naghavi. He advises and receives research support from Pfizer, manufacturer of cholesterol-reducing Lipitor, and consults for and owns stock in Endothelix, which makes a fingertip thermal measuring device that purports to reveal heart attack risk. The FDA approved the device last November even though it has never been studied in a randomized clinical trial.

Naghavi was also the lead writer on the SHAPE guideline. Twelve of 26 co-authors disclosed ties to drug and imaging equipment manufacturers. While the others claimed they had no financial ties to "a corporate organization or a manufacturer of a product discussed in this supplement," many had industrial ties on related subjects or are radiologists, who have a financial stake in increasing the number of cardiac imaging tests.

In his commentary, University of Michigan law professor Peter Jacobson called on the American College of Cardiology (ACC) to convene a consensus panel to determine the objectivity and scientific efficacy of the SHAPE guidelines. Previous reviews have concluded CT scans for measuring atherosclerosis are not superior to other diagnostic tests and generate a high rate of false positive results.

After reviewing the conflicts of interest among the writers of the guideline, Jacobson called on organized medicine to develop criteria for acceptable clinical practice guidelines. "Only those guidelines that meet the criteria should be endorsed," he wrote. However, he opposed banning conflicts of interest on CPG-writing panels. "I'm dubious that it's possible to find an expert committee to draft guidelines that has zero conflicts of interest," he said.

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

Mandate Muddle

One of the key differences among Democratic candidates on health care reform is whether individuals and families should be required to buy health insurance. A mandate is necessary to get to universal coverage in any plan that relies on insurance companies, which all the Democratic plans do. Many economists who've looked at mandates say that some portion of the population -- one estimate I saw was about five percent -- would skirt the law and remain uninsured, even with a mandate.

Yet Sen. Hillary Clinton and former Sen. John Edwards have attacked Sen. Barack Obama for not including mandates in his plan. Former Massachusetts Gov. Mitt Romney, until recently the Republican frontrunner, also backs a mandate, which was a centerpiece of his state's reform plan passed two years ago.

Now, according to the Boston Globe's Health Blog, the intellectual architect of the Mass plan, Jon Gruber of the Massachusetts Institute of Technology, is admitting that a mandate can only work if there are sharp penalties attached to it since many low- and moderate-income households, even with subsidies, can't afford health insurance on their own. It's also likely that some young, healthy workers will skip buying insurance if they can get away with it. "The mandate has to be enforced," he told the paper. “We need to think beyond what looks mean and do what’s right.”

This is a prescription for dooming any national effort for universal coverage. We're going to impose heavy penalties on people who are already having a hard time paying their bills? Don't forget that the bare bones plans they will buy to meet the minimal insurance standards will probably have high co-pays and deductibles. From the perspective of a moderate-income person whose employer doesn't provide health insurance and who doesn't qualify for subsidies, this will cost them more money for the same care they now receive (emergency room care). The only difference is that they won't have the bill collector hounding them (or the hospital forgiving the bill) after they receive care. What kind of plan is that?

Women And Workers Shifted to Hillary

John Judis of The New Republic yesterday posted a convincing analysis that suggests my "it's the economy" stupid explanation for Sen. Hillary Clinton's come-from-behind win last Tuesday was not the most significant factor. He's one of the most astute observers of American politics because of his skill in analyzing polls, and firmly rejects the thesis that working class voters (those with less than a college education) are racist, which had been suggested in this op-ed by Andrew Kohut in Friday's New York Times.

In short, Judis shows that there was a huge shift among educated women voters in the last few days of the election. There was also a smaller but distinct shift to Clinton among well-educated male voters. And among both groups, Sen. Barack Obama's support dropped. Among college educated women, the shift was a full 12 percentage points from one to the other -- about the same as the swing in the pre-election poll to the actual results.

Among voters with only a high school education, Obama actually gained a percentage point from pre-election polls to the final results. Clinton gained five points. Obama wasn't the victim of racism. He just didn't benefit as much as Clinton from the rush away from John Edwards, who in the final hours of the race saw his support plummet. Indeed, the combined vote in every educational category for Clinton and Obama was five to nine percentage points greater in the actual polls than it was in the pre-election polls. Hillary got most of those votes. I stick with my view expressed Friday that "it's the economy, stupid" will be the watchword of this year's campaign, and that will benefit Clinton the most of all the candidates in the race.

