Crawling Toward Better Health Info

Let's get wonky.

In a move that's long overdue, the Food and Drug Administration and the National Institutes of Health are teaming up to create an electronic database for all clinical research data about regulated medical products, "from the earliest research phase to postmarket surveillance," the online newsletter FDA Webview (subscription required) reports. The agency solicited input from private vendors on how to create such a system earlier this week.

This effort bears close scrutiny by researchers and consumer groups, even though it is still years away. The FDA has bungled previous efforts at setting up user-friendly databases, and anybody that spends any time on its website knows that the agency is hopelessly incompetent at developing consumer-friendly tools for imparting information. Moreover, there's likely to be huge fights over who will have access to the data, with industry fighting to keep its proprietary information away from prying eyes.

Such restrictions would make this database much less useful to academic and independent researchers, who need a central repository for all clinical trial outcomes data about drugs, biologics, devices and medical procedures to be comprehensive. That's why NIH's participation is crucial: it already runs ClinicalTrials.Gov, which serves as a central repository for listing the existence and protocols for clinical trials. The next step logical step is creating a central database for listing the results.

Once that's up and running, it should be easier and quicker for researchers to conduct meta-analyses on problematic therapies. In a meta-analyses, a researcher pools the results of numerous trials to show effects that may not have been apparent to any of the researchers who conducted the individual trials in the mix.

In addition, the FDA and NIH could expand the database to include medical outcomes data. Indeed, large insurers and Medicare should be consulted on how to design such a system so that their soon-to-be computerized medical records (yes, some day the U.S. will catch up with the rest of the industrialized world and digitize individual medical records) can be easily incorporated. The agencies will have to take steps to insure that individuals' privacy is properly protected, of course.

How could this outcomes data be used? David Graham, the safety expert turned whistleblower at FDA, used Kaiser Permanente data to prove that Vioxx was causing a significant increase in heart attacks among its users. His job would have been a lot easier if he had access to a centralized repository that incorporated a much wider range of outcomes data.

A central repository of outcomes data would also be a valuable resource for researchers who want to conduct post-treatment comparative effectiveness studies, which is key to holding down skyrocketing medical costs. Sen. Hillary Rodham Clinton, ever the wonkette, has championed comparative effectiveness research on the campaign trail.

Obama Wins Crucial Early Test

This is what I love about political reporting. . . from today's Los Angeles Times:

Clooney Steps Cautiously into Obama's Camp

You can find the story on the Times' website under "Most Viewed Stories."

Income Inequality

Why wasn't this story on page one?

Today's New York Times reports that income inequality in the U.S. last year reached levels not seen since the eve of the Great Depression. An accompany chart shows that the more equal distribution of income that was created during and immedately after World War II began eroding in 1980 and now has been completely reversed.

You should read the whole story, but here's some deflating tidbits:

The new data also shows that the top 300,000 Americans collectively enjoyed almost as much income as the bottom 150 million Americans. Per person, the top group received 440 times as much as the average person in the bottom half earned, nearly doubling the gap from 1980. . .

The analysis . . . showed that the top 10 percent of Americans collected 48.5 percent of all reported income in 2005. That is an increase of more than 2 percentage points over the previous year and up from roughly 33 percent in the late 1970s. The peak for this group was 49.3 percent in 1928. . .

The top 1 percent received 21.8 percent of all reported income in 2005, up significantly from 19.8 percent the year before and more than double their share of income in 1980. The peak was in 1928, when the top 1 percent reported 23.9 percent of all income. . .

The top tenth of a percent and top one-hundredth of a percent recorded even bigger gains in 2005 over the previous year. Their incomes soared by about a fifth in one year, largely because of the rising stock market and increased business profits. The top tenth of a percent reported an average income of $5.6 million, up $908,000, while the top one-hundredth of a percent had an average income of $25.7 million, up nearly $4.4 million in one year. . .

And how about the rest of us?

While total reported income in the United States increased almost 9 percent in 2005, the most recent year for which such data is available, average incomes for those in the bottom 90 percent dipped slightly compared with the year before, dropping $172, or 0.6 percent.

One in Three Dollars Wasted

A new issue brief by the Urban Institute reports that one-third of the subsidy given to workers who lose their jobs to foreign competition to pay for health insurance gets eaten up by administrative overhead. The money goes straight to insurance companies. Read it and weep.

FDA Enforcement: A Story in Pictures

In the wake of 9/11 and the October 2001 anthrax attacks, the government beefed up its efforts to inspect the nation's food and drug supply. It was a logical move, since both represented potential focal points for terrorist activity. But like everything else the Bush adminsitration sought to do in its War on Terror, the effort flagged once the War in Iraq got underway and diverted government resources to that ill-conceived, poorly executied and, as we now see, ill-fated adventure.

Here's the latest statistics from the FDA's Office of Enforcement:

Show Chart

A similar fate has befallen the FDA's efforts to police quality. Here's the agency's record in admonishing manufacturers for poor performance:

Show Chart

Proving the Value of Comparative Trials

Failed the stress test? Suffering from persistent angina? Got partially blocked arteries? Aggressive drug therapy will reduce your risk of suffering a heart attack as much as inserting a stent to prop up clogged arteries, according to a new study released yesterday by the New England Journal of Medicine.

The Veterans Administration study received well-deserved front page coverage in the morning papers (see the New York Times coverage here and the Washington Post story here). The bottom line is that patients who get the expensive, invasive procedure (angioplasty involves sticking a catheter into your thigh and snaking it up to the arteries around your heart to insert the stent) actually have slightly worse results, although the difference was not statistically significant.

There could be enormous financial benefits to the health care system if the implications of this study are widely followed. Many of the drugs used in the trial are available as cheap generics. They used aspirin for blood-thinning, for instance, except for those patients with aspirin intolerance, who then received Plavix. An angioplasty/stent operation, on the other hand, costs up to $50,000.

But don't count on patients necessarily hearing about this study when they get routed to a cardiologist after complaining of chest pain. "I don't think this is going to cause any huge paradigm shift," Gregory J. Dehmer, president of the Society for Cardiovascular Angiography and Interventions, told the Post. "This study was limited to a fairly select group of patients with very stable symptoms."

Not really. Perhaps the most shocking statistic in the study was that fully 20 percent of patients in both groups suffered heart attacks or died within five years of entering the trial (the study enrolled patients between 1999 and 2004). Sadly, while both groups were encouraged to stop smoking, lose weight and exercise regularly, neither group reported a significant reduction in body mass index.

While most of the physicians who conducted the trial had extensive financial ties to drug manufacturers, the trial itself received only unrestricted grants from those commercial interests and the grants went to the VA. The U.S. and Canadian governments provided the bulk of support for the trial.

So what's the takeaway lesson for health care policymakers? For years, trials funded by stent manufacturers have suggested that the invasive procedure should be standard of care for patients with early symptoms of heart disease. Only a well-constructed comparative clinical trial could show that this isn't necessarily the case.

Alas, such trials invariably take a long time and come out long after a train filled with commercially-driven medical interventions has left the station. This trial shows conclusively that the government needs to allocate several billion dollars a year to fund numerous comparative trials on a range of medical interventions. And the Food and Drug Administration should make manufacturers carry out such tests as a routine part of their products' initial approval process. That way, patients and their insurers won't have to wait five or ten years to learn the relative worth of competing medical interventions.

Long Term Care Rip-Off

When it comes to nursing home care for the frail elderly, every family is on its own. States, with federal support, only pick up the tab when you've become destitute. That's why so many seniors buy long-term care insurance -- so they won't become a burden to their families or a ward of the state in their old, old age.

This morning's New York Times has one of the most heartrending, anger-provoking stories I've read in a long time. It involves a handful of health insurance companies that have erected a claims structure designed to deny the frail elderly the very product that they've paid for.

The reporting is drawn from court cases filed by enterprising attorneys who represent the unfortunate families robbed by these insurance companies. At numerous points in the story, former insurance regulators are quoted expressing anger about their inability to curb the companies' abusive tactics.

Are these the same regulators who will police the individual health care insurance plans that will be sold in Massachusetts and California?

The Future of Non-Profit Drug Development

The following is a transcript of the talk I presented this morning to the European Association of Hospital Pharmacists.

My topic this morning is the bright future of non-profit drug development. I’ve taken the liberty of adding the word “bright” to my talk’s listed title because there is a non-profit drug development industry struggling to emerge that holds out great promise of making significant medical advances in the years ahead. But before I get to my predictions for the future, I first must describe where we are in the history of drug development, and why I think present trends will inexorably push many drug developers – especially those concerned with making a significant contribution to the health and wellbeing of mankind – in the direction of the non-profit model.

Also, please accept my apologies for my U.S.-centric view of the world. I have been studying and writing about the pharmaceutical industry for almost a decade now as a U.S.-based journalist interested in trends within the U.S. pharmaceutical industry. For purposes of this discussion, I think that focus works well because it is trends within the U.S. pharmaceutical industry and the U.S. pharmaceutical market that have driven the industry into its current predicament.

And make no mistake about it. The industry is in a predicament. Despite large and rising investments by both the public and private sectors in biomedical research and development, the output of new therapeutics from the global pharmaceutical industry is at a low ebb. This situation defies conventional economic models. Greater investment in research and development is supposed to result in a rising level of innovation in an industry. The drug industry’s situation – rising R&D expenditures, but declining output of new therapeutics – cries out for explanation, which I will seek to provide.

But first let me tell you a little story about how I got involved in studying pharmaceutical innovation because I think it sheds some light on the industry’s current situation. About a decade ago, the U.S. began a debate about how to modernize its senior citizen Medicare program, which is the one universal health insurance system the U.S. has. The discussion about modernizing Medicare at that time boiled down to a single question: Should we add a prescription drug benefit? When President Lyndon Johnson signed the program into law in 1965, it did not include coverage of prescription drugs. At that time, drugs were seen as a relatively minor cost of health care. But in the intervening decades, drugs became a much more significant part of treating and managing disease, especially those that hit us later in life. Moreover, as each new generation of drugs came along for treating the chronic ailments of aging: high blood pressure, acid indigestion, arthritic pain, high blood pressure and the like, industry charged a substantial premium over the cost of the older, generic drugs that physicians previously used to treat those ailments. And those increased costs were being felt directly by the nation’s elderly population. Clearly, if Medicare was going to meet the needs of retirees in the 21st century, it was going to have to cover drugs.

