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AWAITING HEALTH LAW'S PROGNOSIS

By Reed Abelson

With a court decision declaring the health care law unconstitutional and Republicans intent on repealing at least parts of it, thousands of Americans with major illnesses are facing the renewed prospect of losing their health insurance coverage.

The legislation put an end to lifetime limits on coverage for the first time, erasing the financial burdens, including personal bankruptcy, that had affected many ailing Americans.

For example, Hillary St. Pierre, a 28-year-old former registered nurse who has Hodgkin's lymphoma, had expected to reach her insurance plan's $2 million limit this year.  Under the new law, the cap was eliminated when the policy she gets through her husband's employer was renewed this year.

Ms. St. Pierre, who has already come close once before to losing the coverage because she had reached the plan's maximum, says she does not know what she will do if the cap is reinstated.  "I will be forced to stop treatment or to alter my treatment," Ms. St. Pierre, who lives in Charlestown, N.H., with her husband and son, said in an e-mail.  "I will find a way to continue and survive, but who is going to pay?"

As judges and lawmakers debate the fate of the new health care law, patients like Ms. St. Pierre or Alex Eli, a 22-year-old with hemophilia who lives in Portland, Ore., fear losing one of the law's key protections.  Like Ms. St. Pierre, Mr. Eli expected to reach the limits of his coverage this year if the law had not passed.  In 2010, the bill for the clotting factor medicine he needs was $800,000, and his policy has a $1.5 million cap.  "It is a close call," he said.

Exactly what will happen to the law's specific provisions that prevent insurers from imposing lifetime limits and require them to phase out the annual limits now in place is unclear.  While even Republicans concede that a full repeal is unlikely, Congress could strip certain elements of the legislation, like this one.  As challenges to the law move through the courts, patients who have felt an immediate impact now confront added uncertainty.

"We've got to protect people from catastrophic health problems," said Ron Pollack, the executive director of Families USA, a consumer advocacy group that favored the law's passage.  "We don't want people bankrupted."

Protecting people from facing these extremes is one of the main goals of the law, according to its proponents.

Asked about the effect of the law on those who had encountered an insurance ceiling, Kathleen  Sebelius, the health secretary, said in a statement: "The Affordable Care Act is freeing American from worrying about having their insurance benefits run out when they need them the most."

Before the law was passed, an estimated 20000 insured Americans reached the lifetime limits of their coverage each year.  Decades old, these restrictions were put in place when both medical care and health insurance were much less expensive than they are today, said Tom Wildsmith, an official with the American Academy of Actuaries.

In recent years, many employers, if they still had caps, set them fairly high, so that it was rare for someone to exceed to exceed the benefits unless they were seriously ill and required expensive care.

"This is the kind of thing that grabs a CANCER survivor who has had several operations," said Gary Claxton, an executive with the Kaiser Family Foundation, which studies employer overage.  Only the very sick were affected.  "People don't voluntarily use this level of services," he said.

Ms. St. Pierre nearly lost her insurance in 2008.  After her first bone marrow transplant failed, she realized the coverage from her husband's employer would run out before she could receive another transplant.

She remembers reviewing her options and looking into treatments that would be less expensive.  She enrolled in a clinical trial to test an unproved form of CHEMOTHERAPY, for example, because it was free.  She considered divorcing her husband, a move that could qualify her for Medicaid, or moving to Massachusetts, where she thought she might be able to afford and qualify for a policy.  She has written about her experiences on her blog, called BaldiesBlog.

But she was spared from making those decisions when her husband's company was acquired, and she was able to enroll in a new health plan. "Luckily, the cap started over," she said.

Ms. St. Pierre also now qualifies for Medicare, the federal health insurance program, because she is disabled, but her husband's plan remains her primary source of insurance.  Medicare would still leave her with significant medical bills if she lost her husband's coverage because she has no supplemental insurance.

Without the lifetime cap, Ms. St. Pierre says she can now focus on what treatment makes the most sense rather than gamble that the most aggressive care will cure her and allow her to escape the maximum limits on coverage. "It opens up all sorts of options," she said, including viewing her cancer as a chronic condition that she can afford to treat for many years.

Cancer patients like Ms. St. Pierre who are concerned about running out of coverage often try to tailor their treatments to see if they can avoid hitting their lifetime caps, said Stephen Finan, senior director of policy at the American Cancer Society.  "People have to think about what's their strategy," he said.

And while Ms. St. Pierre, who has worked with the cancer society, says she knows she is likely to be able to continue to receive some treatment without insurance, she also knows that it is not likely to be the optimal care.  The same is true for any patient who runs out of coverage, Mr. Finan said.  "You may well continue to get care, but the quality of care is markedly lower." he said.

The last time Mr. Eli neared the maximum on his parents' policies, he had only $77,000 in remaining coverage -- about a month's worth of his clotting medicine.  He had been able to switch plans offered by his parents' employers.  He works part time and is not eligible for insurance from his employer.

Among employers, the feelings are mixed about whether the limits should be eliminated, said Andrew Webber, who is the president of the National Business Coalition on Health.  One of the coalition's members, the Midwest Business Group on Health, recently conducted a survey of opinions by employers.  About a quarter of those surveyed wanted to repeal the new law's ban on lifetime and annual limits to coverage.  While about half wanted to keep the provisions, some employers object on the grounds that they do not want the government to dictate what benefits they offer their workers. "Employers, for so many years, have had so much flexibility to design and change their policies from year to year," Mr. Webber said, and the new law changes that.

The expense of doing away with lifetime limits is fairly modest, said Mr. Wildsmith, the actuary.  If a plan currently has a $1 million limit, eliminating it would add only 1% to the cost of the premium, he said.  Many employers have much higher caps, making it even less expensive to eliminate them.

While proponents of the law favor the elimination of the caps, some Republicans also think health coverage should no longer be subject to cps on a yearly or annual basis.  The plan being proposed by the House Republicans "banned annual and lifetime limits and lowered premiums for millions of people," said a spokeswoman for the House Ways and Means Committee.

Ms. St. Pierre says she knows she will want to continue her treatment, regardless of whether she has private coverage, but she also knows that someone will have to pay the bill.  "Where the problem lies is who is going to pay for that," she said.  "Will they take my house or car?"

