Who Owns Science? Rejuvenating Public Sector Science

Citing the "moral corruption" of organized medicine, Sir John Sulston, the British genome scientist who won the 2002 Nobel Prize for medicine, is launching a new institute on science, ethics and innovation. He wants to put innovation in medicine back on track by limiting gene patenting. According to this BBC report, he also blames disease mongering by the big pharmaceutical firms for distracting researchers from dealing with the serious problems facing millions of poor people around the world. He's holding a conference in London this weekend entitled, "Who Owns Science."

The Center for Science in the Public Interest's Integrity in Science project will hold a conference in Washington, DC today. The featured speaker at "Rejuvenating Public Sector Science" will be James Hansen of NASA, who has been speaking out on global warming since the late 1980s. A 2 p.m. panel on comparative effectiveness in medicine features Gail Wilensky, Ezekiel Emanuel and Gregg Bloche and will be webcast by the Kaiser Family Foundation. If you're in Washington and can make it down to the Reagan Center at 13th and Pennsylvania, registration is available at the door.

Life Expectancy Data Ignores Int'l Comparison

Life expectancy in the U.S. continued its slow but steady upward crawl, reaching an average of 78.1 years in 2006, according to this morning's Washington Post report on the latest data from the Census Bureau. The average woman in 2006 could expect to live to 80.7, the average men to 75.4. Infant mortality was down, the gap between men and women was down, and the gap between racial groups was down, suggesting the recently reported pockets of declining longevity in Appalachia due to rising obesity rates are precisely that, pockets. All good news.

Unfortunately, neither the government press release nor the mainstream reporter put this latest data in an international comparative context. How do we rank compared to other nations?

Not hard to find out, thanks to the Internet. According to the Organization of Economic Cooperation and Development, the U.S. ranked 24th out of 33 nations ranked by that organization. U.S. life expectancy of 77.8 in 2005 (it rose 0.3 years in 2006) trailed the OECD average by a full year and global leader Japan by a half decade.

At least we're not Russia, where life expectancy remains mired at about 65 years, trailing every other nation in the global survey. Others behind the U.S.? Turkey, Brazil, Hungary, China, Poland, the Slovak and Czech Republics, and Mexico. When it comes to the average person's health in the U.S., our descent into second world status is complete.

It would be nice if reporters pointed that out whenever the government offers rosy statistics on how well we're doing.

Big Tobacco Behind Lung Cancer Screening Study

The New York Times reports this morning that the tobacco giant Liggett & Myers contributed $3.6 million to a controversial screening study that suggested using routine CT scans to detect lung cancer early could substantially reduce lung cancer deaths in the U.S. The Cancer Letter recently revealed that when the study first appeared in the New England Journal of Medicine in 2006, the study authors, Claudia Henschke and David Yankelevitz of Weill-Cornell Medical College in New York, failed to disclose they had licensed scan-reading patents to General Electric, which would earn them a bundle if millions of smokers began getting annual CT scans. Now, it turns out that the study was also supported by a non-profit called the Foundation for Lung Cancer: Early Detection, Prevention and Treatment, whose board includes Henschke and top officials at Weill-Cornell Medical School. The Vector Group, which is the corporate parent of Liggett & Myers, announced in 2000 that it was giving several million dollars to the foundation.

“You have to ask yourself the question, ‘Why did the tobacco company want to support her research?’ ” Jerome Kassirer, author of "On The Take" told the Times. “They want to show that lung cancer is not so bad as everybody thinks because screening can save people; and that’s outrageous.”

Near the end of the story, Times reporter Gardiner Harris interviewed Murray Kopelow, chief executive of the Accreditation Council for Continuing Medical Education (ACCME), who revealed that numerous doctors and institutions are setting up foundations to accept money from companies without having to disclose its source.

Physicians who read the original article in NEJM could obtain continuing medical education (CME) credit by answering a few questions online. The ACCME accredits CME providers like NEJM. ACCME rules state that all presenters must disclose financial conflicts of interest during a CME activity. It can revoke accreditation for failing to follow the rules. The NEJM, in a written response to the Cancer Letter and the Center for Science in the Public Interest, which filed an official complaint with ACCME, is claiming that Henschke's and Yankelevitz' patents on how to read CT scans to detect lung cancer were not relevant to the study that appeared in the journal in 2006. The Journal of the American Medical Association, in a corrected conflict-of-interest disclosure on another Henschke article posted earlier this week on the JAMA website, recognized that the patent was relevant.

I wonder if the NEJM editors will now say the same thing about the non-disclosure disclosure in the study that showed it had been supported by the Foundation for Lung Cancer: Early Detection, Prevention and Treatment, but gave no indication as to who stood behind that big tobacco front group.

When Registering Trials Is No Help

The science journals jumped all over the "hidden data from clinical trials" issue this week with editorials or commentaries in the British Medical Journal, Nature, and Science. The trigger was a meta-analysis published in PLoS Medicine suggesting antidepressants in most cases are not much better than placebo.

The authors had to use the Freedom of Information Act to get results of trials they needed to conclude the analysis, and even then were denied crucial studies. The subheads said it all: "Highlights the ongoing problem of how study results may be distorted by failure to make data fully available"; and "Highlights the need for data to be transparent -- and for a mandatory database of all clinical trials."

Congress just passed a law requiring mandatory registration of all clinical trials and the posting of results. But it falls far short of what is necessary. It is not going to solve problems caused by the fact that industry still funds 70 percent of all trials. They get to decide what gets studied and how it gets studied because they foot the bill.

As Science pointed out is its inimitably circumspect way, the new law raises "further issues" that "require examination."

For instance, does the new law protect against a clinical trial not having an appropriate comparator drug instead of just placebo or an inappropriate comparator drug (like a low-dose of a less effective medicine that will no doubt make your newer drug look powerful, indeed)? No, it doesn't.

Does the new law protect against data fraud, like what happened in the Ketek case? No it doesn't.

Does it protect against insufficient informed consent for patients, especially in Phase I clinical trials? No it doesn't. Remember what happened in Great Britain when they tried a brand new biologic for the first time in humans in eight patients simultaneously and wound up killing one and almost killing the rest? Moreover, by not requiring registration of those Phase I safety trials and publishing results, the new law does nothing to warn other companies off dangerous classes of drugs, or unproductive pathways for their increasingly unproductive research-and-development labs.

But the reality is that the anger being expressed now about failure to disclose data in clinical trials should largely become a thing of the past if, and this is the big if, the Food and Drug Administration writes good rules and properly polices the new law. Let's hope that the medical journals and their news sections follow implementation of the new law as closely as they are following the old stories that resulted from the lack of proper registration and posting of results.

Rx Cos. and the Medical Journals

With the FDA considering a proposal to give drug company salespersons the right to distribute journal articles touting the off-label use of prescription drugs, I was motivated this week to reread this small masterpiece by Richard Smith, the former editor of the British Medical Journal. It's title: "Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies."

But don't take the word of a former medical editor. Industry has long seen their approach to science as an extension of their marketing apparatus, and the latest confirmation of that comes from a new survey done by an industry consulting firm. According to Best Practices LLC, most of the country’s leading pharmaceutical companies see publishing clinical trials results as a marketing tool as well as a method of disseminating scientific information.

The report, “Scientific Publications Strategy: Managing Reputation, Clinical Trial Results, and Commercial Relevance,” surveyed scientific directors at 14 leading pharmaceutical companies including GlaxoSmithKline, Pfizer, Bristol-Myers Squibb, Abbott Laboratories, Amgen, Merck, Genentech and Eli Lilly. Eight of the firms included regional or national marketing managers on teams planning their publications strategy. “Scientific publications are an essential tool for both clinical and commercial purposes, as they are intended to influence the target audience by raising both awareness of the disease and awareness of a company’s product,” the report stated.

Portions of this story first appeared in Integrity in Science Watch, published online by the Center for Science in the Public Interest.

Judah Folkman

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

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

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

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

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

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

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

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

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

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

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

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

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

Physician Ethics, Actions at Odds

The following is from Integrity in Science Watch, which is published by the Center for Science in the Public Interest.

A nationwide survey of more than 1600 practicing physicians found a sharp divergence between the ethics of the profession and actual medical practice. Well over 90 percent of doctors agreed they should report significant medical errors, turn in impaired or incompetent colleagues, and put patients’ welfare above their own financial interests. But the anonymous survey, which was released last week, revealed that 46 percent of physicians with knowledge of serious medical errors (about 40 percent of survey respondents) failed to report colleagues’ errors at least once. A similar 45 percent of physicians who knew about an impaired or incompetent colleague failed to report it to the hospital or clinic where they worked, or to other relevant authorities. And a large majority of physicians when queried said they would refer patients to imaging facilities in which they were part-owners, with one in four reporting they would not disclose that fact to their patients. “Such behavior could be illegal under federal Medicare statutes concerning self-referral,” noted the report, which appeared in the Annals of Internal Medicine. “This suggests that physicians may not be adequately aware of the legal restrictions on their behavior.” The study was sponsored by Columbia University’s Institute for Medicine as a Profession, which receives major funding from the George Soros-funded Open Society Institute and the Pew Charitable Trusts.

Study Finds Systemic Bias in Meta-Analyses by Conflicted Docs

A new study in the latest British Medical Journal shows that conclusions of meta-analyses conducted by researchers with ties to industry are frequently at odds with the underlying data. After reanalyzing the results of 124 studies that pooled data on various antihypertensive drugs, the researchers found that 45 of 49 or 92 percent of meta-analyses conducted by researchers with financial ties to a single drug company came up with positive findings about that company’s drugs. However, the underlying data included in the meta-analyses justified that conclusion in just 27 of the 49 or 55 percent of the studies. On the other hand, when non-profit researchers conducted the meta-analyses, either alone or in tandem with researchers with ties to the drug industry, 27 out of 27 conclusions matched the underlying studies. “Meta-analyses, as with other study types, are open to the influence of systematic bias,” concluded Veronica Yank of Stanford, and Drummond Rennie and Lisa Bero of the University of California, San Francisco. “Our study also exposes a failure of peer review.”

Independent Researchers Blast NTP Report on Bisphenol-A

The final bisphenol-A report issued late last month by the National Toxicology Program (NTP) relied on industry-funded assertions that the chemical is harmless, the Milwaukee Journal Sentinel reported. The NTP's expert panel reviewed a literature summary prepared by Sciences International, an industry-funded consulting firm subsequently removed from the process because the firm had worked for companies that manufacture BPA. According to the Journal Sentinel, scientists who follow the issue closely claim the final report still relied far more heavily on industry-funded studies than on studies conducted by university and government researchers. “There was clear evidence of bias” in this process, said Gail S. Prins of the University of Illinois at Chicago, whose work was cited in the final report. “They should have started all over.” The final report concluded BPA may be of some concern to small children and fetuses, but poses little risk to adults.