So a debate ensued over the best way to shape the program. Social liberals in the U.S. Congress believed that if the seniors drug program was going to be affordable for the government and taxpayers, it needed to establish formularies that controlled which drugs would be covered. Also, the government needed to negotiate prices with manufacturers of the drugs that it put on the formulary to hold down costs.

The pharmaceutical industry, represented in the U.S. by the Pharmaceutical Research and Manufacturers Association, reacted with a massive lobbying and public relations campaign against the proposed benefit. They argued that a government program with strict formularies and negotiated prices amounted to a form of price controls that would reduce industry revenue. And if you reduced industry revenue, they argued, it would reduce industry investment in research and development, which was the lifeblood of pharmaceutical innovation. In other words, without high prices, there would be no new drugs for the people who are clamoring for cures for cancer, Alzheimer’s disease, Type II diabetes and other disorders of an aging society.

As I listened to these arguments, I was struck by how different the pharmaceutical industry’s argument was from the other industries that I had encountered over the course of two decades as a business reporter. I had traveled from the U.S. industrial Midwest to Silicon Valley to Japan and New York. I had reported on a half dozen different industries. I had attended dozens upon dozens of corporate meetings. In each context, on whatever continent, corporate executives always told the same story. If they didn’t develop new products and more efficient processes, their firms would lose ground in the race to stay competitive in an increasingly global market. If they didn’t invest heavily in R&D, these executives said, their products would be less innovative, and their prices higher than the competition. Ultimately, they said, a failure to invest heavily in R&D means their firms would die.

But for the first time in my life, I was hearing a set of industry executives – the drug industry’s executives – saying something exactly opposite: If the pharmaceutical firms didn’t get high prices, they said, the firms wouldn’t invest in R&D and you would die. I had what psychologists call a cognitive dissonant moment and began conducting the research that ultimately led to publication of a book, “The $800 Million Pill,” which sought to answer the questions: Where do new, innovative drugs really come from and what do they really cost to make?

That investigation led me to investigate the development of some of the most significant pharmacological advances of the last quarter of the 20th century. They included new biologics like human recombinant erythropoietin, a product of the newly emerging field of genetic engineering. They included the HIV/AIDS triple cocktail -- highly-active anti-retroviral therapy or HAART, whose emergence in 1996 turned that deadly plague into a manageable disease, at least in the advanced industrial world. And they included the new so-called targeted therapies in cancer therapeutics such as trastuzumab or Herceptin for some breast cancers and imatinib mesylate or Gleevec for chronic myeloid leukemia.

What I discovered was that the stories behind each of these breakthroughs had several elements in common:

1. Each was preceded by decades of basic research into the underlying biology and natural history of the disease; this research was universally funded by the public sector – either by government directly or through tax-subsidized non-profit foundations; and
2. Behind each successful drug development program based on that science was a dedicated scientist or team of scientists who had devoted their entire careers to developing cures for that particular patient population, often in a clinical setting.

This is not to say that industry’s contribution to the development of new breakthrough drugs wasn’t significant. Industry was and is the repository of many of the skills of medicinal chemistry that allow drug developers to formulate products with the proper pharmacokinetic and pharmacodynamic properties that allow them to be used effectively in humans. Financially, industry played an essential role because individual companies who held or licensed the patent rights almost always took the experimental drugs through their final and most expensive tests – the third stage clinical trials to prove efficacy that are necessary to gain approval from regulatory authorities around the world.

But when it came to significant breakthroughs, those medicinal chemists would not have targets to go after without the foundation of basic and applied science provided largely by the public sector. And industry wouldn’t have clinical trials to fund without the dedication of physician/scientists who are committed to finding cures for the patients they were seeing on a day-to-day basis.

Perhaps nothing illustrated these relationships better than the story behind the development of Gleevec, a small molecule drug that originated in the Swiss labs of Ciba-Geigy, now part of Novartis. In the late 1960s and early 1970s, researchers at the University of Pennsylvania discovered that a chromosomal mutation was responsible for the explosion of white blood cells that characterized chronic myeloid leukemia or CML. This chromosome would later be called the Philadelphia chromosome because of where the discovery was made. It took another decade for researchers to identify the gene disrupted by the transfer. The gene’s discoverer was Owen Witte, whose work at the University of California at Los Angeles was supported in large part by the non-profit Howard Hughes Foundation. Witte spent another decade trying to convince some company to develop inhibitors of the white blood cells produced by the mutation. He needed something that would block he mutant tyrosine kinase on the surface of the cell. He couldn’t find any company willing to do it. The patient population was just too small.

But in the early 1990s, Brian Druker, a physician/researcher at Oregon Health Scences University and a CML specialist, heard that a tyrosine kinase inhibitor developed by Novartis in another drug development program was active against the CML. With the help of Nicholas Lyden inside the company, he began lobbying the firm to get involved in treating this relatively rare disease. It took FIVE YEARS to convince Novartis to produce the drug in sufficient quantities to conduct proof of concept clinical trials in humans. Throughout this period, Druker’s work was supported exclusively by the government’s National Cancer Institute and the non-profit Leukemia and Lymphoma Society. He later told me: “It was entirely my own lobbying that got the trial going.” Even when preliminary results showed a miraculously high recovery rate, it took a letter-writing campaign by patients from all over the world to convince Novartis chief executive Daniel Vasella to order his managers to produce the drug in sufficient quantities for a third stage clinical trial and to give expanded access to the thousands of patients around the world suffering from the disease.

Of course, Novartis’ initial reluctance to get involved in this program was not because the company was venal or blockheaded. CML is a rare disease, striking a few tens of thousands of patients around the world every year. But during the 1990s, industry, driven by the stock market, had begun demanding blockbuster drugs from its pharmaceutical development programs. If a drug didn’t hold out the promise of generating a billion dollars a year in sales, it received about as much attention as a backbencher in parliament. And a cure for CML just didn’t hold much financial promise, even if the company charged a very high price for the drug, which it eventually did.

There are literally thousands of rare diseases like CML. The U.S. government, which gives special incentives for developing treatments for rare diseases, estimates there are over 6,000 separate rare disorders affecting nearly 50 million people in the U.S. and Europe. They range from inherited metabolic disorders like Gaucher and Fabry disease to rare cancers and auto-immune disorders. But only a small percentage of those diseases have drug companies actively engaged in trying to discover potential new drugs and biologics that might lesson their impact. The market simply isn’t large enough for them to get involved, even if they were to charge exorbitant prices for any drugs they might develop. That leaves these fields wide open for academic researchers working on government or non-profit grants.

The development of a treatment for Gaucher’s disease, which is now sold by Genzyme of Cambridge, Mass., provides the paradigmatic example of how devoted researchers working in the public sector can develop cures with very little help from the private sector. This rare genetic disorder, which leaves carriers of the mutation without the ability to process certain lipids in the blood. It affects an estimated 5,000 people around the world. Untreated, it usually kills people before their 40th birthday. Starting in the 1970s, a researcher at the U.S. National Institutes of Health named Roscoe Brady began researching this disease. Over the ensuing decades, he discovered the enzyme that wasn’t being produced by the defective gene. He then began working on a method for deriving that enzyme from ground up placentas. In the late 1980s, he turned the entire process over to Genzyme, which in the early 1990s got FDA approval for the purified enzyme and began charging over $200,000 a year per patient for the treatment, which they called Ceredase. But even at that price, the company only generated a few hundred million dollars a year in sales. Later, after Genzyme began making a recombinant version of the protein based on the gene that had been discovered by one of Brady’s colleagues and put in the public domain, the price barely came down, even though it was a much cheaper manufacturing process.

Based on the knowledge it had from its experience with Gaucher’s disease, you’d have thought Genzyme’s scientists would have rapidly begun turning out proteins for the other liposomal disorders like Fabry’s disease or the polysaccharide disorders, which were also based on genetic mutations. But it took them more than a decade before they did. Why? There was less money in going after treatments for extremely rare conditions when there were much larger markets – like blood factors in hemodialysis – to go after.

There are many, validated targets for rare diseases that the pharmaceutical industry could go after. But they don’t or they do so half-heartedly. Why? Because the size of the market doesn’t justify the investment or taking the risk of failure. So the research and development is left largely to researchers in government and academic settings, who must dribble the ball almost all the way to goal line before handing it off to a drug company for the score.

In recent years, this model has changed somewhat with the evolution of an active biotechnology sector largely funded by venture capitalists. Today, researchers in the universities are encouraged to patent their early stage basic science discoveries and license them to private firms. In many cases, those firms are start-ups that the researchers themselves either own or are involved with. Indeed, many of these startups in the U.S. receive direct subsidies from university investment funds or local and regional governments. As these companies move their discoveries through the drug development process, each successive step is funded by infusions of cash from either these public partners or venture capital investors. The Holy Grail for these firms is getting their molecule through a successful proof of concept trial in humans. Then the major pharmaceutical firms either buy the firm, license the drug or establish a milestone payment system that finances its final third stage clinical trial development. Again, without the early stage support of the government and, in some cases, non-profit and university sectors, none of this would be possible.

Despite heavy investment of both public and private resources in this biotechnology start-up model, biotechnology firms have been relatively ineffective at bringing new therapeutics to market – at least so far. There are over 1,500 biotech firms in the U.S., and hundreds more around the world. These firms spend more than $20 billion a year in research and development. They have over 300 products being tested for over 200 diseases, according to the Biotechnology Industry Organization, the U.S. industry’s trade group. Yet the industry as a whole has only 12 drugs that sell more than a half billion dollars a year; and only about 125 total products that have been approved by the Food and Drug Administration.

Moreover, most of the industry’s biggest sellers were the low-hanging fruit of the recombinant engineering revolution and have been on the market for quite some time. They include erythropoietin, granulyte colony stimulating factor, human growth hormone, and human insulin. These therapies work well because the underlying condition – kidney failure or diabetes, for instance – led to a failure to produce particular enzymes required for normal human functioning. So if you replaced the missing enzyme with one that was made using genetic engineering, the patient was, if not cured, at least temporarily relieved of the potentially fatal symptoms of not having that missing molecule.

