Integrity in Science Watch -- Week of 3/31/2006

The prestigious Journal of Allergy and Clinical Immunology (JACI) last month failed to disclose two physicians' roles as insurance company defense experts in their scientific review "The Medical Effects of Mold Exposure," which downplayed risks to human health from household mold. According to court documents obtained by the Center for Science in the Public Interest, Dr. Abba I. Terr, Stanford University School of Medicine, and Dr. Andrew Saxon, University of California at Los Angeles School of Medicine, were paid up to $600 an hour for testimony in cases brought by homeowners alleging their illnesses were caused by mold. JACI, the journal of the American Academy of Allergy, Asthma and Immunology (AAAAI), requires authors to disclose conflicts of interest to the editor, who then has discretion in publishing them. In a letter to editor Donald Leung, CSPI urged AAAAI to make disclosure mandatory and prevent authors who fail to disclose conflicts of interest from publishing in the journal for three years.

EPA Administrator Headlines Political Fundraiser Attended by Regulated Firms

Environmental Protection Agency administrator Stephen Johnson, who previously held the top science job at the EPA, earlier this month spoke at a Republican Congressional fundraiser in Colorado attended by top officials from El Paso Natural Gas, the Colorado Mining Association and other regulated industries, the Denver Post reports. The affair first came to light when Greenberg, Traurig, the law firm that organized the event, sent corporate clients an email that used Johnson as a draw. The email included his title, which is forbidden under federal election laws. His name on the official invitation, however, did not contain his title and Johnson attended the event on his own time, an EPA spokesman told the newspaper. "At a certain level of government, you don't get your own time," noted Massie Ritsch of the Center for Responsive Politics, a campaign finance watchdog group.

"Was Confusion Over Global Warming a Con Job?"

The oil, coal and other carbon-emitting industries deliberately sought to confuse the public about the implication of global climate change, ABC News reported Sunday. "Victory will be achieved when average citizens (recognize) uncertainties in climate science," a 1998 American Petroleum Institute memo said. ABC then interviewed Patrick J. Michaels, professor of environmental science at the University of Virginia, a senior fellow at the Cato Institute, and, the report said, one of the "friendly scientists" funded by carbon-emitting industries to sow confusion. The ABC report is part of a recent media trend to point out how global warming skeptics are financially tied to carbon-emitting industries. Michaels, frequently quoted in the press, has extensive ties to industry going back over two decades. In a related development, NASA issued new guidelines this week allowing climate scientists to speak out on global warming issues as long as they say they are speaking personally and not representing the agency.

Is Medical Economics for Sale?

Researchers who looked at nearly 500 medical cost-effectiveness studies published between 1976 and 2001 found that industry-funded studies were more likely than independent- or government-funded studies to justify costly medical interventions, a new study says. Using a commonly accepted ceiling of $50,000 for adding one quality-adjusted life-year (QALY) to a patient's life, the study found that industry funded studies were three times more likely to fall below that level and therefore recommend the use of that particular drug, medical device or diagnostic test. While cautioning that other biases may be in play since only 18 percent of the studies were funded by industry (a third could not be determined) and two-thirds of all studies fell below the $50,000 benchmark, "our results support concerns about the presence of significant and persistent bias in both the conduct and reporting of cost effectiveness analyses," the authors wrote in the British Medical Journal last week.

DoD Cripples EPA in Long-Term Battle Over TCE

Since a 2001 risk assessment by the EPA showed trichloroethylene was 40 times more likely to cause cancer than the EPA previously believed, the departments of Energy and Defense, a major TCE polluter, have undermined the EPA's ability to set more stringent standards, the Los Angeles Times reported. Tougher restrictions would raise the Pentagon's clean-up bill to an estimated $6.5 billion. A National Academy of Sciences report on the issue is expected this summer. That panel, selected in 2004, has at least two scientists who have conducted research for TCE users or producers, but none that have conducted research for environmentally-oriented foundations or think tanks.

Feeling Lazy? Help Is On The Way

Medical journalist Ray Moynihan, whose insights appear regularly in the British Medical Journal, reports this week that a group of Australian scientists have identified a new condition called motivational deficiency disorder or MoDeD (pronounced Moe-dee-dee). It’s another word for extreme laziness.

According to these physicians, as many as one in five Australians may be afflicted with MoDeD, whose symptoms are “overwhelming and debilitating apathy.” In the most extreme cases, people with MoDeD lose the will to breathe.

If you find yourself among the millions of people unable to leave the couch, help may be on the horizon. A small Australian biotech company called HealthTec has developed a new drug called indolebant, which is already in Phase II trials. According to Moynihan’s report, indolebant is a cannabinoid CB1 receptor antagonist. One participant became an investment banker on the drug.

Gentle readers, this is not some put on taken from the Onion. It’s just one of the examples that will be highlighted at a conference on disease mongering that will be held in Australia next month. Attention Deficit Hyperactivity Disorder, Restless Leg Syndrome, now MoDeD. They’ll have lots to discuss.

Given all the attention to the lack of motivation among U.S. males (the current movie “Failure to Launch” starring Sarah Jessica Parker and Matthew McConaughey is not, as I first suspected when hearing the advertising campaign, about erectile dysfunction), HealthTec will undoubtedly find a receptive market here if it gets Food and Drug Administration approval for indolebant.

But don’t be surprised if the doctors hyping this supposed disorder are on HealthTec’s payroll. The physicians who first described MoDeD are.

April Fools!

Part D Is For Dumb, Not Disastrous

Dr. Jerry Avorn, author of the door-stopping Powerful Medicines, issued a broadside against the Medicare drug benefit in this morning’s New England Journal of Medicine. After cataloging the program’s start-up ills, he concludes:

Medicare Part D lives on, responding semiappropriately to noxious stimuli by flailing its limbs as best it can. It even shows some limited capacity for learning, and one important learning opportunity is just seven months away. Elderly citizens vote in droves, and many of them will have hit their "doughnut hole" by early November. At that point, they will let their legislators know how they feel about the program.

Well, I’m on record as predicting that the failing Medicare drug benefit will not be a political fiasco for the Republicans. Nor will it benefit many Democrats, who at this point seem constitutionally incapable of exploiting any issue, much less one that is filled with complexities.

Here’s why I’m sticking with the gut feeling that the drug issue won’t matter this fall. The Center for Medicare and Medicaid Services reported the other day that the government spent nearly $5 billion on Part D last month, the first full month of operation. The program is well on its way to shoveling out the $60 billion per year expected when the program was first announced.

Assume that four-fifths of that went to people who already had drug benefits via their employers or government programs. In other words, it primarily helped big companies, insurance companies and states that were already providing drug coverage, but are now being reimbursed by the federal government for their efforts. No happy seniors there, but nothing to be mad about either.

And that still leaves about a $1 billion a month or $12 billion a year that is going directly to previously uncovered seniors who have high drug bills and signed up for the program.

Will the donut hole piss them off, as Avorn suggests? A few, maybe. But healthier seniors with moderate drug bills under $200 a month will see real savings. The sicker ones will still be getting half their drug bills paid for by their plans. And those two groups are the ones most likely to vote based on this issue. How likely are they to turn against the checkwriters?

Bottom line: Medicare Part D? A mess at the start. Totally inadequate as a benefit. A giveaway to the drug companies on pricing. Yet a non-issue in this fall’s election, in my humble opinion.

That doesn’t make it a good program. By prohibiting CMS from negotiating prices or establishing effective formularies and turning over administration to the insurance industry, the architects of this program created nothing so much as a price support program for the drug industry and, not coincidentally, an opening in their ideologically-driven campaign to privatize Medicare.

President George W. Bush’s crony-filled Washington may be totally incompetent when it comes to war planning, disaster relief or anything remotely connected to public health and safety. But when it comes to creating a price support program for a favored industry with ideological overtones, this administration is filled with Gucci-clad geniuses.

Cephalon Gets Its Patent Extension

Last week, I suggested a hidden reason for Cephalon pursuing ADHD designation for its narcolepsy drug Provigil was to get its patent extended. Pediatric testing of a drug earns it an extra six months of patent protection whether it gets approved for kids or not.

Last week, you'll recall, an FDA advisory committee voted 12-1 not to approve Cephalon's drug for ADHD. The FDA hasn't decided that question yet. But today, the agency granted the company its six month extension.

Now generics won't be able to enter the market until April 2012.

Congress gave the drug industry these six-month extensions as an incentive to conduct pediatric trials on drugs that kids may need (like cancer drugs), but on whom there had never been any testing to determine dose or effectiveness. Now we're seeing more and more companies use this as a loophole to simply get longer exclusivity on their best-selling drugs. Is there no arm of the government willing to look into abuses of this provision? Clearly the FDA isn't up to the job.