FDA Needs More Resources, Better Science

The Food and Drug Administration’s science advisory panel, which is headed by a prominent industry scientist, concluded the agency is woefully underfunded and lacks the capacity to keep up with the latest science. The panel, chaired by Gail Cassell of Eli Lilly & Co., said the agency must beef up its capacity to monitor the safety of the nation’s food supply; develop a program for managing the latest scientific advances in drug development; implement last year’s Institute of Medicine recommendations on drug safety surveillance; and empower scientists at the agency by appointing a top science officer for every division, and a chief scientist for the entire agency. The report called for increasing FDA spending by $1 billion a year by 2013, including an additional $350 million for food safety, $300 million for information technology, and $350 million for drug safety.

Judge: FWS Must Reconsider Sage Grouse Decision

The Fish and Wildlife Service ignored the advice of scientists when it declined to list the greater sage grouse under the Endangered Species Act, a federal judge ruled last week. The ruling by U.S. District Judge B. Lynn Winmill of Idaho found the agency excluded scientific experts from its decision not to list the species and failed to document experts’ opinions as required by the law, thus violating the ESA’s requirement that the “best science” be applied to listing decisions. The decision not to list the sage grouse was one of many agency decisions influenced by former Interior official Julie MacDonald, who resigned in May. The judge cited the Interior Department Inspector General report that found MacDonald, who had no biology background, had meddled extensively in the sage grouse decision. “MacDonald’s principal tactic is to steer the ‘best science’ to a pre-ordained outcome,” the ruling said.

They're Cloning Monkey Cells, But . . .

Setback for Stem Cell Hype in NJ

Today's frontpage news focuses attention on the latest advance in embryonic stem cell research: the successful development of cloned embryonic stem cells from monkeys. But is the bloom off the rose on these breathless takes on a technology that is still years away from usefulness in humans?

. . . Most analyses in the media assert that it was rejected for fiscal, not moral, reasons. Though the evidence remains inconclusive, if this is true, it is noteworthy.

Unlike those of California and Missouri, the New Jersey ballot question originated in the state Legislature and consequently mobilized less on-the-ground support. For example, the website of the state's Citizens Coalition for Cures barely mentions the ballot question.

Furthermore, the public debate - both pro and con - focused much more on the economics than in the previous debates. The state debt, which now stands at $33.5 billion, has been a top issue in recent years. Plus New Jersey is already in the stem cell business. The legislature has already allocated $150 million to construct stem cell research facilities, and allocated another $10 million for research grants.

What's more, New Jersey voters have been historically friendly to ballot initiatives. This one, and one other on the same ballot, became the first to fail in seventeen years. That other was an anti-tax measure, which also would have increased the public debt.

Finally, polls have indicated that state residents support a woman's right to terminate a pregnancy by a 2 to 1 margin. Thus, factors other than the moral status of the embryo must have greatly contributed to the 53% vote against Public Question 2.

Three years ago, in California, the economic cost of the $3 billion Proposition 71 was merely a minor part of the public debate, overshadowed by the promises from the state's top researchers of treatments and the now-prerequisite images of hopeful children in wheelchairs. Missouri's ballot initiative of last year didn't set aside any public funds; it merely enshrined the legality of the work in the state constitution. Despite the efforts of the advocates there to shift debate to purported economic benefits, the issue remained a moral one to most voters, particularly opponents. Missouri's Amendment 2 barely succeeded only after an enormously expensive campaign by its supporters. Also that year, congressional candidates who were vocally supportive of embryonic stem cell research did not fare particularly better than Democrats as a whole. Perhaps the sheen and hype of imminent cures is beginning to wear off of embryonic stem cell research.

EPA Shorts Public on Disclosure

What is an acceptable level for clean air, clean water or toxic cleanups, which are required by the nation's environmental laws? To make those determinations, the Environmental Protection Agency must first determine what level of pollution harms public health, and then make a policy decision as to what level of protection is technically feasible. In theory, the cost of protection isn't supposed to enter into the equation, although as a practical matter it always does.

Weighing the science is key as researchers learn new facts about the relationship between various pollutants and disease. With the nation's children in the grip of a growing asthma epidemic, it should come as no surprise that researchers are finding new evidence that air pollution is a major culprit.

Last week, the EPA announced the candidates for a new outside advisory panel to help the agency sift through this evolving scientific landscape. This subcommittee of the Clean Air Scientific Advisory Committee will make recommendations as to what level of particulate matter -- fine particles of soot -- is acceptable. The EPA has a fairly open process for setting up its advisory committees. It first invites the public to submit nominations. It then publishes a "short list" of candidates and invites public comment on their credentials. And, finally, it publishes its final roster before it gets down to work.

Sounds fair, right? But what good is a transparent process if the information the EPA discloses to the public about the nominees falls short of full disclosure? How can the public, which includes the interested community of fellow scientists, environmental activists and affected industries, comment intelligently on a list of candidates that does not include key elements of their biographies?

For instance, the EPA's short list for the particulate matter panel contained 55 experts, most with sterling biographies outlining long lists of published studies for various government agencies and non-profit institutes. Take Robert Phalen, the University of California at Irvine Professor of Community and Environmental Medicine, for instance. He's conducted research in the field for over 30 years, we're assured. He's received grants from various government agencies and foundations.

What we're not told is that he has also written a book questioning the link between particulate air pollution and adverse health effects and arguing that tighter air pollution standards are premature. His short bio also ignores the fact, disclosed in that book, that he received research funding from the Southern California Edison Company and the Electric Power Research Institute (EPRI), the research arm of the utility industry.

Another example: the short biographical sketch about Peter Valberg mentions that he is an employee of Gradient Corporation, a private consulting firm. But it doesn't disclose that his clients include Carbon Black Manufacturers and an undisclosed mining company, and that he has penned critiques of EPA findings on health risks of air pollution for the Engine Manufacturers Association.

These are flagrant conflicts of interests that, by law, should exclude them from participating on this advisory panel. No doubt environmental groups will criticize these and many other scientists on the short list during the public comment period. But without publishing the full bios of its proposed candidates, the EPA has denied the public what it needs to make informed comment. In this case, partial disclosure is worse than no disclosure at all.

Integrity in Science Watch -- June 18, 2007

Here's the latest Integrity in Science Watch from the Center for Science in the Public Interest:

Cell Phone Firms Exert Hidden Controls in NAS Deal

According to National Academy of Sciences regulations, no more than 49 percent of the money for any study conducted by the quasi-governmental agency can come from private industry. Yet a new NAS panel that will set the research agenda for measuring cell phone health risks (see last week’s Integrity in Science Watch) derives all of its funding from the Cellular Telephone Industry Association (CTIA), the industry trade group. The industry cash was funneled through a 1999 Cooperative Research and Development Agreement between the Food and Drug Administration and CTIA.

The agreement states that the FDA's Center for Devices and Radiological Health (CDRH) will recommend what research will be conducted under the agreement and review the results, but “the CTIA will administer research conducted by third parties.” “Both groups – CTIA and FDA – are engaged in research guidance. Both groups have an input into research goals and responsibilities," said Michelle Chenault, an associate director of the FDA’s CDRH. Responded NAS Executive Director E. William Colglazier: “Our contract is with FDA, and we consider the government to be the sole sponsor and funder of the study.”

Another recent example of industry attaching strings when it underwrites government research involves the Environmental Protection Agency, which has launched the first nationwide study of air quality effects from large-scale animal feeding operations. The study is being financed by livestock producers. The study will measure levels of particulate matter, hydrogen sulfide, volatile organic compounds and ammonia emitted from livestock facilities, which will allow the EPA to determine if they comply with the Clean Air Act. One provision of the agreement exempts feedlots from prosecution for Clean Air Act violations during the study period.

Owl Scientists Cry Foul over Habitat Protection Revamp

Endangered-species experts in the academic community have accused former industry lobbyists now in key positions at the Agriculture and Interior departments of misrepresenting their work in order to override agency scientists and weaken a proposed spotted owl habitat protection plan, which is now open for public comment. The so-called “Washington Oversight Committee,” which includes undersecretary of Agriculture Mark Rey, a former timber industry lobbyist, and deputy secretary of the Interior Lynn Scarlett, the former chief executive of the Reason Foundation, which receives substantial funding from the American Forest and Paper Association, cited several recent studies in quashing the original plan offered by the Fish and Wildlife Service (FWS), which proposed stronger protections for old growth forests.

“The authors of the studies specifically cautioned against using the results to guide forest management actions for spotted owls," said Dominick Dellasala, a scientist involved in drafting the original FWS plan. The studies showed that spotted owls appeared to be thriving in parts of their range outside old growth forests. The former lobbyists seized on that finding to craft a proposal that gives local Forest Service and Bureau of Land Management (BLM) officials greater leeway to determine which owl-dwelling forest lands need protection.

Meanwhile, the tide appears to be turning against government appointees who manipulate science. A federal judge in Idaho has struck down new cattle industry grazing regulations because the BLM ignored agency scientists. The BLM’s rules, proposed by the livestock industry and issued in 2005, loosened restrictions on grazing on 160 million acres of public lands throughout the western U.S. Judge B. Lynn Winmill said the rules violated federal environmental laws and failed to heed warnings from government scientists that the changes could have “significant and long-term adverse effects on wildlife resources and biological diversity in general.” In a similar vein, federal district Judge John C. Coughenour in Washington has thrown out a policy that weakened Endangered Species Act protections for wild salmon by equating hatchery fish with wild fish.

Conflict of Interest Charges Roil Cochrane Collaboration

Officials at the voluntary Cochrane Collaboration have launched an investigation into charges that the author of a controversial guideline challenging the routine use of anticoagulants to treat blood clots that peer reviewers substantially changed his conclusions. David Cundiff, a Los Angeles-based physician and lead author of the guideline, in an article that appeared on Medscape last week, also claimed that four of the seven peer reviewers had conflicts of interest. The review is posted on the Cochrane website and backs continued use of the drugs. In his Medscape commentary, Cundiff claimed there is no evidence supporting the use of warfarin, heparin, and other anticoagulants, which has been standard medical practice for lung and leg blood clots since the 1940s. He also says that epidemiological evidence suggests they cause internal bleeding that leads to unnecessary deaths.