But today, most of the diseases that are the research subjects of biotech companies involve interfering with malignancies whose reproductive systems are out of control. Or they are trying to interfere with the overexpression or underexpression of proteins associated with the degenerative diseases of aging. Decades of research into the microbiology of various diseases has identified hundreds of potential targets for pharmacologic intervention in cancers or degenerative diseases. These targets are part of the complex biological cascade of events that take place when things start to go wrong in the body. But is very unclear at the outset of these development programs whether inhibiting or stimulating further production of these cellular interactions will have much impact on the underlying disease, if it has any at all. I’m not saying that these efforts are doomed to failure. Recently there have been some very excellent results from targeted therapies such as the antiangiogenesis drugs like Avastin. It has proven very effective against macular degeneration. It has had moderate success in staving off the growth of some cancers. But to reverse a degenerative disease like, say, rheumatoid arthritis, which probably involves a cascade of numerous factors, or to inhibit a fast-growing cancer with an monoclonal antibody, is not going to be the slam dunk that replacing a missing protein was.

Indeed, what’s happening in biotechnology is symptomatic of what is happening in pharmaceutical research as a whole. The United States is the world leader in investing in biomedical research and development. In the public sector, the National Institutes of Health spent $28.6 billion in 2005, largely for basic science research. Although that has leveled off in recent years as chronic U.S. budget deficits have been exacerbated by the large expenditures for the war in Iraq, the U.S. in real inflation adjusted dollars spends far more today than it did two decades ago to support basic and applied science in biomedicine. Indeed, it is more than four times greater than it was in the early 1980s!

Yet as fast as government expenditures have grown, they have not kept pace with the pharmaceutical industry, whose investment in R&D has exploded along with its sales. While the drug industry’s critics like to complain about the escalating marketing expenditures of the industry, which take up to 40 percent of total sales, the fact is that R&D budgets have also benefited from rising industry sales. The U.S. industry spent an estimated $39 billion in 2004. This includes investment in the U.S. by U.S.-based firms, investment overseas by U.S. firms, and foreign companies’ R&D expenditures in the U.S.., who have increasingly moved significant R&D resources to the U.S. to take advantage of the U.S. government’s massive investment in scientific research. (It is a little known fact that in licensing its inventions to the private sector, NIH must give first preference to firms whose R&D facilities are located within the the U.S., whether they are U.S.-owned or not.)

All told, over the past quarter century, the private sector’s investment in the search for new medicines has grown eight percent per year on average, significantly faster than the industry’s growth in sales and profits. Total spending is now six times greater than it was in the early 1980s.

Despite this massive public and private effort, output, as measured by the number of new drugs, biologics, vaccines and devices approved for use by regulatory bodies like the U.S. FDA, has slowed in recent years. Last year, the FDA approved just 21 new drugs and biologics, one of the lower totals since 1993. Moreover, about half of these new drugs were not given priority status for review by the FDA, which meant they were not considered a significant new advance in medicine. This significance ratio has held steady for over a decade. Clearly, the steady increase in private and public R&D spending is generating diminishing returns, whether measured by return on investment or public health.

This falloff in R&D productivity has occurred despite extraordinary advances in the technology of drug discovery. The public sector’s massive investment in basic science, mostly conducted at universities, has uncovered the complex details of how cells work and the chemical interactions of their constituent parts. A government-led project decoded the human genome; scientists are rapidly identifying the functions of the proteins that the genome produces; and, for over 30 years, we have had the bioengineering skills to reproduce those proteins and monoclonal antibodies in mass quantities. We can use these tools to identify the biochemical interactions of many diseases. This in turn has given scientists hundreds of potential targets for drug therapy.

To go after those targets, scientists have developed new tools like mass screening. They’ve developed sophisticated bioassays and attached them to computer chips to identify potentially effective new drugs. Advances in biochemistry and x-ray crystallography have given medicinal chemists the ability to design and synthesize new drugs capable of affecting those targets faster and more accurately than ever before. And, the drug industry and government have financed and built an infrastructure for conducting clinical trials that far surpasses what existed in previous eras.

So why is output slowing down? I would offer two simple hypotheses for the decline in R&D productivity. The first one parallels the explanation I gave earlier regarding the limited success of the biotechnology revolution. The small molecule drug revolution pioneered by Europeans like Paul Erhlich and Gerhard Domagk has evolved to the point where it is now a mature industry. In the past century, scientists have developed drugs for most of mankind’s common maladies. We can kill most of the microbes that invade our bodies. We can control blood pressure, allergies, minor aches and pains, and acid indigestion. We can cure a few cancers and prolong life for a few more. We can give drugs to prevent some heart attacks. And, for many of these disease states, we are now on the second or third generation of drugs. If we look at blood pressure control, we’re in our sixth or seventh.

In other words, as in biotechnology, the low-hanging fruit of medicinal chemistry has been picked. To be an innovator today, you must discover cures for chronic diseases like diabetes, most cancers, dementia (Alzheimer’s disease), rheumatoid arthritis, and the other maladies of aging societies. Will there ever be a pill to slow the aging process, or the diseases that accompany aging? That is going to require a lot more investment in basic research to understand the chemical cascades that affect many of us as we age, and then a lot more research beyond that to understand how we can safely intervene in the process. I wouldn’t count on rapid success.

The second reason for declining productivity is that industry R&D largely ignores areas where it is possible to have a tremendous impact very quickly and where there is tremendous need: the neglected diseases of the developing world. Industry does not seek the cures for drug resistant tuberculosis, malaria, leishmaniasis, Chagas disease or hookworm. It could spend its vast resources developing drugs and vaccines for these conditions, but it doesn’t because there is no market. This is the flip side of the rare disease situation I discussed earlier. For a rare disease, there are very few patients. So, even when they or their insurers or their governments are willing to spend a lot of money for a treatment for their disease, for the drug companies, it isn’t a very large market.

This isn’t the case for the neglected diseases of the developing world, where there are billions of potential customers. But those potential customers have very little money. Indeed, they have virtually no money. And when there is no discretionary income for medicine, there is no drug market. It is a classic case of what economists call market failure. Allow me to quote a Nobel Prize-winning economist on this point: Joseph Stiglitz, formerly of the World Bank and now at Columbia University. He recently wrote that:

(Quote) It is a matter of simple economics: companies direct their research where the money is, regardless of the relative value to society. The poor cannot pay for drugs, so there is little research on their diseases, no matter what the overall costs. (Unquote)

But rather than look for ways to artificially stimulate demand in these needy countries (by lobbying for greater aid, for instance), the drug industry instead devotes a substantial share of its R&D budgets to developing new drugs in their existing markets. Many of these new drugs are nothing more than replacements for older drugs that are losing patent protection. Upon occasion, they are superior to the older drugs. But even when they are, it is usually not by much. This strategy of developing what are known in the U.S. as me-too drugs may be good for their bottom lines, but it provides a very small return for public health.

Again to quote Stiglitz: “A me-too drug, which nets its manufacturer some portion of the income that otherwise accrues only to the company that dominates a niche, may be highly profitable, even if its value to society is quite limited.”

Allow me to briefly mention two examples that illustrate how the miraculous discoveries of modern chemistry and biology have been used by the drug industry, not for public health, but to fatten its bottom line. More than two decades ago, scientists discovered that one type of antihistamines – the H2 antagonists – could limit stomach acid production. This breakthrough was better than acid absorbers for acid indigestion, which in chronic cases can lead to ulcers and even death. These H2 antagonists enjoyed a long life on patent, and then went what we in the U.S. call “over the counter.” In other words, you didn’t even need a doctor’s prescription to get them. You could walk into a corner drugstore and buy them yourself at a much lower price than they cost as a prescription drug. Before they went off patent, as they contemplated this huge loss of revenue, the companies that made these drugs discovered a new class of antiacids – the proton pump inhibitors, which counteracted the production of stomach acid at its source, not the signaling histamine that triggered acid production. Omeprazole (Prilosec) and other proton pump inhibitors also enjoyed a long patent life and wracked up billions of dollars in sales for the industry.

But as it reached the end of its patentability, the company that made omeprezole (AstraZeneca) came out with a follow-on drug called Nexium. What was Nexium? It ‘s nothing more than the enantiomer of Prilosec, which was the racemate mixture. In other words, when people took Prilosec, half of what they were taking was Nexium. Did Nexium improve anybody’s outcomes? No. It merely gave AstraZeneca a drug that it could sell as a prescription medicine after Prilosec went over-the-counter. And in the U.S. at least, the strategy has been successful. You cannot pick up a magazine in the U.S. without finding full page ads for Nexium, the “new purple pill.” Physicians are prescribing billions of dollars of these pills for patients with heartburn and excess stomach acid, relief that they could get at a fraction of the cost simply by walking into the corner drug store without a doctor’s prescription.

The other example that I would like to offer about how industry R&D has gone astray is a darker tale. It involves a class of pain relievers known as Cox-2 inhibitors, the most infamous of which was Merck’s Vioxx. Gastroenterologists have long been concerned that a small percentage of people who routinely took traditional pain relief medicine like aspirin, ibuprofen and naproxen, collectively known as non-steroidal anti-inflammatory drugs or NSAIDs, suffered from gastrointestinal side effects. This affected somewhere from 2 to 4 percent of patients. In a small percentage of those, it led to bleeding ulcers, and, in very rare circumstances, could lead to death. By selectively inhibiting just one of the cyclooxygenase enzymes – the one that caused inflammation, not the one that helped control the production of stomach acid – the Cox-2 inhibitor class of medicines held out the promise of eliminating this side effect.

It was an elegant theory. Unfortunately, none of the major clinical trials that showed that these drugs were comparable to previous NSAIDS at controlling pain (and thus able to get regulatory approval) proved that this class of medicines actually succeeded in reducing the gastrointestinal side effects. What the trials did show in some cases, however, was that there was an excess of heart attacks and strokes from taking the Cox-2s. In fact, the pivotal Vioxx trial, published in the medical literature in 2000, showed that the cardiovascular risk from taking the drug was four times higher than the comparison drug, which was naproxen. The authors of that study, which was funded by Merck, speculated that the results could have been the result of naproxen having cardio-protective qualities. Only four years and tens of thousands of deaths later was it shown – in a very large trial aimed at proving that Vioxx protected people against colon polyps – that Vioxx in fact did result in higher rates of myocardial infarction and stroke.

Here we had the perfect storm of misplaced R&D priorities. In order to eliminate a minor problem, the drug industry invested hundreds of millions of dollars in developing a new drug that wound up causing much worse problems than it would have ever solved.

