No Let-Up in Drug Marketing

From today´s Integrity in Science Watch from the Center for Science in the Public Interest::

Mass marketing campaigns by drug and device makers that utilize gifts, free samples and free meals still reach more than nine in ten practicing physicians, a survey released last week shows.

Among the 1,662 physicians who responded to the Boston-based Institute for Health Policy survey in late 2003 and early 2004, 94 percent reported some type of relationship with the pharmaceutical industry – usually in the form of free food or drug samples. Numerous studies have shown that these small gifts influence physician prescribing practices.

More than a third received drug company funding to attend professional meetings or continuing medical education seminars, which are a requirement of continued licensing in most states. And more than a quarter were paid as industry consultants or lecturers or for registering their patients in clinical trials.

In 2002, the American Medical Association, the American College of Physicians, the Accreditation Council for Continuing Medical Education, and the Pharmaceutical Research and Manufacturers Association passed voluntary codes of conduct in an attempt to rein in excessive marketing. The results of the new survey seem to suggest those codes had little impact.

Meanwhile, the movement to require the drug industry to disclose its gifts and grants to physicians is gathering steam. Five states and the District of Columbia have passed laws requiring disclosure. Vermont and Minnesota make those disclosures publicly available.

However, a recent study in the Journal of the American Medical Association found those disclosures “incomplete” and of limited usefulness, and called for “more stringent laws with clear mechanisms for enforcement.” Legislation pending in New York that is backed by the state AARP chapter would require companies to report gifts greater than $75.

The Wyden Plan

I'm on vacation until May 7th. This will be last posting for a week.

Ron Wyden (D-OR) knows health care, knows health insurance, and knows the history of health care reform. He also knows politics. So the carefully considered calculations he put into his universal health insurance bill (S. 334, the Healthy Americans Act) are worth reviewing.

First, he believes the time is right to end the employer based system. He rejects the poll-driven concept that this would scare the bejeezus out of most Americans. His bill would tell employers to end their plans, give their employees a dollar-for-dollar increase in wages with the money (this makes the cost still tax deductible to employers, but taxable to employees), and have those workers go out in a revamped insurance marketplace to buy individual or family plans. Oh, and for individuals and families, buying insurance would be mandatory – like getting a driver’s license.

Consumers will like it, he told the Wall Street Journal-sponsored World Health Care conference last week, because “if they can buy insurance for less than what the employers give them, they keep the money.” Employers will like it because they are freed from all future health care cost increases.

Wyden said insurance executives have told him that they can “thrive and prosper” in this revolutionized environment. That’s interesting because his plan calls for throwing a national regulatory blanket over the entire field, something that has never happened before because of fierce opposition by the industry. When it comes to insurance, regulation remains a state-by-state affair.

He would have the federal government outlaw companies’ ability to discriminate against people in poor health or choose to insure only younger, healthier people (the adverse selection problem). He would impose a community rating system and create a minimum set of services that must be provided by every plan. “The days of cherry picking are over,” he said. “You don’t get to just choose healthy people and send the sickest people over to public programs.”

He also challenged the conventional wisdom that health insurance reform must await the next president. He believes it’s possible to get some traction this year. He has ten senators – Republicans and Democrats – signed onto his bill and he expects something similar to be introduced in the House.

Is this politically feasible? He mentioned in passing that there would be no new taxes and no new health care expenditures under his bill. The Lewin group has projected it would save $1.45 trillion over the first ten years, money that could be redirected to covering those who get either inadequate benefits or no benefits at all now. He would distribute the savings by subsidizing those who can’t afford to buy insurance in the private marketplace.

Sounds pretty good, but let’s get hypothetical. How will this affect the upper middle-class voter who currently has one of those eroding employer plans? These are the folks with the most political clout in this society. They’ll get more money in their paycheck, but probably about the same or less than what it will cost them to buy comparable insurance in the private marketplace. So there’s no benefit there.

However, they’ll also face a higher tax bill because they fell above the line getting subsidy and their privately-purchased plan will probably exceed the standard government deduction. So for many middle class voters, this will look, smell and feel like a tax increase because it will be one. Given all the corporate executives lining up behind the Wyden plan, the chance that someone will point out that his plan relieves employers of their burdens while taxing the "hard-working middle class" has to be rated a better than 50-50 possibility.

And will insurance companies really line up for national regulation of their industry? Perhaps. Why not test that proposition? The current individual insurance market, which will become central under this plan, is usually described as dysfunctional. As an earlier speaker said, “If you’re in the small group or individual market in this country, you’re toast.”

Instead of testing his bill’s overall strengths in this Congressional session, Wyden should introduce as separate legislation the part of the Healthy Americans Act that would impose community rating and forbid cherry-picking on health insurance carriers selling individual and small-group plans.
The President's signature on that legislation would be convincing evidence that the insurance industry is ready for reform.

Prevention, Cost Control

All the Democrats in the South Carolina debate emphasized preventive medicine and cost control as keys to health reform. Dr. Rick Lippin in his Critical Condition blog has a good take on it, so I'm referring readers to him this morning since I only caught snippets of it on the radio.

No Free Lunch?

Are you a physician who wants to "just say no" when the drug industry's reps come knocking on your door? You can get help from the website run by Dr. Bob Goodman, a general internist in New York City. Dr. Bob's No Free Lunch campaign encourages physicians to "sign the pledge" promising to eschew gifts, free samples and meals from drug industry reps.

These unseemly practices were in the news yesterday because of a new study in the New England Journal of Medicine, which confirmed that more than 90 percent of doctors in the U.S. still accept freebies from drug industry reps. This marks no change from a similar survey conducted several years earlier, which suggests the American Medical Association's voluntary program to curb these practices is not having much of an impact.

How about the Pharmaceutical Research and Manufacturers Assn. guidelines, which were also supposed to curb the more unseemly aspects of this subtle form of bribery? Their representative appeared on CNBC yesterday morning debating yours truly. You can see the clip here:

http://www.youtube.com/watch?v=Sde1WlWAogo

The Empire, er, AMA Strikes Back

Every once in a while, someone at a conference makes a statement that stands out from the usual platitudinous palaver. Earlier this week, that honor belonged to William Plested, the president of the American Medical Association. At the World Health Care Congress in Washington, DC, he was asked to comment on the Center for Medicare and Medicaid Services' efforts to set quality standards to inform (and, let's face it, one day determine) payment policy. He declared:

"There is a growing refrain that there is a crisis of quality in American healthcare. I want to make it crystal clear that I categorically reject this assertion. . . If there is a crisis in American medicine, it is a crisis like no other in history. It is not a crisis of failure, but one of unprecedented success."

Forget for a moment the front page New York Times article last Sunday cataloguing the dramatic increase in infant mortality in the American south. Forget for a moment the rising obesity epidemic and demographers' legitimate fear that it will result in a reversal of the past century's slow, steady rise in longevity. Forget for a moment the statistics that show that despite the U.S. spending anywhere from 150 percent to 200 percent of what other industrialized countries spend on healthcare, we have longevity and infant mortality statistics that rank us near Eastern European nations -- somewhere in the mid-20s among the 30 nations that belong to the Organization of Economic Cooperation and Development.