                                * * *

I don't know why this story, first published in 2004 in Washington Monthly, showed up in my inbox this month.  It's admittedly long, but it's worth reading -- and quite scary.  Since it was written, additional restrictions have been placed on drug companies.  But none have the power to impact this very serious situation:

DOCTORS WITHOUT BORDERS

Why you can't trust medical journals anymore

By Shannon Brownlee

With financial ties to nearly two dozen drug and biotech companies, Dr. Charles B. Nemeroff may hold some sort of record among academic clinicians for the most conflicts of interest. A psychiatrist, a prominent researcher, and chairman of the department of psychiatry and behavioral science at Emory University in Atlanta, Nemeroff receives funding for his academic research from Eli Lilly, AstraZeneca, Pfizer, Wyeth-Ayerst--indeed from virtually every pharmaceutical house that manufactures a drug to treat mental illness. He also serves as a consultant to drug and biotech companies, owns their stocks, and is a member of several speakers' bureaus, delivering talks--for a fee--to other physicians on behalf of the companies' products.

But it was just three of Nemeroff's many financial entanglements that caught the eye of Dr. Bernard J. Carroll last spring while reading a paper by the Emory doctor in the prominent scientific journal, Nature Neuroscience. In that article, Nemeroff and a co-author reviewed roughly two dozen experimental treatments for psychiatric disorders, opining that some of the new treatments were disappointing, while others showed great promise in relieving symptoms. What struck Carroll, a psychiatrist in Carmel, Calif., was that three of the experimental treatments praised in the article were ones that Nemeroff stood to profit from--including a transdermal patch for the drug lithium, for which Nemeroff holds the patent.

Carroll and a colleague, Dr. Robert T. Rubin, wrote to the editor of Nature Neuroscience, which is just one of a family of journals owned by the British firm, Nature Publishing Group, pointing out the journal's failure to disclose Nemeroff's interests in the products he praised. They asked the editor to publish their letter, so that readers could decide for themselves whether or not the author's financial relationships might have tainted his opinion. After waiting five months for their letter to appear, the doctors went to The New York Times with their story--a move that sparked a furor in academic circles, and offered the public yet another glimpse into conflict of interest, one of the most contentious and bitter debates in medicine.

In his defense, Nemeroff told the Times he would have been happy to list his (many) relationships with private industry--if only the journal had asked. "If there is a fault here," he said, "it is with the journal's policy," which did not require authors of review articles to disclose their conflicts of interest.

And that is pretty much where the debate over conflict of interest in medical journals stands: Should research scientists who have financial stakes in the products they are writing about be forced to disclose those ties? To which the average person might reasonably respond, of course they should. But the more pertinent question is why scientists with financial stakes in the outcome of scientific studies are allowed anywhere near those studies, much less reviewing them in elite journals.

The answer to that question is at once both predictable and shocking: For the past two decades, medical research has been quietly corrupted by cash from private industry. Most doctors and academic researchers aren't corrupt in the sense of intending to defraud the public or harm patients, but rather, more insidiously, guilty of allowing the pharmaceutical and biotech industries to manipulate medical science through financial relationships, in effect tainting the system that is supposed to further the understanding of disease and protect patients from ineffective or dangerous drugs.

More than 60 percent of clinical studies--those involving human subjects--are now funded not by the federal government, but by the pharmaceutical and biotech industries. That means that the studies published in scientific journals like Nature and The New England Journal of Medicine--those critical reference points for thousands of clinicians deciding what drugs to prescribe patients, as well as for individuals trying to educate themselves about conditions and science reporters from the popular media who will publicize the findings--are increasingly likely to be designed, controlled, and sometimes even ghost-written by marketing departments, rather than academic scientists. Companies routinely delay or prevent the publication of data that show their drugs are ineffective. The majority of studies that found such popular antidepressants as Prozac and Zoloft to be no better than placebos, for instance, never saw print in medical journals, a fact that is coming to light only now that the Food and Drug Administration has launched a reexamination of those drugs.

Today, private industry has unprecedented leverage to dictate what doctors and patients know--and don't know--about the $160 billion worth of pharmaceuticals Americans consume each year. This is an unsettling charge that many (if not a majority) of doctors and academic researchers don't want to acknowledge. Once grasped, however, the full scope and consequences of medical conflict of interest beget grave doubts about the veracity of wide swaths of medical science. As Dr. Drummond Rennie, deputy editor of The Journal of the American Medical Association (JAMA), puts it, "This is all about bypassing science. Medicine is becoming a sort of Cloud Cuckoo Land, where doctors don't know what papers they can trust in the journals, and the public doesn't know what to believe."

Clinical trial and error

How did we get to this point? What effect is industry influence having on the treatment of patients? And why are the medical journals not more vigilant to weed out papers that have been distorted by conflict of interest? The answers to these questions begin, oddly enough, with an amendment to U.S. patent law called the Bayh-Dole Act. Passed in 1980, Bayh-Dole for the first time permitted universities to commercialize products and inventions without losing their federal research funding, the seed money for innovative research. The brainchild of George Keyworth II, President Reagan's science advisor, who was watching the United States get beaten in world markets by the Japanese, Bayh-Dole was intended to stimulate advanced technological invention and speed its transfer from university labs into private industry, where it could be put to work spurring U.S. productivity.

It seemed like a win-win proposition. Indeed, Bayh-Dole has helped launch the biotech industry and has propelled several life-saving products to market. The basic research behind Gleevec, for instance, an incredibly effective new anti-cancer drug, was done by a university scientist. The drug's manufacturer, Novartis, stepped in and provided additional funding for development. In 1984, private companies contributed a mere $26 million to university research budgets. By 2000, they were ponying up $2.3 billion, an increase of 9,000 percent that provided much needed funds to universities at a time when the cost of doing medical research was skyrocketing.

That's the upside. The downside is that Bayh-Dole has also fostered increasingly cozy relationships between the academics upon whom the nation depends for unbiased medical information and Big Pharma, private companies whose main goal, let's face it, is making a profit. And we're talking serious money here. In addition to the salaries built into company-sponsored research grants, academic clinicians at medical schools can pad their already decent incomes with $1,000-a-day consulting contracts with pharmaceutical companies, patent royalties, licensing fees, and big-payoff stock options. Nemeroff stood to reap as much as $1 million in stock from a company that manufactured one of the products in his Nature Neuroscience paper. At many of the top research universities and medical schools around the country, a substantial percentage of the faculty enjoys the perks of industry relationships. At MIT, 31 percent of the science and engineering faculty has outside income; at Stanford Medical School, it's 20 percent.