WARF Pushes Stem Cell Patent Claims

The latest dust-up over stem cell patents took place earlier this month in California when the Wisconsin Alumni Research Foundation's chief counsel told a conference she expects California to pay royalties to her agency. WARF owns the original patent filed by James Thomson of the University of Wisconsin on deriving human embryonic stem cells, and believes anyone who uses any variation of the technology must obtain a license.

There is a research exemption (in which case WARF only charges $5,000 per use), but, according to the California Stem Cell Report, WARF had a change of heart regarding California because the state's Institute for Regenerative Medicine (CIRM is the body set up by Prop 71, which established California's $3 billion stem cell research fund) recently approved rules that "give the state roughly 25 percent royalties on inventions developed by CIRM-funded research at non-profit institutions."

However, attorney Lawrence Ebert, who publishes a widely read blog on intellectual property issues, warns:

"The folks at WARF ought to be careful. CIRM is a state agency. Accusations of patent infringement against states play out a bit differently than the garden variety suit against a garden variety defendant."

QALY Time

The field of medical economics is a tricky minefield filled with false dichotomies and dubious assumptions. Medicine is, after all, a healing art, hopefully informed by science. What could be more dismal than applying the rubric of cost-benefit analysis to humankind's eternal quest to ward off illness?

These thoughts are provoked by the latest issue of the British Medical Journal, which contains a fascinating review of a half decade's worth of economic studies analyzing the value of new medical technologies.

Most Americans would probably recoil in horror if they knew their medical care was rationed based on cost-benefit analyses, which compares the costs of an intervention against its medical benefit. But insurance companies do it all the time and Medicare is moving in that direction. It is also the cornerstone assumption behind consumer-driven health care, where the determination of whether a particular therapy is worth its cost gets outsourced to the individual patient by the insurer.

Medical economists conduct these cost-benefit studies to determine if a new drug, medical device or surgical procedure is worth its pricetag. But how do they determine benefits? Over the years, the profession has developed a tool for measuring medical value known as the quality adjusted life year, or QALY. One year of perfect health gets a score of one QALY. If a patient is bedridden and in constant pain for that entire year, it might be considered a .3 (three-tenths of a year) QALY.

Let's use a hypothetical example to show how this works. If a medical intervention can, say, eliminate the pain, but not get that patient out of bed, it might raise the QALY for that year to .5 or a half-year. The economists then compare the improvement (.2 QALY) to the cost of the intervention and adjust it to show its price tag in terms of how much it would cost to achieve one QALY.

In this example, say the pain medication cost $12,000 a year. The cost per QALY would be $60,000. While it is by no means a hard and fast rule, most discussions about the value of achieving a QALY peg the acceptable cost threshold at $50,000 (based on the amount Medicare pays each year for dialysis patients on average). Below that and your technology gets paid for; above that and the insurers pull out the green eyeshades.

The problem with this approach is its inherent subjectivity. Who said reducing pain was only worth two-tenths of a year? Why not three-tenths? Though still in bed, the patient is enjoying a painfree existence, right? That’s got to be a .6 on the QALY scale. If the cost-benefit analyzer uses that measure, the cost per QALY for the pain medication drops to $40,000 per QALY, which just happens to be under the $50,000 threshold and likely to meet with the approval of the green eyeshade crowd.

The vast majority of the QALY studies that appear in the medical literature say the interventions are worth the price. And, according to the Tufts University study that appeared last week in the BMJ, only 18 percent of more than 500 studies evaluated by the researchers (most were conducted in the late 1990s) were funded by industry.

But sorting those studies by funding source showed a remarkable disparity in outcomes. “Studies sponsored by industry were more than twice as likely as studies sponsored by non-industry sources to report ratios below $20 000/QALY and over three times more likely to report ratios below $50 000/QALY,” the study’s authors said. “It is unclear whether publication bias occurs at a conscious or unconscious level. In any case, our results support concerns about the presence of significant and persistent bias in both the conduct and reporting of cost effectiveness analyses.”

Chaim Bell of St. Michael’s Hospital in Toronto, the lead author of the study, concluded that “more rigor and openness is needed in the discipline of health economics before decision makers and the public can be confident that cost effectiveness analyses are conducted and published in an unbiased manner."

He was too polite to ask, in the manner of Marcia Angell’s attack on academic medicine a few years ago, whether medical economics is for sale.

Integrity in Science Watch -- Week of 3/24/2006

Coalition Demands NAS Kick Weyerhaeuser Off Forest Committee
A coalition of environmental and public interest groups is demanding the National Academies of Science remove a top Weyerhaeuser scientist from the panel analyzing forest management practices' impact on water quality. In a letter sent to NAS chairman Ralph Cicerone, the Center for Science in the Public Interest, the Natural Resources Defense Council and 14 other organizations urged NAS to adhere to its own policy of "balance and objectivity" by removing George Weyerhaeuser Jr., vice president at the forest products giant. Weyerhaeuser clearly has a stake in the outcome of the committee's deliberations, the groups charged.

The letter also called on NAS to add several conservation-oriented scientists to the panel to offset the committee's industry consultants, Suzanne Birmingham Walker of Azimuth Forestry Services and Michael Kavanaugh of Malcolm Pirnie, Inc. The groups identified five qualified candidates for those slots. Though NAS is nominally independent of the federal government, it must follow the conflict of interest and balance requirements of the Federal Advisory Committee Act when working on studies funded by Congress.

American Cancer Society Chief Financially Tied to Drug Companies
The press last week reported John Seffrin, chief executive officer of the American Cancer Society, endorsed Andrew von Eschenbach to lead the Food and Drug Administration. However, the widely used quote from an Associated Press story failed to mention the extensive financial ties between ACS and the companies von Eschenbach will regulate.  ACS raises over $100,000 each year a wide assortment of major drug, food and health care-related firms including Amgen, Novartis, Pfizer and Quest Diagnostics. ACS last year also helped launch a major cancer prevention and treatment initiative called the CEO Cancer Gold Standard that is led by top officials from major drug companies. "You have a mixture of talent, experience and sensitivity that make [von Eschenbach], I think, uniquely qualified to be a regulator at an agency as important as the Food and Drug Administration," Seffrin said. Von Eschenbach, while simultaneously head of the National Cancer Institute and interim head of FDA, endorsed the CEO Cancer Gold Standard initiative.

British Government Scientist Questions Clinical Trial Conduct
The British drug trial that sickened six men and left two in a coma last week was poorly run, says a top British physician. Parexel, a large U.S.-based contract research organization in the business of conducting clinical trials for the pharmaceutical and biotechnology firms, ran the trial, which was for a new leukemia drug. "The idea that you give six people an injection at the same time is unusual," Kate Law, head of clinical trials for Cancer Research U.K., told the Associated Press. "In any of our tests, we never test drugs on the volunteers all at the same time." The drug maker's chief scientist, Thomas Hanke of TeGenero AG of Wuerzburg, Germany, said tests in monkeys left some with swollen glands, but nothing to predict disastrous effects in humans.

Oregon Congressman Fights for Integrity in EPA Research
Congressman David Wu (D-OR), member of the House Science Subcommittee on Environment, Technology and Standards, heavily criticized the EPA at a hearing Monday on the agency's proposed research and technology budget.  Wu and 78 other members of Congress have introduced the "Restore Scientific Integrity to Federal Research and Policymaking Act," which would protect federally-funded scientific research from being altered or censored by any federal employee.  Jeffrey Ruch, executive director of Public Employees for Environmental Responsibility, testified on behalf of federal research scientists. "Until EPA offers its scientists some meaningful protection...the agency's entire science program will be tainted in the eyes of both the scientific community and the general public," Ruch said.  EPA's Chair of the Science Advisory Board, M. Granger Morgan, stated, "We all want environmental decision-making to be based on sound science. However, our nation is not investing adequately in producing that sound science."

If EPA's PM Standards are Accepted, Litigation Could Follow
The EPA could face a court challenge if it doesn't adapt particulate matter standards in line with its scientific advisory committee's suggestions, Inside EPA (subscription required) reported Tuesday. Members of CASAC (Clean Air Scientific Advisory Committee) recommended lowering the annual PM 2.5 standards to 13-14 micrograms per cubic meter (ug/m3) instead of the current 15 ug/m3. The Clean Air Act requires EPA decisions be "based on the best available science," warned University of Pittsburgh professor Bernard Goldstein. The EPA may have "illegally made an important regulatory decision without obtaining advice as to its scientific soundness from its congressionally-mandated scientific advisers."