Plested's outburst came in response to Herbert B. Kuhn, the acting deputy administrator, who gamefully outlined the agency's goal of moving "from just paying bills to helping people get well and avoiding costs." They've given hospitals a small financial incentive (0.4 percent!) to report performance data; they've set up a physician group practice demonstration project; they've worked with the AMA in establishing physician performance standards, Kuhn said.

Plested's view on where all this is heading? "You and your loved ones may find yourselves in the hands of someone who foresakes ethics and for a pitifully insignificant reward will follow a cookbook of care designed primarily to reduce costs."

Physicians have embraced evidence-based medicine, he declared. Treatment must be based on careful scientific research and he insisted that payment reform be held to the same standard. "We are witnessing a pell mell rush to pay for performance programs based entirely upon grandiose predictions of great improvements in quality and massive savings in costs, predictions that are completely without any basis in historical fact. There is even a rapidly escalating body of literature that suggests that the exact opposite outcome -- lower quality and higher costs -- is much more probable."

I'm not familiar with that literature, so perhaps readers of this blog can enlighten me. Plested's insistence that the practice of medicine is strictly according to ethical standards and driven by evidence is way off the mark, though. Every study I have ever seen on the subject suggests that the massive variations in practice and outcomes around the country prove that quality and cost have almost nothing to do with each other.

Moreover, I wish he would have spent a few sentences in his talk addressing the myriad conflicts of interest that have enmeshed more than 90 percent of physicians. Is that what he meant by the ethical practice of evidence-based medicine? Yesterday, the New England Journal of Medicine released a study showing that free lunches, free samples and small gifts from drug reps are still the coin of the realm when it comes to determining physician prescribing patterns, and the physicians who sit on the committees that write clinical practice guidelines are still largely doubledipping on the payrolls of the providers with a stake in the outcomes of those guidelines.

It has been said many times that health care reform will not succeed unless reformers can gain the cooperation and collaboration of the nation's 700,000 physicians. I tend to agree. But hearing Plested this week reminded me that organized medicine -- the AMA -- has fought every successful reform movement of the 20th century -- from the coming of employer-based insurance and Blue Cross-Blue Shield to expansion of government services through Medicare and Medicaid. Yet after each successful reform, the profession adapted and thrived as never before.

Why did I ever think that the movement to contain costs while improving quality -- a must if we are going to weather the twin tsunamis of an aging society and advancing medical technology -- was going to be any different? Based on Plested's comments, it seems to me that the AMA is gearing up to be the bulwark against reform. This is one more war where organized medicine will be in its foxholes lobbing shells at the reformers.

Where's Wolfowitz on World Malaria Day?

While the Al Kamen of the Washington Post is reporting the latest emails emanating from Paul Wolfowitz's bunker at the World Bank, the Financial Times has uncovered evidence that the architect of the Iraq War has also been busy censoring reports on global warming.

For those not following this saga, the erstwhile Bush administration Middle East policymaker is enmeshed in a conflict-of-interest scandal that involves giving his companion a big raise and a prestigious job at that institution. If I'm reading between the lines properly, she didn't deserve the job, or at least didn't deserve it as much as some other long-time employees at the Bank.

Now that Wolfowitz is in the press's crosshairs, an enterprising reporter could tackle another major flaw in Wolfowitz's leadership at the Bank. It's especially relevant to raise this issue today, which has been designated as World Malaria Day.

Three years ago, an Institute of Medicine committee chaired by Nobel Prize-winning economist Kenneth Arrow issued a report called "Saving Lives, Buying Time." It outlined a strategy for bringing life-saving anti-malarials to the developing world. Nearly two million people, most of them children, die from the disease every year. In many parts of the world, the mosquito-born parasite has grown resistant to chloroquine, an extremely cheap drug that can be bought for pennies in most developing world pharmacies or local dispensaries. The parents who buy the drug for their children discover too late that it doesn't work.

There is a proven therapy for treating resistant malarial strains. It is a combination of drugs that includes artemisinin, a derivative of the sweet wormwood bush. For a history of its development and more background on this issue, you can click here to read my story that ran in last December's The Scientist magazine.

Despite the efforts of Doctors Without Borders to develop less expensive versions of this drug, the cheapest version now on the market still costs $1 a day, ten times the price of chloroquine. The IOM report came up with a plan for overcoming this problem: the global health agencies should get together, establish a centralized purchasing fund, and buy enough artemisinin-based combination treatments to treat everyone in the world who needs it. This would cost less than $500 million a year.

Then, the centralized authority could simply sell its supply into normal distribution channels as the same price as chloroquine (about 10 cents a dose) and let the market do its magic. The good drug would rapidly supplant the bad one.

The World Bank was given the job of bringing this plan to fruition. Last month, I spoke to the coordinator of public health programs at the World Bank "on background." (They always make you do that over there, especially if you're a lowly blogger.) He brought me up to date on the plan.

Netherlands and Tanzania are co-chairing a group that is creating the "mechanism" for implementing the plan. They still haven't raised the money. They've decided they can't create another bureaucracy but need to find a "partner" who can execute the plan. They're debating whether it should be direct purchase or a voucher system. They hope to launch by the end of the year.

Sound like typical bureaucratese to you? It sure did to me. Where was the sense of urgency, I kept asking. "The discussions are ongoing," he said. "They're intense."

Novartis, which makes the expensive formulation of the combination drug (theirs is called Coartem), announced a major charity program in Tanzania this morning. They'll deliver 4.7 million free doses of the drug to a country where malaria is the leading killer. My morning paper has large ads from ExxonMobil assuring me how much they are worried about the global malaria epidemic. Is there any problem on earth that their p.r. department can't address with a full page ad?

What I would like to see on World Malaria Day is Paul Wolfowitz come out of his bunker and announce the formation of a fully-financed global purchasing authority for artemisinin-combination therapy -- the best hope in the world for rapidly curbing the devastating impact of this disease.

Health IT addendum

As if on cue, today's Wall Street Journal has a page-one story about a young whistleblower who unmasked flubs and conflicts of interest in Kaiser Permanente's efforts to computerize its medical records. Forget about the scandalous elements of the story. It reveals the difficulties even one of the best health care systems in the country is having in moving to computerized medical records. What will it take to get the physicians that Porter wants to reorganize (see the below post) to move in this direction? And if it cost Kaiser $1.5 billion for a faltering program, what will it cost them?

Getting Doctors to Compete

I've been doing some guest blogging at WorldHealthCareBlog, which is affiliated with an all-star health care conference sponsored in part by the Wall Street Journal now underway at the Washington, DC Convention Center. I'm sitting in on a session each day to hear what some leading thinkers have to say about the evolving health care reform debate. On Sunday, I heard Harvard Business School professor Michael Porter, who has been stumping the country for five years touting competition as the solution to the nation's health care woes:

"Universal insurance is not enough to address the fundamental challenge facing our health care system," he told the 1,600 attendees. "The fundamental problem at the end of the day is the value of the health care we deliver."