What's in it for the pharmaceutical companies? Simple economics. It's Marketing 101. By penetrating the wall that once existed around academic researchers, drug companies have gained access to the "thought leaders" in medicine, the big names whose good opinion of an idea or a product carries enormous weight with other physicians. Companies target academic KOLs, or Key Opinion Leaders, in the lexicon of marketing, and woo them with invitations to sit on scientific advisory committees, or to serve as members of speakers' bureaus, which offer hefty fees for lending their prestige to a company and touting its products at scientific meetings and continuing medical education conferences. Of course, KOLs must be convinced of their own impartiality, says Carl Elliott, a moral philosopher at the University of Minnesota and author of Better Than Well: American Medicine Meets the American Dream. "If they understood that they were being used as industry mouthpieces, they would probably pull the plug on the whole enterprise." Drug companies encourage their KOLs to consult for multiple companies so the appearance of objectivity can be maintained. But the drug industry's most powerful means of boosting the bottom line is funding research, which allows companies to control, or at least influence, a great deal of what gets published in the medical journals, effectively turning supposedly objective science into a marketing tool.

"These are not benign people who are interested in helping people with their new wonder drugs," says Drummond Rennie. "The drug companies are run by hard-nosed marketers, not by the physicians and the scientists. They use what works, and money works." Rennie, who has a thatch of unkempt white hair and remnants of the accent of his native Leeds, England, got a clear picture of the extent to which drug companies will go to control the results of studies they fund in 1993, when a colleague at University of California San Francisco tried to publish a paper in JAMA in 1993 on the metabolic activity of four different forms of thyroid hormone. Betty J. Dong, a pharmacologist, had been contracted in 1987 by Flint Laboratories to run a clinical trial comparing Synthroid, Flint's synthetic version of thyroid hormone, to that of three competing formulations. At the time, Synthroid was the market leader and the most expensive drug in its class. Dong and Flint signed a lengthy agreement detailing the design of the study, and both sides fully expected the results would show that Synthroid was superior.

But all four drugs turned out to be essentially equivalent. In 1990, as Dong prepared a paper for JAMA, the company that was at first so eager to solicit her help, launched a vigorous campaign to discredit the study. Flint then rushed its own paper into press at a less prestigious journal, concluding--surprise!--that Synthroid was superior. After numerous attempts to address the company's criticisms, Dong finally submitted her paper to JAMA, only to withdraw it three months later when the firm threatened to sue for breach of contract. It took the FDA and U.S. Department of Health and Human Services to get the company to back down. Dong's paper did not see print in JAMA until 1997.

In this case, it might seem as if the only real harm to the public during the seven years that elapsed from the time Dong completed her study to its publication was higher prices to patients and insurers. To Rennie's way of thinking, the Dong imbroglio and others like it have a more insidious effect by sending a chilling message to scientists, namely, don't bite the hand that feeds you. In a recent survey of clinical researchers, nearly 20 percent of respondents admitted to delaying publication of their results by more than six months at least once in the last three years to allow for patent application, protect their scientific lead, or to slow the dissemination of results that would hurt sales of their sponsor's product--often without overt pressure from the company. "If you're getting a lot of money from a corporate sponsor, it's easy to get the impression that you'll get even more for future research if you don't write up the negative results," says Rennie--and that your funds will dry up if you do.

The bottom line is that articles appearing in medical journals contain a lot of happy talk about medical products. At least eight studies have shown that industry-sponsored research that gets published tends to produce pro-industry conclusions, according to a review by Yale University researchers that appeared last year in JAMA. By reanalyzing data from eight separate studies of the effect of conflict of interest on 1,140 published scientific papers, the researchers found that papers based on industry-sponsored research are significantly more likely to reflect favorably on a sponsoring company's drug or device than research that is supported by a non-profit entity or the federal government.

How can this be? Isn't science, well, scientific, an objective search for the truth? That's what many academic clinicians, especially those who are mixed up with corporate sponsors, would have the public believe. A typical comment comes from Niels Reimers, an early promoter of industry-university ties, who told the Hartford Courant, "You may think I'm a Pollyanna or something, but most people are honest. It's sort of the ethos of academic research." Here's Dr. Irwin Goldstein, a Boston University urologist who has consulted for at least seven companies developing impotence therapies: "Science is science. It comes down to the bottom line. What the data shows, the data shows."

Such statements reflect the ideal of science, not the reality, says Dr. Marcia Angell, former editor in chief of The New England Journal of Medicine. Public protestations aside, she says, "Clinicians know privately that results can be jiggered. You can design studies to come out the way you want them to. You can control what data you look at, control the analysis, and then shade your interpretation of the results." Even the most careful research can be fraught with murky results that require sifting and weighing, a measure of judgment that the researcher hopes will bring him closer to the truth. Was this patient's headache caused by the antibiotic you gave her, or does she have a history of migraines? Is that patient's depression lifting because of the drug you are testing, or because a kindly doctor is actually listening to him?

Sometimes there isn't much that journal editors can do to separate good science from that which has been weighed, sifted, and jiggered according to a corporate sponsor's needs. Increasing numbers of studies that get published are actually written by PR firms, "medical communications" specialists, who then go out and recruit an academic willing to put his name on the paper, for a fee. Other studies simply omit data that detract from the sponsor's message. In September 2000, for example, JAMA published a paper comparing the prescription painkiller Celebrex to over-the-counter ibuprofen. The manufacturer of the prescription drug, known as a selective Cox-2 inhibitor, launched the study in order to show that Cox-2 inhibitors, a class that also includes the prescription drug Vioxx and was already worth $3.5 billion a year, cause fewer instances of bleeding in the stomach and intestine than either aspirin or ibuprofen. The huge study, which looked at six months of data from more than 8,000 patients, produced unambiguous results: There were fewer side effects among patients on the Cox-2 drug.

