Strong Medicine   

The New England Journal of Medicine is a dominant, authoritative force in the world of medical news. But its embargoes, insistence on exclusivity and periodic conflict of interest problems stir controversy.

NEWS COMES IN MANY DIFFERENT PACKAGES, but only rarely does it arrive in such stark black and white. Okay, there are some maroon accents on the cover of The New England Journal of Medicine, and inside the occasional colorful graphics and photos really pop out. But it's mainly black and white, seemingly dry as dust, about as newsworthy as a pile of last week's press releases.
Yet there it was--a study destined to be a front page story in 17 of the country's largest newspapers, rate some kind of play in dozens of others, and get coverage on CNN, NBC and NPR. In the Journal, it had the dry title ``Association between Cellular-Telephone Calls and Motor Vehicle Collisions." By combing through cellular phone records and matching calls with the times of car accidents, Toronto researchers had linked cell phone chat to car wrecks.
For Dan Haney, the Associated Press' medical editor, this was just one of the hundreds of times the Journal has delivered pay dirt to his desk. Sure, says Haney, it may have seemed obvious that talking on a cell phone while driving is risky, but here was objective evidence in a prestigious medical journal to support the hunch. ``There is a function to proving the obvious,'' says Haney. Rob Stein, the Washington Post's deputy national editor for science, says the cell phone study was an ``easy sell'' for front page play. And at the Journal itself, there was an inkling that the cell phone study would probably hit a nerve and add another 15 minutes to the eons of fame the Journal has banked over the years.
The cell phone study and how it was covered is just one example of why ``according to a study published in The New England of Journal Medicine'' has become one of the great totem phrases in American medicine and newsrooms. Publication in the Journal is one of the world's best press releases; a badge of scientific excellence; and a big, fat acceptance letter from the elite medical establishment. For medical researchers, who live in a publish-or-perish world, having a paper accepted by the Journal can be an important rung on the ladder to tenure or, at the very least, an impressive bauble on the curriculum vitae. For medical reporters, the Journal is in many ways a dream source: arriving every week, credible, and with brand-name cachet. But it comes with strings (some say chains) attached: an embargo, which can put a straitjacket on enterprise, and the controversial ``Ingelfinger rule,'' a warning that the Journal's editors will reject any paper that has been previously published--a rule critics say has become a gag order on scientists and a disservice to the public.
And working in a world dominated by big research money and highly competitive pharmaceutical and other medical companies, weeding out conflicts of interest is a continual problem. In November, the Journal was embarrassed when it published a critical review of ``Living Downstream,'' a book about the environmental causes of cancer by prominent breast cancer activist Sandra Steingraber. The reviewer, Jerry Berke, was the medical director of W.R. Grace, a chemical company, at the time he wrote the review. This was not disclosed. In an editor's note, the Journal's book review editor admitted that Berke had given his address as W.R. Grace, but ``this escaped my attention.''
As an editorial entity, the Journal is really one of a kind. Like all scientific and medical journals, it is supposed to be the written record of medical and health science. And science, in the ideal, is supposed to be an objective enterprise with strict protocols, rules of evidence and analysis. Certainly the Journal and other publications like it are passive participants in the scientific field. The Journal doesn't pay the authors it publishes. It is not the Journal editors who decide to do a study on Persian Gulf War illness or breast implants. Those decisions are made primarily by researchers and by the people who hold the researchers' purse strings--foundations, the National Institutes of Health and, to an increasing extent, private industry. Ultimately, what the New England Journal publishes is ``more a function of what we get than what we like,'' says Jerome Kassirer, the Journal's editor in chief.
But Kassirer would be the first to admit--even boast--that the Journal is anything but passive about what it chooses to publish. In fact, it is intensely judgmental. Only about one out of every 10 of the original research studies submitted to the Journal makes it into its prestigious pages. Like editors everywhere, Kassirer and Marcia Angell, the executive editor and second-in-command, worry about keeping their publication lively and accessible. ``We look at ourselves as the canaries,'' says Angell. ``You know, if we choke, it is too much. We stand in as proxies for the readers.''

THE JOURNAL HAS BEEN AROUND SINCE1812, though it has been published under its current name only since 1928. Historically, the Journal has been about as Crimson as you can get without actually being part of Harvard. Until Arnold Relman became editor in 1977, virtually every editor of the Journal had close ties to Harvard or one of its numerous teaching hospitals. In a talk Relman gave a few years ago, he credited Joseph Garland, the Journal's editor from 1947 to 1967, with transforming the publication from ``essentially a local journal to a world-class institution.'' But more often the credit for making it a major league magazine goes to Franz Ingelfinger, who succeeded Garland. By publishing only signed editorials, Ingelfinger shook off the Journal's identity as a house organ for its owner, the Massachusetts Medical Society.