And how would he reorganize health care to deliver better value? "Where we need to go is an integrated practice model," he said. His model entails patient-focused practice groups that knit together every specialty needed to treat an individual's medical condition. It's not that physicians will no longer specialize; it's that they're no longer going to practice in specialty silos divorced or only marginally connected to all the other people providing that particular patient's care.

Competition enters this new system by giving individuals information about the relative performance of these integrated practices. That way, consumers and payers will be able to use outcomes and price data to not just hold down health care costs, but choose those practices that deliver better outcomes.

It's a compelling vision, and one I'm somewhat sympathetic with. It also tracks very closely with another long-time observer's perspective on how the health care system has to change, one who has a very different political perspective from Porter.

Dr. Arnold Relman, the former editor of the New England Journal of Medicine, has a new book coming out called "A Second Opinion," where he, too, calls for the total reorganization of the practice of medicine around the integrated practice model in order to deliver patient-focused care to the chronically ill people who account for 75 percent of all health care expenditures.

However, where Porter would have various systems compete by making available pricing and outcomes data, Relman would simply have the state or non-profits employ all the specialists needed to deliver integrated care. He's also a backer of a single-payer national insurance model where Porter still sees a major role for both insurance companies and for-profit physician practices in the system.

Though he admitted that computerizing medical records is a tool, not a solution, Porter suggested at several points in his talk that this tool could resolve the fragmentation implicit in leaving the current structure of physician practices (with most doctors belonging to specialty groups) alone. That salutory view about the promise of health information technology was echoed by the two commentators the Congress lined up to respond to Porter's talk: Ron Williams, chief executive officer of Aetna Inc., and George C. Halvorson, chief executive officer of the Kaiser Foundation Health Plans and Hospitals, more commonly known as Kaiser Permanente.

"We need care connectivity and electronic databases," said Halvorson. "Only 8 percent of the diabetics in this country get the right care. We haveto move than to 80 percent. To get there, we have to create an architecture that requires people to be in registries."

Is Health IT really our savior? Thank goodness John Iglehart, the founder of Health Affairs and currently a national correspondent for the New England Journal of Medicine, asked the obvious question -- on that could just as easily be posed to Relman as to Porter: "What would force providers to restructure?"

Perhaps the organizers of the conference weren't interested in generating heat to go along with the light shed by Porter. But I would have loved to hear how the president of the American Medical Association, who speaks Monday, would respond to Porter's (or for that matter, Relman's) plans for reorganizing the practice of medicine. Moving physicians away from fee for service payment to paying them for integrated treatment for conditions (the Porter model) or to salaries in integrated practices (the Relman model) represents nothing less than a revolution in the practice of medicine, one that would entail significant income losses for thousands of doctors.

Yes, it's happening in many places. Yes, younger physicians are more open to computerization and working within integrated practice models. Yes, employers are no longer looking to beat up on the insurance companies for failing to hold down costs, but rather want value for the money they spend on employees' health care.

But until someone comes up with a concrete payment model that actually encourages the physicians we have (not the next generation coming along) to move into integrated practices, health care reform is going to stay a debate about insurance and not a debate about how to get better quality for the money we spend.

Medicare Proposes Paying for Comparative Clinical Trials

From today's Integrity in Science Watch:

Medicare may soon begin paying for drugs and devices used in clinical trials that compare the effectiveness of competing FDA-approved therapies.

A draft memo circulated earlier this month by the Center for Medicare and Medicaid Services would reverse a policy that has been in effect since June 2000. Under that policy, the agency pays for the routine physician costs of seniors who participate in clinical trials, but not for the “investigational” drug, device or test, even if it is already FDA-approved and routinely covered by the Medicare outside the clinical trial.

This policy prohibited Medicare from participating in trials comparing competing treatments, which could save taxpayers money by steering seniors to less costly but equally effective medicines and procedures. “We’re proposing a change so that we will be able to participate in these studies,” said Leslye Fitterman, an epidemiologist with CMS’ Coverage and Analysis Group. “We would pay for the drug if (CMS) already pays for it outside the study.”

At stake is the ability of Medicare to generate objective, scientific data for making payment decisions that can save taxpayers money without harming beneficiaries. The issue came up earlier this year when CMS refused to pay

for the routine cost of care for seniors who took part in a National Institutes of Health-sponsored clinical trial comparing two Genentech drugs for macular degeneration (MD). According to the Wall Street Journal, Genentech refused to provide NIH with free drugs, which made the cost of the trial prohibitively expensive for the agency to manage alone. Lucentis, which costs about $2,000 a shot, is already approved for the condition and costs Medicare over $200 million a quarter. Avastin, which is essentially the same drug but is only approved for use against cancer, costs $40 a shot when used for MD. Physicians using Avastin off-label have reported results comparable to Lucentis. A successful government-sponsored test, if published a major peer-reviewed journal, would allow Medicare to pay for the cheaper alternative.

The CMS draft policy should give a boost to legislation co-sponsored by Sen. Hillary Clinton (D-NY) that would create a new federal agency free from conflicts of interest to conduct comparative effectiveness trials. In a recent review in Health Affairs(subscription required), Gail Wilensky, the head CMS in the George H.W. Bush administration, noted that “there is widespread agreement on the attributes that need to be associated with a comparative-effectiveness center: objectivity in the selection of what is studied, credibility in the findings, and independence—from political pressures generated either by government or by private-sector stakeholders.”

Temporary Reprieve

Amgen reported this afternoon that a closely watched trial of its anti-anemia drug Aranesp in lung cancer patients had no impact on overall mortality. Relieved stockholders bid up shares in heavy trading. The last trial of Aranesp in cancer patients speeded up patients' demise.

It's important to remember that cancer patients who use Aranesp and J&J's Procrit

are not looking for any survival benefit from the drugs. Doctors inject it to relieve the symptoms of other chemotherapy drugs, which include suppression of red blood cell production and its attendant run down feeling.

However, the entire strategy was called into question when a study in head-and-neck cancer patients was released a few months ago by European researchers, not Amgen, a coverup whose unveiling by the Cancer Letter sent Amgen's stock plunging. That study showed that the anti-anemia drugs reduced survival times. Scientists who've argued all along that stimulating red blood cell production may actually feed the cancer had their moment in the sun.

If I were an Amgen stockholder (full disclosure: I most assuredly am not; I make it a point not to invest in any drug or health care-related stocks to avoid any conflicts of interest in my writing), I would not jump to any conclusions about this latest study. The Food and Drug Administration's May 10 meeting of the Oncology Drugs Advisory Committee to discuss anti-anemia drug use in chemotherapy is shaping up to be quite a doozy.

PhRMA Power

Headline: Senate Rejects Medicare Drug Price Negotiations

Headline: Senate Committee Passes Drug User Fee Reauthorization

Headline: Breast Cancer Rates Decline After Hormone Use Declines

You don't have to be a political scientist to connect the dots. It's business as usual on Capitol Hill, even as evidence for the need for more thoroughgoing reform at the Food and Drug Administration continues to mount.