The Cochrane Collaboration, founded in 1993 to promote evidence-based medicine, now has a strict policy forbidding conflicts of interest for its authors, editors, and peer reviewers. But at the time the review was commissioned, the voluntary organization had no policy, according to Gerald Fowkes, a professor of epidemiology at the University of Edinborough and head of the group that approved the guideline. An independent check by the Center for Science in the Public Interest confirmed that at least three of the peer reviewers – Martin H. Prins of the Netherlands, David Bergqvist and William Hiatt the University of Colorado – have recent ties to drug makers. Though Cundiff has no ties to industry, he reported to Cochrane’s editors that his research interest in anticoagulants resulted from a malpractice case involving a patient’s death after he failed to prescribe anticoagulants. The case eventually resulted in his losing his medical license.

Polluters Cite Oil Industry-Funded Scientist to Cloud Ozone Picture

Permissible levels of smog-producing ozone should be lowered, an Environmental Protection Agency science panel unanimously agreed in March. But in a series of closed door meetings this month at the White House’s Office of Management and Budget, the first of which excluded the EPA, industry lobbyists claimed the science is still in doubt. According to Inside EPA, the lobbyists cited the work of William Adams, a retired professor of exercise science at the University of California-Davis, who claims the EPA proposal to lower the permissible ozone level misinterpreted his findings that lung capacity improves at the lower levels. Adams’ research was supported in part by an unrestricted grant from the American Petroleum Institute. A final standard will be issued next year.

Cheers and Jeers

• Cheer: To psychiatrist Daniel Carlat, who, in an op-ed in the New York Times, called for revoking the accreditation of continuing medical education courses sponsored by commercial interests. Over half of all CME courses are now paid for by the drug industry.
• Jeer: To psychiatrist Daniel Carlat, who failed to disclose in his op-ed that he could personally benefit from the change. His newsletter, the $109-per-year Carlat Psychiatry Report, offers “up to 12 hours per year of Category One CME credit” for passing the CME post-test contained in each monthly issue. The newsletter takes no money from the pharmaceutical industry.

ExxonMobil Lobbyist: "I Had the Authority"

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

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

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

Researching Our Way to Prosperity

New York looks to become the next state to jump on the stem cell bandwagon, with newly-installed Gov. Eliot Spitzer (D) promising to put a $2 billion bond issue on the ballot. The investment "will pay for itself many times over in increased jobs, economic activity, and improved health," he said during his inaugural address.

Those of us who raise a cocked eyebrow over out-of-control health care spending need to speak out about this new state arms race (California, Connecticut, New Jersey, Ohio, Florida -- the number of states lavishing direct and indirect taxpayer subsidies on this one area of medical research is growing faster than a bacteria on a petri dish).

Stem cell research is promising, and it shouldn't be impeded by a bunch of anti-science right-to-lifers with God and the president on their side. But like any strain of research, the likelihood of a major medical breakthrough coming from stem cells is probably not that much greater than gene therapy, the human genome project, the war on cancer or any of the multi-billion-dollar medical research programs that came before it. A lot of knowledge and a few good things will come out of stem cell research, but will it make those with severed spines stand up and walk? Call me irreligious, but I'm skeptical.

How about jobs and economic development? Well, the venture capital cycle in biotech is about as boom and bust as they come. Not for nothing is biotech called the rich man's lottery. The angels and funds pour in lots of money to lots of start-ups, hoping one of them will pay off. Today, we're at the top of a business cycle when there is plenty of money to pour into fruitless ventures. But how much will there be when unemployment is higher and the dreamers behind a few stem cell business plans come up empty?

Of course, there will be some new jobs created for university researchers, their underpaid foreign graduate students, and the white coat crowd in the biotech industrial parks subsidized by the taxpayers. But is this really the best use of government subsidies, especially at a time when the health care sector -- 16 percent of GDP and still growing -- is sapping the vitality of the rest of the economy? Has anyone given any thought to how much some of these breakthrough stem cell technologies might cost, and how the rest of the economy might pay for them?

Progressive thinkers like former Labor Secretary Robert Reich and Robert Kuttner of the American Prospect magazine have long provided the intellectual rationale for strategic government investments to spur economic development. But as Democrats once again get their hands on a few levers of power, we should probably have a public debate about what would best serve the overall economy NOW.

Can you say alternative energy and mass transit? That also would create high tech jobs, and it would help the rest of the economy, not tax it. Just because the religious right is against it doesn't mean we should write the stem cell researchers a blank check.

EPA Names Exxon Scientist to Panel

and other outrages from Integrity in Science Watch, a Center for Science in the Public Interest newsletter:

The Environmental Protection Agency has placed ExxonMobil scientist Robert Schnatter and two industry consultants on the 16-member panel that will review the agency's risk assessment for ethylene oxide, despite protests from the Natural Resources Defense Council, the Center for Science in the Public Interest, and other health and environmental advocacy groups. EPA's draft risk assessment recommends reclassifying ethylene oxide to "carcinogenic to humans" from a "probable human carcinogen. "It also proposes tighter restrictions on the chemical, which is used to make antifreeze and polyester and is emitted in vehicle exhaust. The risk assessment review panel, whose deliberations could affect future air pollution and occupational safety and health regulations, meets Jan. 18-19, 2007.

In addition to Schnatter's employment in the oil industry, James Klaunig of the Indiana University School of Medicine and James Swenberg of the University of North Carolina at Chapel Hill have financial ties to companies or industry groups that have a stake in the outcome of the ethylene oxide reassessment. Klaunig has received research support from ethylene oxide manufacturer DowAgro and the American Chemistry Council, and Swenberg has received funding from the Chemical Manufacturers Association and the International Institute of Synthetic Rubber Producers.

USDA's Committee on Grain Skirts Law

Despite a 2004 Government Accountability Office study calling for reform, the Agriculture Department continues to ignore the Federal Advisory Committee Act (FACA) when staffing its outside advisory panels. The Grain Inspection Advisory Committee includes numerous industry stakeholders who vote on scientific and technical issues such as the best way to measure the nutrient content of grain. For instance, a scientist with ties to Monsanto, which manufactures a test for measuring the linolenic acid content in soybean oils, sits on the committee as an industry "representative" and earlier this year voted on the test's scientific validity. The representative designation allowed the USDA to skirt FACA's conflict-of-interest and bias rules. In a letter sent today to the Grain Inspection, Packers and Stockyards Administration (GIPSA), the Center for Science in the Public Interest called on USDA to establish an independent committee made up of scientists without ties to the regulated industry. CSPI also called on USDA to appoint a designated ethics officer to monitor the agency's compliance with FACA. GIPSA's Grain Inspection Service establishes standards for grain and related agricultural products.

Tougher CMS Policy on Clinical Trials Urged

The Center for Science in the Public Interest last week asked the Center for Medicare and Medicaid Services to strengthen its registration and conflict-of-interest disclosure requirements for clinical trials that are used to justify payment for the off-label use of anticancer drugs. Physicians and their patients can be reimbursed for a non-Food and Drug Administration approved use of a chemotherapy drug as long as a study suggesting the use is effective has appeared in a peer-reviewed journal that lacks publication bias and has a conflict-of-interest disclosure policy.

CMS currently lists 15 journals as acceptable outlets for those studies. It is considering adding eight more. But a CSPI Integrity in Science survey found that none of the eight proposed additions requires clinical trial registration prior to publication, which helps eliminate publication bias; and three of the eight do not automatically publish conflict-of-interest disclosure statements. Several of the 15 journals already in use by CMS have similar gaps in their policies. CSPI asked CMS to strengthen its guidelines by prohibiting payment for the off-label use of a drug if the prescription is based on a trial that had not been registered prior to enrolling patients. It also asked CMS to require all journals to publish conflict-of-interest disclosures if necessary, and require authors to declare the presence of such statements in the abstracts that are submitted to the National Library of Medicine's PubMed.

FDA Warns Against Using Guidelines Backed by National Kidney Foundation

The New England Journal of Medicine last week published a Johnson & Johnson-funded clinical trial showing that patients with failing kidneys who were given high doses of Amgen's anti-anemia drug Epogen suffered 34 percent more heart attacks and strokes than patients given lower doses nearer to the FDA-approved standard. A comment that appeared in the Lancet online pointed out that the higher dose achieved in the study was within guidelines recently issued by the National Kidney Foundation, which received 57 percent of its $19.7 million budget in 2005 from corporate and organizational partners, including $4.1 million from Amgen and $3.6 million from J&J. Amgen and J&J compete with variants of Epogen sold as Aranesp and Procrit, respectively, in the oncology market. The Food and Drug Administration late last week warned physicians not to exceed agency-approved prescribing levels for Epogen, Aranesp and Procrit.

Climate Skeptic Misleads Viewers About Funding

Global warming skeptic S. Fred Singer denied that he has received substantial funding from the oil industry, despite evidence of his long-standing ties to energy companies. In an interview during the Canadian documentary program "The Fifth Estate," Singer claimed he didn't remember whether the oil industry had given him money. "I don’t think so," he said. When reporter Bob McKeown pressed Singer further, relying on ExxonMobil documents showing the company gave $10,000 to Singer’s Science and Environmental Policy Project (SEPP) and $65,000 to a foundation located at the same address as Singer's office for a climate change conference featuring Singer, he admitted receiving a one-time donation of $10,000 that "came in over the transom." Singer gave similar answers during an interview on E&ETV's "OnPoint" interview program, which also aired last week. In a telephone interview with the Center for Science in the Public Interest, Singer said he only remembered receiving one check from ExxonMobil "10 or 12 years ago" for $10,000.

Yet, the Science and Environmental Policy Project, which Singer founded and leads, has received at least two $10,000 grants from ExxonMobil, in 1998 and 2000. In a 1993 sworn affidavit, Singer also admitted to receiving consulting fees from the Global Climate Coalition – a now defunct group of businesses including Exxon, Shell, Texaco and BP that opposed implementing mandatory greenhouse gas emission reductions -- and doing climate change research on behalf of oil companies. SEPP's website claims it does not solicit support from government or industry and that it receives contributions from charitable foundations and individuals. The project's most recent tax filings show the organization received $102,260 in contributions and $14,700 for lecture fees last year. (Singer has also served as a fellow or adviser for several organizations that receive funding from ExxonMobil, including the Advancement of Sound Science Coalition, American Council on Science and Health, Cato Institute, Frontiers of Freedom and Heritage Foundation.)