But to many of today's medical reporters and researchers it is Relman, not Ingelfinger, who is most closely identified with the Journal's ascendancy. It was Relman, a kidney specialist, who turned the Journal editorship into a bully pulpit, assailing the commercialization of medicine and the greed of doctors. Relman was so outspoken ``you'd think he was against doctors and against medicine,'' says Peter Gorner, a former science writer for the Chicago Tribune. One Boston-based researcher, who would speak only anonymously, says researchers used to joke that no matter how half-cocked a study's methods or conclusions might be, it stood a chance of getting published in Relman's Journal as long as ``for-profit hospitals stink'' appeared somewhere in the conclusion.
Judging by its location, it would be almost impossible not to assume that the Journal is part of Harvard. Its editorial offices occupy the entire sixth floor of Harvard's medical library. Inside, the Journal's offices have the authoritative feel of a white-shoe law firm--lots of dark wood, a deep rose carpet and about 40 editorial employees. To anyone accustomed to the clutter and chaos of a newsroom, the offices are eerily clean and orderly. Just about the only noise is a receptionist answering phone calls and the low-level chatter of computer keyboards.
Kassirer, 65, seems slightly rumpled in contrast to the office he runs. He has unruly eyebrows, heavy bags under his eyes, a whitish-gray mustache and a careful, slightly labored gait that suggests he is not in any great rush. Managed care and profit motive in medicine are his favorite editorial punching bags. Taped above his computer screen is a pull-out quote from a Boston Globe story that repeated a line from his July 6, 1995, Journal editorial titled ``Managed Care and the Morality of the Marketplace.'' The yellowing clip reads, ``Jerome Kassirer: We gave up too easily.'' Kassirer has also come to the defense of public hospitals and assailed the National Rifle Association for its attacks on federal health research into gun injuries. In a surprise last year, Kassirer came out in favor of allowing physicians to prescribe marijuana.
Unlike Kassirer, Marcia Angell, 56, has never practiced medicine but is a virtual Journal lifer, having worked there for almost 20 years. She was Relman's protegé and his presumed heir in 1991 when Kassirer was named editor in chief. Angell is personable, witty and is at ease in front of an audience (when she spoke at the National Press Club last September, the laughs outnumbered the tough questions by a wide margin). Her writing is lucid--a rare quality in medical writing--and the views she expresses can be refreshingly provocative. Her 1996 book, ``Science on Trial,'' argued against the Food and Drug Administration ban on breast implants, for example. And last year she wrote an editorial favoring physician-assisted suicide, which included an account of how her 81-year-old father committed suicide the night before he was to be admitted to the hospital for metastatic prostate cancer.
Lately Kassirer and Angell's opinions have been making as much of a splash as any of the studies they publish. Their January 1 editorial questioning the public health benefits of weight loss was a fresh take on the obesity-as-illness idea permeating health coverage about the fattening of America. The bitter controversy over whether U.S.-sponsored experiments with the anti-AIDS drug AZT on pregnant women in the Third World should include a subset of women who would receive placebo treatments was covered in Science magazine and elsewhere last year.
But it took a sharply worded editorial by Angell and commentary by critics Peter Lurie and Sidney Wolfe last September for the issue to get wide attention. Angell invoked the infamous Tuskegee Study, in which black men were deliberately infected with syphilis, in her editorial criticizing the trials. Two weeks later, two prominent AIDS researchers on the Journal's editorial board, David Ho and Catherine Wilfert, resigned in protest over not being consulted about the editorial beforehand. Lawrence Altman's front page story in the New York Times on the resignations quoted Harold Varmus, head of the National Institutes of Health, as saying that the Journal was ``trying to attract more attention by making political, ethical, philosophical and economic statements that have traditionally not been in that journal in such an inflammatory way.''
Though the value of the placebo trials remains a hot controversy, Angell was vindicated in February when the trials were canceled because a cheap way of using AZT for pregnant women was proven to be effective. But Varmus' put-down also rang somewhat true. Despite the staid appearance and editors' solemn invocation of objective science, the fact is that medical journal journalism is bruisingly competitive these days in part because big money is at stake.