I attended the Senate mark-up hearing yesterday that passed the reauthorization of prescription drug user fee act. The full Senate will take it up in a few months.

The bill contains some improvements in the FDA's ability to protect the public from unsafe drugs. But it safety provisions are a far cry from the structural changes called for in last year's Institute of Medicine report. Nor does it include key changes demanded by insiders who've been blowing the whistle about failures at the agency.

Today's New England Journal of Medicine has an article documenting one such case -- the antibiotic Ketek -- by former FDA reviewer David Ross. Ketek, which causes severe liver injuries in some instances, was approved after a "non-inferiority" trial -- it was compared to a drug of only marginal effectiveness -- where some of the data was later exposed as fraudulent. The bad data was presented to an outside advisory committee AFTER the FDA knew about the possiblity that it was not accurate.

Summing up, Ross concluded the approval process was marked by:

. . . the use of fraudulent data, the substitution of uncontrolled postmarket safety reports for controlled clinical trial data, and the acceptance of trials that could not show efficacy. There was also overt internal pressure brought to bear on FDA reviewers to alter their conclusions.

The FDA response, also contained in NEJM, was hardly reassuring. "There was no intention to deceive the advisory committee," a slew of top officials wrote. The agency had referred one of the clinical trial sites for criminal investigation, but "the FDA did not discuss data-integrity issues at the second advisory committtee meeting to avoid compromising the ongoing investigations, recognizing that the FDA retained the ultimate decision authority."

Ross held out hope that the Ketek example and other recent slip-ups at the FDA will lead to reform. But the bill passed out of committee yesterday will do little to halt similar instances in the future. For instance, it doesn't create an independent safety department that can put its foot down when the new drugs division -- whose salaries come largely from industry user fees and whose guidelines are driven by the need for faster approvals -- passes out a questionable drug.

Nor does it contain provisions calling for total independence of outside advisers. Nearly a third of all FDA advisers on its 30 advisory committee have financial ties with drug and biotech firms, usually in the form of lucrative ocnsulting deals and speaking gigs.

Nor does it put a moratorium on direct-to-consumer (DTC) advertising for new drugs for the first three years on the market. This wise precaution would enable epidemiologists to determine if the drug was damaging patients in ways not forseen or only hinted at in the clinical trials submited to the FDA to gain approval. Marketing campaigns that include DTC advertising get millions of people using a new drug whose therapeutic advantages are often minimal compared to previous drugs. That can result in tens of thousands of people suffering side effects that were only hinted at in the relatively small clinical trials that led to the drug's approval. The ill-fated Vioxx is the classic example.

The committee's debate over DTC was a classic. Sen. Pat Roberts (R-KN) waived around a reporter's notebook (he's an editor and publisher in his hometown of Dodge City) while defending commercial freedom of speech. "This turns the FDA into an editorial review board," he fumed.

Sen. Ted Kennedy, chairman of the committee, responded that the legislation only gave the FDA the authority to hold back ads if a drug seemed problematic. "This is for that rare circumstance," he said. Sen. Tom Coburn, the Oklahoma Republican who is the only physician on the committee, wondered why the FDA would approve the drug in the first place if it thought it was problematic enough to forbid DTC advertising for its first few years on the market.

Not a bad point. How likely is it that the FDA will use its new authority? Not likely, as Kennedy said. The advertising sales managers at the newsweeklies and evening news shows, which depend on the largesse of the pharmaceutical industry, have nothing to fear from this bill.

How about the risk assessment plans required by the legislation, which are its centerpiece? Every time a new drug gets approved, its sponsor will have to show the FDA a plan for monitoring and assessing the ongoing risk as it gains wider use in the marketplace.

Here's an interesting thought experiment. Imagine such a law in place when Wyeth won approval of its estrogen hormones allowing pre-menopausal women to stay "forever female." Would it have prevented millions of women from taking the drugs and exposing themselves to an increased risk of breast cancer, documented by the latest epidemiological evidence in today's NEJM?

The user fees in the act would triple the size of the FDA staff conducting post-marketing surveillance, which will allow the agency to conduct more epidemiological studies of drugs' effects on large populations. But it's still a tiny fraction of the total staff committed to reviewing new drug applications. And the safety department still won't have the institutional clout represented by having its own chief and the power to withdraw drugs it deems unsafe.

The IOM report talked about a "culture" problem at the FDA. The heart of that problem is an attitude at the FDA that says approving new drugs, only some of which are really significant medical advances, is a more important goal than the FDA's stated mission of protecting the public from unsafe and ineffective drugs.

Before the day was over, the committee agreed to consider a couple of amendments to the legislation. None are key to improving safety. Sen. Sherrod Brown (D-OH) got Kennedy to agree to consider a limitation on citizens petitions when the "citizens" are pharmaceutical companies or their proxies and the petition is an attempt to delay the introduction of generic competition once a patent has expired.

Kennedy also agreed to consider an amendment from Sen. Orrin Hatch (R-UT), best known in this arena for his efforts to keep dietary supplements free from FDA regulation. His amendment would make it easier to approve new antibiotics; reauthorize and expand the orphan drug act; and give extra patent protection when a company brings a chemical derivative of an already-approved drug to market. This latter provision bears some scrutiny, since it could open a huge loophole for extra patent life for the most useless forms of me-too drugs.

Finally, Kennedy agreed to reconsider an earlier decision to exclude giving the FDA explicit authority to approve generic biologics, a provision pushed by Sen. Hillary Clinton (D-NY) in the Senate and Rep. Henry Waxman (D-CA) in the House. Last month, Kennedy told his hometown Boston Globe that he opposed any measure that would not require follow-on biologics to conduct the same clinical trials as the original patent owner, a move that would remove much of the financial benefit of follow-on biologics for consumers.

So, as the legislative calendar moves toward its September 30th deadline for PDUFA reauthorization, it is still possible that FDA reform and PDUFA reauthorization will turn into a Christmas tree for every drug and biologics issue. It will be a field day for Big PhRMA lobbyists, who already are the most ubiquitous presence on Capitol Hill.

As things stand now, the Kennedy-Enzi bill, which will be subject of intense behind the scenes meetings before it goes to the full Senate, will do very little to change the culture at the FDA. Let's hope the House bill, which had its first hearing this week, will do a better job.

Overdosing for Dollars

I walked into a dialysis clinic for the first time about a decade ago. It was in Baltimore, and it was an inner-city non-profit clinic run by a kindly, white-haired gentleman named Dr. Sandler. I learned a lot about medicine and the financial inducements that lead doctors astray from him, and for that I will always be grateful.

I raise that this morning because Dennis Cotter and his colleagues at the Medical Technology and Practice Patterns Institute have a new study out in the Journal of the American Medical Association showing that for-profit dialysis clinics use up to three times more anti-anemia drugs than non-profit clinics with comparable patient populations. Amgen's Epogen is the sole approved product for the anemia that accompanies kidney failure (Epogen is the genetically engineered version of the protein produced by the kidneys that stimulates red blood cell production), and dialysis clinics make a hefty mark-up on the wholesale price of the drug.