State Legislators Push for the Publication of All Clinical Trial Results
Two Minnesota state legislators have introduced a measure that will require public posting of all clinical trial results, including those that fail. State Rep. John Lesch (D) and State Sen. John Hottinger (D) said their bill would require disclosure of every clinical trial conducted since 1990 when a new drug enters the market. "We think it's only fair that doctors and consumers have all the available results to make informed choices about the safety of these drugs," Lesch said. Drug companies currently report some of their clinical trial results to the FDA- those needed to get the drug approved and any post-market studies required by the regulatory agency. However, firms are not required to make those results public and usually only favorable results get published. Major drug companies have begun listing clinical trials on a website, but critics say it is far from complete.

Data Quality Act Suffers Setback
According to Science Magazine, the Northern Virginia U.S. Court of Appeals last week rejected a Salt Institute suit challenging a National Institutes of Health study that showed lower sodium intake lowers blood pressure and reduces heart disease. The suit was brought under the Data Quality Act, the business-backed 2000 law that opens government science findings to challenges based on the underlying data. Environmental and public interest groups hailed the ruling since DQA challenges have, for the most part, been used by business groups seeking to challenge the science behind health-related government regulations.

Will Cephalon lobby FOR a black box warning?

The FDA's advisory committee turned thumbs down on Cephalon's request to use modafinil (an anti-narcolepsy drug) for ADHD. According to press accounts, company officials were "shocked."

Really? Some kids in the clinical trials developed serious skin rashes and the drug had one of the highest rates of psychotic episodes among ADHD drugs. It's hard to see why they found the bad news so upsetting.

Yet, as I pointed out Monday, the backstory to this drug involves the company's desire to get any pediatric designation it can to extend its patent life. That's why the competing comments from FDA officials on the future prospects for the drug were so interesting. Thomas Laughren, the chief of the psychiatric drugs division, was downbeat. But Robert Temple, the second-in-command at the new drugs division, said the drug may yet get to market, but with a black box warning.

After getting voted down 12-1 by an advisory committee and getting an extremely negative review from the in-house staff, it will still get to market with a black box warning? What's he been taking?

Perhaps company officials are already lobbying for that outcome. "We will continue our discussions with the FDA to determine the next steps in the review of this drug application," Paul Blake, Cephalon's executive vice president for worldwide medical and regulatory operations, told TheStreet.com.

Can Government Go Green?

The following article appears in the April issue of The American Prospect.

By Merrill Goozner

If the “mission accomplished” photo-op was the defining moment of the Bush administration’s foreign policy, the president’s recent visit to the National Renewal Energy Laboratory in Golden, Colorado, defined its energy policy. One week after he embraced alternative energy in his State of the Union address, Bush’s budget axed 32 employees at the nation’s premier alternative energy lab, a facility that developed key technologies for hybrid cars and photovoltaic cells. His political operatives didn’t even know what they had done until a few hours before his visit, triggering a mad scramble to restore the jobs to avoid embarrassing the president.

Too late. Reporters had a field day. But they should have paid more attention to the rest of the administration’s proposed federal budget, the ultimate arbiter of national energy policy. Bush’s TV rhetoric was disconnected from reality.

Programs that could reduce greenhouse gas emissions and lower U.S. dependence on foreign oil got short shrift. Instead, the president proposed lavishing new resources on long-range research programs that had more to do with rewarding key corporate backers -- “clean coal” and nuclear power, as well as corn-based ethanol -- than with building a comprehensive, sustainable energy system.

Under the president’s plan, home weatherization assistance programs will be cut by nearly a third; investment in geothermal, hydropower, and solar heating and lighting programs will be eliminated; and aid for upgrading local building codes (a key element in improving energy efficiency) will be ended. “The states will now have to become the true laboratories of innovation because the federal budget is not helpful,” said New Mexico Governor Bill Richardson, who headed the Department of Energy in the Clinton administration.

In the decades since president Jimmy Carter donned a cardigan to declare energy efficiency the moral equivalent of war, the United States has essentially relied on market mechanisms to wean itself from oil. This was a departure from the 1975 Energy Policy Conservation Act, which required automakers to achieve specific fleet averages in miles per gallon. Unfortunately, corporate average fuel economy (CAFE) standards, which were remarkably successful in achieving their initial goals, were abandoned as a strategy. The CAFE goal was last raised in 1990.

As inflation-adjusted oil and gas prices fell from their 1980s highs, markets responded the way markets do: mindlessly. The U.S. transportation sector became even more dependent on cheap foreign oil; the unanticipated SUV loophole made a mockery of the fuel standards (SUVs are counted under the weaker light-truck standard, not the tougher passenger vehicle one, even though that’s how most are used); the electricity sector adopted natural gas as the primary supplement for coal; and the overall economy lagged far behind its European and Japanese rivals in both energy efficiency and adding renewable sources like solar, wind, and geothermal into the energy mix. Concerns about global warming, air pollution, and defense outlays required to maintain access to Middle Eastern oil were ignored.

During the current Bush administration, these trends accelerated. In earlier days, political proponents of alternatives were driven from the national dialogue by an administration with deep personal, political, and financial ties to fossil fuel industries. Vice President Dick Cheney, launching an energy strategy hatched in secret with his energy industry cronies, famously claimed that energy efficiency and alternatives may be signs of “personal virtue” but have no place in the national strategy. Even after 9-11, which presented the nation with a golden opportunity to move down a different energy path, nothing changed.

However, energy markets have belatedly begun to reflect some of the hidden costs of U.S. reliance on fossil fuels. Hurricane Katrina and global warming, instability in many of the oil-producing regions of the world, growing competition for supplies from China and India, and accumulating evidence that the globe has finally reached its peak oil-producing capacity have kept oil more than $60 a barrel and gasoline prices well above $2 a gallon. Home-heating oil and natural gas prices have increased 16 percent and 24 percent, respectively, in the past year.

Mr. Market is responding to the changed circumstances, sort of. The use of alternatives to oil and gas is exploding. Demand for hybrids, solar installations, and wind power is rising at a 30 percent annual clip. But this consumer-driven response begins from such a small base that it would take decades to push fossil fuels from their preeminent position. Bush’s contradictory strategy both promotes more oil exploration and hopes to hasten energy diversification by giving a push to the supply side. At some point, the cost of alternatives, presumably, will fall below the cost of importing oil.

Unfortunately, it’s the same strategy that minimalist proponents of energy alternatives and reduced dependence on foreign oil have used for three decades without success. The sunk costs of oil, gas, and coal dependency -- the transportation infrastructure, the sprawl, the power plants, the industrial and commercial buildings and processes (not to mention their political influence) -- create inertial forces that adjust to every increase in fossil fuel prices the way a frog adjusts to rising water temperatures. It doesn’t know that it is cooked until it’s too late.

Three potentially powerful political streams could push the government toward more active intervention in energy markets. Labor and its allies have launched an Apollo project to promote the good -- jobs and technological potential of alternative energy strategies. Environmentalists continue to sound the alarm about the consequences of global climate change. And in the wake of 9 -- 11, a vocal element within the national security establishment recognizes that breaking the foreign oil habit requires breaking the oil habit entirely. Operating under the umbrella Set America Free Coalition, they responded to the president’s speech with a call for “a focus on deployment, not only R&D.”

A comprehensive government strategy would proceed on multiple fronts: not just biomass fuels, but higher fuel efficiency standards; not just more research into wind, solar, and geothermal power, but increased state requirements that they be deployed; not just industrial energy efficiency, but higher efficiency standards for lighting, home-heating systems, appliances, weatherization, and building codes. “There is no slam dunk,” says Scott Sklar of the Sustainable Energy Coalition.

Energy consumption in the united States can be divided into three distinct sectors: transportation, electricity generation, and the industrial/commercial/residential sectors. Each consumes roughly one-third daily demand for energy. Each requires its own strategy.

In transportation, the United States should raise the CAFE standard while giving the U.S. auto industry a three-year breathing space for retooling. In addition to lifting the SUV/light truck exemption (except for legitimate working vehicles), the fleet average should be raised to 40 miles per gallon (mpg) in 2010, 50 mpg in 2013, and 60 mpg in 2016. Every vehicle coming off the assembly line should, starting in the next model year, be a flexible-fuel vehicle that can run on any type of alcohol or gas-alcohol blend -- roughly a $150 per car add-on that will have less impact on the new car market than requiring seat belts and air bags.

Transforming the electricity sector will require a mix of federal and state policies, because most utilities are state-regulated. Twenty states and the District of Columbia already ask utilities to obtain a certain percentage of their electricity from renewable sources like wind, geothermal, solar, or hydroelectric power. At least 15 states have taxed electricity consumers to fund investment in renewables and energy efficiency, which provides a far greater return on investment than building new power plants. All states need to adopt such standards. The federal government should play a stronger role in easing the permitting process for new renewable energy facilities. It should also make permanent the current temporary tax breaks for renewables. “Business won’t invest based on a tax credit that needs to be renewed every two years,” says Michael Eckhart, president of the American Council on Renewable Energy. “Globally, the market demand is quite good. The question now is whether we’ll have a domestic industry producing it.”