As a result of the Vioxx and other near scandalous situations, I believe the era of the blockbuster drug is coming to an end. Over the next few years, some of the drug industry’s best-selling drugs will be coming off patent. Very good drugs for lowering cholesterol, lowering blood pressure, minor pain relief, allergies, and blood sugar control will all be either available as inexpensive generic medicines or will even become non-prescription drugs. But because of the intense pressure generated by aging societies and tight public budgets, the games that have been played in the past – substituting an enantiomer for a racemate or introducing a new class of drugs for a condition where control agents are already 90 percent effective – simply will not be tolerated by the public or public agencies responsible for paying for health care.

So where will real innovation come from in the years ahead? One area generating tremendous excitement is using genomics to create personalized medicine. Technology and science are driving drug developers in this direction. Why do some people suffer from the side effects of drugs, and others don’t? Why do some people respond positively to a cancer chemotherapy regimen, while others don’t?

We all have slightly different genetic make-ups. These slight variations may account for the different reactions different people have to different drugs. If we could test people in advance for this variations, then it might be possible to tailor prescribing to the exact needs of individual patients. This would be vastly superior to what happens now, which is that physicians try one drug after another until they figure out which one works best for that particular patient. Many scientists are working to identify these differences, and developing tests that could be used in advance of prescribing individual drugs.

But what are the financial implications of this potential innovation? Genetic testing will become common. Indeed, people will demand it since they will want to know what works best for them. So we have added new costs to the system in the form of tests. But at the same time, we will have reduced revenue to the drug industry by limiting the number of people who are able to take an individual drug. This may be a tremendous boon to the practice of medicine, but it is a threat to the industry’s bottom line.

So allow me to recapitulate what I see as the most significant opportunities for medical innovation in the years ahead:

1. Understanding the basic science and natural history of the diseases of aging so that biomedicine has not just targets, but validated targets for therapeutic intervention;
2. Developing personalized medicine based on genomics, which will allow drug developers and physicians to target their interventions in the most effective way possible; and
3. Coming up with treatments for the neglected diseases of the developing world.

In each of these arenas, governments and the non-profit sector will play a leading role or innovation will continue to lag. But they must do so in a way that builds upon lessons learned from past successes.

1. Governments must step up their investment in basic and applied research. But it must do so in intelligently. Governments must embrace the fact that many of its most successful research programs have been targeted research campaigns aimed at specific goals, whether it was drugs for HIV/AIDS or basic research programs like the human genome project.
2. Governments must restructure the incentives for innovation, especially the patent system. Scientific collaboration will be necessary to achieve the promise of personalized medicine, but the current patent system may be undermining that collaboration. There will also need to be innovations in how we bring these breakthroughs to market, since personalized approaches to health care financed through current pricing models will either bankrupt health care systems of aging, advanced industrial societies or make these breakthrough technologies unaffordable for everyone but the upper classes; and
3. Non-profit drug developers and generic manufacturing must be at the heart of our approach to developing therapeutics for the diseases of the developing world, an approach that is increasingly being recognized by donor nations.

Let me address these one at a time.

To leap ahead in our efforts to come up with therapeutics for chronic diseases of aging, governments will need to increase their investment in basic science. Let’s take one example: the fight for a cure for Alzheimer’s disease (AD). Great Britain’s National Institute for Health and Clinical Excellence is under pressure from the two companies that make cholinesterase inhibitors, including donepezil or Aricept, to make them available for the early stages of the disease. Yet the Cochrane Collaboration last year said that “there is little evidence that donepezil improved cognitive function, and no evidence that donepezil delays progression to AD.” Does this mean that the years of basic and applied research that went into developing the cholinesterase inhibitors was wasted? No. It only means that the mechanism that they inhibit does not by itself halt the progression of the disease.

To make progress against AD and other degenerative diseases of aging, our governments need to step up to the plate with targeted research campaigns. We must learn so much about the natural history of the various forms of this disease that drug developers not only have targets, but have validated targets. This strategy has a proven track record. The targeted research campaign that developed the drugs that can now control HIV/AIDS was initiated and largely funded by the U.S. government. Public and non-profit sector researchers identified the virus, characterized its genome, identified targets and even came up with the first drugs that inhibited its replication. The U.S. government also helped financed a huge clinical trial network to test those drugs. Lost in the celebration over the arrival of HAART therapy in the mid-1990s was the fact that it was a targeted research campaign, largely funded by the U.S. government which spent over $10 billion on research into HIV/AIDS between 1987 and 1996, that laid the groundwork for the companies that brought the final pieces of that triple cocktail – the protease inhibitors – to market.

Does that mean that a targeted government program aimed at conquering dementia can have the same type of rapid progress? One need only look at the U.S. government’s war on cancer to be reluctant to make bold predictions. But very large, targeted research campaigns aimed at elucidating the basic science puzzles behind the chronic diseases of aging remain the best hope for making any progress in any of those fields, whether it be dementia, most cancers or neurological disorders like Parkinson’s disease.

The same can be said about the emerging field of stem cell therapy, which holds out the promise of regenerating destroyed or non-functioning cells, whether in the brain, pancreas, heart or spine. Here, again, government funded programs for researchers in the non-profit sector are leading the way. In the U.S., because of the Bush administration’s stance against federal funding for embryonic stem cell research, states like California are leading the way with fairly large investments in the field.

I want to spend a few minutes talking about stem cells because this new field provides a textbook example of how over-commercialization by researchers in the non-profit sector can actually retard a field. As I mentioned earlier, the new paradigm since passage in 1980 of the Bayh-Dole Act in the U.S. is for non-profit researchers to patent their early stage discoveries and form venture capital-funded companies to pursue the next stages of research. Venture capitalists are willing to fund these early stage start-ups because these firms control the intellectual property that their founding scientists argue hold out hope of leading to a cure for some disease. It’s led to a mad rush to the patent house by basic science researchers, which has been aided and abetted by a very liberal patenting policy enabled by the U.S. Patent and Trademark Office and the courts. The PTO has granted thousands of patents for genes, for single nucleotide polymorphisms, and for proteins, cell receptors and other molecular pathways whose role in disease states are merely surmised.

In some cases, the discovery turns out to be the building block of an entire field, which gives that discoverer an intellectual property claim on all subsequent developments in the field. This is precisely what happened in stem cell research. James Thompson of the University of Wisconsin was the first scientist to isolate embryonic stem cells. His university’s technology transfer office won a patent that embraced virtually all potential uses of that invention. The university subsequently licensed some of the major uses of that invention to a single firm, Geron Inc., which had funded Thompson’s research. Wisconsin also made the invention available to other researchers for other purposes, but at a steep price. What happened next was covered in Nature Magazine. In 2005, the magazine reported that a San Diego researcher named Jeanne Loring watched her start-up firm collapse when it couldn’t get access to the Wisconsin line at reasonable rates. Academic researchers complained of similar roadblocks.

Thompson was hardly alone. A recent survey conducted by the United Kingdom’s Stem Cell Initiative identified over 18,000 stem cell patents issued around the world, with two-thirds of them in the U.S. Patent law firms in the U.S. are warning their clients that any firm or research institution that is planning to pursue stem cell projects may face blocking patents that they must license – if they are available. This emerging patent thicket represents a distinct threat to the traditions of open science required for progress in the non-profit and university sectors, where the basic building blocks of therapeutic advancement have always been laid. It chokes off collaboration. It adds transaction costs to everyday laboratory encounters. It’s impossible to quantify the damage done by this early stage scientific patenting because how can one count the number of researchers who abandon a line of research because they can’t get access to the necessary licenses or execute the necessary material transfer agreements? How does one count the number of researchers who never even consider a line of research because someone else has already locked up the key patents?

Some researchers have suggested a way out of this impasse. They’ve called for creation of a common patent pool supervised by a non-profit organization that would make licenses freely available to any researcher who agrees to contribute their subsequent inventions to the pool. Patent pools have been successfully used in other high-technology industries like consumer electronics and software. Open access pools are being created in the field of agricultural biotechnology where a quarter of all patents reside in the public sector. The Public Intellectual Property Resource for Agriculture (PIPRA) is seeking to create patent pools that can deliver advanced farming technologies to poor countries at low or no cost. Even large pharmaceutical firms are experimenting with pool arrangements for single nucleotide polymorphisms, which could turn out to be the building blocks of personalized medicine.

These arrangements are going to be necessary if the products that result from this research are going to be affordable. Unlike patent pools in consumer electronics or even in agriculture, the end stages of the research process in biomedicine – which are the second and third stage clinical trials – are the most expensive part of the process. They also entail the greatest risk of failure. Traditionally, we’ve relied on the private sector to carry out these final stages of research. In exchange for footing the bill and taking that risk, we allow pharmaceutical and biotechnology companies exclusive rights to the intellectual property, which allows them to charge enormously high prices – somewhat lower here in Europe than in the U.S., but high nonetheless. As we can see from escalating health care costs all around the world, this model is no longer sustainable.

But there is an alternative to the exclusive rights-high price model. Governments could establish a prize system for medical innovation, with the size of the prize driven by the public health need and the investment required to bring the therapy successfully to market. Under the prize system, once the therapy has been approved by regulatory bodies and the prize awarded, the intellectual property would be turned over to any generic manufacturer who could then make it on a cost-plus basis for their nation’s health care system.

You are probably asking: Well, wouldn’t the prize on top of generic manufacturing equal the same high prices that we currently have? The answer is no, because there would be no prize or very small prizes for me-too drugs. A prize system would eliminate the billions of dollars wasted on pharmaceutical industry marketing. And it would channel research resources into fields where there is the greatest public health need. Instead of driving health care costs higher, which is often now the case with new technologies, biomedical research would begin to accomplish what research and developjment achieves in every other field: delivering better outcomes for patients at lower costs.

A very interesting experiment is already underway in this kind of non-profit drug development. It is taking place in the neglected disease arena, where well-financed charities like the Bill and Melinda Gates Foundation and international donors operating through the Global Fund are laying the groundwork for an alternative drug development model for the 21st century.

In the neglected diseases arena, non-profit drug developers like Medicines for Malaria Venture, based in Geneva, One World Health, based in San Francisco, and the Global Alliance for TB Drug Development, based in New York, are blazing the trail to the future. These organizations are not only developing drugs, often in partnership with the pharmaceutical industry, but they are reaching intellectual property agreements that ensure that their products will be affordable in the developing world if and when they are developed.