Dr. Sandler said two things that day that have always stuck in my mind. He worried that too much Epo use might harm his patients, so he rarely dosed them over the FDA label. (The FDA last month slapped a black box warning on Epogen, Procrit and Aranesp -- the latter two are used for cancer -- because using too much of the drug causes heart attacks and early death, according to recent studies).

And the nephrologist also said that to understand the "guidelines" for Epogen's use that had been written by his professional peers, you had to look at who was behind those guidelines. Last week, the National Kidney Foundation's panel of renal docs issued proposed new anemia guidelines that ignored the FDA warning. Two-thirds of the physicians on the panel had financial ties to Amgen.

Today's Wall Street Journal quotes Rep. Pete Stark (D-CA). He wants to eliminate the financial incentives that encourage overuse of Epogen, which is harming patients. I also spent a lot of time talking to Stark's aide in those days, Bill Vaughan, who now plies his trade at Consumers Union. Stark's office was saying the same thing back then.

When will the Center for Medicare and Medicaid Services (the taxpayers pick up the tab for most dialysis patients in America) change its policy and eliminate payments for the excessive and dangerous overuse of this drug?

Inadequate FDA Reform Bill Moving in Senate

The Senate's Health Education Labor and Pensions committee will hold a mark-up hearing Wednesday on FDA reform legislation that fails to adequately deal with many of the agency's flaws. Opinion pieces in the New England Journal of Medicine and the Boston Globe, widely circulated in committee chairman Ted Kennedy's home turf, have taken the bill to task.

Even the conflict of interest provisions fail to take into account recent proposed changes at the FDA (see this article from yesterday's Integrity in Science Watch from the Center for Science in the Public Interest, which I edit). The question becomes: Why are the Democrats in the Senate going along with this clearly inadequate bill?

More Bad News for Merck

The Wall Street Journal ran a front-page story today questioning the efficacy of Merck's new cervical cancer vaccine. The story covers all the key issues: the relative rarity of the disease; how it's been reduced by 80 percent in the U.S. through Pap smears; and the relatively low 70 percent effectiveness rate of the new vaccine. One key detail new to me: Merck cancelled its lobbying push in the states after consulting with key members of the Centers for Disease Control advisory committee and the American Academy of Pediatrics that had recommended the vaccine. They told the company that it was too soon to make the vaccine mandatory.

The story was also notable in pointing out that all the cost-effectiveness studies arguing that the vaccine would reduce health system costs (fewer Pap tests and fewer cancers down the road versus the multi-billion upfront costs of the vaccine) were funded by the companies that made the vaccine.

FDA Advisory Panel Nixes New Cox-2

A Food and Drug Administration advisory panel voted 20-1 today against approving Merck's new arthritis pain pill, known as Arcoxia. After listening to the company's presentation, the FDA reviewer's analysis, and a devastating critique offered by FDA safety officer David Graham, one could only wonder why Merck brought this Vioxx clone before the committee.

It also makes one wonder why over 60 European countries have approved the drug, which appears to have all the same heart attack risks of other Cox-2 inhibitors. The evidence that the drug reduced the gastrointestinal side effects of other pain pills like ibuprofen or naproxen (sold over-the-counter as Aleve) was marginal at best, and was clearly outweighed by the more serious cardiovascular side effects.

And, the bottom line was that the drug provided no more additional pain relief than any other non-steroidal anti-inflammatory drug (NSAIDs). I could not believe this morning's radio report by Helen Palmer on Marketplace. She called Arcoxia "super aspirin" and quoted a Merck p.r. flack claiming the drug was superior to other NSAIDs. The evidence offered at the hearing today was incontrovertible on that point: it provided no more pain relief than any other drug.

Despite the presence of a number of physicians on the committee who clearly would like to see more and better pain relievers for their arthritis patients, Merck stepped forward with an extremely weak set of data. They tested the drug in a staggering 34,000-plus patients, half of whom took diclofenac (sold as Voltaren or Cataflam), which has very low market penetration in the U.S. What it does have is a heart attack risk profile that is very similar to other Cox-2 inhibitors.

"What is the value of comparing it to diclofenac, which has an elevated cardiovascular risk?" asked Graham near the conclusion of his devastating critique. "It has no value."

According to Graham, if Arcoxia had been compared to naproxen, it would have shown cardiovascular risk nearly three times higher than the over-the-counter medication.

How about the supposed G.I. benefits of Arcoxia? For the first time, one of the Cox-2s appears to have actually shown that there was some reduction in the gastrointestinal side effects found in most NSAIDs (it only effects around 2 percent of the people who take them). In Merck's massive study, the number of GI adverse events (those needing physician and medical intervention) declined to 176 in the Arcoxia group compared to 246 in the diclofenac group (a reduction from 1.4 to 1.0 percent of the overall population taking the drugs). Virtually all the reductions came in non-life threatening bleeding and ulcers. More serious conditions like G.I. tract perforations and obstructions were about the same in the two groups.

On the other hand, both groups had over 300 serious cardiovascular complications, including more than 100 heart attacks. Had either group (Arcoxia or diclofenac) been taking naproxen, they would have suffered nearly 60 percent fewer cardiovascular "events." David Egilman, a physician at Brown University who works as a plaintiffs expert in Vioxx litigation and testified during the public portion of the meeting, called the Merck trial "unethical."

There was one personally gratifying moment during the hearing. David Graham began his presentation by debunking claims, often carried in the media, that NSAIDs lead to 16,500 deaths a year from G.I. side effects. He estimated that G.I. complications in the U.S. cost about 4,714 lives a year, and many of those have nothing to do with NSAIDs.

After his presentation, James Fries, a gastroenterologist from Stanford University and a member of the advisory panel, grabbed his microphone. "I've been ashamed of that number ever since it came out," he said. A former colleague at Stanford generated the 16,500 deaths number in the late 1990s and it became a major talking point for the marketing departments at Pfizer and Merck when they began pushing Celebrex and Vioxx.

Caught in the hallway during a meeting recess, Fries explained that the original estimate had been based on 1992 data that included a high number of rheumatoid arthritis sufferers. These are people who take lots of pain pills and are more likely to suffer G.I. side effects.

Moreover, he explained, the incidence of G.I. complications from NSAID use began declining almost immediately after that data was compiled due to better painkillers and better acid indigestion fighters (like Zantac and later Prilosec). "The incidence rate has been cut by a third. The death rate is at most 2,500 now and even that may be too high," he said.

I've been making this point for years. Now there will be confirmation in an FDA hearing transcript. Hopefully, we've heard the last press claim that NSAIDs cause "16,500 deaths annually."

Study Slams DDT Use in Malaria Control

The conservative campaign to bring back DDT to combat malaria got some bad news today. South African researchers report that the widespread use of DDT for indoor spraying to control mosquitoes has dramatically lowered sperm counts and disrupted reproductive systems among men exposed to the pesticide. The study involved 300 men in Limpopo province.