That said, the energy and enthusiasm that Obama's legions have brought to the race will need to be translated to her campaign if the Democrats are to win in November. Given the consultants, pollsters, party insiders and centrist thinkers who dominate her camp, that's going to be one tough transplant operation if she gets the nomination.

Duh: Economy Tops Campaign Agenda

The front page of today's Washington Post confirms my New Year's Day analysis: the economy has surpassed health care as the number one domestic issue for American voters. According to exit polls in New Hampshire, it even exceeded Iraq or terrorism as a concern, and that was for Democrats and Republicans alike.

It's always nice to be ahead of the pack. And, in hindsight, I'm sorry I didn't draw the obvious conclusion from this shift in opinion. Growing fears about the economy undoubtedly contributed to Hillary Clinton's win in New Hampshire. It wasn't just women who rescued her candidacy, but voters lower down on the income scale, who turned out in droves along with every other constituency.

Why would these voters stampede to Clinton? Was it race (distaste for Barack Obama), as so many pundits have suggested? Actually, they were already there. Over the past 30 years, the only time the lower middle-class registered real (higher than inflation) gains in their take home pay was in the latter half of Bill Clinton's time in office. When it comes to economic matters, the name "Clinton" is a proven brand.

The increasing likelihood of a full blown recession this year should benefit whomever is the Democratic nominee. Their roughly comparable approaches on fiscal stimulus, tax breaks, and regulatory policy will offer voters a sharp break from the Republican mantra of tax breaks uber alles, deregulation, and "you're own your own" economics that led us into this fix.

Yet as I flipped through the op-ed pages of the nation's leading newspapers over the past few days and read the political commentary in the wake of New Hampshire's "upset," I've yet to read one pundit who has addressed the centrality of the deteriorating economy to the emerging dynamics of the race. "Populism" as a response to "middle-class anxiety" is as close as anyone gets. But that's John Edwards' 2007 formulation in the context of a still surging economy. Look where that has gotten him. And after New Hampshire, all the pundits can write about is the tear and the sneer and the woman and the black, as if the voter at the margin who considers such issues after endless television gazing is all the matters.

Frankly, I think they should take all the pundits' columns away, give them notebooks and microphones, and send them off to the boondocks to do some real reporting. They might learn something from the people.

The Latest Health Wonk Review

Want to read the "best of the blogosphere" on health? Check out the latest Health Wonk Review, this week hosted by Robert Laszewski of the Health Policy and Marketplace Review. Every two weeks, one of the nation's leading health care bloggers summarizes noteworthy postings on the web on health care issues. Bob is a health insurance consultant who in recent months has provided a even-handed analyses of all candidates' health care reform plans. It will be must-reading for the rest of this election year, and into next year as the post-election health care reform battle takes shape.

The Iraqi Death Toll

The point isn't whether its 600,000 deaths in a population of 24 million since the war began, as claimed in a previous Johns Hopkins study, or 150,000, as reported yesterday in a study conducted by the World Health Organization and the Iraqi government. Both are well beyond what has been admitted by the Bush administration (30,000), and social disaster for that relatively small country. And given that we're now approaching year six of the war and the estimate only covered the first three years, it's likely the more conservative estimate would be near 300,000.

Much has been made of the long-term costs of the war in Iraq for America -- now well over one trillion dollars. Add to that the inevitable and justifiable demand by the Iraqi people for reparations for what was done to them. At just $1 million per life, that would total $300 billion. And if we add in the physical destruction caused by the war, a demand for a half trillion dollars in foreign aid would not be unreasonable.