A Patent Worth This Much Is Worth Disclosing

This story comes from the latest Integrity in Science Watch, which I edit:

It was the science story of the week. Cartoonists had a field day. A compound in red wine called resveratrol keeps fattened mice healthy, and they live longer, too. Now that was something that the researchers could grab onto and rush, not into print, but first to the patent house. As stories in the New York Times, Wall Street Journal, and Washington Post pointed out, Harvard researcher David Sinclair has developed chemical derivatives of resveratrol and started a company called Sirtris Pharmaceuticals to commercialize their use for glucose control in diabetics. Sinclair applied for a patent on the resveratrol-like substances in May of this year. However, the subsequent science article by Sinclair and colleagues, which didn't appear in Nature until last week (and triggered the media onslaught), did not reveal that fact, nor his relationship to Sirtris.

Nature also ran a cheeky essay entitled "Grapes versus gluttony" that was co-authored by University of Washington scientist Matt Kaeberlein. For the record, neither Nature nor New York Times reporter Nicholas Wade, who quoted Kaeberlein to throw some cold water on the idea that resveratrol itself is the best way to get the desired results, revealed that Kaeberlein has applied for a patent on his own version of a resveratrol-like substance. The other major player in the news accounts was Leonard Guarente of the Massachusetts Institute of Technology, who discovered the gene that produces the protein that triggers the desired responses in yeast. Only the Wall Street Journal reported that he is a co-founder of Elixir Pharmaceuticals, "a biotech company that competes with Sirtris." Guarante has several patents on the gene and its use. His latest patent application filed last year is entitled simply, "Method of Extending Life Span." None of the pending patents, all of which are products of government-funded research, were revealed in the news accounts.

Meanwhile, the Journal of Medical Ethics, last week published a study by the advocacy group GeneWatch UK that analyzed Nature's patent disclosures in a sampling of articles published over a six-month period last year. Two-thirds of the articles did not disclose that their authors had either outstanding patents or connections to the biotech industry. The study called for journals to impose sanctions on authors who fail to disclose conflicts of interest and suggested "universities and institutes establish a public register of scientists' interests."

Integrity in Science Watch

The latest from the Integrity in Science project at the Center for Science in the Public Interest:

Industry-Backed Skeptics File Brief in Global Warming Lawsuit . . .

Eight global warming skeptics, many with well-established ties to the fossil-fuel industry, last week filed a Supreme Court amicus brief in support of the Environmental Protection Agency's 2003 decision against regulating carbon dioxide emissions under the Clean Air Act. The Competitive Enterprise Institute-sponsored brief argued that "it is simply impossible to conclude that the net effect of greenhouse gases is an endangerment of health and welfare." A coalition of 12 states and nonprofit organizations have filed a lawsuit challenging the EPA's decision. After the U.S. Appeals Court in Washington, D.C., last year sided with the federal government, the Supreme Court agreed to hear the plaintiffs' appeal. Oral arguments are scheduled for Nov. 29.

The climate-change skeptics who filed last week's brief include

· astrophysicist Sallie Baliunas, who has received funding from the American Petroleum Institute and serves as a senior scientist with the George C. Marshall Institute, which has received $630,000 from ExxonMobil since 1998;
· University of Delaware climatologist David Legates, who has written reports and served as an adjunct scholar for the National Center for Policy Analysis, an organization that has received funding from ExxonMobil, DaimlerChrysler Corp. and the El Paso Energy Foundation;
· Patrick Michaels, a senior fellow at the Cato Institute and a recipient of funding from the German Coal Mining Association, Edison Electric Institute, Cyprus Minerals Co., Western Fuels Association and Intermountain Rural Electric Association; and
· Joel Schwartz, a visiting fellow at the American Enterprise Institute, which has received more than $1.6 million from ExxonMobil since 1998.

Three of the four other signers of the brief have frequently contributed to publications of CEI, George C. Marshall Institute and other Exxon-funded organizations that downplay the risks from global warming.

Meanwhile, two senators asked ExxonMobil last week to stop funding global warming skeptics, ABC News reported. Sens. Olympia Snowe (R-Maine) and Jay Rockefeller (D-W.Va.) wrote ExxonMobil chairman and CEO Rex Tillerson with a request to "end any further financial assistance" to groups "whose public advocacy has contributed to the small but unfortunately effective climate change denial myth."

. . . While AP Fails to Disclose Climate Skeptics' Ties to Industry-Funded Think Tanks

The Associated Press ran a story that appeared in the Indianapolis Star and several other papers last week that cited global warming skeptic John Christy but failed to mention his long involvement with conservative think-tanks supported by money from the energy industry. In an article about the development of global warming "hot spots," AP cited Christy's belief that concerns about an increase in heat-wave related deaths due to climate change were without foundation. The widely used wire service identified Christy only as an atmosphere sciences professor at the University of Alabama at Huntsville, but did not note his frequent appearances and published work for the George C. Marshall Institute, Competitive Enterprise Institute and Independent Institute - conservative think tanks that receive funding from ExxonMobil and other energy companies.

Meanwhile, an AP story in the Washington Post earlier this month quoted global warming skeptic Patrick Michaels without noting his ties to the fossil-fuel industry. In a feature story showing how local communities are enacting their own versions of the Kyoto protocol, the AP allowed Michaels to dismiss the significance of those moves without reporting that, as a previous AP report noted last July, Michaels recently received "at least $150,000 in donations and pledges" from Colorado-based electric utilities, including the Intermountain Rural Electric Association.

Astroturf Patient Groups Exposed: Major Funding Comes from Rx Industry

Pharmaceutical companies provide a significant share of financial support for many of the patient groups that advocate for people with conditions requiring long-term treatment, an investigative report by the New Scientistfound. An investigation into a random sampling of 25 groups revealed that seven received 20 percent or more of their funding from drug and device companies. The Colorectal Cancer Coalition, founded in 2004, topped the list with 80 percent of its funding coming from the drug and device industry. The Restless Legs Syndrome (RLS) Foundation received a substantial amount of money from two major drug makers with products directly related to the syndrome: GlaxoSmithKline, which makes the RLS drug Requip, and Boehringer Ingelheim, whose RLS drug is pending approval, have collectively contributed more than $628,000 to the foundation, almost half of its total revenue.

FDA's Orphan Drugs Czar to Join Amgen

Marlene Haffner, the long-time head of the Food and Drug Administration's orphan products office, has retired from the agency after 35 years to take a job with Amgen, the nation's biggest biotech firm. Amgen was one of the first companies to take advantage of the seven years of market exclusivity granted under the Orphan Drug Act, which is given to firms that are first to market a drug for treating conditions with fewer than 200,000 patients. Amgen's Epogen, now taken by more than 300,000 Medicare-reimbursed dialysis patients, racked up $2.5 billion in sales last year. When she joins Amgen on Jan. 1, Haffner's new title will be Executive Director of Regulatory Affairs for Global Government Affairs. Three years ago, FDA whistleblower Robert F. Steeves accused Haffner of taking numerous wasteful and fraudulent overseas trips at government expense. In a suit filed in a Virginia federal district court, Steeves, now a private consultant, accused Haffner of making false charges and improperly suspending him from the agency after he made those allegations, which have never been investigated by FDA's top management, according to FDAWebview (subscription required). On the other hand, Abbey Meyers, president of the National Organization of Rare Diseases, praised Haffner's tenure at FDA, but expressed "surprise that she's going somewhere where they don't really focus on orphan drugs."

NAS: Conviction No Bar for Former FDA Head

Lester Crawford, the former head of the Food and Drug Administration who pleaded guilty two weeks ago to hiding conflicts of interest, has been named by the National Academy of Sciences to the new Army Science and Technology board that is charged with reviewing hygiene standards at a U.S. Army chemical disposal facility in Utah. Margaret Novack, the NAS official in charge of the committee, defended the choice by saying the board will be "looking at military chemical policy, which is a far cry from the type of things he was previously involved with."

Fired Scientist Accuses USGS of Blocking Study, Seeks Data

A scientist who claims he was fired by the U.S. Geological Survey after refusing to alter his findings on the effects of chemicals in the water supply has filed a federal lawsuit seeking access to his data and the right to talk to government colleagues who collaborated in the studies. Tim Gross' suit alleges that the USGS wrongfully fired him last January by claiming his ongoing affiliation with the University of Florida was a conflict of interest, even though USGS knew about his university ties when it first hired him in 1998. In an interview Gross said that he wants to publish the results of two government-funded studies: one conducted primarily while he was working solely for the University of Florida that found wastewater chemicals were affecting fish populations nationwide; and another USGS-sponsored study suggesting pollution in southern Nevada’s Lake Mead is having a greater effect on its fish than previously believed. However, the agency confiscated his data and forbade other USGS scientists from talking to him, which, Gross claims, makes it impossible for him to publish his interpretation of the data. The USGS, which has assigned a new team of researchers to the Lake Mead study, did not return phone calls seeking comment.

Internal Survey: Mixed Attitude Toward New NIH Ethics Rule

Almost 40 percent of 512 tenured and tenured-track research scientists at the National Institutes of Health said they are actively looking for other work or are considering doing so because of new conflict of interest rules, according to an Associated Press story in the Washington Post. However, just 18 percent of 3,336 NIH scientists surveyed stated that they are active looking for or would consider other employment. Nearly nine in 10 scientists reported they intend to work at NIH a year from now and the scientists reported a job satisfaction rate of 81 percent, one of the highest in government. There was no comparison to employee attitudes prior to the new rules. NIH strengthened its ethics rules last year after learning that some senior scientists had formed lucrative consulting agreements with biotechnology and drug companies without agency permission.

Odds and Ends

An open letter in Science Magazinethis week calls on Libya to release the five Bulgarian nurses and one Palestinian doctor who are facing execution after the government of Moammar Kadafi convicted them of intentionally infecting 400 Libyan children with HIV. The six health care workers, who've been in jail for nearly eight years, were tortured to extract confessions and then sentenced to death by a firing squad. The "Plea for Justice for Jailed Medical Workers" is being coordinated by AIDS research pioneer Robert C. Gallo at the University of Maryland, who can be reached at gallo@umbi.umd.edu . . . Senior Bush appointee Julie MacDonald, deputy assistant secretary of the interior for fish and wildlife and parks, has ignored staff recommendations that at least six times in determining whether animal and plant species should be protected under the Endangered Species Act, documents obtained by the Washington Post show . . . The Environmental Protection Agency has closed its Office of Prevention, Pollution and Toxic Substances Library in Washington, D.C., which provided research services to EPA scientists who review industry requests for the introduction of new chemicals into the market, according to documents released today by Public Employees for Environmental Responsibility.