The study was conducted by Tiaan de Jager of the University of Pretoria. According to the Mercury newspaper:

The researchers said there was mounting evidence from around the world that DDT acted as an endocrine-disrupting substance, which altered the normal human hormone balance, lowered testosterone levels and possibly interfered with sexual accessory organs such as the seminal vesicle and prostate gland.

And, despite recent assurances by the World Health Organisation that DDT can be used safely in controlled anti-malaria campaigns, the new Journal of Andrology study has shown a direct link between high DDT exposure levels in people whose houses had been sprayed with the pesticide.

Concentration levels of DDT in some of the Limpopo men were among the highest recorded in the medical literature.

The researchers say the World Health Organization may have made a mistake in calling for the return of DDT to control malaria. They recommend switching to safer pesticides for indoor residual spraying to hold down mosquitoes.

FDA Reform by the Numbers

It's crunch time in the Senate on Food and Drug Administration reform. The Health Education Labor and Pensions committee, chaired by Sen. Ted Kennedy, will hold a mark-up hearing next week on a bill that lumps together safety, generic biologics, medical devices and pediatric drugs. Lobbyists will get to see the first draft of the bill later this morning.

I'll have more to say on its contents after I see it. But here's a few public opinion measuring points:

Will it give adequate new powers to the FDA to pull unsafe drugs off the market? According to a recent Consumer Reports poll, 58 percent of the American public are either "very concerned" or "concerned" about the safety of prescription drugs.

What new limits will it put on direct-to-consumer advertising? Just under 60 percent "strongly agree" that advertising should be prohibited if there are safety concerns about a drug. There is strong pushback from the drug industry lobby about limiting commercial "freedom of speech."

Will it require public disclosure of the results of all clinical trials, whether or not they were submitted to the agency for getting a new drug approved? Fully 68 percent of the public "strongly agree" to full disclosure.

Will companies be punished if they don't complete in a timely fashion follow-up trials ordered at the time of drug approval? Again, two-thirds of the public want those studies done.

And, finally, will it prohibit the FDA from hiring outside advisers who have financial ties to the companies (or their competitors) whose products are being evaluated? Two-thirds of the Consumer Reports poll expressed deep concern about these conflicts of interest, mirroring a Harris Interactive poll from last summer which showed that 70 percent of the public thought they ought to be banned.

Meanwhile, billions of dollars are at stake in the generic biologics portion of the bill. With three-quarters of the American public worried about the rising cost of drugs (despite the new Medicare prescription drug benefit), will the bill provide an easy pathway for firms seeking to bring generic versions of complex proteins to market once the original goes off patent?

According to lobbyists for generic manufacturers like Barr Laboratories, the science isn't as complex as Amgen, Gemzyme and Genetech (makers of Epogen, Cerezyme and Human Growth Hormone, respectively) have claimed. The FDA's top officers have testified before Congress that they have the technical expertise to determine that generic biologics are comparable to the original version without demanding the full range of human clinical trials.

It will be interesting to see how the Senate's HELP committee, now under Democratic leadership, resolves these questions. Will it side with the people, or will it bend over backwards to accommodate the drug and biotechnology industry lobbyists who are swarming over Capitol Hill?

CMS and Amgen

This morning's Wall Street Journal has a front-page overview of recent developments in the Amgen/dialysis/cancer saga. It recaps the Food and Drug Administration's recent decision to put a blackbox warning on the Epogen/Aranesp labels cautioning against overusing the drugs. Such overuse has been enabled by the Center for Medicare and Medicaid Services' payment policy. Over the past decade, the agency, under lobbying pressure from Amgen, steadily raised the hematocrit levels at which it would reimburse providers like dialysis clinics.

The article contains this warning issued last Friday by Rep. Pete Stark (D-Cal.):

"CMS must immediately rethink its payment policy and remove any incentives to use EPO at dangerous levels." (Stark) added: "If CMS fails to act, Congress will have no other choice than to step in and protect [dialysis] patients from providers and drug companies who are more worried about profits than patient safety."

Why hasn't CMS acted in the wake of last month's FDA warning? Could rumors that a former high CMS official has been retained by Amgen to lobby the FDA, and perhaps his former agency, be true?

Student Loans and Other Scams

Can you imagine the outrage lately among parents (like me) over the burgeoning student loan conflict-of-interest scandal? The mad scramble to raise the perfect résumé had the unintended side effects of sending college tuition bills into the stratosphere and burdening young adults with mountains of debt.

Intermediaries in government and the universities were supposed to get students a better deal. Instead, some saw it as an opportunity to feather their own nest.

The collapse of ethical restraints in this one corner of academic life is illustrative of what is happening on a routine basis in almost every professional sphere.

Perusing the backpages of the Wall Street Journal's online version, last week I saw that MarketWatch, a Dow Jones & Co. publication, admitted that another journalist had crossed a line that at one time was considered sacrosanct among practitioners of the trade: you don’t invest in companies that you write about. I spent decades in daily and weekly journalism, I signed documents every year revealing what I owned and promising my employer that I wouldn’t invest in anything remotely connected to my beats.

But in this case, MarketWatch columnist Bambi Francisco (is this a pseudonym?) touted companies that posted video clips on a hosting service she had invested in. Okay. Scratch that outlet off my list of trusted investment advisers.

Which brings me to the latest flare-up at the Food and Drug Administration. Later this week it will impanel an advisory committee to consider the merits of a painkiller called Arcoxia, which is a Cox-2 inhibiter produced by Merck & Co. Merck’s last Cox-2, you may recall, was pulled from the market because it increased the risk of heart attacks. It was called Vioxx.

Will this committee include cardiologists skilled at ferreting out cardiovascular risk from the mountain of data the company has submitted? We don’t know because the agency won’t release the roster of the full committee until the day of the meeting.

What we do know is that three of the members needed conflict-of-interest waivers to participate (the waivers get released two weeks ahead of time because of a sunshine provision passed by Congress in the wake of the Vioxx fiasco). They included Dr. Robert Levine, a gastroenterologist at the State University of New York who owns somewhere between $25,001 and $50,000 in Merck stock. The FDA deemed his participation crucial because of “the uniqueness of (his) qualification.”

Whom are they kidding? The only potential medical justification for this class of drugs is its purported ability to reduce the gastrointestinal side effects of traditional non-steroidal anti-inflammatory drugs like ibuprofen. With 125 medical schools in the U.S., is the FDA really claiming they couldn’t find another gastroenterologist capable of reviewing the data who that didn’t have a financial relationship with Merck?

A century ago, the progressive era gave rise to a professional class whose values and ethics arose from the need to mediate the power of newly ascendant corporations on behalf of a public that didn’t have the time or expertise to protect itself from unsafe products and monopoly power. Today, each of the institutions created or empowered in that era to act as counterweights to that power – non-profits and universities, the Fourth Estate and the regulatory agencies – have been subverted by incestuous financial ties with the corporations they’re supposed to influence and oversee.

To restore balance to the system, those ties have got to end.

Mandating Mis-Insurance

A couple of new reports take aim at the obvious flaws in proposals that would throw people into the individual insurance market as part of their "cure" for the nation'a health care financing crisis.