I recently had the opportunity to travel to the Thai-Burmese border to see this emerging system in action. I saw researchers connected to the non-profit Shoklo Malaria Research Unit in Mae Sot conducting clinical trials to develop new drugs to combat malaria, one of mankind’s age-old scourges. Virtually wiped out in the advanced industrial world, malaria still strikes a half billion people in the developing world every year. Its main victims are small children suffering through their first bout with the disease. Somewhere between one and two million children under the age of five die every year from the disease.

In many parts of the world, especially Africa, the most virulent form of the disease – plasmodium falciparum – has developed resistance to existing drugs like chloroquine, which since the 1960s has been the main way to treat the disease. But starting in the mid-1980s, Thai, French and British scientists working in Thailand have conducted a series of pathbreaking clinical trials that showed that a new class of drugs – artemisinin-based compounds – were effective against chloroquine-resistant p. falciparum. Where did artemisinin come from? It is derived from the sweet wormwood bush. Traditional Chinese doctors first identified that a cold tea made from sweet wormwood leaves and bark was effective against high fevers nearly 1,700 years ago. It’s modern derivative form was discovered by Chinese scientists in the 1970s as part of a program that began during the Vietnam war after Ho Chi Minh asked Mao Tse Tung for help for his soldiers living in the jungle. He told Mao that he was losing more of his soldiers to malaria than he was to American bombs!

The chemical form of the drug came along too late to help the Vietnamese, but its isolation and manufacture gave the world a new weapon in its war against drug-resistant malaria. It took nearly two decades for university- and non-profit-based researchers to prove its effectiveness through clinical trials, to identify that its best use was in combination with other drugs to prevent the emergence of resistance, and, finally, to convince the World Health Organization that it should be first-line therapy throughout the developing world. That finally happened in 2002.

But price was still a roadblock. Because most Chinese versions of the drug do not meet first-world standards of good manufacturing practices, they are not approved by western regulatory bodies and cannot be purchased by western aid programs like the Global Fund to Combat AIDS, TB and Malaria. The only WHO-approved version of artemisinin-based combination therapy until recently was manufactured by Novartis. But Coartem, as the Novartis drug is known, cost over $2 for the three-day treatment. That’s 20 times the price of chloroquine, which, even if often ineffective, was at least something people in poor countries could afford.

But the price is coming down. Why? Competition recently arrived. A partnership between Sanofi-Aventis and the Drugs for Neglected Diseases Initiative, which is a non-profit offshoot of Medicines Sans Frontieres, recently completed final clinical trials and began the worldwide registration process for a new arteminsin-based combination therapy treatment that will cost under $1 per adult course and under 50 cents for each child’s course. The final clinical trials were conducted at low-cost by researchers in Africa and Latin America. And Sanofi-Aventis, who will manufacture the product, has agreed to turn over the intellectual property to any generic manufacturer anywhere in the world if they can produce it at a price lower than their plants.

Getting this new drug out to the world’s poor is still a problem. Health care delivery systems are woefully inadequate. The aid bureaucracies at the World Bank and the WHO are still moving far too slowly. For instance, a U.S. Institute of Medicine committee chaired by Nobel Prize-winning economist Kenneth Arrow issued a report three years ago that called on aid agencies to purchase a sufficient supply of artemisinin-combination therapy pills each year to treat everyone in the world. This would cost less than a half billion U.S. dollars a year. Then, this centralized supply should flood the developing world’s distribution channels, from the village dispensary to the national hospitals and clinics, at a low enough price to essentially push ineffective chloroquine out of the market. This would also have the important side effect of eliminating the counterfeit artemisinin pills and the monotherapy pills that are coming out of around 18 factories around the world, according to the WHO. This must be stopped if physicians are to avoid losing this new drug to resistance like all the malaria drugs that have come before it.

Unfortunately, the World Bank still hasn’t come up with a plan for creating this subsidy and lining up sufficient manufacturing capacity to produce enough of this drug to fight the disease everywhere, which is necessary if the world is going to make a serious dent in malaria’s death toll. When I attended a press briefing on the new Sanofi-Aventis – DNDi drug at the French Embassy in Washington two weeks ago, an Institute of Medicine official said the World Bank plan was due sometime later this year. That’s three years after the original report calling for the subsidy, which is longer than it took DNDi to conduct the final clinical trials.

But let me not end on a negative note. What we have seen in the development of artemisinin-based combination therapy is happening on a dozen fronts. Non-profit groups are working to develop new drugs for drug-resistant tuberculosis; leishmaniasis; and microbicides to prevent the transmission of HIV/AIDS. Next month, I will travel to Brazil to report on the start-up the first efficacy trial for the world’s first hookworm vaccine, which is being led by the non-profit Sabin Institute in Washington with funding from the Gates foundation. Is success guaranteed? Of course not, just as it is not guaranteed in any drug development program, whether attempted by the for-profit or non-profit sectors. But what is guaranteed is that these therapies, if successfully developed, will be made available to the global poor at prices that they and their governments can afford.

I would suggest that the advanced industrial world can learn something from these non-profit efforts. We live in aging societies. The new therapies that will emerge to treat conditions particular to aging societies threaten to bankrupt all of our national health care systems. We need to restructure our incentive systems along the lines I discussed earlier – patent pooling, prize systems, generic manufacturing – if we’re going to continue to provide the latest advances in medicine to all of our citizens.

As currently structured, the private sector’s profit imperative prevents it from tackling the world’s most pressing public health problems. The innovations it does come up with come at too high a price. This emerging non-profit sector and its model has the potential to step into the breach and make advances in medicine affordable to all. And I’m sure it will. Because as we’ve seen so many times before in medical history, it is human needs and the tireless efforts of committee scientists that drive pharmaceutical innovation, not private profit.

FDA Shifts; Amgen, J&J in the Dock

Maybe I should leave the country more often.

I'm in Bordeaux to give a speech, but the morning papers bring news of major developments on two major issues I've been working on and writing about for the past several years. First, the Food and Drug Administration announced yesterday that it will no longer allow scientists with conflicts of interest valued at more than $50,000 a year to serve on advisory panels; and no one with lesser conflicts who gets a waiver allowing them to serve will have a vote.

It's a start in cleaning up the advisory committee process, and, as this Washington Post story points out, tacit admission that there are scientists and physicians without conflicts available to fill these slots. However, that $50,000 cut-off point seems awfully high, especially since the medical literature is filled with scientific surveys suggesting even small gifts like meals and meeting chotzkes can influence prescribing patterns. Moreover, even non-voting scientists with ties to industry can influence the direction of committee deliberations.

Congress will stlll have a say in this matter, and if it doesn't want to go to an outright ban, the Hill might consider limiting the number non-voting members with conflicts to one or two per committee, or even designating two or three key committees (Cardiovascular Drugs, Oncology Drugs and Drug safety come to mind) where the agency can "experiment" for a year or two with having no one getting waivers. Let's put the ban to a test to see if it really affects the quality of advice the FDA receives.

The other issue in the news involves the House Energy and Commerce committee launching an investigation into Amgen's and Johnson & Johnson's (its Ortho Biotech division) marketing practices for the anti-anemia drugs, Epogen, Procrit and Aranesp. Topping the list of questions was when the companies knew there was scientific proof that overuse of these drugs has needlessly harmed dialysis and cancer patients.

It was 1999 when I first wrote about the harm caused by raising red blood cell counts to near normal levels in dialysis patients. I heard about the issue from a patient advocacy group. The following year, Amgen stopped providing financial support for that group. If Energy and Commerce actually gets around to holding hearings on this issue, I suggest it adopt a standard that any patient or physician group that testifies disclose any and all financial support -- including dollar amounts -- that they receive from companies whose products are under investigation.

Creative Ways to Help Kids

A few days ago, I mentioned that the Democrats are scratching around for creative ways to refinance the kids health insurance plans run by the states, which are running out of money. They'd not only like to shore up the existing programs, but expand them to cover the 9 million children in this country without health insurance. Today's Kaiser Daily Health Policy Report suggests Rep. Pete Stark (D-CA), chairman of the House Ways & Means Subcommittee on Health, may be going after the Medicare Advantage plans to raise the dough.

What are Medicare Advantage plans? A few years ago, the Republican Congress allowed Medicare to make extra payments to insurance companies to begin enrolling seniors in health maintenace organizations (HMOs) instead of traditional fee-for-service Medicare. Now, I had always thought that HMOs were supposed to cost less money. But as every report about the launch of these so-called Medicare Advantage plans has shown, they are costing more -- a lot more.

How much? According to the Medicare Payments Advisory Commission, it's about 12 percent more. And according to the Congressional Budget Office, paying the insurance companies the same fees as regular Medicare would save $65 billion over the next five years. Hmmm. That's almost exactly how much it would cost to cover 9 million kids, and if I'm not mistaken, the money would count as the "pay-for" under House rules since Medicare Advantage payments come out of the general treasury, not the Medicare trust fund.

The insurance company spokesperson quoted in the piece defends the extra payments as necessary to meet all the extra benefits the seniors get in their HMOs plus lower co-pays. That's a politically loser of an argument. If it boils down to extras for seniors who already have insurance versus money to insure every kid in America, the kids should win hands down. This is one grandfather nearing Medicare age who'd certainly vote for giving it to the kids.

Industry-Backed Kidney Docs Dismiss FDA Warning

An industry-backed doctors' group last week cautioned renal physicians to carefully scrutinize a Food and Drug Administration warning that anti-anemia drugs made by Amgen and Johnson & Johnson's Ortho Biotech division could increase the risk of death, blood clots, strokes, and heart attacks in patients with chronic kidney failure when given in high doses. The Renal Physicians Association, which receives funding from Amgen and J&J, released a statement last week calling the advisory potentially "misleading" and asserting that some of the recommendations do not apply to chronic kidney disease patients. The association encouraged doctors to make treatment decisions on a case-by-case basis.

Reprinted from the Center for Science in the Public Interest's "Integrity in Science Watch" newsletter.

ExxonMobil Lobbyist: "I Had the Authority"

ExxonMobil lobbyist Philip Cooney on Monday admitted making 181 editing changes to climate change reports while serving as chief of staff for the White House Council on Environmental Quality. In sworn testimony before the House Government Reform and Oversight Committee, Cooney said he relied on a 2001 report prepared by the National Academy of Sciences. "I had the authority and responsibility to make recommendations to the documents in question, under an established interagency review process," Cooney said. Cooney spent 15 years working as a lobbyist for the American Petroleum Institute before assuming his role at the White House.