The building and industrial sectors also need a boost from government to leapfrog ahead on efficiency. Revamped building codes and appliance standards and the strategic use of tax incentives would create thousands of jobs retrofitting America’s industrial and commercial sectors. This could reduce energy usage, increase profitability, and restore the competitiveness of lagging U.S. industries.

Greening the U.S. economy has obvious security and environmental benefits. But it is also a high-growth strategy that can provide millions of well-paid jobs for working-class Americans, who are currently the biggest losers from oil dependency. It will never be achieved without the strong hand of government leading the way. In 1961, President John F. Kennedy vowed to put a man on the moon in less than a decade, and the U.S. government got the job done. Is there any reason to think that this nation couldn’t rise to the energy challenge?

Merrill Goozner is a Prospect senior correspondent.

Big Pharma and the Trolls

A battle dividing the nation’s corporate elite landed in the Supreme Court this week in two important cases, LabCorp. V. Metabolite Laboratories and eBay v. MercExchange LLC. I’ll write more on these cases later. But it’s worth noting today how disappointing the commentary has been from the mainstream media. Both today’s New York Times’ editorial and Alan Murray’s Wall Street Journal column (subscriptions required for both) ignored the impact the court’s decisions will have on pharmaceutical pricing. It’s another case of myopia by journalists with Blackberries.

To get a sense of what’s really at stake, you had to read the back pages of today’s business sections in both papers. Sanofi-Aventis and Bristol-Myers Squibb, two of the biggest drug companies in the world, paid an “undisclosed amount” of money to Apotex, a Canadian generic manufacturer, to keep their exclusive rights to Plavix, a blood thinner, until 2011. Apotex was preparing to sell a generic version of the drug.

The stocks of both big companies leaped ahead after the announcement, which wasn’t surprising since Plavix generated over $6 billion in sales last year. What was the basis of the Sanofi-BMS suit against Apotex that led to the settlement? A patent. Not the original patent on the drug, which ran out in 2003. But a patent that runs out in 2011. This secondary patent covered the process for extruding the active half of the drug from the originally patented mixture (for those of you who understand organic chemistry, it’s the process of getting the active enantiomer out of Plavix’ racemate version). This is the same process that allowed other drug companies to substitute Clarinex for Claritin and Nexium for Prilosec, and allowed them to continue marketing these high price prescriptions to gullible doctors and unwitting patients who otherwise might have used generic versions.

Will the court’s decisions get in the way of this specious patenting? Clearly, Big Pharma is worried, or it wouldn’t have weighed in against companies like eBay that want to get around people who sit on patents in hopes of collecting fees from eventual users (the so-called “patent trolls,” of which Research in Motion, the company that sued the Blackberry maker and won a $612 million settlement, is only the best known).

But Big Pharma isn’t really worried about trolls. They’re the trolls. They want to maintain their right to run to court to get injunctions whenever generic firms try to get around secondary patents, no matter how specious.

These are complicated cases. If we had a Federal Trade Commission or Justice Department antitrust division that did their jobs, we wouldn't have to worry about how big companies game the patent system to rip off consumers. Now it's up to the Supreme Court. Given the recent pro-business appointments, it's hard to imagine anything far-reaching coming out of these decisions.

Pawns in Their Game

Does the world need another ADHD drug?

With nearly a half million kids on six different mind-bending drugs, you’d think the psychiatric profession already had enough options for attention deficit hyperactivity disorder. But that’s not the way our drug approval system works. It’s a free market out there, open to all comers. So this Thursday the Food and Drug Administration’s Psychopharmacologic Drugs Advisory Committee will consider another drug for ADHD – Cephalon’s Sparlon, which is generically known as modafinil.

Late night truckers and shift workers are already familiar with this drug. In their sleep-disordered world, it is known as Provigil. It’s not an amphetamine. It’s mechanism of action, to use the mystifying argot of the drug scientists, is “poorly understood.” In layman’s language, that means they have no idea how or why it works.

For its FDA submission, the company conducted a clinical trial on less than 700 children. They compared it to a placebo. Drug companies coming out with me-too drugs don’t have to compare it to existing therapies, which in this case would have been Ritalin or any of the other drugs for ADHD. They only have to prove it is better than nothing. And apparently it was. According to the trial, modafinil improved kids’ scores on exams designed to measure attentiveness.

But there wasn’t much other good news for Cephalon in that clinical trial. According to a report by FDA reviewer Andrew Mosholder released last week, two kids experienced psychotic or manic episodes; four kids considered suicide; and nine kids engaged in serious “aggression events” in the modafinil trial. That was the equivalent of 20 negative reactions for every 100 patients who take the drug for a year. Only Adderall and a skin patch had a worse record. In the cautious words of the reviewer, “patients and physicians should be aware of the possibility that these events, when they arise in the course of drug treatment of ADHD, may represent adverse reactions to drugs.”

Given those risks, why is Cephalon so gungho to get this drug approved? ADHD drugs have been in the news a lot lately, but not for any reasons that would encourage new entries in the market. In February, the FDA safety advisory committee voted 8-7 to slap a black box warning on all the drugs because they increase the risk of heart attacks and strokes, even in kids.

One possible explanation for their dogged pursuit of modafinil for ADHD can be found in the company’s annual report, which was filed with the Securities and Exchange Commission last week. Modafinil accounted for nearly half of Cephalon’s $1.2 billion in sales last year. And while some of that came from physicians prescribing it for ADHD off-label, the vast majority came from narcoleptics, shift workers, and truck drivers looking for a non-addicting stimulant. Unfortunately, the original patent on modafinil ran out in December, and four generic manufacturers were preparing to enter the market with cheap generics.

But Cephalon had an ace up its sleeve. It filed suit against the four firms for patent infringement based on a recently modified patent that claimed modafinil’s particle size had something to do with its effectiveness. Unlike the original patent on the drug, that patent doesn’t run out until 2014.

We’ll never know if that patent could withstand a court test since the Frazer, Pa.-based firm dropped its suit after agreeing to pay the generic makers over $200 million to withdraw their applications. Rather than fight for early access to the market, the generic firms agreed to hold off selling modafinil until October 2011 – in effect splitting the difference with Cephalon.

If that smells like a bribe to you, welcome to the wacky world of generic drug manufacturing, where not making a drug can be just as lucrative as making and selling it – and, of course, a lot less work.

But there was one more clause in the contract, according to the SEC filing. Cephalon will get an extra six months of exclusivity for modafinil if they get a pediatric use designation from the FDA. ADHD will do just fine, thank you.

So now let’s do the math. They currently sell just under $500 million a year without generics in the market. Another six months of exclusivity from a pediatric designation will earn them at least half that in sales five years now. That will be just about enough to pay for the bribe, er, the cost of the patent suit settlement.

I’m sure we’ll hear from plenty of testimony on Thursday from parents and physicians who swear by this new drug. But the jaded business reporter in me wonders if the kids are just pawns in the company’s patent game.

Integrity in Science Watch -- Week of 3/17/2006

Chair of FDA Committee Evaluating ADHD Drug Has Ties to Competitors

The chair of the Food and Drug Administration advisory committee that will consider a Cephalon, Inc. drug for pediatric attention deficit hyperactivity disorder heads a university department that receives hundreds of thousands of dollars a year in research support from other ADHD drug manufacturers. Wayne Goodman, chairman of the psychiatry department at the University of Florida, disclosed his department receives major grants from two of Cephalon's direct competitors. Another member of the Psychopharmacologic Drugs Advisory Committee, Andrew Leon of Cornell University, owns less than $25,000 in stock in a Cephalon competitor.

Cephalon's Provigil (modafinil) is a non-amphetamine stimulant for adult sleep disorders. The company now wants to sell it in the booming ADHD drug marketplace, which already has six approved drugs for nearly 700,000 patients, including a half million children. Earlier this week, FDA reviewers recommended stronger mental health warnings for all ADHD drugs because numerous adverse events like mania and psychosis were reported in clinical trials, including those for modafinil. Last month, the FDA's Drug Safety advisory committee recommended by an 8-7 margin that all ADHD drugs carry a black box warning because of increased risk of heart attacks. The FDA has so far rejected the recommendation, including head of the psychiatric drugs division, Thomas Laughren, who said he felt the warning was not necessary.