A year later, news surfaced that patients had actually been followed for 12-15 months at the time the JAMA paper came out, not six, and that during the second half of the study, the group taking the Cox-2 drug suffered higher rates of gastrointestinal side-effects than patients on the over-the-counter painkiller. To make matters worse, patients on the Cox-2 developed serious heart problems three times more often than those on ibuprofen. The authors of the paper--all of them either consultants to the manufacturer or employees"defended their decision to report only the first, positive, half of their study, saying several patients who weren't taking the Cox-2 drugs dropped out after six months, making the statistics more difficult to analyze. But Dr. Catherine D. DeAngelis, JAMA's editor in chief, told The Washington Post: "I am disheartened. We are functioning on a level of trust that was, perhaps, broken."

Disheartened? Not furious? No, because DeAngelis could not know for certain whether or not the authors held back half the data in order to make their sponsor's drug look better "no matter how likely that explanation may seem". When researchers submit papers to a journal, the editor has little choice but to trust the authors have employed a ruthless skepticism when viewing their own results, that they have bent over backwards to minimize self-delusion. Editors and peer reviewers can ferret out sloppy reasoning, look at how an author has designed and executed a study, and correct faulty statistics, but as Angell remarked, "We don't put bamboo slivers under their nails. If they wanted to lie, they could lie."

Articles of faith

Dr. Arnold Relman began worrying about this problem way back in 1977, when he became editor-in-chief of The New England Journal. That year, Relman got a call from a reporter about a paper that was due to appear in the next issue, discussing serious side effects--including lowering a man's testosterone and sperm counts--of a popular antacid. The reporter wanted to know what Relman intended to do about the fact that Wall Street analysts had acquired early copies of the paper and now the stock of the company that made the drug was falling.

Relman, who began practicing medicine in the 1950s and calls himself a "relic," says before that reporter's call, it had never occurred to him that medical research could have financial consequences for industry. But the more he thought about it, he told me recently, "The more I became convinced that the commercialization of medical practice and medical research, and the use of the information for commercial purposes, was a major threat to the integrity of the whole system." He recognized that medical researchers, being only human, would have trouble applying that ruthless skepticism that was so necessary to good science when there was money at stake.

The obvious solution to Relman and Angell, who was by then a deputy editor at The New England Journal of Medicine, was disclosure. Forcing authors to tell the world they were taking industry money, the editors reasoned, would prompt a little soul-searching among researchers who might otherwise be inclined to turn a blind eye to negative results or shade conclusions in favor of a corporate sponsor. It would put them on notice that readers would be watching. The editors also figured that disclosure would help readers judge the validity of an author's conclusions. "They could evaluate the data for themselves," Relman told me recently. "But the discussion, the interpretation by the author can be slanted . . . it was still important for readers to know when articles were sponsored by industry." JAMA, largely at Rennie's urging, followed suit soon after.

Six years later, Relman upped the ante by barring researchers with conflicts of interest from writing editorials or review articles--like the one penned in Nature Neuroscience by Charles Nemeroff"because they carry great weight with doctors in private practice. Angell explains their decision like this: "Imagine a judge who has before him a case involving two companies suing each other--and he owns one of the companies. And he says, 'Not to worry. I'm a judge and I learned how to evaluate things in a dispassionate way.' He'd be laughed out of court." She and Relman argued that just as judges must recuse themselves from cases in which they have financial ties to a litigant, editorialists and review authors with conflicts of interest should refrain from offering medical opinions.

Angell was still defending that decision a decade later, as editor in chief at the Journal, when she wrote in 2000 that disclosure was not sufficient to preserve the integrity of the science that appeared in her journal's pages: "We believe that a policy of caveat emptor is not enough for readers who depend on the opinion of editorialists." Why was it necessary to defend the Journal's policies? Partly because authors were ignoring them. In 1997, when Sheldon Krimsky, a professor of public policy at Tufts University, surveyed 61,134 articles in some 181 journals, he found that only 0.5 percent disclosed a conflict of interest related to the topic of the article, an impossibly low number given the fact that a quarter of biomedical researchers at the time were receiving funding from industry. The reason for this low rate of disclosure, as Krimsky notes dryly in his book, Science in the Private Interest, is that "author compliance is not especially high."

"Lots of eminent people took great offense at being accused of being influenced," Relman told me recently. "'What an insulting thing to say. I value my reputation; doctors and scientists know best. Trust us.' I spent the first 25 years of my career doing clinical research and being one of them, and I know the feeling." As Harvey Lodish, professor of biology at MIT, huffed to Technology Review in 1984, when Relman first required disclosure at the Journal, "Scientists have all kinds of private consulting arrangements with biotechnology companies and many own stock in these companies, but that's nobody's business. It has nothing to do with the quality of their research."

"They actually believe that they aren't influenced," says Angell. Aside from the fact that it's not in physicians' self-interest to acknowledge the effects of corporate money, they may have a hard time seeing the problem for the same reason fish don't know they're swimming in water: Doctors are surrounded by conflicts of interest almost from the moment they arrive at medical school. Pharmaceutical companies begin wooing young doctors with small tokens at first, pens and coffee mugs emblazoned with drug logos, then escalating to pizza night for medical residents, dinners at expensive restaurants and tickets to sporting events. Most schools offer a class in medical ethics, but there's no requirement that they discuss conflict of interest. Besides, a few lectures can't outweigh the message young doctors absorb every day, as they watch the icons in their profession--their professors, visiting lecturers, heads of departments--taking gifts, speaking on behalf of companies, flying first-class to medical meetings in Paris and Honolulu. By the time medical residents enter private practice or the lab, the gifts from industry no longer seem like gifts, but entitlements just another way to be compensated for all those brutal, slogging years of lousy pay and long nights.

A journalist friend of mine recently told me about the day his then-girlfriend, who was a neurosurgeon, received a check for several hundred dollars in the mail, along with a note from a drug company representative. It seemed his girlfriend had made favorable mention of a particular drug during a lecture she delivered a few days earlier, and the money was just a little thank you from the manufacturer. When my friend told her she could not in good conscience cash the check--that it was a conflict of interest--she looked at him, he said, as if he were speaking in some unintelligible language.

This deafness to the power of money to corrupt medical science leads physicians and scientists to display an arrogance and a remarkable naïvete, both of which were very much in evidence in a snippy editorial entitled, "Avoid Financial 'Correctness,'" written in 1997 by the editors at Nature. They derided disclosure as a waste of time, writing, "This journal will persist in its stubborn belief that the research as we publish it is indeed research, not business."