MEDLINE Mulls Outing Corporate-Backed Studies

The National Library of Medicine will consider a major revamp of its indexing policies in the wake of revelations that industry-sponsored supplements without full conflict-of-interest disclosures are slipping into MEDLINE, the government-funded database for health studies. The issue arose last week when Integrity in Science Watch revealed a recent supplement in the Journal of the American College of Nutrition was sponsored by the International Life Science Institute's Salt Committee, which is made up of major food corporations. Articles in the supplement did not list the corporate ties of their authors.

MEDLINE's existing policy states any supplement sponsored by "private, for-profit" organizations must contain disclosures before it is indexed. ILSI, though largely funded by industry, is a non-profit organization, thus allowing it to slip through the loophole. "We will review our policy and strongly consider changes that would require author disclosure for any supplement funded by an outside source in the future," NLM head indexer James Marcetich said. "It may not be practical in a large scale production operation like MEDLINE to investigate whether a sponsor represents non-profit, for-profit, or non-profit but funded by for-profit interests -- so it may be best to require disclosure for all outside sources."

For more from this week's Integrity in Science Watch, click on.

Harvard Prof Told FDA About Bayer's Hidden Study

It was Alexander Walker, a professor at Harvard University's School of Public Health, who first reported Bayer's failure to tell the Food and Drug Administration that an ongoing study showed serious safety concerns with its best-selling blood clotting drug, Trasylol, Bloomberg News reports. Walker was conducting the study for a private firm hired by Bayer. An FDA advisory committee met on September 21 to review evidence from two small trials that Trasylol, which is used to control bleeding during heart surgery, caused kidney failure, heart attacks and strokes. But the committee never heard about Walker's much larger, 67,000-patient study, which was first revealed to the FDA on September 29. Bayer conceded its failure to release the data in time for the advisory committee meeting was a mistake. Several advisory committee members told Bloomberg that the additional information would have convinced the committee to recommend that the FDA issue a stronger safety warning.

Scientists Protest as EPA Delays Dry Cleaning Rule

Environmental Protection Agency scientists are protesting demands by a senior political appointee at the agency for further tests on perchloroethylene, or perc, a widely used dry cleaning solvent, InsideEPA reports. The new in-house tests were requested by Office of Research and Development head George Gray, who previously ran the Harvard Center for Risk Assessment. He wants the tests completed before the assessment moves on to the National Academy of Sciences for review.

The NAS study itself is a product of industry delaying tactics. In June, the American Chemistry Council and Halogenated Solvents Industry Alliance met with the Office of Management and Budget to protest the pending perc regulation. The EPA subsequently threw the entire issue to the NAS for an independent review. At issue is the use of threshold levels for determining toxicity, with industry claiming that low levels of exposure do not cause harmful effects. EPA scientists say there is no scientific justification for using this theory in regulatory proceedings. "George Gray uses uncertainty to delay decision-making," said Judy Schreiber, with the Attorney General's Office of New York, who works with affected citizens who live above dry cleaning facilities in apartment buildings, "Its time the EPA sits down and makes a decision."

Scientists Resign from Unbalanced EPA Advisory Panel on Toxins

Three members of a federal science advisory panel on pollution prevention resigned last week, citing excessive industry influence over the board's agenda. Richard Denison, senior scientist for Environmental Defense, Joseph Guth, executive director of the California League for Environmental Enforcement Now, and Joel Tickner, assistant professor at the University of Massachusetts, resigned October 2 from the Environmental Protection Agency's National Pollution Prevention & Toxics Advisory Committee, which is charged with reviewing the agency's assessment and management of chemicals under the Toxic Substances Control Act. The three scientists said the seven industry representatives on the 15-member panel have limited its agenda to "narrow, short-term issues" that do not warrant the time or expense to EPA. The panel includes representatives from Dow, Procter & Gamble, the American Chemistry Council, and the American Petroleum Institute.

Integrity in Science Watch -- Oct. 2

Nutrition Journal Failed to Disclose Editor's and Authors' Ties to Salt Industry

The Journal of the American College of Nutrition's June supplement on sodium intake and human health failed to reveal that its editor and several authors had long-standing ties to the food industry. Then, in violation of the National Library of Medicine's rules, the editors allowed MEDLINE to index the supplement.

Guest editor Alexander G. Logan, a physician at Mt. Sinai Hospital in New York, is a consultant to the salt industry and scientific advisor to the International Life Sciences Institute's North American Technical Committee on Sodium, which sponsored the supplement. The committee's members include Frito Lay, Heinz Co., Kraft Foods, Inc., and Proctor & Gamble. The editors at JACN allowed ILSI to select Logan to edit the articles, which did not undergo the journal's peer review process.

Supplement authors included Suzanne Oparil, a paid consultant to the Salt Institute, and former editor of an American Journal of Clinical Nutrition supplement that included papers from a salt conference that was also sponsored by ILSI. A second author, Michael H. Alderman, is an unpaid consultant to the Salt Institute. His article concluded, "the available data provides no support for any universal recommendation of a particular level of dietary sodium." Robert P. Heaney, a paid consultant to the dairy industry, reviewed calcium and salt effects on bone density. None of those ties were revealed in the articles.

ILSI did not inform JACN's editors about Logan's ties to the salt industry, according to editor-in-chief John Cunningham, who sent a formal inquiry to Logan and ILSI after the Integrity in Science Project at the Center for Science in the Public Interest and other groups inquired about the lapses in the journal's normal conflict-of-interest disclosure rules. Cunningham also said he will investigate the authors' undisclosed conflicts of interest. In a letter to JACN, CSPI demanded that the next issue contain a formal apology to readers, full conflict-of-interest disclosure information for all authors and a prominent notice that the supplement did not undergo peer review. In a separate letter to the National Library of Medicine, CSPI requested that the abstracts be withdrawn from MEDLINE since the journal failed to follow NLM policy. The agency recently ruled that privately-sponsored journal supplements must contain conflict-of-interest disclosures for all authors and editors before they can be indexed in the government-funded database.

Risk Analysis To Carry Conflict-of-Interest Disclosures

The Society of Risk Analysis has agreed to start printing conflict-of-interest disclosures in articles published in its journal Risk Analysis. The new policy, announced in its fall newsletter, also prohibits officers and appointees of the Society from using their positions for financial gain or to give their industrial clients preferential treatment. The change in policy comes after documents unearthed from the Legacy Tobacco Documents Library at the University of California, San Francisco revealed that Risk Analysis' editor-in-chief, Elizabeth Anderson, who currently works as an industry consultant for Exponent Inc., offered to use her editorship to expedite publication of her own tobacco-industry funded study downplaying the risk of phosphine, which is used in rodenticides.

Affected companies, fearing tighter Environmental Protection Agency regulations, had formed the Phosphine Coalition to fund her study. "A scholarly paper prepared for publication and then submitted to the EPA as a pre-publication paper can be just as effective as a published paper," she noted in a memo to her new clients. "Since I am currently Editor-in-Chief of the international journal Risk Analysis, perhaps the peer review process could be expedited if we decide that it is the journal of choice." Risk Analysis eventually published the paper in October 2004. That paper did not disclose that two of her co-authors were employees of R.J. Reynolds Tobacco Co.

Coincidentally, in August of 2004, the Center for Science in the Public Interest asked the editors of Risk Analysis to adopt a conflict-of-interest disclosure policy. Managing editor Richard Reiss, who now is also employed as an industry consultant by Exponent, replied in an email that "Risk Analysis employs a double-blind review process to ensure that all papers are evaluated on their scientific merits alone. That is principally how we manage conflicts of interest."

Feds Restrict Report Showing Global Warming Increases Hurricane Strength

A federal agency blocked an internal National Oceanic and Atmospheric Administration report that concludes hurricanes are intensifying due to climate change, the journal Nature reported last week. The seven-member panel was created after NOAA scientists complained their views were being stifled. While NOAA and Department of Commerce officials deny suppressing this latest global warming report, lead author Ants Leetmaa was reported as saying he received an email in mid-May from an official telling him that the report would not be released because it was too technical.

EPA Clean Air Panel "Disappointed" with Administrator's Decision on Soot

The scientific advisory panel for the Environmental Protection Agency is up in arms after agency administrator Steven Johnson ignored the 22-member panel's near unanimous advice to strengthen regulations on soot. One published report last week quoted Johnson saying he had received advice from private sources, which caused him to override the recommendations of the official advisory committee. Rogene Henderson, chair of the Clean Air Scientific Advisory Committee, said that she is worried that their current report on ozone, due in October, will be rejected in the same manner. "The scientific advice he heard in private trumped the scientific advice he heard in public," she said. "[EPA] is paying for CASAC, and then just disregards" its advice.

Scientists Form Group to Back Pro-Science Candidates

A group of prominent scientists last week launched Scientists and Engineers for America to back politicians who support a scientists' bill of rights. They want to eliminate political manipulation from federal policymaking that is supposed to be based on science, and are demanding that the government never intentionally publish false information, as has happened on reproductive rights and global warming issues. The group leaders include John H. Gibbons and Neal Lane, former science advisers to the Clinton administration, Nobel laureates Peter Agre and Alfred Gilman, and Federation of American Scientists' president Henry Kelly.

Integrity in Science Watch -- the latest

This is a copy of the newsletter I publish weekly at the Center for Science in the Public Interest. If you'd like to get this emailed to you directly on Mondays, send a copy of your email address to science@cspinet.org.

New Study Confirms Butadiene Cancer Link, But Creates Loophole

A new study that will be released Tuesday by the Health Effects Institute (HEI), the Boston-based non-profit jointly funded by the automobile industry and the Environmental Protection Agency, confirms that 1,3 butadiene, a major air pollutant from automobiles and chemical plants, causes leukemia and other cancers, but only at high exposures. Leukemia mortality among rubber workers in the study was 170 to 270 percent higher than unexposed groups. However, the HEI researcher, Elizabeth Delzell of the University of Alabama, who has also received funding from the International Institute of Synthetic Rubber Producers and the American Chemistry Council, is about to publish a related study that will claim that the workers who got cancer were the ones who were occasionally exposed to especially high doses of butadiene. A number of industry consultants are co-authors of the paper. If accepted by regulators, this "peak exposure" theory could be interpreted to mean that butadiene is not as dangerous as previously thought. The peak exposure theory is based on sophisticated modeling that assigned exposure values to various jobs held by workers as long as 30 years ago. No measurements were ever taken.