Cephalon gets nearly half of its $1.2 billion in annual sales from modafinil, whose original patent ran out last December. Late last year, the company agreed to pay four generic manufacturers over $200 million to postpone marketing generic versions of the drug until October 2011. The company will get a six-month extension of that agreement if it wins a pediatric designation for the drug, according to documents filed with the Securities and Exchange Commission earlier this week. Last October, the FDA issued an "approvable" letter to Cephalon for the pediatric use of modafinil pending the March 23 advisory committee meeting.

Majority of CMAJ Board Quits Protesting Lack of Independence

The Scientists reports only four of nineteen Editorial Board members of the Canadian Medical Association Journal remain today after most members resigned their positions in solidarity with colleague Jerome Kassirer, who resigned earlier this week. Board members began questioning the journal's publisher, the Canadian Medical Association, last month after it fired the journal's top editors, John Hoey and Anne Marie Todkill because they revealed how Canadian pharmacists questioned buyers of the morning after pill about their sexual history. The Editorial Board members told CMA president Ruth Collins-Nakai that they lost "trust in CMA leadership" and CMA's "efforts at promoting independence at the journal are 'cosmetic.'"

NRC Panel Backs Stricter California Air Emission Standards

A National Research Council panel has concluded states like California can set air emission standards that go beyond federal rules. The unit of the National Academies of Science also said California's proposal to require catalytic converters on lawnmower engines makes sense. The 11-member panel's conclusions, reported in the Washington Post, represent a setback for Missouri Republican Kit Bond, who wanted support for his efforts to get the EPA to veto the lawnmower rule on behalf of Briggs & Stratton, a major employer in his state. The environment-friendly report comes despite the presence of former auto industry lobbyist Gary Marchant on the NRC panel. The benefits of having California set cutting-edge standards for the nation "outweighed the costs" to manufacturers and consumers, said Marchant, who is now a law professor at Arizona State University.

WHO Bird Flu Data Policies Challenged by Italian Scientist

Pressure is building on the World Health Organization to open its database of more than 2,000 genetic sequences of avian influenza to scientists around the world. Opening the database would give scientists a better understanding of the potential pandemic threat and allow more rapid development of a human vaccine. In February Italian veterinarian Ilaria Capua refused to give her bird flu data to WHO because it would only be accessed by a "select group of scientists." Instead, she released her virus sample to GenBank, a publicly accessible database run by the National Center for Biotechnology Information in Maryland. WHO claims it developed the closed system because scientists and governments often keep their data hidden to boost their own careers. "I understand you have post-docs, and I understand you have to keep yourself going," Capua said. "But for heaven's sake, you don't have to publish a paper every two months. Let other people look at this data."

Rooting Out Scientific Fraud a Joint Responsibility

Responsibility for the investigation and prevention of misconduct must be shared by all parties involved – the research institution, co-authors and journal editors, a forthcoming article in the Annals of Internal Medicine concludes. In the wake of the Hwang Woo-Suk-Korean stem cell scandal, journal editors around the world are scrambling for new ways to prevent fraudulent articles from appearing in the scientific literature. The Annals article describes the case of Dr. Eric Poehlman, former faculty member of the University of Vermont, whose editors failed to catch his defective research, failed to withdraw it after publication and failed to warn other authors his articles contained faked data. In 2003, the University of Vermont notified three journals that they had published Poehlman's fraudulent research. But, according to the federal Office of Research Integrity, only one of the three journals retracted Poehlman's work. Meanwhile, authors continued to cite the retracted article.

Financial Motive May Be Why Negative Clinical Trials Go Unpublished

Published clinical trials funded by industry are more likely to demonstrate positive conclusions than trials supported by non-profit or government, a Nature article revealed this week. Since clinical researchers are not required to publish their findings, many unfavorable results "languish in filing cabinets," said Christine Laine, editor of Annals of Internal Medicine. In 2005 a group of French scientists showed that over an 18 year span, only 40 percent of the country's registered trials were published, although twice that many had been completed. Because inconclusive or negative data in the drug industry can be vital to "informing decisions about the licensing of drugs," the WHO and other groups want more clinical trial disclosure, including a "list of mandatory entries for trial data, including primary outcome." The WHO will issue a policy statement in April on the issue.

Revolving Door Keeps Swinging At FDA

The day before President Bush appointed Andrew von Eschenbach as permanent head of the Food and Drug Administration, the one-time cancer surgeon asked former Biotechnology Industry Organization lobbyist David W. Boyer to run the FDA's legislative shop. While at BIO, Boyer lobbied Capitol Hill on health care and biodefense issues. He's also worked on Capitol Hill and at the Health and Human Services department headquarters, where he was a special assistant reviewing legislation.

A New Ad for Aricept?

Today's news: Aricept, the Alzheimer's drug that doesn't do much, may cause death from heart attacks and strokes if the cause of AZ is vascular dementia.

Memo:
From: Pfizer/Esai Marketing Team
To: Ad Agency

Here's an idea for a new ad for Aricept. See if you can't work something up:

Scene: A middle-aged woman leads her slouched-over, elderly father to the kitchen sink. She runs some water in a glass and hands it to him. She wipes the drool from his chin while opening her hand and placing a pill gently on his tongue. He drinks and swallows. She turns to the camera.

"Aricept. It probably won't help much, and it may cause a heart attack. (She smiles.) Either way, he's better off!"

What's the Bush Administration's Plan B?

President Bush this afternoon officially nominated Dr. Andrew von Eschenbach to run the Food and Drug Administration, setting off an immediate firestorm of criticism. Senators Hillary Clinton (D-NY) and Patty Murray (D-WA) pledged to block his appointment until the FDA comes up with a decision on over-the-counter Plan B, the morning-after contraceptive. All the science points to allowing its use; only the Bush administration's fealty to its religious base has held up approval.

What's the administration's strategy? Three possibilities. First, and most likely, is that Bush merely wanted to get Republicans like Sen. Charles Grassley (R-IA), who had been pushing for a permanent appointment, off his back. Von Eschenbach can continue running FDA as interim head while blaming the lack of hearings on the Democrats.

This fits in well with a Karl Rovian polarization strategy for the fall elections. It mobilizes the conservative religious base by demonizing Hillary, pro-choicers and blue-staters generally as libertines who promote promiscuity.

Anther possibility is that von Eschenbach will finally come up with a decision. Just say no to Plan B. That mobilizes the base while giving Clinton, Murray and others middle-of-the-road Democrats an out from blocking his confirmation. They will still vote again him, of course. But he would win a party-line vote.

Of course, this runs the risk of antagonizing anyone who believes in science, freedom of choice and separation of church and state. But in the Bush-Rove imagination, that is a shrinking share of Americans anyway.

The third and most remote possibility is that von Eschenbach will approve Plan B. which is what he probably wants to do (I'm basing this on Connecticut Democratic Rep. Rosa DeLauro's kind words for von Eschenbach during a House appropriations hearing a few weeks back; she said she looked forward to his permanent appointment as head of FDA). If anyone other than ideologues were running the Republican Party, he'd be allowed to.

In an election year where the president's approval rating is hovering around 35 percent, the vice president's approval rating is among the lowest on record, and the lobbying scandals show no sign of abating, tacking to the middle to win centrist voters would seem to be the wise and prudent choice.

But as we long ago learned about this administration, prudence, wisdom and centrism are not qualities it has in abundance.

Death Knell of the Media Barons?

With Knight-Ridder no more and major city newspapers on the block, is the era of the internet finally at hand? No less an authority than Rupert Murdoch thinks so. Today's Guardian has the media baron "comparing today's internet pioneers with explorers such as Christopher Columbus and John Cabot."

"Power is moving away from the old elite in our industry - the editors, the chief executives and, let's face it, the proprietors," Murdoch said.

Now that makes me, plugging along here in obscurity, feel much bertter. As the old saying goes, from his lips to God's ear.

Details, Details

About four years ago, government-funded researchers completed a comprehensive eight-year study comparing various blood pressure control medications. The results were trumpeted across the front page of nearly every American newspaper. Cheap generic diuretics, which have been around since the 1950s, turned out to be just as effective as expensive brand name drugs for treating high blood pressure.

This news held great promise for millions of senior citizens, since high blood pressure is associated with aging and is a major contributor to heart disease, which remains the number one killer of Americans. The authors of the study pledged to engage in a massive education campaign to bring the good news to physicians and their older patients: You don’t have to go broke medicating your high blood pressure.

Did they do it? And did it work? I was motivated to look for answers to these questions this morning by a front page story in the Wall Street Journal, which documented a small project run by Dr. Jerry Avorn of Harvard University that engages in just such “counter detailing.” The name comes from the pharmaceutical industry’s term for its sales representatives, who go from physician's office to physician's office providing details about the latest drugs pouring out their companies' labs. To counter-detail is to substitute science for this marketing, which, the story revealed, now employs 90,000 detailers and cost drug consumers about $12 billion annually.