Cows into Gas

R. James Woolsey headed the Central Intelligence Agency under President Bill Clinton. He now spends his time trying to convince Americans that national security requires ending U.S. dependence on oil. In Sunday's Washington Post, he had a hilarious mock-conversation between a K-Street lobbyist and "Tehran," whose greatest fear was that politicians will listen to those who think the U.S. would be better off if it shifted 20 million acres to producing corn for ethanol instead of corn for cattle feed. Says Tehran:

"My regime is much better off if nobody understands that. If you'd ever eaten grass-fed beef, you'd know it's quite tasty. The only thing you add to a cow by feeding it corn instead of prairie grass is fat. And since the corn makes cows huge and sick, they need lots of antibiotics, which are used so massively on the dumb animals that it helps make bacterial strains grow immune to the antibiotics more quickly. Sooner or later, that means Americans will find that their antibiotics don't work. So your stupid country now has 20 million acres' worth of corn that basically does nothing but promote cardiovascular surgery and infectious disease."

Clinton's Win

The public pollsters got it wrong and the candidates' pollsters got it wrong, and as a result, the media got it wrong. Had reporters only reported what they saw, the story of tonight's vote in New Hampshire would have been the extraordinary surge of young and independent voters who came out for Obama and almost defeated the well-funded, Clinton juggernaut and the Democratic Party establishment.

She won by capturing the party's most consistent supporters over the past several decades: middle class women, seniors, and blue and gray collar workers who haven't defected to the Republicans and evangelicals over cultural issues. These people are voting Democratic no matter who gets the nomination.

Now we have a race. And whoever emerges the winner will be a stronger candidate for it. But Barack Obama has already defined the motif of the November election. Incrementalism is out. For the Democrats to win, they're going to have to inspire young voters. Obama's message does that. There's hope again in America. It's time for a change. Yes, we can.

Health Care Spending Growth Slows

But Respite May Be Temporary

Health care spending grew at a pace only slightly higher than the overall economy in 2006, the second straight year of moderate growth, according to the latest data from the Center for Medicare and Medicaid Services.

The nominal growth (actual dollars) was 6.7 percent, slightly higher than 6.5 percent in 2005. If you subtract out inflation, you get real growth of about 3.5 percent, which is only a half percentage point higher than overall economic growth in 2006.

However, everything isn't rosy. We now spend over $7,000 per person on health, and it absorbs 16 percent of gross domestic product. Prescription drug spending continues to soar, although the 8.5 percent increase in retail drug spending is much less than the 13.4 percent average annual growth between 1995 and 2004.

A large part of that was due to Medicare increases in prescription drug costs. Fully 74 percent of the 13.8 increase in fee-for-service medicine in Medicare came from increased spending on prescription drugs after the benefit became fully operational. If one discounts that huge jump in spending, Medicare spending actually rose just 6.0 percent, the same percentage as private insurance costs.

State taxpayers were among biggest beneficiaries of the jump in Medicare drug spending as Medicaid outlays declined 1.3 percent last year. Poor seniors now have their drug bills picked up by Medicare instead of Medicaid.

Overall, the drug benefit costs caused public sector spending to grow at a faster rate than private sector spending -- 8 percent versus 5.4 percent. While utilization rates were higher (insured seniors are much more likely to fill prescriptions than uninsured ones), generic drugs garnered a larger share of the market -- 65 percent of prescriptions in 2006, up from 56 percent in 2005.

The report said drug prices were relatively tame -- up just 3.5 percent on average. But it's clear that the failure to give Medicare the right to negotiate drug prices is having a major impact on spending. As noted above, drug spending on Medicaid, where the law mandates that drug companies provide the lowest available price, got transferred to Medicare, where the sky is the limit.

As I've noted many times in the past, only through the alchemy of Washington politics can a benefit for seniors be transformed into a price support program for industry.

An accompanying perspective by Paul Ginsburg, president of the Center for Studying Health System Change, warns that the good news may be temporary. Health care costs are poised to resume their rapid growth because of a "medical arms race," he claims. Hospitals are adding beds by expanding imaging facilities and operating rooms; entrepreneurial physicians are coping with declining fee-for-service payments by opening clinics for imaging, endoscopies and cardiac tests; and self-referrals by these physicians are on the rise.

"With the loosening of managed care restrictions, the medical arms race has resurfaced," he writes. "Whether supply is inducing or responding to demand, building booms lead to more spending on health services."

Paying for Hope for the Dying

Hard cases, it is often said, make bad law, and the same can be said for dying patients and health care reform.