The Nemeroff case has not changed the editors' view substantially, although they did alter their policy after it broke. Nature Publishing now requires editorial and review writers, along with the authors of original research papers, to inform readers whether or not they have conflicts of interest, or to say they decline to declare. Charles Jennings, executive editor of Nature, says they have no intention of following the New England Journal in barring editorialists who have conflicts. "I flatly disagree with that policy," he told me. "That would exclude many of the leading experts. You don't want a policy that prevents Thomas Edison from writing about the future of electricity. Our position is for readers to decide for themselves about whether an author is biased."

Of course, most readers, especially practicing physicians, don't have the expertise or the resources to decide for themselves--to know how the studies might have been constructed differently, whether the conclusions have been shaded to favor the author's sponsor, or which data the author decided conveniently to leave out of the article. Knowing that an author might be biased doesn't aid in determining the extent and nature of the bias. It's not as though there will be two articles, one by a biased writer and one by an unbiased writer, published side by side to allow readers to identify the differences. Besides, conflicts of interest are now so pervasive, says Rennie, many readers scarcely take note, even when they're disclosed.

Race for the cure?

It's tempting to wonder what medical research would look like if universities and medical associations and editors of journals stopped talking about how to manage conflict of interest and started thinking about how to expunge it. Just say no. Proponents of Bayh-Dole will object, claiming the pace of medical advances will slow to a crawl, but bear with me for a moment and just imagine a different universe. Let's start with the medical schools "those temples of higher learning. They would be the first to cast out the drug merchants. Hospitals would pay their medical residents a decent wage so they can afford to buy their own beer and pizza. FDA advisory panelists who have a financial stake in the drug being considered would not be allowed to vote. And if the journals stopped publishing papers and editorials penned by academic clinicians with conflicts of interest, authors would be forced to choose between taking scientific credit and taking the money.

Of course, that's not going to happen unless academic clinicians somehow decide there's something wrong with the status quo. In Sheldon Krimsky's view, the only way to deter conflict of interest is for academics to feel shame. Maybe so, but as a journalist who has spent a decade and a half peering at medicine from the outside, nose pressed to the glass, I'm struck more than anything by the apparent lack of shame among clinicians when it comes to this issue.

Here's a little thought experiment. Imagine that a medical journalist "me, for instance" makes a tidy sum writing press releases for, say Pfizer, the manufacturer of Viagra. I don't make a fortune, maybe just enough to cover a year's tuition for my son's private high school. And let's say for the sake of argument I also buy a few dozen Pfizer shares. Then I turn around and write a story for The New York Times about several new drugs for treating erectile dysfunction.

What would you think, dear reader, should my financial relationship with the pharmaceutical company that makes one of the drugs featured in my story come to light? Would you have reason to doubt its objectivity and accuracy? Of course you would. Not only that, I would be ashamed to show my face in any newsroom, and I would not be writing for the Times again. I'm not trying to claim that journalists are paragons of virtue, but we have no illusions about our ability to withstand temptation and avoid shading what we say when faced with a wad of cash.

Not so in medical research. In that world, the author of a review article can have direct financial relationships with the manufacturers of drugs he is critiquing and still argue he has done nothing unsavory. What that suggests is a sense of fiduciary responsibility is not built into the professional code of medicine, a doctor's internal compass of right and wrong.

And of course there are also pecuniary reasons not to acknowledge the power of money. The fact is, universities and doctors have become so dependent on industry largesse they can't even imagine disentangling themselves. Repeal the Bayh-Dole Act? Not on your life. Kick the drug representatives who wheel their little carts filled with sample packets of drugs out of your office? Who would pay for all those trips to medical meetings in exotic locales?

Company line

And so they try to manage it. About half of universities require that faculty disclose their conflicts of interest. A scant 19 percent set limits on the outside financial interests faculty may hold. Harvard University, long considered a paragon of scientific virtue, is now considering relaxing its rules governing industry collaborations. Now that Angell is gone, even the once-starchy New England Journal has loosened its restrictions on editorialists and review writers, who are now free to enjoy some corporate largesse, just not too much. "They think it's possible to be virtuous and rich at the same time, to take money from companies and then manage it," says Angell. "They come up with rules that are so complicated in order to give the appearance of worrying about this, when what they are really worried about is the money might go away."

All their managing doesn't seem to be working, and we are the ones who will suffer the consequences. In March 2000, the FDA yanked a diabetes drug called Rezulin off the market after it had been linked to at least 90 cases of liver failure and 63 deaths. The withdrawal came three years after the agency had approved the drug to great fanfare. Articles in the popular media quoted diabetes experts who praised Rezulin, calling it "a truly novel approach," and the manufacturer, Warner-Lambert, enjoyed a spectacular 144 percent rise in its stock price.

By the fall of 1997, however, the FDA had already begun to receive reports of patients on Rezulin suffering liver failure, a side-effect that the agency's advisory panel glossed over during its deliberations. A paper published in the New England Journal also made scant reference to liver toxicity, saying the drug was "well tolerated, and most adverse events were considered to be related to the underlying diabetes." Several clinicians with ties to the company subsequently urged the FDA not to withdraw the drug, even as the body count was rising. According to a Los Angeles Times investigation, at least 12 of 22 scientists who played a central role in the federally-funded study of Rezulin received research funding or other compensation from Warner Lambert, while four of the 12 voting members of the FDA advisory panel that approved Rezulin, and kept it on the market an extra 30 months, had financial ties to the company.

When industry has penetrated every level of medicine from the lab bench to the FDA advisory panels, from the pages of the medical journals to your doctor's prescription pad, how are physicians to make decisions about treating their patients? How are they to know whether or not expensive calcium channel blockers are really better than over-the-counter diuretics for high blood pressure? (They're not.) Should you take a mildly depressed teenager to a psychotherapist, or put him on an antidepressant and risk sending him into a suicidal tailspin? Maybe a cholesterol-lowering statin drug will prevent this patient from suffering a heart attack, as the studies claim. Then again, maybe it will simply cause her muscles to break down and destroy her kidneys, one of the drug's side effects.