This $80 million government study – which could have saved taxpayers billions of dollars now that they are helping to pay for seniors' drugs – has not had a major impact on physician prescribing practices. According to IMS Health, which tracks prescription data in the U.S., the number of diuretic prescriptions rose to 103.6 million in 2005, about a 3.5 percent increase over the previous year. Prescriptions for other blood pressure control medications looked like this: ACE inhibitors, 149 million prescriptions, up 4 percent over 2004; beta blockers, 127 million prescriptions, up 6 percent; calcium channel blockers, 89 million prescriptions, up 1 percent.

It is difficult to draw precise conclusions from this broad data because many people take more than one blood pressure control medication. But it is probably fair to say that the massive shift to diuretics as first-line therapy, which had been the hope of the National Heart Lung and Blood Institute researchers, has not taken place.

This is not just a dollars and cents question. People who take generic or low co-pay medications stick to their regimens at higher rates than people who must pay higher prices. A February study in the Archives of Internal Medicine looked at compliance data from patients in three-tier pharmacy benefit plans (these plans usually have low or no co-payments for generics; higher co-pays for “preferred” brand name drugs; and the highest co-pays for the most expensive, non-preferred drugs in the plan formulary).

The results? About 58.8 percent of patients took every pill in their prescription and returned for a refill if the drug was a generic with a low or no-copay. However, only 52.2 percent of patients with high co-pays completed their prescriptions. There was also a smaller but statistically significant improvement in compliance among patients in the middle co-pay tier compared to the highest priced drugs.

The bottom line is that counter-detailing that encourages consumers to take generics isn’t just about saving money. It can save lives when the generic is just as good as the pricier product. Why? People who can afford their medicine tend to take it all. And they tend to stick to the schedule, which, after all, is what the doctor ordered.

Alas, Dr. Avorn’s little counter-detailing shop at Harvard is moving forward at a snail's pace. It has a million-dollar-a-year grant from the state of Pennsylvania. That's about the same amount of money it takes the pharmaceutical industry to put about seven detailers in the field.

Seven down, 89,993 to go.

Integrity in Science Watch -- 3/10/06

NAS Taps Three Industry Execs, No Enviros to Forest Management Panel

The National Academies of Science has appointed three scientists with close ties to the forest products industry to a committee studying how forest management practices affect water quality. The group includes George Weyerhaeuser, Jr., whose numerous jobs at Weyerhaeuser have included running containerboard plants and sawmills. Other industry consultants on the 11-member panel included Michael Kavanaugh of Malcolm Pirnie, Inc. and Suzanne Birmingham Walker, a former Forest Service staffer who now runs Azimuth Forest Services, Inc.

When questioned about the lack of environmentalists on the committee, NAS staff officer Lauren Alexander said scientists at environmental groups did not have the "necessary expertise for the statement of task." A Nature Conservancy official had been asked to sit on the Committee, but was unavailable, she said. The Hydrologic Impacts of Forest Management Committee will meet March 22 to kick off the 24-month study.

Former Corps' Chief of Engineers Latest Profiteer from Revolving Door

The consulting firm run by retired General Robert Flowers, Chief of US Army Corps of Engineers from 2000 to 2004, has been selected to lead major reconstruction of the New Orleans levee system. Public Employees for Environmental Responsibility (PEER) said Flowers' tenure as Chief of Engineers was marked by "questionable navigation projects in New Orleans at the expense of flood and hurricane protection." Flowers, now CEO of HTNB Federal Services Corporation, will act as the Corps' general contractor, offering technical services to assist in the rebuilding of the same flood control systems he previously neglected. "This is like hiring Michael Brown to reform FEMA," Jeff Ruch, executive director of PEER, said.

Former Head of FDA Under Investigation for Disclosed Stock Sales

Lester Crawford, the former FDA Commissioner who abruptly resigned amid allegations of conflicts of interest last September, sold stock in a medical device firm just weeks before his resignation, the Associated Press reported. Financial documents released by the AP showed Crawford sold more than $50,000 worth of shares in Teleflex in the fall of 2005 after claiming on financial disclosure forms a year earlier than he had sold a smaller block of shares in the firm at the request of an ethics officer. Crawford is now senior counsel at Policy Directions, Inc., a Washington firm that lobbies on behalf of pharmaceutical companies. The government is investigating Crawford's financial dealings.

Stronger Coal Waste Rules Urged After Protests Remove Industry Consultants

The National Academies of Science last week recommended "robust" government oversight of coal combustion wastes deposited in abandoned coal mines. Environmental groups and local residents in mine areas say the wastes pose a hazard to local water supplies. In October 2004 The Clean Air Task Force, the Center for Science in the Public Interest's Integrity in Science project and 40 other groups protested the presence of industry-funded scientists on the Managing Coal Combustion Residues in Mines Committee. The NAS subsequently removed two of the scientists with close ties to the coal industry and another resigned. "If the committee composition had not been changed so radically, the report would be very different...[and would have] likely resulted in a recommendation that federal minimum standards are not needed," said Lisa Evans, a staff attorney for the Clean Air Task Force.

Proposed EPA Standards for PM Challenged by Outside Scientists

A second outside Environmental Protection Agency advisory committee has challenged the agency's proposed particulate matter (PM) rule. The Children's Health Protection Advisory Committee wrote a consensus letter last week to EPA Commissioner Stephen Johnson recommending that the EPA's proposed fine and coarse PM standards issued last December be lowered because they do not "provide adequate protection for infants and children." The EPA proposed lowering the limit to 35 micrograms per cubic meter daily for PM2.5 (fine airborne particles less than 2.5 microns in diameter that typically come from burning fossil fuels). This was the highest possible level recommended by the Clean Air Scientific Advisory Committee, which itself urged Johnson to reconsider lower PM2.5 standards. CASAC's February letter criticized EPA for not analyzing lower PM2.5 levels below 14 micrograms per cubic meter annually and 30 micrograms per cubic meter daily.

A stricter standard received scientific support Wednesday from an EPA- and National Institutes of Health-funded study published in the Journal of the American Medical Association. The study concluded that 11.5 million elderly Americans were at risk of increased cardiovascular and respiratory disease when exposed to an average of 13.4 micrograms per cubic meter of PM2.5, which is below the agency's proposed annual limit of 15 micrograms. "These findings provide compelling evidence that fine particle concentrations well below the national standard are harmful to the cardiovascular and respiratory health of our elderly citizens," said National Institute of Environmental Health Sciences Director David A. Schwartz.

The EPA will take final action on the proposal for particulate matter on Sept. 27, 2006. The comment period on the proposal runs until March 17 and can be accessed here: here.

Industry Launches New "Grassroots" Group to Gut Environmental Laws

Timber industry lobbyists in Oregon have launched another phony environmental group aimed at gutting environmental laws, the journal Environmental Science & Technology reports. Save Our Species Alliance (SOSA) is the second organization run by Tim Wigley, executive director of PAC/West Communications and a timber industry fund-raiser/lobbyist. The new group's goal is to weaken the Endangered Species Act. Wigley previously created Project Protect, which pushed passage of President Bush's Healthy Forests Initiative to increase logging on federal lands. Richard Pombo (R-CA), chair of the House Committee on Natural Resources, recommended Wigley for an award for his work on the Healthy Forests legislation. "Tim's efforts in leading the grassroots campaign 'Project Protect' without question helped position the Healthy Forests Restoration Act for successful passage in the U.S. Congress," Pombo said.

A Conflicted FDA?

The Wall Street Journal and Bloomberg News confirm reports from earlier this week that Dr. Andrew von Eschenbach will get the Bush administration's nod to run the Food and Drug Administration. He's been interim commissioner since Lester Crawford resigned last September amid financial conflicts of interest allegations.

While the news accounts suggested Plan B, condoms and other culture war issues would dominate Senate hearings on a von Eschenbach appointment, the central issue from where I stand is his simultaneously holding the highest post at the National Cancer Institute. There were no indications in today's news reports that he plans to resign from that job.

This is a structural conflict of interest, not to mention a conflict of commitment (how can one person devote full attention to both of these complicated jobs?). As I've said in this space many times before, NCI's job is to investigate the causes of and, more importantly, develop cures for cancer. The agency's scientists file applications to the FDA to start human clinical trials, those trials are overseen by the agency, and, in some cases, it even submits new drug applications to the FDA.

In his role as head of NCI, von Eschenbach has repeatedly said that it is his personal goal to end the pain and suffering of cancer by 2015. The unrealistic assumptions behind that statement aside, it is a statement that one would expect from an advocate.