This morning's Wall Street Journal looks at a case used by John Edwards on the campaign trail to illustrate the heartlessness of insurance companies. A 17-year-old girl died of leukemia shortly after being denied a liver transplant by Cigna Corp. Though the insurer reversed its decision on the day she died, its excuse for denying the treatment was that there was no data to suggest it would improve her chances of survival. As the story pointed out, the transplant wasn't curative. It had a 65 percent chance of extending her life another six months.

This story is very similar to the case that Michael Moore used in his film, "Sicko." In the film, an African-American, dying of cancer, was denied an experimental treatment.

Any system of universal health coverage will ultimately require reining in rising health care costs to be affordable. Affordability requires moving toward some form of evidence-based medicine, where medical interventions only get paid for if they are based on scientifically validated medical evidence.

As Shannon Brownlee's new book "Overtreated" points out, an estimated 30 percent of all U.S. health expenditures are wasted: physicians, hospitals, and drug and device companies padding their bottom lines by selling and administering unnecessary or ineffective tests, drugs and procedures. That's far more waste than the 15 percent that insurance companies skim off the top for administration and profit, or pad their own bottom lines by denying people necessary care.

But trying explaining that to the public in a 30-second sound bite. And can you imagine what the horse race reporters and theater reviewers who cover politics would do to a candidate who stood on a podium with his or her arm draped around a 57-year-old man who just went through an unnecessary colonoscopy because he was given an inaccurate stool test, or a 62-year-old woman whose cholesterol level and heart attack risk profile makes her prescription for Lipitor completely inappropriate?

Moving toward evidence-based medicine will require creating and constantly updating a trusted base of evidence that can be used by paying agencies, whether in the public or private sectors. A new institute to create that body of evidence is high on many candidates' agendas. But none of them are willing to tell the public that, in some cases, evidence-based medicine means denying payment for heroic but probably useless interventions.

The lesson for health care reformers in the story is that serious reform will make official what already exists: the nation's two-tier health care system. If the family brought on stage by Edwards was rich, there would have been no question about her ability to get a liver transplant. They would have paid for it themselves. If the evidence suggests they are probably wasting their money, well, it's their money.

A universal system must ensure that everyone gets a high standard of care, and that all the treatments, even for life-threatening conditions, are made universally available as long as they have been proven effective. But should a universal system also have a cost-effectiveness standard, like they do in every other advanced industrial nation? That ultimately leads to denying care to patients when the benefits -- perhaps a few months of extra life -- come at a very high a price, and what someone -- the government, the insurance companies, an outside panel representing all stakeholders -- has determined is too high a price.

As the Baby Boom heads into its declining years, this is a debate that the nation cannot avoid. It's also a debate that will only be harder to have after the election because of what got said on the campaign trail.

Obama's Speech

If you stayed up to watch Obama's victory speech last night, you, like me, might have become an instant convert. I felt like the young Jewish kid falsely accused of murder in the movie "My Cousin Vinnie," who, after hearing Joe Pesci's Vinnie demolish a witness, dumped his legal aid lawyer and cried out: "I want him!"

Obama has clearly captured the vital "hope for the future" center, which Bill Clinton rode to victory in 1992. My choice -- John Edwards -- offered in defeat populist rhetoric that sounded all the right themes yet made him sound like a sourpuss. And Hillary Clinton? She looked and sounded like a machine pol, pushing all the rhetorical buttons but lacking passion. That's going nowhere this year. If she loses in New Hampshire, the Obama momentum may well be unstoppable.

New Warnings on EPO Use in Cancer Patients

Remember those Procrit television and magazine ads showing bright-eyed, middle-aged women declaring they were ready for chemotherapy because they'd taken a biotech wonder drug? Last spring, after reviewing the evidence, a member of a Food and Drug Administration advisory committee suggested a better name for the drug might be Miracle-Gro for cancer.

Turns out he wasn't far off the mark. Breast cancer and cervical cancer patients who use erythropoiesis-stimulating agents (called ESAs by the FDA and EPO by most physicians) to keep up their strength while on chemotherapy saw their tumors grow faster and suffered higher death rates compared to patients not given the drug. The data came from two new trials whose results Amgen, which manufactures the drugs, submitted to the FDA in November and December.