Stephie Woolhandler and David Himmelstein, Harvard Medical School researchers who have been leading the fight for single-payer national health insurance on behalf of Physicians for a National Health Program, this week show how the high deductible policies contained in the Bush, Schwarzenegger and Massachusetts plans will penalize women. The reason is simple: women spend a lot more on health care than men.

The study showed that "in 2006, the median health costs for women age 18-64 was about $1000 higher than for men ($1,844 vs. $847)." This other fact from the study may shock a lot of young women, since most polls show young people are more supportive of the high-deductible, individual mandate approach. Younger women (ages 18-44) had median health care expenditures nearly three times higher than their male counterparts ($1,266 vs. $463).

“High deductible plans punish women for having breasts and uteruses," Woolhandler said. "Our costs are higher than men’s because we need Pap tests, cervical cancer vaccine, mammograms and birth control, and because pregnancy is expensive. When employers raise deductibles, they’re giving women a pay cut. And when politicians offer tax breaks for high deductible plans, they’re discriminating against women.”

The tax break issue was front and center this week in a New England Journal of Medicine perspective by Robert Reischauer, president of the Urban League (he used to run the Congressional Budget Office and now chairs the Medicare Payments Advisory Commission). Giving people tax breaks forces people into an individual insurance market that has, to use his judicious words, "significant shortcomings."

To wit: "In many states, carriers can refuse to insure anyone whom they consider to be high-risk, policies can exclude coverage for preexisting conditions, and premiums vary with enrollee health status, making coverage prohibitively expensive for people in poor health."

Of course, there is a way around those problems. "States could be required to revise their individual insurance-market regulations to meet some minimum federal standards," he writes.

That should be the first question out of any reporter's mouth when anyone, from President Bush to Gov. Schwarzenegger, proposes an individual mandate as part of their cure for the health insurance crisis. "Are you willing to impose national regulation of insurance carriers so they can't discriminate against people with preexisting conditions or age?"

The purpose of health insurance is to pool risk for those who suffer sudden illnesses and provide a social safety net for those who because of age or circumstances need more health care. Only risk pooling can accomplish those twin tasks. And the most efficient and effective way is to cover everyone with adequate insurance is to throw them all in the same pool, i.e., Medicare for all.

Abigail Alliance v. FDA

Here's a copy of a column that appeared in February in the Bay Area Oncology News. Contractual obligations forbade me from publishing it here until now. If I could only figure out how to make this website pay . . .

In the wake of the Vioxx fiasco, the Food and Drug Administration has come under attack for failing to protect the public from unsafe drugs. An Institute of Medicine report released last fall blamed the agency’s internal culture, which emphasizes faster new drug approvals over monitoring the safety of drugs already on the market. Legislation to improve the nation's drug safety system is moving forward on Capitol Hill.

Given these heightened concerns about safety, you’d think the FDA would be extremely wary of opening the door to greater use of unproven drugs. But that’s precisely what the agency proposed in mid-December, largely in response to court rulings in a suit filed by the Abigail Alliance, a patient advocacy organization formed in 2001 by Virginian Frank Burroughs shortly after his 21-year-old daughter died of head and neck cancer.

Last May, a three-judge panel in the U.S. Court of Appeals for the District of Columbia ruled that terminal ill patients like Burroughs’ daughter have a constitutional right to unapproved drugs as long as the hoped for benefit exceeds the risk. When you’re talking about cancer drugs, that’s almost always the case. As a practical matter, the ruling opened the door for any critically ill patient to gain access to any drug that had passed the minimal testing characteristic of small-scale Phase I safety trials.

The FDA immediately appealed the ruling, since, as two attorneys writing in the Journal of the American Medical Association pointed out in early January, it threatens “the ability of the FDA to protect public health.” If the full appeals court refuses to overturn the ruling, the agency will probably appeal to the Supreme Court.

Given the libertarian leanings of the Bush administration’s most recent appointments to the high court, it’s not surprising that the agency has moved to head off the suit by widening its existing expanded access rules, which are sometimes called compassionate use rules. Community oncologists have a lot riding on the final disposition of this proposed regulation because it is going to increase pressure to find experimental medicines for dying patients, even if they are not enrolled in clinical trials.

The FDA first created expanded access rules in 1987 in the midst of the HIV/AIDS crisis. Dying patients demanded access to the handful of experimental drugs then in the pipeline. After numerous demonstrations by militants at FDA headquarters, the agency complied.

However, those regulations upheld the primacy of the scientific process over the patient’s right to experiment on themselves. The scientific evidence “taken as a whole” had to suggest the drug would work, and the company had to be actively seeking FDA approval through controlled clinical trials. The idea was to extend treatment to dying patients who might have been excluded from Phase III trials because they were too sick or in other ways didn’t meet the trial’s inclusion criteria.

The FDA estimates that in the succeeding two decades, more than 100,000 patients received investigational drugs under expanded access programs. But most were run through company programs under FDA-approved protocols. The rules did allow for individual patients and their physicians to seek out experimental drugs, but the very few did, largely because no criteria were spelled out for treating physicians.

The proposed rule opens the door wide for community physicians who want to go down that path. They will be able to obtain experimental drugs for their patients as long as they tell the FDA that the risk from the experimental drug is not greater than the risk from the disease being treated. They also must certify that the patient can’t get the drug from a company program like an ongoing clinical trial. At the end of the treatment, the physician must provide a written summary of the results, including any adverse effects. The rules allow both physicians and drug companies to get reimbursed for these “treatments.”

Note what’s missing from the criteria. There is no mention of the “weight of scientific evidence” to justify prescribing the drug. There’s also no requirement that these individual patients be organized into a systematic clinical trial, although the rule states the FDA “may ask the sponsor to submit an Investigative New Drug application or protocol for the use.”

There are huge risks in this approach. For drug companies, it’s going to make it much more difficult to recruit patients for legitimate clinical trials. Moreover, the medical literature will undoubtedly become flooded with case studies and small-scale observational trials of dubious quality or predictive power.

Doctors will come under enormous pressure from sub-cults of dying patients who exchange hot tips over the Internet about the latest “miracle” drugs. Those who are leery of participating may face lawsuits from surviving family members or dying patients who feel they were denied information about all their options. Even if doctors properly caution patients about how little is known about the drug, they may be accused of malpractice if the drug turns out to be dangerous.

The biggest risk of all may be to medical science. Most cancer drugs fail. It’s hard not to sympathize with patients who want to fight for their lives with every available weapon. But they doesn’t give them the right to drag down evidence-based medicine with them.

A Victory for Open Science

Stem cell research, though promising as an approach to treating diseases ranging from Type I diabetes to Parkinson's disease, has a long way to go before something shows up on the Food and Drug Administration's doorstep claiming to be a cure for a disease. Most of the advances breathlessly reported in the daily press are basic science insights or suggestive animal experiments. No one has conducted the successful animal safety test that would allow researchers to inject an experimental therapy derived from stem cells in humans.