As head of FDA, he has said that streamlining the process by which drugs get brought to market will be his highest priority. The FDA does need to reevaluate the way it monitors and approves drugs. But no one on either side of the aisle on Capitol Hill, not to mention the American public, would want that streamlining and modernizing to jeopardize the agency's core mission of protecting the safety of the U.S. food and drug supply.

If the White House pursues his nomination, Congress should demand a full accounting of his actions at NCI that might present future conflicts of interest in matters that come before the FDA. What clinical trials has he had a personal hand in organizing? How many cooperative research and development agreements has the agency signed under his tenure? How many grants has he approved for companies whose products will eventually come before the FDA? Will he recuse himself from all of these matters?

There's a role in the world for advocates like von Eschenbach. It's just not as the head of the agency whose job it is to serve as policeman over companies that account for one-quarter of the U.S. economy. Someone on the Hill should inform the White House that the former cancer surgeon is not the right man for this job.

The Biotech Conundrum

I'm off this week to speak at the BioAgenda conference, an annual gathering of biotechnology industry supporters. I'm on a panel debating drug pricing and pharmaceutical innovation. Here's one of the points I plan to make:

The biotechnology revolution is a major pillar of America’s claim to global high-tech preeminence. Its medical and economic promise has enthralled two successive generations of biologists and medical entrepreneurs, so much so that today the Biotechnology Industry Organization (BIO) claims nearly 2,000 member companies and most cities and towns have pinned their economic futures on grabbing a piece of what is presumed to be an ever expanding biotech pie.

But has this revolution paid off for investors, communities, scientists, and patients? Beyond the early big winners who picked the low-hanging fruit of the biotechnology revolution – companies like Amgen, Genentech and Genzyme – have the thousands of companies populating this industry filled the therapeutics pipeline with promising new biotech drugs that will revolutionize the practice of medicine?

This week’s Food and Drug Administration hearing on a new treatment for multiple sclerosis demonstrated both the promise and the perils facing these biotech firms. The 12-member paneled voted unanimously to let Biogen/Elan’s Tysabri back on the market despite rare occurrences of a fatal brain disease. At the same time, it voted just 7-5 to make it a drug of first choice for “some patients,” reflecting the sad truth that this monoclonal antibody is far from a slam dunk in treating the progressive, neurological disorder.

Tysabri is a symptom of the general disease affecting the biotech industry. FDA data reveals that the number of new biotech products has fallen from more than 30 a year in the early 1990s to less than 15 per year in 2003, and many of those that come on the market have only marginal effects on the medical conditions they seek to treat.

This trend bodes ill for both patients and biotech investors. The vast majority of the 2,000 firms that belong to BIO have no products on the market, minimal sales and a long string of investment-driven losses to show their investors. Not for nothing is this field known as the rich man’s lottery.

How about patients, like the more than a dozen multiple sclerosis patients who showed up for the Tysabri hearing? They hear the hype. They have the hope. And they suffer. Only they don’t suffer in silence. Often organized into patient advocacy groups funded by industry, they’re more than willing to raise their voices in support of even marginal new drugs.

Why has the promise of the biotech revolution not been fulfilled? There are many contributing factors. For instance, the low-hanging fruit has been picked. There are only so many diseases where one protein is missing and replacing it leads to a cure. Then there’s the corporate focus on “me-too” drugs, which has even infected successful biotech firms. Look at Amgen, whose biggest product in recent years is Aranesp, a follow-on drug to its blockbuster Epogen, which treats anemia.

But most significantly, the most pressing medical problems today (Alzheimer’s; obesity; cancer; chronic degenerative diseases like Parkinson’s, rheumatoid arthritis, etc.) result from either social causes or a biological cascade of events. There is no single triggering factor. Therefore, they cannot be easily “cured” by a single drug or biologic intervention.

The sad truth is that major innovations in medicines are rare, and usually result from intense collaboration over many years among dedicated scientists and teams of scientists focused on understanding and curing a disease. Yet today’s innovation system encourages atomization of scientists. They're encouraged to patent their scientific insights and pursue proprietary products through start-up biotech firms.

The future of innovation in biotechnology and biomedicine will require greater resources and greater collaboration than ever before. It’s not clear to me that atomized biotech firms, each working on their own intellectual property in the hope that it will turn out to be a financial home run, is the best way to get the job done.

Von Eschenbach Throws Hat in Ring to Run FDA; Pledges Faster Drug Approvals

The Baltimore Sun reports today that Dr. Andrew von Eschenbach, the acting head of the Food and Drug Administration, is actively seeking a full-time appointment.

In an appearance before the Personalized Medicine Coalition, an industry-sponsored group, the cancer surgeon (who right now also runs the National Cancer Institute) said he wanted to "improve" the drug approval process. He vowed to make faster drug approvals "one of my highest priorities."

Two weeks ago, von Eschenbach told a Congressional appropriations committee considering the FDA's 2007 budget that "we are making a tremendous commitment to the whole area of safety."

It is, of course, possible to both hasten drug approvals and still ensure that they are safe. But one can't help but think that he's talking out of both sides of his mouth depending on the audience.

Word among lobbyists is that von Eschenbach's wish for a permanent appointment at FDA has already been greeted cooly by Sen. Michael Enzi (R-Wyoming), who chairs the Senate Health Education Labor and Pensions Committee. He's probably not anxious to hold hearings about the embattled agency in an election year.

Promises to Keep

In the early 1990s, the Food and Drug Administration responded to the AIDS crisis by allowing accelerated approval of new drugs for serious or life-threatening illnesses. Under accelerated approval, experimental drugs are rushed to market based on trials involving a relatively small number of patients. In many cases, the proof they work rests on a diagnostic test that provides only the most tentative evidence that the patient will in fact get better with the drug.

There’s a quid pro quo for these rapid approvals, of course. The drug company promises to conduct a post-approval trial to determine whether the claims made for what is known as a surrogate marker in fact panned out.

Late last week, the FDA reported that the drug industry hasn't even started two-thirds of the more than 1,200 promised post-approval trials. Deputy Commissioner Scott Gottlieb said the agency would take a year to study the problem, prompting Vanderbilt medical school asssociate dean Alastair Wood to tell the New York Times: "Who would turn in their homework if they didn't have to?"

Drug companies pursuing new oncology drugs have been enthusiastic supporters of the accelerated approval, often using surrogate markers like tumor shrinkage to show efficacy for new drugs. But they're no better than the rest in carrying out the promised post-approval trials.

There have been 25 cancer drugs for 29 indications given accelerated approval status since 1995. Yet only a third have so far submitted data confirming their efficacy. Moreover, at least six of the drugs entered the market before 2002 – giving the companies plenty of time to conduct the trials.

What happened? At an FDA Oncology Drugs Advisory Committee (ODAC) held last fall, the companies behind the six drugs discussed their reasons for not meeting the requirements. Johnson & Johnson, whose Doxil received accelerated approval for AIDS-related Kaposi’s Sarcoma, said the success of highly active anti-retroviral therapy (HAART) meant there are no longer enough patients around to conduct a valid trial. Curiously, the company then produced a physician who begged the FDA not to repeal its approval since she still saw plenty of patients with the syndrome who needed the drug.

Good data for Genzyme’s Campath, a monoclonal antibody for treating chronic lymphocytic leukemia, was hard to come by because of FDA incompetence, the company suggested. When the company designed its post-approval trial in 2000, the FDA insisted on comparing it to chlorambucil, then the only approved treatment. But within a few years, almost no one in the U.S. was using chlorambucil and the FDA wasn’t flexible enough to change the protocol. The company had to go to Eastern Europe to conduct the trial. Results are expected later this year.

And so it went for all six companies. Each had their excuses. The FDA’s expert advisers fumbled for a solution. Dr. Bruce Cheson of Georgetown University Hospital decried the “crappy study design” and the fact that “the bar is set way too low” for accelerated approval of many drugs.

The FDA clearly needs to drive a harder bargain with companies seeking accelerated approval. First, it should change the name to Conditional Approval, which was suggested by one member of the ODAC. The accelerated approval tag creates an unfortunate image for patients and physicians that the drug is someone better than what’s out there, when it fact it may be worse.

Second, the agency should forbid the off-label use of any drug given Conditional Approval unless the patients are enrolled in an active clinical trial.

Finally, the FDA should create a publicly accessible registry where physicians must record the results of every clinical use of a conditionally approved drug. Given the cost of new cancer drugs, a small surcharge to reimburse oncologists for providing this data will appear as a pittance on insurers’ bills. Yet it will provide epidemiological data that, while it won’t have the rigor of a controlled clinical trial, should provide clinicians with crucial information about the actual value of the conditionally approved drugs.