The HEI synopsis of the report, which reflects the views of its peer reviewers, left the door open for accepting the "peak exposure" theory. While the synopsis does say that butadiene exposure estimates in the study "may be too high," and the cancer risks identified in the study "could actually be associated with lower measured concentrations of exposure," it goes on to say that if the forthcoming study from Delzell and the industry consultants "confirms that (exposure) estimates from the current investigation are accurate, this study will provide a firm basis" for assessing risk. That would eliminate the need for chemical plants to engage in further clean ups under the EPA's so-called residual risk rules; it also could affect future automobile emission rules. A residual risk rule now under consideration at the EPA has "do nothing" as one option for chemical plants that produce butadiene and routinely emit small amounts into the atmosphere.

Groups Protest Nomination of Industry Sympathizer to Top OMB Position

The Bush-appointed nominee to head the Office of Information and Regulatory Affairs, an arm of the Office of Management and Budget, has drawn sharp criticism from environmental and health advocacy groups. A report released last week by Public Citizen and OMB Watch said Susan Dudley's "ideological opposition to regulation, support for radical policies that would impair public safeguards and ties to industry" made her unfit to manage the highly influential regulations department, which has the power to weaken, delay, or eliminate public health measures. As past director of regulatory studies at the industry-funded Mercatus Center at George Mason University, Dudley opposed the EPA's attempts to strengthen policies regulating arsenic in drinking water and levels of smog. "Dudley is little more than an industry factotum," said Gary D. Bass, OMB Watch executive director. "Not since OIRA was created in 1980 has there been a less appropriate nominee."

FDA Finally Ousts Advisor Over Conflict of Interest, But Only After A Company Protests

The Food and Drug Administration booted a physician from its Anti-Infective Advisory Committee last week after receiving a complaint about his conflicts of interest from the company whose drug was about to come before the panel. Dr. Thomas Fleming, a long-time member of numerous FDA advisory panels, in 2002-3 reviewed studies on the antibiotic Factive for Oscient Pharmaceuticals' predecessor firm. He subsequently questioned the company's use of non-inferiority trials, which had been used in the initial approval of Factive. The company then protested his presence on a new committee looking into the company's request to expand the use of the drug, which also relied on a non-inferiority trial. The FDA denied him a conflict-of-interest waiver and he was not permitted to serve. (In a non-inferiority trial, the drug is compared to an already approved drug rather than a placebo. Since many antibiotics are only marginally better than placebo, critics - including several FDA examiners - believe that the statistical margins of error in antibiotic non-inferiority trials can lead to approving drugs that may not be effective.)

According to a report in the Wall Street Journal, FDA officials said their refusal to grant Fleming a waiver was unrelated to Oscient's complaint or his concerns about non-inferiority trials. The FDA let stand waivers granted to Peter Gross, a professor of medicine at the University of Medicine and Dentistry of New Jersey, and John Bradley of Children's Hospital in San Diego. Both waivers were for consulting with competitor firms. Fleming told the Journal that he is concerned that the integrity of the advisory committee process "would be significantly compromised if there is a possibility that a company could intervene in the committee-making process." The flap had no bearing on the ultimate vote, since the full panel voted 11-2 against Oscient's application to use Factive for sinusitis. The FDA usually follows the advice of its advisory committees.

NIH Passes Buck on Conflict-of-Interest Cases

The second-ranking official at the National Institutes of Health last week told a House subcommittee that only "minimal" disciplinary actions had been taken against employees who broke conflict of interest rules to consult with industry. The excuse? Technically, the high-ranking employees were members of the Public Health Service, a quasi-military corps within the Department of Health and Human Services. The "NIH concluded that the facts [warranted] referral to the corps, which has independent authority to determine the most appropriate level of discipline for its commissioned officers," said Raynard Kington, deputy director of NIH. He also revealed that Trey Sunderland, chief of the geriatric psychiatry branch at the National Institute of Mental Health, and Thomas J. Walsh, a top officer at the pediatric oncology unit of the National Cancer Institute, had not yet been punished for receiving hundreds of thousands of dollars as consultants for drug companies while on the government payroll. John Agwunobi, Assistant Secretary for Health for the Department of Health and Human Services for the Public Health Service, refused to discuss displinary cases that were still underway. The HHS Office of the Inspector General also came in for criticism during the hearing for failing to investigate conflicts of interest at NIH.

Harvard Prof Cleared of Ethics Violations Gave Major Gift to Dental School

It turns out that Dr. Chester Douglass, who last month was cleared of violating Harvard Medical School ethics rules after misrepresenting a graduate student's research linking water fluoridation to cancer in young boys, gave $1 million to the university in 2001 for its new $22 million dental research facility, which was completed in 2004, the Harvard Crimson reports. According to the Environmental Working Group, a number of Harvard alums involved in public health have asked interim president Derek Bok, who recently authored University in the Marketplace: the Commercialization of Higher Education,to release the details of its investigation into Douglass, who consults for Colgate-Palmolive Co. and edits its publication, "The Oral Care Report." A Harvard spokesman said the university has turned the results over to the federal Office of Research Integrity, which found no further cause to investigate.

That FDA Pledge

At a Center for Science in the Public Interest forum yesterday, Scott Gottlieb, the deputy commissioner of the Food and Drug Administration, promised to revamp the agency’s rules for granting conflict-of-interest waivers when physicians with ties to drug manufacturers sit on its advisory panels. I look forward to seeing the new guidance when it actually comes out. If I understood the intent correctly, the FDA will start excluding those docs who are actively engaged in marketing drugs and devices, but continue to put them on committees if their relationship with the companies was purely scientific – as in having done clinical trials.

The announcement drew major news coverage (see here and here, for instance). Since I have been a major proponent of a total ban on granting conflict-of-interest waivers to scientists who have ties to industry in any capacity, let me lay out once again why I think this proposed new rule doesn’t go far enough.

First, there are plenty of people out there who don’t have any financial ties to firms who can provide just as good advice as the FDA is currently getting from folks on industry’s payroll. There are 125 medical schools in the U.S. About a third of all clinical trials conducted in the U.S. are sponsored either by government – primarily through the National Institutes of Health – or health charities and non-profits. Those trials require all the same skils as industry-funded trials: physicians to enroll patients, biostatisticians, data safety monitoring boards, etc. Why can’t the FDA find experts from that crowd? Either they’re not trying or they don’t want to.

Why does it matter? Isn’t an industry-funded clinical trialist just as “objective” as someone who has not worked for industry? I think not. When one has been part of a study that comes up with a certain result, one becomes intellectually committed to that result. It is only natural to defend your previous conclusions, even when confronted with new evidence. Sometimes the new evidence becomes overwhelming and anyone who is intellectually honest eventually changes their mind, but letting go of previous conclusions takes time – it’s only human. Can that happen in the course of a one-day meeting at FDA where the clinical trial specialist is not only hearing contrary evidence but is hearing evidence presented by the company?

It’s the rare scientist who would arrive at anything other than their pre-conceived wisdom under that scenario. If these advisory committees are going to be real science courts that weigh the evidence, the FDA needs to appoint jurors who don’t have preconceived opinions about the new drug or device under consideration. Period.

That is the theory. Now to the practice. The New York Times Science section this morning has a pretty good
commentary analyzing the machinations of the hired brains behind the Cyberonics Vegus Nerve Stimulator for severe depression. Harold Sackeim, a professor of psychiatry and radiology at Columbia, told the paper that if device makers could not hire the field’s top experts, effective new devices would never be approved. “This is not like pharmaceuticals, where the companies are much bigger and have their own experts,” he said. But a few paragraphs down, we learn that:

Now the company has focused on promotion, as have some of its consultants. At an American Psychiatry Association meeting in May, Dr. (John) Rush sat in the Cyberonics booth, describing the benefits of the therapy to curious psychiatrists. In one of several presentations about the device, doctors reviewed its use for obesity, anxiety and Alzheimer’s disease, purposes for which it is not approved.

This isn’t science, it’s marketing. If the FDA does in fact come out with the new guidance promised yesterday, and it does in fact end forever the inclusion of such scientists on its advisory committees (whether their promotional activities take place for the company with a new drug up for approval or one of its competitors), then it will be a major improvement over the current rules and I’d applaud it. Hopefully, we’ll get to see the new rules sooner rather than later.

The Times on Our Conflicted Medical Journals

Last week, the Wall Street Journal's David Armstrong wrote several stories raking the Journal of the American Medical Association and Neuropsychopharmacology over the coals for failing to disclose to readers that their contributors had ties to drug manufacturers. The most notable part of the New York Times editorial today that played off that news was the paper's call for journals to "try much harder to find authors free of conflicts. That is the best hope for retaining credibility with doctors and the public." It took a few years, but even the Times now realizes that disclosure doesn't go far enough.

Journal Editor Again Misled

Catherine DeAngelis, the editor of the Journal of the American Medical Association, says that for the third time in as many months researchers have ignored JAMA's policy requiring disclosure of conflicts of interest in published articles. The excuse by the six physicians who studied the link between migraines and cardiovascular disease was that they didn't think their relationships with drug companies were relevant since the study didn't involve a test of any company's drug.

Some people just don't get it. The study authors, led by Dr. Tobias Kurth of Harvard, had relationships with numerous firms that sell drugs for treating migraines. Yet the authors, after being confronted by their failure to disclose those relationships, claimed those financial ties were not "relevant to our describing a biological link between migraine and cardiovascular disease."

DeAngelis snapped back: "Financial interests and relationships with manufacturers of products that are used in the management of migraine or cardiovascular disease certainly are relevant and should be disclosed." The authors' letter contained the disclosure.

This situation graphically points out why conflicts of interest must be taken into account when judging the results of "basic science" studies conducted by physicians or scientists with financial dealings with the drug industry. Those ties can subtly influence the interpretation of results in many ways. After all, if I'm committed to a treatment regimen for treating migraines, wouldn't it be nice to think that it was also helping my patients prevent heart disease?

Many researchers, like Dr. Kurth and colleagues, continue to think that their attitude toward a field of research has no impact on the way they conduct that research. Yet study after study has shown that the financial ties of researchers do in fact correlate with positive outcomes for their sponsors. This can only be explained by almost impossible-to-detect influences like how they framed the questions for study, how they chose patients for their sample, and how they interpreted the data.