Late this afternoon, the agency issued a new warning asking oncologists to rethink using the drug at all. They also asked them to promptly report adverse events. EPO is marketed as Epogen and Aranesp by Amgen and Procrit by Johnson & Johnson.

After last year's advisory committee meeting, the agency slapped black box warnings on the three drugs that cautioned patients and physicians to avoid excessive use. In today's announcement, the FDA said it plans to hold another advisory committee meeting in the next few months. Given the latest data, it's possible that outside advisers may recommend banning use of the drugs in cancer patients entirely.

The breast cancer trial involved 733 German patients receiving chemotherapy who were given Aranesp prior to surgery and compared to a placebo group. The cervical cancer trial, run through the National Cancer Institute's Gynecologic Oncology Group, enrolled just 109 of the planned 460 patients treated with chemotherapy and radiation before the trial was stopped "because of a higher rate of potentially life-threatening blood clots occurring in the patients who received an ESA."

According to the FDA, both studies "showed higher rates of death and or tumor progression in patients who received an ESA compared to patients who did not receive an ESA."

The agency asked oncologists to compare the risks of tumor progression and decreased survival to the risk from blood transfusions before prescribing EPO. "FDA strongly recommends that healthcare professionals discuss the risks of ESA-associated tumor progression and shortened survival with their patients before starting or continuing ESA therapy," the agency press release said.

Kenya in Flames

Kenya, historically one of the more prosperous and stable countries in Africa, is in flames. These extraordinary photos by local blogger/journalist Joseph Karoki reveal the depths of the chaos enveloping that country. I was especially struck by this picture of Barack Obama calling for calm and reconciliation in his father's native land.

Pushback on Federal Preemption

California sued the Environmental Protection Agency yesterday over the Bush administration's refusal to allow the nation's largest state to impose stricter greenhouse gas emission rules than those contained in the milquetoast energy bill signed by the president last month. More than a dozen states are supporting the suit.

California has always been a leader in environmental standards, and more than 60 requests for waivers from weak federal rules over the past four decades have been granted. Given that track record, it's not surprising that the EPA career staff warned the administration that its first ever denial would trigger a lawsuit, and the government would lose. It also faces the wrath of Congress, where Rep. Henry Waxman (D-CA) and Sen. Barbara Boxer (D-CA) have launched investigations into a decision that, as Waxman put it last month, defies science and common sense.

This case is one more reminder about the extent to which President George W. Bush turned the world upside down during his disastrous eight years in office. There once was a time when the Republican Party believed in limited federal intervention in the economy and upheld states' rights. No more. This president abusively wields executive power to thwart state efforts to deal with significant environmental and social problems that the administration militantly refuses to confront. It has used the executive branch to trample on civil liberties, violate habeas corpus, sanction torture, and interfere with justice.

States have always been our laboratories of democracy, taking the lead when the federal government refuses to act. Republicans once championed that approach. It was the Democrats who used the strong arm of the national government to end the patchwork quilt of state economic regulations that bred inefficiency or lagged behind a high standard (raising the national minimum wage is a typical example). Democrats have also wielded federal power to override actions by states -- such as those of the Deep South during the 1960s -- that denied citizens their civil rights and liberties.

No doubt we'll see a re-reversal of these roles should the Democrats win the White House next year as well as maintain their control of Congress. Bush has taught everyone that federal preemption is a two-way street. It once was a tool to set high standards. This president has shown that it can also be used to drag the country into the gutter.

Answer: Send the Editor into Space

This is a multiple-choice question pulled from the MCAT to get into the DeVry School of Newspaper Editing:

You're the page one editor of the world's leading financial newspaper. Your political editor comes to you with three story ideas to illustrate the ideas behind the candidacy of left-wing Cleveland Congressman Dennis Kucinich. You choose:

A) Single-Payer Swan Song. As the only candidate in the race championing a Canadian-style government-run health insurance system, this story uses the Kucinich candidacy to trace the declining fortunes of an idea that once commanded substantial political support within the Democratic Party.