And what about us patients? What are we to do with the knowledge that much of what passes as science in medicine is little more than gussied-up marketing? There isn't much we can do. And so, I say if you're ill, if you are ailing, or just sick at heart, go find a doctor who listens, who holds your hand. Just make sure you find a doctor who looks at evidence, not opinion, and when she pulls out the prescription pad, start asking a lot of questions.

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Now, here's one designed to scare anyone over ... you'll have to guess at the arbitrary cut-off age:

NEW KIDNEY TRANSPLANT POLICY WOULD FAVOR YOUNGER PATIENTS

BY Gardner Harris

Younger patients would be more likely than older ones to get the best kidneys under a proposal being considered by the nation's ORGAN TRANSPLANT network.

The new policy would replace the current first-come-first-served system and is intended to provide better matches between the life expectancies of recipients and the functional life of donated kidneys.

"Right now, if you're 77 years old and you're offered an 18-year-old's kidney, you get it," said Dr. Richard N. Formica, a transplant physician at Yale University and a member of the panel that wrote the proposed policy.  "The problem is that you'll die with that kidney still functioning, while a 30-year-old could have gotten that kidney and lived with it to see his kids graduate fro college."

Under the proposal, patients and kidneys would each be graded, and the healthiest and youngest 20% of patients and kidneys would be segregated into a separate pool so that the best kidneys would be given to patients with the longest life expectancies.  The remaining 80% of patients would be put into a pool from which the network that arranges for organ matches, called the United Network for Organ Sharing, would try to ensure that the age difference between kidney donors and recipients was no more than 15 years.

The proposal is supported by many transplant surgeons and medical ethicists, but it faces an uncertain reception y kidney transplant patients and legislators.  A previous proposal to better match the health of patients and donor kidneys was scrapped in 2005 after the network was flooded with negative comments.  The network is hoping that this effort, which relies on a less complex formula than the earlier one, will get a better reception.

Donation systems for liver, hearts, lungs and other organs have already been reformed or changed in recent years, said Anne Paschke, a spokeswoman for the organ network.  However, kidney donations are by far the most common.

The kidney proposal does nothing to fix geographic disparities that cause patients in New York and Chicago to wait years longer than those in Florida.  Such local distribution results not only form concerns that far-away organs might not arrive in time but also because of distribution issues and turf battles between transplant centers.

The Best Organs Would Go To Those Most Likely To Live Longer

Dr. Lainie Friedman Ross, associate director of the McLean Center for Clinical Medical Ethics at the University of Chicago, said she opposed the new kidney transplant policy because "the biggest problem is geography, and they're doing nothing to fix that."  Dr. Ross said she also worried that any policy that favored young patients for the provision of kidneys from dead donors might reduce or redirect to the elderly donations from living donors who are unaffected by the proposed policy.

Dr. Trent Tipple a 37-year-old neonatologist from Columbus, Ohio, who got a kidney transplant when he was 21 and is again on a transplant waiting list after his donated kidney failed said he favored the proposal.  As the scope of kidney transplant expanded in recent years older patients began to crowd out younger ones from waiting lists "and I think there has to be some degree of reset," he said.  Dr. Tipple would benefit from the new proposal.

Medical rationing in the United States is common but not usually done by default.  Proposals to systematize ration9ing are rarely embraced, and Drl Formica and others involved with the proposal took great pains to explain it would not disadvantage most patients on waiting lists.  Dr. Formica admitted, however, that older patients would have a harder time getting a kidney under the proposal.

Dr. Ross was even more blunt.  "Under this policy, if you're 65, you might as well give up before you even get on the wait list."

The most common causes of kidney failure are hypertension and diabetes, so some of those waiting for kidney transplants got there because of their own poor choices.  Both diabetes and hypertension are linked with genetic and lifestyle factors.

Nearly 90,000 people are currently waiting for kidney transplants  In 2009, there were 10,442 kidney transplants fro dead donors and another 6,387 from live donors who generally specify the recipient.

The intent of a syste that favors the youngest and the healthiest is to ensure the best and longest use of donated kidneys.  But its effect will likely be to favor those for whom lifestyle choices are less likely to have played a role in their illness.

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, said the proposed policy was sensible.

"If it's a choice between saving grandpa or granddaughter, I think you save granddaughter first," Dr. Caplan said.  "It doesn't make sense to give people equal access to something if some people fail to benefit."

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TEST APPROVED TO MONITOR LEVELS OF KIDNEY REJECTION DRUG

A new test to monitor blood levels of a drug used to prevent rejection in kidney TRANSPLANT patients has been approved by the U.S. Food and Drug Administration.

The Novartis drug Zortress (everolimus) was approved in 2010 to help suppress the immune system and prevent rejection of a transplanted kidney. But if too much of this type of drug -- called an immunosuppressant -- builds up in a patient's blood, it could be toxic, said the FDA.

The just-approved QMS Everolimus Immunoassay helps doctors monitor blood levels of Zortress, which like other immunosuppressants must be taken by transplant patients for the rest of their lives.

QMS Everolimus is manufactured by Thermofisher, based in Waltham, Mass.

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MANY PATIENTS DON'T TAKE PART IN CANCER STUDIES

Just an estimated 2% to 4% of adults who are newly diagnosed with cancer  participate in clinical trials even though there are more than 8,000 such trials that are actively recruiting. One reason is that they may not know about these trials because their doctors may not tell them, suggests a new study in the Journal of the National Cancer Institute.

Of 1,522 doctors responding to a survey who treat colorectal and lung cancer, 56.7% said they had referred or enrolled at least one person in a clinical trial during the past year. Those doctors who saw more patients and who spent more time with new patients were among the most likely to refer their patients to clinical trials.

The survey was conducted by the Cancer Care Outcomes Research and Surveillance Consortium.

Medical oncologists and radiation oncologists were more likely to refer patients to clinical trials than surgeons. In addition, doctors who taught medical students or residents, and who were affiliated with a Community Clinical Oncology Program -- a network for community-based physicians to partner with academic investigators -- or a National Cancer Institute-designated cancer center were also more likely to refer patients to clinical trials.

"Low and slow accrual to cancer clinical trials limits the availability of state-of-the art therapies in routine clinical practice," conclude study researchers led by Carrie N. Klabunde, PhD, of the National Cancer Institute. "Closer examination of nonparticipating physicians in these settings might identify interventions that could be used to increase their willingness to participate in clinical trials."