Several Democrats questioned Cooney's objectivity. "When I look at the role you played at API and at the White House, they seem virtually identical," Chairman Henry Waxman (D-Calif.) said. The issue of censorship is also being pursued by the House Science and Technology Committee, which sent letters to the heads of 11 agencies last week asking how they handle media requests for scientific information. The letters were prompted in part by revelations earlier this month that the Fish and Wildlife Service had instructed employees in Alaska not to discuss climate change, polar bears, or sea ice while traveling in countries around the Arctic region. The House last week passed a whistleblower protection act that would prohibit political appointees and high-ranking agency officials from interfering with government scientists' right to publish and speak out on public issues.

Reprinted from the Center for Science in the Public Interest's "Integrity in Science Watch" newsletter.

The Schwartzenegger Plan

Gov. Schwartzenegger spoke yesterday to a conference of health care journalists that I'm attending here in California. I was struck by his confidence that a universal health insurance plan will pass the California legislature this year. If he's right, that as much as anything will set the tone for the 2008 presidential debates, since if Sacramento passes a version of the Schwartzenegger plan, the nation will have two major states (Massachusetts is the other) that passed plans that have mandates requiring individuals to buy insurance at their core.

What are the hallmarks of the Schwartzenegger plan? It contains a statewide pool for the working poor and near-poor without insurance funded by an employer pay-or-play payroll tax of 4 percent. For everyone else who doesn't have insurance, it contains an individual mandate to buy catastrophic plans. Responding to questions expressing fears that this would reduce access to routine and preventive care, his experts replied that they're working on providing additional benefits from the pool for everyone with catastrophic plans.

As far as I can tell, there was very little in the California plan to reduce costs for the entire system; restructure the delivery of care to reduce error, improve outcomes and improve satisfaction; or do much beyond lip service to encourage wellness and prevention. In other words, Schwartzenegger's plan is designed to achieve a political consensus on getting everyone into the system by raising taxes marginally on lousy employers (4 percent of payroll for low-wage workers is far less than the cost of a good insurance policy) and impose mandates for lousy plans.

It fails to take on any of the providers who profit from the current system. Indeed, he gives them additional profits so they won't complain.

In 1993, Bob Dole, then the minority leader in the Senate and a key player in the emerging health care debate, told President Clinton that he could have an employer mandate to get everyone in the system. Clinton turned him down and instead opted for a Rube Goldberg contraption to control costs that drew the ire of every special interest in the system. Now, we're seeing proposals for Rube Goldberg machines on the financial side to get everyone in the system, with virtually nothing to hold down costs or improve quality of care.

The problem of the uninsured is a moral blot on this nation, and a major reason why there is political impetus (again) for reform. But how we do it is crucial, since getting everyone the same inefficient, mistake-prone, over-technologized, overpriced care I get only postpones the day of reckoning for the U.S. health care system.

Those Uppity Thais

It hasn't gotten much attention in the mainstream press, but Thailand's decision to issue compulsory licenses for several critical HIV/AIDS drugs has drawn a heated reaction from the global pharmaceutical industry. Abbott Labs announced earlier this week that it would no longer market its drugs in Thailand.

Abbott makes several protease inhibitors that are very important components of many AIDS regimens because they have the desireable side effect of delaying the body's metabolism of other drugs in the triple-cocktail. That allows for less frequent dosing schedules, which increases compliance.

But two years ago, Abbott established prices for their latest version of the drug that was well beyond affordability for most developing countries, including Thailand. That country responded by issuing a compulsory license, which voids intellectual property rules enforced by the World Trade Organization. However, WTO rules also allow for compulsory licenses when a nation thinks it is in its interest to do so.

Abbott's decision to strike back drew a heated response from Medecins Sans Frontieres (Doctors Without Borders) yesterday.

"Thailand's move to issue compulsory licenses is an important way to help bring prices down and increase availability of medicines," said Ellen 't Hoen, Policy Director at MSF's Campaign for Access to Essential Medicines. "In light of this, Abbott's move is appalling."

According to MSF, Abbott offered its latest drugs for $500 per patient per year for the least developed countries and $2,200 per patient per year in middle income countries like Thailand. That's a huge markup over the $140 per patient per year costs of older, less effective regimens.

Abbott was one of the first companies to get involved in AIDS research. Its HIV/AIDS research program began in the late 1980s after receiving a five-year U.S. government grant.

Docs Blast FDA's PDUFA Proposal

A coalition of nearly two dozen leading physicians and scientists have called on Congress to scrap the Food and Drug Administration's proposal for reauthorizing the Prescription Drug User Fee Act (PDUFA) and move to general tax revenues to support the agency.

The legislation is the subject a hearing this morning in the Senate Health Education Labor and Pensions Committee, chaired by Sen. Ted Kennedy.

The letter submitted to the committee this morning said PDUFA has limited the FDA's ability to monitor drug safety. The agency's proposal, negotiated behind closed doors with the drug industry, "does not come close" to meeting the standards outlined in an Institute of Medicine report last year.

That report called the FDA a broken agency whose culture needed a thorough overhaul. "PDUFA has helped to foster the public’s perception that industry has become the primary client of FDA rather than the American people," the letter said.

Signatories included two former high-ranking FDA staffers, two former editors of the New England Journal of Medicine, and one of the co-chairs of the IOM report. The effort was organized by Susan Wood, the former head of the Office of Women's Health at FDA and now a professor at George Washington University, and the Project on Scientific Knowledge and Public Policy.

The letter called on Congress to replace the $300 million collected in user fees with a direct appropriation, which "is the most effective way to ensure FDA’s independence and commitment to drug safety."

If Congress pleads poverty and insists on reauthorizing PDUFA, the letter said the legislation should:

• Allow FDA leadership to determine how the agency allocates the fees collected to fulfill all aspects of its mission.

• Deadlines or targets for speed of review must be eliminated or modified to allow flexibility and adequate time for evaluation and analysis by reviewers.

• New performance goals must be linked with safety or other public health outcomes, not just speedy approval decisions.

• Adequate resources must be made available for scientific research and training for FDA scientific and medical staff, including in drug safety epidemiology and risk management.

PDUFA's authorization expires at the end of September. Some observers believe Kennedy is seeking to sweep PDUFA reauthorization, an FDA reform bill and his generics biologics bill into a single omnibus package that will protect both the agency and the industry from serious reform.

Biotechnology and the Divine Right of Kings

Today's Wall Street Journal reports on the efforts of Barr Laboratories and its affiliate in Yugoslavia to develop copycat versions of some of the costliest drugs sold in America: biologics like Amgen's Epogen and Neupogen, and Genentech's human growth hormone. Europe has already set up a regulatory framework for allowing generic biologics on the market. Rep. Henry Waxman (D-CA) and Sen. Hillary Clinton (D-NY) are pushing for something similar here.

The story was deficient in several notable aspects.

First, there was no mention of the Food and Drug Administration's role in the process. What do officials at the FDA think it would take certify that a genetically engineered protein that rolled out of one lab was chemically comparable to another one? How would the "good manufacturing practices" certification that the FDA gives to generic manufacturers of small molecule drugs differ from a GMP certification given to a biologics manufacturing plant? When Johnson & Johnson ran into problems with its version of Epogen in Europe, it wasn't caused by differences in the molecule. It was caused by a flaw in the manufacturing process. Catching those flaws should be right up the FDA's alley.

Second, there was no discussion about patent law in the story. In passing, the reporters mention that Amgen's Epogen has patents that last until 2015, suggesting the arrival of a biologic generic is still a far off question. If memory serves me correctly, Amgen's original patent on recombinant human erythropoietin was issued in 1984. That was 23 years ago! Patents are supposed to last for 20 years, and then the work is supposed to enter the public domain. That's the whole point of patenting -- to give inventors incentives, but to make their work eventually free and available to the rest of mankind.

Clearly, the patent system isn't working in this case. What happened? Amgen has surrounded Epo (as the molecule is familiarly called) with various "blocking" patents, effectively giving the drug extended patent life beyond its alloted term. Similar tricks have been played by virtually every drug and biotech company with lucrative franchises they wish to protect.

Sen. Ted Kennedy (D-Mass), whose home state is a major biotech research and manufacturing center, is leading the charge against easy entry for generic biologics. The industry wants every new cell line to be subjected to same safety and efficacy testing that the original molecule went through. If that passes, the price of generics will be almost as high as the original molecule, and the health care system will be burdened with paying high prices for biologics forever.

Generic manufacturers argue that while proteins are larger than traditional chemical drugs, the FDA should be able to test their chemical comparability, just as they're doing in Europe. If Congress, because of the clout of the industry, can't see its way clear to allowing that, then perhaps it should come up with an alternative.

What might that be? First, it should amend patent law to prohibit the kind of games that give any drug, whether small molecule or biologic, exclusivity beyond 20 years. Congress has authorized extensions to patent life to promote pediatric testing and to encourage development of drugs for rare diseases. But these additional grants usually make up for some of the exclusivity lost during the development process. A flat 20-year limitation time will not eliminate these incentives.

Second, once a drug, any drug, reaches its 20th year of exclusivity without a generic version ready to hit the market, insurers -- including the government -- should have the right to negotiate a price with the original manufacturer that reflects the traditional generic mark-up over the cost of production.

If the White House and the Congress refuse to allow science to provide an alternative, and they refuse to give purchasers the right to negotiate generic prices with the original innovator, then the government is essentially granting biotech firms with lucrative products a perpetual monopoly. I thought that went out with the divine right of kings.

Generic Prices Too High

Confirming my seat-of-the-pants analysis yesterday, this morning's Wall Street Journal (subscription required) has a story showing that recent generics have entered the market at lower discounts to the brand-name drugs than previous entries. Medicare refusing to negotiate bulk discounts is one part of the problem. Another is that the drug store chains are gouging individual consumers not in group plans. A telling anecdote from the story: After the reporter called, CVS lowered its price on the first generic statin (simvastatin, the brand name drug formerly known as Zocor) by over 25 percent.

Prescription Drug Sales Soaring

If you thought that drug companies' declining profits and sales staff layoffs were due to declining drug usage, think again. The latest survey from industry consulting group IMS Health shows that drug sales surged 8.3 percent to $274 billion last year, and is expected to grow from 6 to 9 percent a year at least until 2010. Sales growth was significantly faster than the growth in prescriptions, which rose just 4.6 percent.