For years, critics of the growing influence of private corporations over scientific research have fought for conflict-of-interest disclosure policies as one way to alert readers to these potential biases. Yet most of them now recognize that disclosure doesn't go far enough. They say it is time to reduce the influence industry exerts over research by setting up independent institutes for the conduct of clinical trials and basic health research. Attitudes like those exhibited in this most recent exchange by Dr. Kurth and colleagues graphically demonstrate why such changes are sorely needed.

Having Your Trials and Eating Them, Too

Government collaborates with industry all the time, especially in the development of new drugs. The National Cancer Institute pioneered in this process (it is the oldest of the National Institutes of Health) and continues to push collaborative clinical trials to test new cancer therapies emerging from industry's labs.

Over the weekend, the Los Angeles Times reported how one researcher at NCI, Thomas Walsh, between 1997 and 2003 worked on a succession of clinical trials for new antifungal drugs for treating serious lung infections associated with cancer, and, at the same time, took consulting fees from the companies that manufactured those drugs, including Pfizer and Merck.

The investigation also went on to question the protocols of the second of the two trials, which compared the newer Merck drug to the older one made by Fujisawa and marketed by Pfizer, which Walsh had also worked on. Critics complained that the NCI-funded trial underdosed the older drug, a classic drug industry tactic for showing that a new drug is superior to an older, often off-patent drug.

There wasn't enough evidence in the article to prove that latter point. But a number of physicians in letters to the New England Journal of Medicine raised questions at the time. Based on David Willman's reporting, it would seem that there are still serious questions about whether the nearly $1 billion spent on Merck's drug is doing patients any more good than previously available generics, which would cost a fraction of that amount.

These are precisely the types of questions that government-funded studies should be answering. Whether Dr. Walsh violated one of NIH's rules for disclosing conflicts of interest is hardly the most important question here. What's really important is giving health care professionals the best information possible for conducting the most effective and most cost effective medicine.

When NIH was debating its new rules in 2004 in the wake of Willman's previous articles documenting undisclosed conflicts of interest at the agency, I was one of the few people to stand up and call for a total ban on such arrangements. It's not that the government shouldn't collaborate with industry to bring exciting new therapies to market, I said. Rather, the government has a crucial role to play as independent designer of those trials and arbiter of the evidence. It must ensure that the information generated by government involvement in clinical trials testing the drug industry's latest medicines furthers public health.

It would appear that the government-funded studies that Walsh conducted failed these basic tests. I said it then. I'll say it again. NIH should prohibit all consultancies, stock dealings, speakers gigs or whatever for its scientists since they will inevitably bring at least some of those scientists into conflict with the agency's basic public health mission.

JAMA's Inadequate Response

David Armstrong of the Wall Street Journal followed up his scoop (see yesterday's post if you didn't see the original story) with a report on the Journal of the American Medical Association's plans to "toughen up" its conflict-of-interest disclosure rules. Pretty damn weak, in my view, which was reported in the paper. Here's the relevant parts of the story:

Under the journal's new guidelines, its authors -- often medical researchers from top-flight universities and hospitals -- are instructed to more broadly report their connections to drug companies and medical-device makers. Some critics say the measures don't go far enough and called for a publication ban on authors who fail to disclose they are receiving money from industry. . . . "Authors should err on the side of full disclosure," the new policy states. JAMA has experienced at least three cases this year where authors failed to disclose industry ties.

The Center for Science in the Public Interest, a Washington, D.C., advocacy group, published a report two years ago that found JAMA had the highest rate of nondisclosure of conflicts among four medical journals studied. Merrill Goozner, who studies scientific integrity for the center, said the JAMA changes were inadequate and urged the journal to adopt penalties such as a three-year publishing ban on authors who don't disclose industry ties.

"It's clear that [JAMA] does not evaluate conflict-of-interest disclosures when articles are submitted," Mr. Goozner said. "As a result, some authors with blatant conflicts of interest apparently feel they can ignore the journal's policy with impunity."

Mr. Goozner said the International Committee of Medical Journal Editors, a group including the editorial heads of the most prominent journals, should agree to apply a ban by one of its members to all of its members.
. . .
Catherine DeAngelis, JAMA's editor in chief, says she is averse to a publication ban, but she rejected the idea that offending authors go unpunished. She says in several cases where researchers failed to disclose industry ties, she asked the medical schools where they work to investigate their behavior. In some cases, those probes resulted in sanctions, she said.

"We take this very, very seriously," Dr. DeAngelis said, but added she is "not an FBI agent" and "there has to be a certain level of trust" between the publication and authors who publish their research in it. "The day that certain level of trust disappears, I will hang it up," she said.

Memo to Dr. DeAngelis: That's how the Securities and Exchange Commission treated the accountants before Enron. And look what it got them: Sarbanes-Oxley.

We could use a Sarbanes-Oxley for medical research. But that's a subject for another day.

A Major Failure at JAMA

Two years ago, in my role as director of the Integrity in Science project at the Center for Science in the Public Interest, I conducted a study that warned the editors of the Journal of the American Medical Association and other leading scientific journals that there was a persistent pattern of non-disclosure of conflicts of interest by physicians and scientists publishing original articles within their pages. At that time, CSPI said a voluntary disclosure policy needed teeth – a ban on publishing if an author failed to disclose – if it was going to work. The advice was ignored.

Today’s Wall Street Journal documented a major failure to disclose relevant conflicts by seven authors of a JAMA article involving the safety of anti-depressant use by pregnant women. At least two of those authors, including lead author Lee S. Cohen, a Harvard Medical School professor and director of the perinatal and reproductive psychiatry research program at Massachusetts General Hospital, had their conflicts of interest documented in the Integrity in Science Database at www.integrityinscience.org prior to publication of the article.

It’s clear now that the editors of the Journal of the American Medical Association take no steps to evaluate conflict of interest disclosures when articles are submitted. As a result, physician-authors with numerous conflicts of interest feel they can ignore the journal’s policy with impunity.

The only solution is to adopt strong penalties for authors who fail to disclose – a three-year ban from publishing in the pages in the journal. The International Committee of Medical Journal Editors should also make any ban by any of its member reciprocal.

Integrity in Science Watch -- July 3

President to Name Anti-Regulation Zealot to OIRA?

Greenwire reports that the Bush administration is about to announce the appointment of Susan Dudley to run the Office of Information and Regulatory Affairs, the White House arm that reviews all agency regulations. Dudley is director of regulatory studies at George Mason University's Mercatus Center, which opposes most regulations on ideological grounds and received $40,000 grants from Exxon Mobil for "regulatory improvements (climate change)" in 2003 and 2004.

Industry-Supported Food Scientists:
Cutting Antibiotics in Food Won't Slow Growth of Resistant Strains

Eliminating antibiotic drugs from livestock production may have little positive effect on resistant bacteria that threaten human health, according to a report released last week at the annual Institute of Food Technologists (IFT) meeting in Orlando. Michael P. Doyle, director of the Center for Food Safety at the University of Georgia, chaired the 15-member panel that wrote the report. While most of Doyle's research is supported by the U.S. Department of Agriculture and the Food and Drug Administration, he has also received numerous grants from the American Meat Institute and is currently principal investigator on food safety projects funded by Kraft Foods and Great Eastern Mussel Farms. The IFT, a 22,000-member society made up of food scientists from industry, academia and government, receives financial support from the food industry as well as from its membership.

FDA Sides with Industry Consultant on Breast Implant Toxicity

Citing a recent review in the science journal Biomaterials, the Food and Drug Administration two weeks ago told consumers that platinum leaks from silicone breast implants pose no threat to women's health. What the FDA failed to note was that the review author, Michael Brook of McMaster University in Hamilton, Ontario, appeared last year at an FDA hearing as a paid consultant for Inamed, which manufactures the devices.

Both the Brook review and the FDA review dismissed a recent study in Analytical Chemistry, which determined women with breast implants had elevated levels of the toxic form of platinum in their breast milk and blood. Platinum in some forms is a known neurotoxin, and consumers fear the inert version used to manufacture implants may become toxic once in the body. That study's corresponding author, S. Maharaj of the Center for Environmental Medicine in New Market, Md., disclosed she has no ties to either manufacturers or plaintiffs' attorneys. The study's lead author, E. Lykissa, has consulted with plaintiff attorneys in the past, but has no current ties, according to Maharaj. The study was funded in part by Chemically Associated Neurological Disorders, a patient advocacy group that does not disclose its funding sources on its website. Consumer groups are seeking an independent study of the issue before the FDA rules on Inamed's application to market a silicone breast implant.

Doctor-Run Charities Create Fertile Ground for Conflicts of Interest, Bias

Tax-exempt charities set up by doctors to engage in medical research or education are a growing channel for industry money and have become a niche for conflicts of interest, the New York Times reports. Corporate donations to these charities may lead to bias in the treatment decisions of physicians, suspect research findings and violations of federal anti-kickback laws, especially when the money is used for fellowships or covering business expenses.

The Midwest Heart Foundation, created in 1988 by the for-profit group Midwest Heart Specialists, has doubled corporate funding in the last few years to $1.7 million, including hundreds of thousands of dollars from Amgen, AstraZeneca, and Scios. Earlier this year the foundation was subpoenaed by the Justice Department as a part of an investigation into the marketing of a potential harmful heart failure drug made by Scios. According to the Times, Mitchell Saltzberg, a paid consultant for Scios at Midwest Heart, was telling Medicare that the drug posed no risks at the same time Scios was sending safety alerts to doctors.

FDA Inspections and Serious Warning Letters Drop by Half

Rep. Henry Waxman (D-CA) released a report last week showing that the Food and Drug Administration's severe warning letters to industry and on-site inspections at manufacturing plants have been halved over the last five years. In32 cases, the agency sent letters to food and drug companies noting only possible problems even though field inspectors had recommended that they issue serious warning letters, seize the product or seek a court injunction. The agency's Center for Devices and Radiological Health, which oversees defibrillators and other devices that have been recalled, showed the biggest decline, issuing 66 percent fewer warning letters in 2005 than in 2000. The FDA's Center for Drug Evaluation and Research dropped its number of warning letters by 39 percent. "Under the Bush administration, enforcement efforts have plummeted and serious violations are ignored," Waxman said.