B) Pax Americanus? Kucinich is in good company when he proposes a cabinet-level Peace Department to promote a reduction in global hostilities. Even George Washington thought it was a good idea for the newborn nation. This story looks at how a Peace Department might work.

C) What Kucinich Saw. This story, based on exclusive interviews with Kucinich's companions at Shirley MacLaine's mountain hideaway a quarter century ago where he saw a flying saucer, gives voters a behind-the-scene blow-by-blow account of the wacky Congressman's close encounters of a third kind.

Correct Answer: The wise editor ever attuned to readers' needs would, like the editors of today's Wall Street Journal, choose C.

Is Health Care Reform Fading As An Issue?

As the nation enters a new year and its quadrennial bout of temporary insanity, the latest polls show the economy has eclipsed health care as the most important domestic issue among voters. Even the health care-oriented Kaiser Family Foundation's latest poll shows the number of Americans who name health care as their primary concern fell to 30 percent in early December from 38 percent just two months earlier. When offered a list of possible issues the candidates ought to address, the economy had pulled even with health care.

The escalating fear that the nation may be heading into a recession because of the sub-prime mortgage meltdown and sky-high gas prices has certainly played a role in the turnabout. In that sense, 2008 is beginning to look a lot like 1992. The year before that election, health care dominated the national discussion after Harrison Wofford used the issue to win a surprise victory in a special Senate election in Pennsylvania. But by the time Arkansas Gov. Bill Clinton stormed to victory in the primaries, "it's the economy, stupid" had become the Democratic standard bearer's watchword.

That appears to be the way things are shaping up in Iowa and New Hampshire, which will hold caucuses and cast the first ballots over the next week. On health, the Democrats have coalesced around a common strategy to pursue safe, incremental reforms that rely in the insurance industry to get everyone insured. Meanwhile, the Republicans have become the radicals in the debate by calling for subsidies and tax breaks for individuals so they can "go it alone" as consumers in the dysfunctional individual insurance market.

These policies will mark a clear differentiation between the parties that should favor the Democrats come the general election. But the fine distinctions between the various Democratic plans, which are worthy of debate, are lost on the general public, and as things stand now, won't play much of a role in the primaries.

This, of course, is bad news for wonks like me who would like nothing better than to debate the fine points of the competing Democratic plans. Are individual mandates really the best way to go or is it a political trap? Should employers who don't provide their workers with health insurance be required to pay a payroll tax into a common fund to cover the uninsured? Should the government expand Medicare to people under 65 who lose their health coverage? Should the government set up another "Part" to Medicare to cover the uninsured and compete directly with the insurance industry plans?

A debate over these fine points would set the stage for political battles to come. Given the entrenched special interests that earn their living from the status quo, reform ain't going to be easy. If nothing else, the debate would educate the public about the complexities of the issue. Wouldn't it be nice if single-payer advocate Dennis Kucinich got a chance to explain to the public that having the government run a single, common insurance pool (sort of like Medicare) is not the same thing as socialized medicine?

Alas, it hasn't happened in Iowa and New Hampshire and probably won't elsewhere. One reason is that covering the uninsured and outsized health care costs simply aren't big issues in those early voting states. In the Commonwealth Fund's latest ranking of states' performance in covering the uninsured and delivering affordable health care, the two states ranked second and third in the nation, trailing only Hawaii.

In Iowa, fully 88 percent of the adult population has health insurance compared to a national average of 82 percent. In New Hampshire, the number was 86 percent. Moreover, both states did extremely well in quality measures such as delivering preventive care and treating adult diabetics. And both states had below average costs for Medicare enrollees, fully 20 percent below the national average in Iowa's case where the first blood in the presidential race will be drawn on Thursday.

If the candidates emerge from Iowa and New Hampshire in a dead heat as some polls now indicate, it's still possible that we will have a debate in the Democratic primaries about what is the best approach to health care reform. But if, as some pundits are predicting, Sen. Hillary Clinton's strategy of going for the early knockout proves successful and Super Tuesday in early February seals the nomination, then it looks like health care reformers come November are going to have to rely on the pol and not the plan.