Even though sales of generics grew by 22 percent last year based on a 13 increase in prescriptions, the unbranded sector accounted for just 10 percent of industry sales. Overall, generics are now an estimated half of all prescriptions.

The number one reason offered for the increase by IMS? The onset of the Medicare prescription drug benefit, which accounted for 17 percent of all sales in 2006, the survey said.

But my quick analysis of the numbers in the press release says that industry is pushing rapid price increases through for its branded drugs, especially the new ones coming on the market. How else to explain the total sales increase while cheaper generics are seizing overall market share? Yes, generics are costing more, too. But their total share of the revenue pie is so small that only higher prices on brand name drugs explains the size of the overall increase.

The implications are obvious: The Bush administration's refusal to grant Medicare the right to negotiate prices with manufacturers has opened the door for both brand name and generic manufacturers to ram through sharp price increases.

FDA Shows Its Stripes

The FDA late Friday afternoon issued its official warning against giving cancer patients erythropoietin drugs (Epogen, Procrit, Aranesp) for anemia. This warning comes after six studies in recent months showed that stimulating red blood cell production in both cancer and dialysis patients may increase the risk of early death.

What struck me most about yesterday's announcement was its timing. It has long been a hallmark of White House public relations staff that the best time to release bad news was late on Friday afternoons. That way, the least number of people will hear about it through traditional news media sources. It's too late to make the Friday evening newscasts; and the print stories (see here and here, for instance) usually wind up inside the Saturday papers, which are the least read of the week. (The New York Times story, at least, got mentioned on the front page.)

Is this what the FDA wanted for this important warning? Is this the best way to counter the torrent of direct-to-consumer TV ads touting this drug by asking "if you're ready for chemotherapy"?

This late Friday afternoon release shows as much as anything how the culture of the agency has been transformed in recent years from industry watchdog to industry lapdog.

What Works Best?

It's amazing how little physicians know about what works best when it comes to treating their patients. They know plenty about what works because the drug industry's salespersons give it to them. "This drug is effective in reducing your risk of heart disease." "This chemotherapy regimen will definitely increase your chances of living for five years with this cancer."

But perhaps there is something else the physician can prescribe or suggest you do (like improving your diet or increasing exercise or taking a different pill) that would do more to reduce your risk of a heart attack or increase your chances of surviving? Does your physician know how well the two options compare?

In testimony before the House Ways and Means subcommittee on health earlier this week, the former Republican head of the Center for Medicare and Medicaid Services, Gail Wilensky, who is now publisher of the health economics journal Health Affairs, discussed the need to reform Medicare's physician payment system if the nation is going to hold down costs and improve outcomes. Any alternative system should align the incentives for physicians to give the best and most cost-effective care, she wrote.

To that end, she renewed her call for creation of a new agency to conduct comparative effectiveness studies, which would require a large increase in government funding. Her testimony was posted today on the magazine's blog. Here's the relevant section:

As important as it is to realign incentives, it is also important to provide both payers and providers with better information on the relative clinical effectiveness of alternative medical procedures and technologies. A number of other countries have been involved with the concept of comparative clinical effectiveness, but generally only for new pharmaceuticals and medical devices. Similar information needs to be available for medical procedures as well, since that’s where most of the money is spent.

Even if incentives are appropriately aligned, we can hardly expect to “spend smarter” if clinicians and payers (and patients) don’t know “what works when, for whom, under what circumstances.” Getting such information will require a significant investment and take several years to develop. But in a sector that is now spending $2 trillion, it is hard to explain why that type of investment would not be appropriate.

The bottom line: “We need to know more and pay for it better.”

Sen. Hillary Clinton (D-NY), the frontrunner for the Democratic presidential nomination, has championed legislation in the Senate that would create an arm of the government capable of conducting comparative effectiveness trials. Her bill promotes better and more cost-effective health care for the American people much better than the bills now moving through the Senate's Health Education Labor and Pensions committee.

For instance, chairman Ted Kennedy (D-Mass.) is pushing a drug safety bill that has drawn fire from most drug safety advocates and is considered woefully inadequate by Food and Drug Administration whistleblowers. As I reported earlier this week, Kennedy is also pushing a bill that would protect the biotechnology industry from generic competition.

Clinton sits on the HELP committee. It will be holding a mark-up hearing on March 28 to consider Kennedy's drug safety reform bill. One way for the frontrunning presidential candidate to show she is serious about health care reform is to offer an amendment to Kennedy's bill that would create an agency that could not only conduct comparative effectiveness trials, but also conduct the post-marketing drug safety trials that the FDA orders but the drug companies never seems to get around to doing.

Drug Safety Data Mining on the Way

Wonky but important topic: The Food and Drug Administration's bungled effort to modernize its drug safety reporting system was exposed in last Saturday's Wall Street Journal. Now, an industry newsletter called RPM Reports has a fascinating overview (this one report is free if you register) of the coming age of data mining as a tool for early identification of safety problems in commonly prescribed drugs.

Private firms are now selling software that will enable almost anyone to do it from their desktop! Companies are already using it to help market their own drugs as safer than others' drugs in the same class. Academic researchers, sometimes in league with FDA researchers, are jumping on the bandwagon (the compulsive gambling story associated with the anti-Parkinson's drug Mirapex that made all the papers last fall was a great example).

Will the FDA be the last one to get on board with a modern system for reporting adverse events? The Institute of Medicine's drug safety report called for it. Consumer groups want it. There's legislation moving slowly through Congress that would establish it. To borrow a teaching from Rabbi Hillel in the Pierket Evot: If not now, when?

More on the Cervical Cancer Vaccine

Dr. Benjamin Brewer, who writes "The Doctor's Office" column in the Wall Street Journal (subscription required), takes a skeptical look at Merck's new cervical cancer vaccine, and comes down against states requiring vaccination. Here's the crucial paragraphs:

How much health care can we afford?

A lot of the costs associated with human papillomavirus are not due to cancer. The costs are associated with annual exams and for evaluation of abnormal pap smears. The Gardasil vaccine isn't going to eliminate the annual pap smear.

Thanks to the development and availability of the low-cost Pap smear, cervical cancer has become a rare disease in the U.S. Newer versions of the test have cut down on false positive results and improved cancer screening.

Despite the fear induced by diagnosis of an abnormal pap smear, only a minority of women with high-risk HPV ever develop cervical cancer. It often takes years to develop and happens mainly to women who don't have access to annual exams. I've seen one case of cervical cancer in my practice in nine years and it was treated successfully with surgery.

Too many women still die of cervical cancer; however, the real problem is lack of access to preventive medical care for low-income women and not the lack of a vaccine.

AFL-CIO on Universal Heath Care

The AFL-CIO's executive board issued a comprehensive statement about what a universal health care program should look like. Worth reading.

Quality and Effectiveness Enter the Debate

Two stories from today's papers suggest that the coming debate over health care reform may be more informative than the last time the nation, via the Hillary-care proposal, sought to adopt a universal system of coverage. Key to creating a long-term affordable system that covers everyone is reforming the health care system itself, which requires improving quality and lowering the cost of medicine. One way to lower cost is to get rid of useless procedures and tests.

On that score, a new study in the Journal of the American Medical Association showed that CAT scans for early detection of lung cancer among smokers did not reduce the death rate. A previous study by a radiologist had suggested people lived longer. It turned out that was merely an artifact of earlier detection coupled with false positives identified by the CAT scans (the test probably identified minor tumors that would never have proven fatal or even malignant if left untreated).

The second story comes from the New York Times' David Leonhardt, an economics correspondent who understands health care. Today, he reports on the movement to require hospitals to report quality indicators, which are now reported on a Medicare website. His example is the time hospitals take to treatment for heart attack patients. The longer it takes, the more likely the victim will suffer permanent disability or death.

In theory, requiring the reporting of these times would provide consumers with more information so they can choose which hospital to drive to. But how likely is a person in the midst of a heart attack to do that? How likely is an ambulance driver going to go past one hospital because the one five miles down the road delivers better care? That's a lawsuit waiting to happen.

Yet publication of data has gotten hospitals to improve their performance. How? It turns out that peer pressure is a powerful incentive. Having bad ratings forced the hospital -- in Leonhardt's example, the University of California at San Francisco -- to dramatically cut the time heart attack patients spent waiting for treatment.

Kennedy Opposes Easy Entry for Generic Biologics

In a huge blow to everyone concerned about skyrocketing health care costs, Sen. Ted Kennedy (D-MA) is promoting legislation that will make it extremely difficult for generic biologics to enter the market.

According to this morning's Boston Globe, Kennedy's bill would require a follow-on biologic (like a generic for Amgen's Epogen, now in its 20th year of patent exclusivity) to conduct all the same efficacy trials as the original drug. The Senate Health Education Labor and Pensions Committee will hold a hearing Thursday.

Rep. Henry Waxman (D-CA) has introduced legislation that would speed the introduction of generic biologics, but he has run into stiff opposition from the Biotechnology Industry Organization, now headed by former Congressman James Greenwood. BIO has Kennedy's ear. Why? Massachusetts is home to numerous biotechnology companies, including Genzyme, which has lobbied hard against Waxman's bill. Genzyme's patent on Cerezyme, the recombinant protein for Gaucher's disease and, unless I'm mistaken, still the most expensive drug in the world, has another decade to run.

Kennedy and the biotech industry say every protein line is distinct, and each one must be tested for safety and efficacy before being allowed on the market. Firms that want to produce copycat versions of biologics say that traditional testing for similarities in chemical composition should be sufficient, as it is in the rest of the drug world. Requiring efficacy tests will make every product, even if a generic with regard to patent law, distinct, and make follow-on biologics more like me-too drugs than true generics, which are usually half the cost of the original molecule. Me-too drugs usually enter the market at a small discount to first-to-market drugs.

VA Formulary Not Restrictive

One of the classic drug-industry inspired assaults on the Veteran Administration's formulary is that it contains only 1,300 drugs, a tiny fraction of the more than 5,000 drugs on the market. This supposedly dooms vets' physicians to restricted and therefore inferior choices, leading many to seek care outside the system.

Here's another permutation of this big lie, offered by Charles Dent and Jim Gerlach, Republicans from northeast Pennsylvania. It appeared in early February in their hometown Allentown Morning Call:

The price may be lower for some drugs, but one should also understand that the VA list of covered drugs is quite small, covering just 31 classes of drugs, while Medicare Part D requires that beneficiaries have access to drugs in 209 therapeutic classes.