That's why yesterday's announcement by the Patent and Trademark Office that it was voiding three seminal patents in the field previously awarded to James Thompson of the University of Wisconsin is good news for patients. Thompson was the first to isolate human embryonic stem cells, and in that discovery's wake, his university claimed all subsequent uses of the technology.

While, as this New York Times report points out, the university promises to litigate the decision, the PTO decision marks a welcome turning point in the battle against the unnecessary and unproductive privatization of mankind's quest to understand the natural universe.

Since passage of the Bayh-Dole Act in 1980, scientists receiving government funding have been encouraged to patent their discoveries if they were commercially viable. The patent fever set off by the law extended to virtually any research conducted at universities, whether publicly or privately financed. Because of U.S. government restrictions on funding embryonic stem cell research, Thompson's research was funded by Geron Corp., which ultimately received an exclusive license to the most promising uses of Thompson's discovery.

But that didn't stop the Wisconsin Alumni Research Foundation, which manages patents for the university, from charging private firms $100,000 and academic and non-profit institutions $5,000 every time they wanted to use the Thompson stem cell lines. This aggressive posture set the tone for the entire field, and encouraged other researchers to patent their discoveries.

This profusion of patent applications, what economists call a patent thicket, will inevitably retard the pace of research as researchers scramble to secure the necessary licenses and material transfer agreements. A British survey several years ago identified nearly 18,000 patents and patent applications in the stem cell field.

There are ways for researchers to collaborate in this aggressive intellectual property environment. In an article that appeared in PLoS Medicine a year ago, I proposed a patent pool for the stem cell field as a possible path through the patent thicket.

But another way to cut down the underbrush is by eliminating those patents that are most appropriately considered scientific discoveries about the workings of the natural universe. For something to receive a patent, it has to be a previously unknown invention that reflects the hand of man. Discovering human embryonic stem cells, which have been around since man first walked the earth, is more like Isaac Newton discovering gravity than the Wright Brothers building the first airplane.

The Public Patent Foundation and the California Foundation for Taxpayer and Consumer Rights, which challenged the Thompson patents, have provided a valuable service for the entire science community. Unfortunately, the PTO ruling relied on the traditional tenets of patent law. The examiners, upon reexamination, claimed the patent was obvious based on previous papers that had appeared in the literature. Obviousness and previous publication are cause for rejecting a patent application.

WARF's top officer immediately restaked their claim on those grounds. “It is inconceivable to us that Dr. Thomson’s discovery, which Science magazine heralded as one of the greatest scientific discoveries in history, would be found to not be worthy of a patent,” said Carl E. Gulbrandsen, the managing director of WARF.

In a bygone era, "one of the greatest scientific discoveries in history" would have gladly been shared with all mankind, not seen as a building block of academic alchemy that would turn basic science into gold. Basic science that may ultimately lead to useful products should be free and open to all who would build those useful products. Its inventors should not be allowed to become toll collectors on the road to innovation. Hopefully, the PTO decision yesterday is the first step on the road back to a reasonable standard for establishing where basic science ends and commercial invention begins.

The New Celebrex Ad . . .

. . . goes on for two-and-a-half minutes, emphasizing that all pain relievers cause heart attack risk. At one point, the ad says that "clinical studies" show Celebrex reduces the stomach distress experienced with some other NSAIDS. Earlier in the ad, Pfizer necessarily mentions that the Celebrex label carries a warning about those very same stomach distress side effects.

That ought to help clear up the confusion. The only thing this is an ad for is why there shouldn't be any direct-to-consumer advertising, especially on television.

Not mentioned in the ad: Our drug will cost you and/or your insurer $90 a month plus the cost of a doctor's visit versus the $10 a month it costs for over-the-counter ibuprofen.

It starts running on ABC tonight. You can watch it here.

Breast Cancer Risk -- the Missing Element

In the wake of Elizabeth Edwards' breast cancer recurrence, the New York Times ran six op-eds and one op-art that all drew a similar conclusion: the answer lies in more research.

Susan Love, a prominent advocate, wants research aimed at more far-out approaches, including resuscitating the hunt for the elusive cancer viruses that dominated the research agenda in the 1970s. Harold Varmus, former head of NIH now running Sloan Kettering Memorial Cancer Center in New York, wants more genomics research. Ralph Moss, whose newsletter usually casts a critical eye at the anti-cancer establishment, laments that generic chemicals that might be good drugs rarely get tested for their efficacy on cancer because of the patent system. Even journalist Shannon Brownlee, who spent most of her op-ed lamenting the cost of cancer care, the profits generated by the system, and the limited efficacy of that care, winds up calling for, you guessed it, more research.

The op-art had some interesting tidbits about how much money is spent advertising cigarettes and on soda pop. That suggests public health measures, not more publicly-financed research, is the most cost effective way to bring down cancer rates. But even artist Marisa Acocella Marchetto (I just had to reprint that name, say it softly it's almost like praying) wound up with her final panel filled with white-coated researchers "desperate" for more funding.

I also did a little research this week on breast cancer among younger women because of the Edwards setback. It might have been nice if at least one of the op-eds was given over to discussing her risk of disease. She is only 57 years old. But she had children, probably by in vitro fertilization with its attendant hormone injections, when she was 48 and 50. That immediately puts her in a high risk category.

So, my next logical question was what overall impact on breast cancer risk has late childbearing, rising in vitro fertilization rates, and rising smoking and obesity rates had on among Baby Boomer women? The pink ribbon advocacy groups frequently point out that women's overall risk of contracting breast cancer in their lifetimes has risen to one in eight compared to one in eleven some years ago.

Yet it turns out that female Baby Boomers' overall risk of contracting invasive breast cancer is actually below previous generations, according to a recent study by former National Cancer Institute researcher Robert Tarone, who is now at the International Epidemiology Institute. Breast cancer incidence is falling among Baby Boomers despite greater risks posed by environmental and social factors.

In a brief e-mail exchange, he told me researchers are enmeshed in furious debates over the role of late childbearing, early detection through increased mammography and changing diets on overall cancer risk. But the bottom line is that women are experiencing less invasive cancer at younger ages, and the increasing long-term risk is attributable almost entirely to women living longer since older women (over 65) get breast (as well as other) cancer at much higher rates.

I'm not trying to make an argument against more research. Is the $11.5 billion mentioned in the Marchetto op-art too little? In the best of all possible worlds, it would be nice to have a larger pot of money to give to those white-coated researchers, who, she points out, only get 18 percent of their grant applications funded. If we compare it to the billions wasted in Iraq, then more money for breast cancer research seems like a no-brainer.

But even in a post-Iraq world, we're going to be dealing with limited resources. It's worth pointing out that today's level of public investment in cancer research is over twice the government's investment in ALL energy research (from oil and coal to solar and wind), and that sector has been steadily declining since the Carter era.

If people think we need more money for breast cancer research specifically and cancer research generally, perhaps we should levy dedicated taxes on cigarettes, soda pop, meat and milk products, air polluters, and the hormone pills and injections that are contributors to overall cancer risk. That way, we'll be killing two birds with one stone -- generating more money for research while cutting down on the behaviors and corporate actions that led to the need for the research in the first place.