Rhode Island AG Defends Contributions from Lead Defendant

The Attorney General for Rhode Island last week defended contributions made to his campaign by a company who was being sued by the state in a lead-paint case. Patrick C. Lynch, who accepted over $4,000 in campaign donations from a DuPont Corp. lawyer and lobbying firm while settling with the same company in litigation over clean up of lead paint manufacturing, said there was no reason to return the contributions because he had fought as hard as possible "on behalf of all Rhode Islanders against the paint producers." Lynch's opponent in the upcoming election, J. William W. Harsch, has filed a complaint with the state Ethics Commission, saying Lynch's acceptance of money from a company he was prosecuting is in "substantial conflict with his duties."

Odds and Ends

National Institutes of Environmental Health Sciences has abandoned efforts to privatize Environmental Health Perspectives, its award-winning journal. But director David Schwartz says he is seeking an outsider to serve as editor-in-chief while cutting back its news and commentary sections and discontinuing foreign translations to save money. . . Unions representing 10,000 Environmental Protection Agency scientists, over half the agency's workforce, sent a letter to Congress Thursday protesting the Bush administration's proposed 80 percent cut in the agency's library budget.

Integrity in Science Watch -- June 19

Groups Protest EPA Choices for Evaluating Pesticide
The Environmental Protection Agency's candidates for reviewing a staff analysis of the carcinogenicity of a common sterilizing agent drew a sharp protest from 15 health and labor advocacy groups last week. The Natural Resources Defense Council, Service Employees International Union, and the Center for Science in the Public Interest among others asked EPA to remove three scientists who co-authored an industry-funded study on ethylene oxide (ETO) risks. The letter suggested they be replaced with independent health and occupational experts to balance the other industry consultants tentatively named to the committee. In 2004, Christopher Kirman and Michael Gargas from The Sapphire Group and Mary Jane Teta from Exponent conducted an industry-funded study recommending values for cancer risk about equal to those that were generated from the EPA's draft three years earlier, which those same authors helped write. The EPA is reviewing the carcinogenicity of ETO for its Integrated Risk Information System (IRIS) database, which numerous government agencies in the U.S. and around the world use to determine health risks.

Meanwhile, the EPA's Office of Pesticide Programs is conducting its own risk assessment of ETO in order to meet an August deadline for re-registering the chemical. Comments submitted last fall by producers and users of ETO slammed the OPP's draft risk assessment. The industry groups complained that the OPP's preliminary standard, 180 times stricter than the Occupational Safety and Health Administration's standard of 1 ppm for exposed workers, is impossible to achieve.

Time Runs Andrew Weil Advertorial
This week's Time Magazine includes a column by Dr. Andrew Weil touting the benefits of fish oil supplements. The column was sparked by a recent report in the Journal of the American Medical Association showing that fish oil supplements did not reduce the risk of serious abnormal heart rhythms. The article failed to disclose that Dr. Weil sells his own brand of fish oil supplements on his website.

Pfizer's NIH Researcher Gave Firm Tissue Samples
A top-ranked National Institutes of Health researcher who failed to comply with the agency's conflict-of-interest disclosure policy provided pharmaceutical giant Pfizer government-owned tissue samples. In a report released last week, House Energy and Commerce Department investigators concluded Trey Sunderland, chief of the geriatric psychiatry branch at the National Institute of Mental Health, failed to tell agency officials about his arrangement with Pfizer Inc. after sending the company thousands of NIH fluid samples he had worked on for Alzheimer's research. Sunderland received over $500,000 in consulting fees from Pfizer. The House investigators were tipped off by a former NIMH scientist who had worked with Sunderland and was unable to locate spinal fluid samples she had collected in the 1990s. Sunderland pleaded the fifth amendment when called by the committee last week. He had previously blamed his failure to disclose the conflict of interest on his office staff. The case has caused NIH to clarify its rules for managing tissue samples. "All transfers of human samples will require an appropriate agreement signed off by a senior official," said NIH spokesman John Burklow.

Texas Crony Sought White House Help to Weaken Rule
Four years after Texas oilman Ernest Angelo made a special appeal to hunting buddy Karl Rove, the EPA last week approved a weakened rule that aims to decrease groundwater contamination from oil drilling and construction sites, the Los Angeles Times reports. Angelo, a former mayor of Midland, told the White House's top domestic adviser that a more comprehensive groundwater rule from an early EPA draft would cause "our strongest supporters to openly express doubt as to the merit of electing Republicans when we wind up with this type of stupidity." Rove promised Angelo that the administration would consider the "economic, energy and small business impacts" of the rule. In 2005, the EPA draft was changed by the White House's Office of Management and Budget (and now finalized) to allow sediment from energy production sites to flow freely into streams and underground water. "We can't say that Karl Rove walked over to OMB and demanded these changes," said Sharon Buccino, director of the Natural Resources Defense Council's land program. "But it is clear that there was direction coming from the top of the White House."

Industry Asks OSHA to Limit Access to Documents
Industry groups have asked the Occupational Safety and Health Administration to deny a former high-ranking employee access to its data on OSHA inspectors' exposures to toxic beryllium, according to Inside OSHA. Adam Finkel, who resigned from the agency in January, wanted the documents for an academic research project. Industry officials claimed turning over the documents would disclose confidential commercial or trade secret information, threaten national security and initiate new lawsuits. Finkel, now a professor of environmental and occupational health at the University of Medicine and Dentistry of New Jersey, has filed a Freedom of Information Act suit against OSHA.

FDA Opposing Conflict-of-Interest Waiver Ban
Top FDA officials continue to speak out against an amendment to the agency's appropriations bill that would ban physicians with direct ties to drug and device manufacturers from sitting on FDA advisory panels. That amendment, sponsored by Rep. Maurice Hinchey (D-NY), passed the House last month and is now before the Senate. Center for Devices and Radiological Health director Daniel Schultz told a Medical Device Manufacturers Association meeting in Washington last week that the bill "could present major, major problems for the agency" by denying it needed expertise, according to the online publication FDA Webview. The Center for Science in the Public Interest, which backs the bill, says there are numerous experts without financial ties to regulated firms that could serve the agency equally well.

Odds and Ends
The House of Representatives Science Committee rejected an amendment to the National Oceanic and Atmospheric Administration appropriations bill that would prohibit NOAA supervisors from punishing employees who disseminate scientific research. . . The British Medical Journal is reporting that the International Obesity Task Force, which is closely affiliated with the World Health Organization and became part of the non-profit International Association for the Study of Obesity in 2002, draws two-thirds of its funding from Hoffman-La Roche, which makes the antiobesity drug orlistat (Xenical), and Abbott Laboratories, which makes sibutramine hydrocholoride (Reductil). . . The revolving door is swinging at the Food and Drug Administration as deputy commissioner Steve Niedelman departments the regulatory affairs office for a job at Quintiles, the clinical trials consultancy. . . The Energy Department's National Coal Council defends its lack of environmentalists by claiming none wanted to be associated with the coal industry officials who dominate the advisory panel. The Natural Resources Defense Council told Inside EPA it would likely accept an offer to join.

What Next? Body Parts?

The headline over David Willman's December 2004 investigation in the Los Angeles Times read: "Dr. P. Trey Sunderland III: $508,050 from Pfizer, but 'No Outside Positions to Note.'" A story that began as a failure to disclose gross conflicts of interest has now morphed, allegedly, into a profiteering scheme using human tissue samples drawn from vulnerable seniors.

According to a story out today, the House Energy and Commerce Committee unveiled a 26-page report accusing Sunderland of essentially selling Pfizer 3,000 NIH samples of human spinal fluid and plasma taken from patients with Alzheimer's disease. His price tag, according to press accounts? $285,000.

Sunderland's lawyer released a statement saying his client, who is still employed at NIH, "acted legally and ethically . . . There is no connection between his receiving funds from Pfizer and Pfizer's access to any tissue samples."

Integrity in Science Watch -- 6/12/06

Each week, the Integrity in Science project at the Center for Science in the Public Interest publishes Integrity in Science Watch. Here's the latest:

EPA May Pick Chem Industry Consultants to Review Ethylene Oxide Update

The Environmental Protection Agency has proposed naming three scientists with current or former ties to ethylene oxide manufacturers to peer review the final draft of a health assessment for the chemical. The International Agency for Research on Cancer considers ethylene oxide (ETO) a known carcinogen. Environmental and labor groups are preparing a challenge to the committee's make-up, which must be filed by Thursday.

Ethylene oxide is used to manufacture ethylene glycol and for sterilization of medical equipment, spices and other agricultural products. In the mid-1980s, the Occupational Safety and Health Administration adopted a stringent one-part-per-million standard on workplace exposures based on a California analysis showing ETO slightly increases leukemia among exposed workers. Last fall, a preliminary draft of the new health assessment drew heated protests from industry groups because it might lead to significantly lower thresholds for regulating the chemical. The EPA has not yet released the final draft.

In late May the agency published a list of 31 proposed nominees to a Scientific Advisory Board panel that will review the final draft when it is published. The list included three consulting toxicologists who published a 2004 paper in Risk Analysis concluding that exposures many times higher than the OSHA standard "are not likely to pose an appreciable risk of leukemia in human populations." That paper contained no conflict-of-interest disclosure. However, the three industry consultants, Christopher Kirman and Michael Gargas of the Sapphire Group and Mary Jane Teta of Exponent Inc., either are currently serving on or previously served on the American Chemistry Council's Ethylene Oxide Industry Council, according to the EPA website and a 2001 email communication received by the Natural Resources Defense Council. The editor-in-chief of Risk Analysis recently joined Exponent.

The chemical industry is pushing for a new cancer risk assessment in time for the EPA's August deadline for re-registering the chemical as a pesticide. An assessment based on industry-funded science and peer-reviewed by the industry consultants who conducted that science could lead to weaker pesticide regulations and OSHA standards. Protests over the make-up of the panel should be addressed to Sue Shallal at shallal.suhair@epa.gov.

Tobacco Scientist Moves On to Particulate Matter

A new industry-funded study downplaying the risks of particulate matter (PM) was authored by a researcher who previously published studies downplaying the risks of second-hand smoke, documents available at the Legacy Tobacco Documents Library at the University of California at Los Angeles show. The Electrical Power Research Institute hired James E. Enstrom of the University of California at Los Angeles to analyze 30 years of air pollution data. His recently published analysis, which showed PM had no effect on mortality after the initial ten years of the study, is now being used by industry trade groups in their letters to the EPA arguing against a tighter PM standard. Enstrom's study, published in Inhalation Technology, was subsequently questioned in the same journal by Bert Brunekreef, a highly-regarded professor of environmental health at Utrecht University in the Netherlands.

In 1997 Enstrom asked Philip Morris scientific