Why Doctors Don't Tell Patients About Trials

The new study puts a number on something that the medical community has been aware of for a long time, says Leonard Saltz, MD, a medical oncologist specializing in colorectal cancer at Memorial Sloan-Kettering Cancer Center in New York City.  "The minor problem is that patients are declining the study, but the major problem is that patients are not being offered the studies," he says.

There are many reasons that doctors may fail to mention available clinical trials, Saltz says.  "It may be that a doctor doesn't have access to trials, and the patient would have to leave their practice to participate or have to travel," he says. "It may be that the doctor is simply unaware of what clinical trials are out there, and it takes a lot of time to find out, and that is not time that anyone reimburses them for."

Some patients may be unwilling to participate in clinical trials, but if they are unaware of these trials, they may not be able to make the most informed decision about their treatment.  "When a patient is diagnosed with any disease, especially one as terrifying as cancer, and hears that there is an established standard treatment, there is a tendency to tune out any limitations," Saltz says. "Doctors, wanting to be optimists, may not offer a whole lot of information on these limitations unless asked.  There is also the tendency to think about trials only after all else has failed, but by this time many people are no longer candidates or are too sick to participate."

Concern Over Random Treatment

Sometimes people are concerned that studies often randomly assign treatments to different groups of patients. Trials may compare standard care with the experimental treatment, but it is luck of the draw as to who gets which therapy.

"This is necessary, and the right way to do the study, but on the other hand, a fair number will say they are uncomfortable with it and not willing to leave the decision to chance," he says.

Informed consent on the part of the patient is critical, he says. When discussing clinical trial participation, Saltz says, "If you go on the study, it is because we hope it will be the right thing for you, and we will evaluate as we go always have the right to opt out. You can never say a trial is better for a patient because if we knew it was better, it wouldn't be a trial."

While clinical trials have advanced cancer care, "first and foremost, you owe it to yourself and people around you to make the best decision for you," he says.

Making an Informed Decision

Lori M. Minasian, ND, the chief of the National Cancer Institute's Community Oncology and Prevention Trials Research Group, co-authored an editorial that accompanies the new study.  "Most people learn about clinical trials from their physicians, and many do Internet searches when they are looking for newer or better approaches than the standard approach and some hear about trials that use public advertisement to recruit specific patient populations," she says in an email.

If your doctor doesn't mention clinical trials, "the simplest approach for patients is to ask about the trials in the context of the treatment discussion or at the end of that discussion," says Dr. Minasian.  The patient needs to know all their options to make an informed decision. "Many patients are willing to participate because they wish to try something better or they because they want to help the next generation, but clearly there are some who are afraid of participating or who are highly skeptical about participation," Minasian says.

Educating Doctors

Aman Buzdar, MD, vice president of clinical research at the University of Texas M.D. Anderson Cancer Center in Houston, says the new article is "right on target."

"It's important to educate physicians that we need more patients in clinical research and to inform the patient that participation may help them, but may advance the knowledge so that the next patient down the line gets the benefit of these types of therapies," Buzdar says.

Doctors have to take time to explain the upsides, downsides, and unknowns of both standard and experimental treatments to patients, he says.  "We must be very candid with the patient that there is preclinical data that the new treatment may be more effective or safer than the standard treatment, but we don't know. This may take one, two, or three visits and is time consuming."

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Evidence appears to be growing about a new, controversial treatment for MULTIPLE SCLEROSIS:

MS TREATMENT HELPS WOMAN

When Lesley Carlberg started noticing that even walking the family dog through the neighbourhood was taking its toll, she decided to be proactive with her MS with a recent Liberation Treatment in San Diego.

Carlberg used to look forward to taking her dog for a walk through her Clarkson neighbourhood.  But, diagnosed with Multiple Sclerosis (MS) 20 years ago, the chipper, upbeat mother of three began to notice last spring she could hardly make it around the block.  MS was taking its toll on her physical abilities and she wondered if it would just worsen as the years wore on.

To avoid that outcome, and an unknown future, Carlberg, with her husband's research and encouragement, made the decision to undergo MS ³liberation² treatment last fall in California.  She says it worked and she notices a big difference in her physical abilities.

This winter for the first time in many years, Carlberg went cross-country skiing. And now, she can walk as far as the big dog feels like walking.  The tightness in her chest that she'd been feeling for years, but had difficulty describing to doctors, went away.  The only MS symptom that hasn't changed much is the stiffness in her hands.  "But that's minor," laughed the real estate agent and stand-up comic. "I can't complain about my MS. I have such minor problems compared to others."

The still-experimental treatment involves inserting a balloon into the veins in the neck that connect the heart and brain and expand them, effectively stretching the vein. The treatment is still unrecognized in Canada, which means patients must travel elsewhere and pay for it themselves. It cost Carlberg $13,000, a portion of which she can get back through tax write-offs.

Doctors who worked on the first procedures had found a reduction of blood flow from the brain to the heart due to the narrowing of veins. It is believed that that condition is what causes build-ups of iron to form in the brain. Eventually, these would then cause the development of lesions and MS symptoms.

When doctors first started performing the treatment there was mixed opinion about its success.  Carlberg didn't read much about the procedure before heading to the Dr. David Hubbard Clinic, and she certainly wasn't afraid when the procedure began.  "I preferred not to know too much about the controversies," she said. "I'm glad I didn't read a lot. Sometimes it's better to be in the dark."

Walking out of the clinic hours later, Carlberg knew right away that she felt different.  Now, several months later, her quality of life is better and she recommends the treatment to other MS sufferers.

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STUDY IDENTIFIES ENZYME THAT MAY PLAY A ROLE IN CHEMO'S TOXICITY TO THE HEART

Scientists at Queen's University Belfast have made a discovery that could reduce the prevalence of heart failure and increase the survival rates of patients who have CANCER.

Lead investigator David Grieve and his colleagues from the school's Centre for Vision and Vascular Science have identified an enzyme called NADPH oxidase, which can cause life-threatening damage to the heart when a patient undergoes CHEMOTHERAPY. These toxic effects have restricted how much treatment an individual can receive.