Here's the truth: An article today on the website of the American Society of Health-System Pharmacists (the 30,000-member organization represents pharmacists at hospitals, nursing homes and other primary care facilities) reports on the VA's completion of its national formulary, a ten-year effort. Yes, the VA formulary has just 1,300 drugs on the list. But those are chemical compounds. It doesn't reflect differing dosage levels, which account for two-thirds of FDA approved drugs. If one accounts for dosing, fully 4,800 currently approved drugs are on the VA formulary, the article says.

Then there's the architect of the VA formulary, Michael Valentino. He stepped into the lion's den at the American Enterprise Institute in January and presented all the relevant facts and figures. Click here if you want to see his excellent presentation. The relevant slide: The VA covers 478 or 11 percent MORE drugs than Medicare Part D, which is run by the insurance industry.

The real question is what drugs will make it onto the formulary. Will it be every me-too drug offered by cash-desperate drug companies? Or will it be those that have been scientifically proven to be medically necessary with a centralized buyer capable of negotiating prices?

Glad we cleared that up. Next lie.

VA Under the Microscope

The debate over the adequacy of care at the Veterans Administration is underway over at the Health Care Blog. Maggie Mahar, author of "Money-Driven Medicine," weighed in yesterday with a defense of the VA system's superior care, and how it is being undermined by systematic underfunding by the Bush administration. The blog's sponsor, industry consultant Matthew Holt, highlighted an interesting article in the trade journal of the managed care industry that suggested executives in the nation's beleaguered HMOs could learn a thing or two from the VA. The article also contains a number of charts showing how the VA routinely surpasses other health delivery organizations in meeting best medical practice standards.

That said, Mahar's rejoinder to several commenters winds up making the same point I tried to make yesterday: the VA has been overwhelmed by Iraq war casualties, which are running at five times the rate of previous wars due to the military's ability to save the lives of the wounded. That means the physically and emotionally scarred veterans of this ill-conceived war will be with us in numbers comparable to previous wars. Meanwhile, the Bush administration and Congress have consistently funded the VA at levels well below the rate of medical inflation. The result? This exemplar for single-payer health care delivery is being overwhelmed by its challenges.

A final note: I was shocked while listening to C-span yesterday morning by the number of complaints from veterans and/or their spouses that poured in from around the country. A number of callers complained about lost paperwork. This suggests that the VA's much-ballyhooed information technology revolution still has a long way to go -- at least in the front end that touches people directly. It's great if the charts are computerized, which eliminates duplicative tests and faulty prescribing. But the lesson here is that people (patients) are just as likely to remember the way they are treated as the treatment that they receive.

Footnote: Former Food and Drug Administration deputy commissioner Scott Gottlieb has an opinion piece in today's Wall Street Journal attacking the FDA's new requirement that companies more carefully manage the distribution of risky new drugs (so-called risk management plans), a requirement that would be greatly expanded under several reform bills now before Congress. Back at the American Enterprise Institute, Gottlieb winds up defending all forms of off-label marketing and accusing those who would restrict it as mandating "cook book medicine." It's a perfect contrast with the debate over the VA. By restricting payments for pricey drugs that are no more effective than generics and adhering to evidence-based standards, the VA has been able to deliver a very high level of care at low cost for millions of vets and their families. The phrase "evidence-based medicine" never appeared once in Gottlieb's article. In his world, paying the highest prices in the world for second world outcomes is a desireable outcome. It's restrictions on physicians' choices that are the real problem.

Collateral Damage

In the two weeks since the scandalous conditions at Walter Reed Hospital’s Building 18 were exposed in a front page Washington Post article, the media has been filled with accounts of the military's neglect of America’s wounded veterans. The Army Times this weekend has a depressing story about the Pentagon’s efforts to suppress further complaints from wounded Iraq returnees at the facility.

The response by the Bush administration and the army, at first denying responsibility and then firing the generals in charge, has been nothing short of pathetic. In his Saturday radio address, the president, without admitting responsibility, vowed to make amends.

Let’s briefly review the extraordinary record of this two-term president. He’s gone from ignoring warnings that “Osama Bin Laden Is Determined to Strike in the U.S”; to lying about the casus belli for war in Iraq; to failing to plan for the war’s aftermath; to bungling the response to Hurricane Katrina. Now, his administation must bear responsibility for mistreating the very people whose lives have been devastated by his war policies.

The next victim of this administration’s incompetence could well be the Veterans Administration, which in recent years has earned a well-deserved reputation for excellence. This morning's Washington Post follows up on a torrent of emails from veterans around the country complaining about conditions at the nation's VA hospitals. The story includes some horrifying stories about mistreatment of recently wounded Iraq veterans. "It is just not Walter Reed," the headline said.

Advances in battlefield medicine have changed the calculus of war-time casualties. During Vietnam, there were three wounded for every death in battle. In Iraq, that ratio has skyrocketed to 15 to 1, with many more seeking treatment for the post traumatic stress that hadn’t been recognized in the immediate wake of prior wars.

As Linda Bilmes, a Harvard Kennedy School of Government researcher, wrote recently in the Los Angeles Times:

So far, more than 200,000 veterans from Iraq and Afghanistan have been treated at VA medical facilities — three times what the VA projected, according to a Government Accountability Office analysis. More than one-third of them have been diagnosed with mental health conditions, including post-traumatic stress disorder, acute depression and substance abuse. Thousands more have crippling disabilities such as brain or spinal injuries. In each of the last two years, the VA has underestimated the number of veterans who would seek help and the cost of treating them — forcing it to go cap in hand to Congress for billions of dollars in emergency funding.

The VA system has a reputation for high-quality care, but waiting lists to see a doctor at some facilities now run as long as several months. Shortages are particularly acute in mental health care. Dr. Frances Murphy, the VA's deputy undersecretary for health, recently wrote that some VA clinics do not provide mental health or substance abuse care, or if they do, "waiting lists render that care virtually inaccessible."

Two years ago, New America Foundation senior fellow Phillip Longman offered an eye-opening account in the Washington Monthly of the VA's transformation from an object of scorn into one of the best health care delivery systems in the country. His book on that turnaround is due out in a few weeks.

Bad timing. What should have been a poster child for what a single-payer health system could do for America has been undermined by the incompetence of this administration. Now, a large part of the public will see it -- unjustifiably -- as just another institution failing the American people.

Adverse Events Overhaul Years Away

The Food and Drug Administration is years away from overhauling its adverse events reporting system due to a bungled effort at revamping its computer system, the Wall Street Journal (subscription required) reports this morning.

The Avoidable Death of Deamonte Driver

Earlier this week, I was invited to post a comment on the Guardian of London's website after the Washington Post reported on the avoidable death of Deamonte Driver from untreated tooth decay. You can read it here, but I suggest you go to the Guardian's site to read the substantial commentary that poured in after my posting.

How can the US spend 40% more per capita on healthcare than any other advanced industrial country in the world and still have worse outcomes than most?

Just ask 12-year-old Deamonte Driver of suburban Washington, DC.

Actually, you can't ask Deamonte anymore. He's dead. According to a story that appeared in this morning's Washington Post, he died of complications of a brain infection caused by untreated tooth decay.

Because he lacked health insurance, Deamonte couldn't see an oral surgeon before it was too late. The so-called safety net for uninsured poor people (his mother worked but none of her employers provided health insurance) utterly failed this bright boy, who enjoyed doing math. Medicaid, which is supposed to provide health care for the uninsured poor, may have sent his paperwork to the homeless shelter where the family briefly lived before his destitute single mother sent the kids off to grandma. His mom had to cancel his appointment with the oral surgeon, who wouldn't see him without insurance.

When his toothache worsened, the infection spread to his brain. The second week in January, he was rushed to the hospital where he received an estimated $250,000 in emergency care. After two brain surgeries and a temporary recovery, he relapsed and died.

If the US had universal insurance that covered dental care, the system would have paid under $1,000 for Deamonte's routine dental visits and he would still be alive.

If the current Medicaid system functioned properly, the boy would have received a more timely appointment with an oral surgeon, for under $10,000, and would still be alive.

If the states (which administer Medicaid) had a proper Children's Health Insurance Plan that was sufficiently funded and organized to reach all children, Deamonte would still be alive.

Instead, the hospital that treated Deamonte will collect the quarter-million dollars spent on his failed care by raising rates on its insured patients, and Deamonte's mother will pay for his funeral.

In his state of the union address and in subsequent public relations events, President Bush has touted tax breaks as the way to get the poor to buy "catastrophic" health insurance policies and set up individual health savings accounts to pay for routine care. Well, we can see what catastrophic coverage did for Deamonte. And how much money do you think his hard-working mother, who couldn't even afford rent on her low-salaried jobs, would have socked away for routine dental care?

Just this week, the president and Health and Human Services Secretary Mike Leavitt told the nation's 50 governors that the growing shortfalls in their CHIP programs could be solved with "better management". Meanwhile, states like Maryland (where Deamonte lived) are scrambling to raise cigarette taxes as part of an effort to shore up their faltering programs.

The death of Deamonte Driver is a testimony to the moral bankruptcy of these piecemeal efforts to salvage a collapsing US health insurance system. Medicaid pays the least of all the nation's safety-net programs, and, as a result, doctors and dentists don't want to participate. Programs like CHIP, which rely on aggressive outreach to find uninsured kids, inevitably miss many of the needy - especially if they are tough-luck cases, like Deamonte.

These programs are part of the problem, not the solution. Let's get on with the business of reforming the entire system. As the Deamonte Driver case dramatically demonstrates, comprehensive reform wouldn't necessarily cost more money, since a health insurance plan that delivers timely, preventive care will avoid many monstrous catastrophic expenses.

California Congressman Pete Stark, for instance, has introduced legislation that would expand Medicare to cover everyone without insurance - a plan that would institute a small tax employers who don't provide insurance in an attempt to cover the costs. And if Deamonte Driver tells us anything, it's one place to start.

Chafee's Timely Reminder

Former Senator Lincoln Chafee of Rhode Island, now at a think tank, in today's New York Times offers a timely reminder of the political debate leading up to the 2002 resolution authorizing war in Iraq; the political choices available to all Senators at that time; and the votes of all the presidential candidates who were in the Senate at that time (Biden, Clinton, McCain, for instance). Read it and weep.