Integrity in Science Watch -- 3/3/06

FDA Puts Five Scientists with Conflicts of Interest
On Committee Evaluating Controversial MS Drug
Five of the eleven scientists so far selected to judge the safety of the new multiple sclerosis drug Tysabri have financial ties to either the drug's sponsors, Biogen and Elan Pharmaceuticals, or their competitors. The Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee will meet March 7 to reconsider Tysabri, which was pulled from the market last year after a handful of patients developed a rare brain disorder. Permanent committee member Lily Jung and Karl Kieburtz, special appointee, disclosed they earned between $10,000 and $50,000 from either Biogen and Elan by serving on their speakers bureaus or consulting. In addition, committee members Steven DeKosky, Larry Goldstein and Ralph Sacco consulted for or sat on the speaker bureaus of direct competitors. The FDA claims it cannot find experts without conflicts of interest to serve on advisory panels, whose advice it usually follows.

EPA To Get Suppressed Industry Chromium Study
The hidden industry study that showed chromium-6 poses a significant lung cancer risk will be submitted to the Environmental Protection Agency to become part of the permanent record on the dangerous chemical, the researchers who uncovered the study said. Without being able to consider the industry's incriminating data, The Occupational Safety and Health Administration this week adopted a feeble rule regulating workplace exposure to chromium-6. David Michaels, director of the Project on Scientific Knowledge and Public Policy (SKAPP) at George Washington University, called on federal agencies to require full disclosure of industry-funded studies during regulatory proceedings. Michaels and Public Citizen uncovered the industry study and recently published its findings in a report in the online journal Environmental Health, suggesting any organization participating in policy-setting proceedings should "certify that all relevant data have been submitted to the public record, whether published or not."

P&G Issues Bill of Rights; Outside Researcher Still Without Data
Under fire from a British researcher denied access to data for his study, Proctor & Gamble this week issued a one-page "bill of rights" for scientists funded by the corporate giant. The company said researchers will have access to all relevant data and authors "will define and control any publications resulting from their work." Yet attorneys for UK scientist Aubrey Blumsohn said P&G is still withholding critical data from his study of P&G's osteoporosis drug, Actonel. The Cincinnati-based consumer products company also submitted their version of the study's conclusions for publication under Blumsohn's name without his consent. "If P&G is acting in good faith, the place to start is releasing the necessary data to [Blumsohn] and to allow proper scrutiny," said Mark Cohen, an attorney with the Government Accountability Project, which is representing Blumsohn. P&G officials said there was no connection between Blumsohn's allegations and its new bill of rights.

CSPI: New IP Rules Could Make Medical Innovation Cheaper
California should use its new $3 billion stem cell research program to modernize the medical innovation system in a way that would both spur research and make its results affordable. In a major policy forum article in the open-source journal Public Library of Science: Medicine, Integrity in Science director Merrill Goozner said California should require researchers to donate intellectual property derived from stem cell research grants into a patent pool similar to the open-source patent pool that developed Linux, the computer operating system. Open-source patent pools allow anyone to use an invention as long as future patents that rely on patents already in the pool get donated into the pool. The pool would be coupled with large prizes for major breakthroughs, which would be distributed among the patent holders. The pool authority could then issue manufacturing licenses to generic manufacturers, Goozner asserts this reform would break down barriers between scientists and "eliminate the 30 to 40 percent of pharmaceutical industry revenue generated by wasteful marketing costs."

Politics Overrules Science at FDA, Former Top Staffer Says
In a Washington Post op-ed piece this week, former assistant commissioner of women's health at the FDA, Susan Wood, continued her challenge to the federal health agency's "lack of independence." Wood resigned from the FDA six months ago after agency officials refused to approve over the counter status for Plan B for women 17 and older despite overwhelming scientific evidence indicating it should be approved. Wood said that acting Commissioner Andrew von Eschenbach, like his predecessor, is continuing to hide "behind a wasteful and pointless bureaucratic process" and damaging the FDA's credibility. She said the "American public does not want to -- nor should it -- have to think twice about the quality and reliability of information it is getting from the FDA."

Senate Rejects Slowing the Revolving Door
The Republican-controlled Senate Rules Committee on Wednesday rejected legislation proposed by Sen. Mark Dayton (D-Minn) that would create a two-year waiting period before members of Congress could become "personally and substantially" involved in lobbying. Sen. Trent Lott (R-Miss), chair of the Committee, stated that Sen. Dayton's amendment to the lobbying reform bills did not "fall under the committee's jurisdiction." The Senate Committee approved modest curbs on earmarks and privately financed trips.

Oncologists Rebel Against Amgen's Marketing Tactics

Last spring, the nine physicians at Marin County’s California Cancer Care received an offer they wanted to refuse. Amgen, which sells Aranesp, Neupogen and Neulasta for chemotherapy-related anemia, told the oncologists that unless they purchased a quarter of its red cell stimulator from Amgen, the goliath of the biotech world would cut off their discounts on white blood cell products. After much internal grumbling, they agreed.

Six months later, Amgen’s drug representatives came back with another offer. Unless the practice purchased 65 percent of its red cell product from Amgen, the discounts on Neupogen and Neulasta – which have no competition – would be withdrawn.

This time, they rebelled. “We have an aversion to being bullied,” said Dr. Peter D. Eisenberg, a senior member of the Cancer Care team. The firm ended its research project for Amgen, cancelled an Amgen-funded training program and withdrew a pending grant application. “Maybe this kind of aggressive behavior is okay when you buy four tires instead of two tires. But when it comes to the practice of medical oncology, this is something new.”

And possibly illegal. Last October, Johnson & Johnson’s Ortho Biotech Products division, which sells Procrit to stimulate red blood cell production, filed suit in U.S. District Court in New Jersey alleging that Amgen’s Aranesp marketing practices amounted to an anti-competitive tying arrangement designed to monopolize the market for red blood cell products, which would be a violation of the nation’s antitrust laws. Although Aranesp costs more than Procrit, Amgen has seized approximately two-thirds of the $2.8 billion oncology market since launching the tying scheme, the suit alleged.

Amgen denies the charges and will vigorously contest them in court, the company said.

Marketing disputes between the two companies have a long history. In the mid-1980s, Amgen, then a struggling start-up looking to develop the original form of human recombinant erythropoietin, which is now sold as Epogen, signed away the cancer market to J&J in order to raise cash for clinical trials. Procrit and Epogen are identical.

When it turned out that the cancer market exceeded the dialysis market, which Amgen had kept for itself, the company launched a plan to develop a longer-acting version of Epo to go after J&J’s market, which had grown to include a burgeoning population of HIV/AIDS survivors. The Food and Drug Administration approved that drug –Aranesp – in 2001.

Amgen subsequently launched a massive marketing campaign that included direct-to-consumer advertising on television to promote the use of Aranesp for treating chemo-related fatigue. J&J launched its own advertising campaign. Patient demand for the drugs soared.

Yet the medical evidence supporting the increased usage was scant and often funded by Amgen itself. Amgen also seeded the literature with economic justifications for increased use of its new drug. A typical example was a recent open-label study led by economist Ernst Berndt at the Massachusetts Institute of Technology, which appeared last year in the journal PharmacoEconomics. It claimed reduced anemia from Aranesp led to increased productivity.

However, an independent study by physicians at the M.D. Anderson Cancer center in Houston that appeared in the December issue of the Journal of Palliative Medicine concluded, “Anemia is not one of the major contributors to fatigue in patients with cancer receiving palliative care.” Citing the multi-factorial nature of fatigue in cancer patients, Journal editor Charles von Gunten wrote that "these data will help physicians resist the patient and family pressure to use erythropoietin because they saw it on television . . . Erythropoietin is ineffective in relieving fatigue if anemia is not the cause. It is an expensive placebo.”

That argument resonates with many physicians. “If we were doing our jobs right, we would work up a patient’s fatigue appropriately from beginning to end,” said Eisenberg. “It’s a lot easier to send the patient down the hall to get a shot of Procrit or Aranesp and it’s a lot more profitable. I’ve read the literature that says people feel better when their hemoglobin is improved on these products. But it’s difficult for me to get my mind around. I understand differences in survival. I understand time to tumor progression. I have a harder time understanding quality of life issues and what the real impact is,” he said.

Meanwhile, many physicians who use the drugs with their Medicare patients are faced with an economic dilemma. According to Dr. James Cohen, a community cancer specialist in Los Gatos, his practice loses $209 on every dose of Neulasta unless it receives a discount from Amgen. And, “the Neulasta rebate is linked to how much Aranesp I use,” he said. “Unless I exclusively use Aranesp without Procrit I will never achieve the volume necessary for the rebate.”

This story first appeared in the Bay Area Oncology News.