"Our research findings hold clear potential for the creation of new drugs to block the action of the enzyme, which could significantly reduce heart damage in cancer patients," Grieve explained. "Ultimately, this could allow for the safer use of higher doses of chemotherapy drugs and make the treatment more effective against tumors."

The team is concentrating its efforts on defining the exact role of NADPH oxidase in causing heart failure as a result of cancer therapy. They believe that these findings may help pave the way to the creation of a drug that could save the lives of many patients who are undergoing chemotherapy.

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GM VIRUSES OFFER HOPE FOR BRAIN TUMORS

New research shows that oncolytic viruses, which are engineered to destroy cancer cells, might be more effective in treating deadly brain tumors if equipped with an enzyme that helps them penetrate the tumor.

The enzyme, called chondroitinase, helps the cancer-killing virus clear its way through the thickets of protein molecules that fill space between cells and impede the virus's movement through the tumor, say researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, who conducted the study.

When tested in animals transplanted with a human glioblastoma, the most common and deadly form of BRAIN CANCER, the enzyme-armed virus improved survival by 52 percent compared with controls and in some cases eliminated the tumor entirely.  The findings were publisheD in the journal Clinical Cancer Research.

"Our results show for the first time that an oncolytic virus with this enzyme can spread more effectively through the tumor and underscores the potential of using chondroitinases to enhance the capacity of oncolytic viruses to destroy cancer cells," says study leader Balveen Kaur, associate professor of neurological surgery.

The enzyme is derived from the intestinal bacterium called Proteus vulgaris. The enzyme removes sugar chains that branch from molecules called proteoglycans, which fill the narrow spaces between cells. By cutting away these branches, the enzyme clears a path that helps the virus spread through the tumor.

During this study, Kaur and her collaborators injected human glioblastoma cells under the skin of eight animals, and then, after tumors developed, treated the tumors with the enzyme-armed virus. These mice survived an average of 28 days, with two remaining tumor-free after 80 days. Control animals, treated with a virus that lacked the enzyme, survived 16 days.  In another experiment, mice with human gliobastomas transplanted into the brain survived 32 days versus 21 days for control animals, an improvement of 52 percent. Again, two animals lived more than 80 days and showed no trace of the tumor afterward.

Additional studies showed that the enzyme-laden virus had penetrated tumors in the animals' brain significantly better than the enzyme-free control virus.

"Overall, our results indicate that an oncolytic virus armed with this enzyme can have a significantly greater anticancer effect compared with a similar virus without the enzyme," Kaur says.

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POPULAR BONE DRUGS LINKED TO REDUCED COLON CANCER RISK

People who take drugs called bisphosphonates to prevent bone loss may also reduce their risk of developing COLORECTAL CANCER by almost 60% compared to those not on the drugs, a new study suggests.

Bisphosphonates include such common drugs as Fosamax (alendronate), Boniva (ibandronate), Actonel (risedronate) and Reclast (zoledronic acid). These drugs work by increasing bone thickness, thereby reducing the risk of fractures, the researchers said.  In prior studies, bisphosphonates have already been shown to be associated with a reduced odds for BREAST CANCER.

"These [new] findings are meaningful because they point to a possible protective effect of this class of drugs being relevant to prevention of many different cancers," said lead researcher Dr. Gad Rennert, from the Technion-Israel Institute of Technology Faculty of Medicine and chairman of the department of community medicine and epidemiology at the Carmel Medical Center of Clalit Health Services in Haifa, Israel.  "This is [similar] to the effect that we and others have shown for [cholesterol-lowering] statins," he said, noting that "bisphosphonates and statins share the same metabolic pathway."

The results of the U.S. National Cancer Institute-supported study are published in the Journal of Clinical Oncology.

For the study, Rennert's team collected data on almost 1,900 postmenopausal women who took part in the Molecular Epidemiology of Colorectal Cancer study, which is a population-based trial in northern Israel.  The researchers found that taking bisphosphonates, mostly Fosamax, for at least a year was associated with a significant 59% reduction in relative risk for colorectal cancer. 

"The magnitude of the reduced risk is less important because this is an association study; however, it is very significant after controlling for a dozen other known risk factors," Rennert said.  They took into account factors such as family history, ethnic background, diet, physical activity, weight, vitamin D consumption and the use of other drugs such as aspirin, statins and hormone replacement therapy.

The findings in this study show that bisphosphonates are associated with a reduced risk of developing colorectal cancer, but they cannot confirm a causal effect -- that is, the study doesn't prove that the use of bisphosphonates is responsible for the lower risk of colorectal cancer.  However, the lowered risk of colorectal cancer seen with bisphosphonates may be due to the way the drug acts in the body, which is similar to how cholesterol-lowering drugs called statins work, according to Rennert. These same researchers also found in another study that statin use also reduced the risk of colorectal cancer.

"We also found a similar effect last year with risk of breast cancer, which has already been replicated by three other groups," Rennert added.

A randomized trial is need to prove that bisphosphonates are protective against colorectal cancer, Rennert said. "It should be relatively easy, as it seems that all that is needed is a year of treatment to see the effect," he said.

The researchers noted, however, that the risks of using bisphosphonates include the possibility, in rare cases, of osteonecrosis of the jaw (destruction of the jawbone or jaw tissue). Bisphosphonates used for osteoporosis have also been linked to a rare fracture of the thigh, according to the U.S. Food and Drug Administration.

"The adverse effects profile is of major importance if bisphosphonates are going to be recommended for cancer prevention in healthy people," the study authors cautioned.

Commenting on the study, Eric Jacobs, Strategic Director of Pharmacoepidemiology at the American Cancer Society, said that "the lower risk of colorectal cancer risk seen among bisphosphonate users in this study is intriguing."  However, these results should be interpreted with caution and require confirmation by additional studies, he said. "Results from the only other study of bisphosphonate use and colorectal cancer, a recent large study from the United Kingdom, do not support an important protective effect," Jacobs noted.

Fortunately, there are other proven ways to help lower risk of colorectal cancer, he said. "In particular, all Americans, 50 or older, should get a screening test so that precancerous polyps can be detected and removed before they turn into cancer."

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Ready for Spring, anyone?  See you next month ...

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And if you have any thoughts of how this newsletter could be improved, please email me directly, at jesmer_e@pacbell.net

Elaine Jesmer

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