True to its Boston roots, the Journal affects a Brahmin, above-it-all air, and money is not a fit topic for conversation. Both Kassirer and Massachusetts Medical Society officials declined to comment on Journal revenue. And the society's IRS filings aren't much help: Figures for the Journal are not broken out in the three most recent publicly available tax filings. Perq/Healthcare Communications Inc., a Princeton, N.J.-based company that tracks medical journal ad revenue by counting display ads, estimates the Journal's 1997 display ad revenue to be $26 million, a figure understood to be inflated because it doesn't include volume discounts. The Journal comes in second behind the Journal of the American Medical Association (JAMA). But unlike JAMA, which is free to members of the AMA, the New England Journal makes a lot of money from subscriptions. Simple arithmetic (at least 200,000 paying subscribers multiplied by the $122 annual subscription price) suggests subscription revenue in the neighborhood of $24 million.
But the hurly-burly doesn't end with the scramble for ads and subscribers. The unpleasant fact of life for the Journal, and every other medical publication, is that medical research itself is increasingly competitive, commercialized and fractious. There is a long and fruitful history of private industry paying for medical research in this country, but it now covers more than half of the nation's medical research budget. The NIH estimates that in 1994 industry money accounted for 52 percent of $33 billion spent on U.S. medical research.
With all that private cash flowing into research labs and studies, medical research has become a petri dish for conflicts of interest, with researchers vying for patent rights. And though how often it happens is an open question, sponsoring companies have moved to stifle research results if studies they pay for make their products look bad. Recently, Boots Co., a British drug company, tried to block publication of a study that showed that its huge money maker, the synthetic thyroid drug Synthroid, was no better than rival products. After Ralph T. King Jr.'s story in the Wall Street Journal exposed the attempted cover-up, the study was published in JAMA, along with an extraordinary six-page editorial by a JAMA editor detailing the whole saga.
For research that does get published, the thin line of defense against conflicts of interest and tainted findings is an honor system that depends on researchers disclosing to the medical journals their financial dealings with private industry. In the case of the Journal, those dealings are then disclosed to readers when the paper is published, albeit in small print at the end of the article. For editorial and review writers, the Journal has one of the strictest policies in the business: They are not supposed to have any financial dealings related to the subject at hand.
In 1996, it was found that the coauthors of a Journal editorial favorable toward obesity drugs like Redux--one of the drugs the FDA yanked off the market last September because it caused heart valve damage--had worked as industry consultants. Kassirer and Angell responded by writing a long editorial criticizing the authors. They also tightened up their editorial and review policy, requiring writers to sign a statement saying they have ``no current, recent past, or planned future'' associations with a company that stands to gain from a product discussed. That policy is hardly a guarantee, as shown by the fiasco involving book reviewer Berke and his W.R. Grace affiliation. It was all the more embarrassing because W.R. Grace is one of the defendant companies featured in ``A Civil Action,'' the Boston-set bestseller and soon-to-be-released movie about the court fight over cancer-causing pollution of the water system in Woburn, Massachusetts.
``We can sometimes go through six people before we find someone'' to write an editorial, laments Kassirer. ``Some companies will try to buy every investigator in the field. They put a scientist on an advisory board or they'll have them come up and give a lecture or something like that.''
Nonetheless, Kassirer loves his job. ``People take potshots at you all the time. But the rewards of this job are extraordinary. How many people have an opportunity to reach 240,000 subscribers, plus at least half again the number of readers, every week, plus the kind of publicity we get in the media? How many people have that opportunity to speak about what is important in medicine?''

LAWRENCE ALTMAN, ONE OF THE MOST influential medical journalists of his generation and the New York Times medical reporter since 1969, is often credited with being the first to see that front page news did, indeed, lurk in those dry, statistics-laden pages of the Journal. ``I always accuse Larry Altman of creating this mess because he was smart enough to see that there was good medical news in The New England Journal of Medicine,'' says Mark Bloom, a veteran medical reporter and editor of the New York City-based Physician's Weekly. Altman says he didn't set out to cover the Journal per se, but that he was hired as part of a concerted effort by the Times and then-Executive Editor A.M. Rosenthal to beef up its medical coverage.
But in many newsrooms, it is Dan Haney's byline on the national AP wire that is most closely associated with The New England Journal of Medicine. Haney gives credit to Warren Leary, now a New York Times science writer, for first mining the Journal for news in the early 1970s. ``He established the idea that someone in the press was looking at the New England Journal on a regular basis,'' says Haney. When Leary took a job in the late 1970s as a science writer in the AP's Washington bureau, Haney started to cover the Journal for the wire service. ``The week after Leary left, the news editor came by my desk with The New England Journal of Medicine, plopped it down and said, `See if there is anything in there,' '' says Haney.
As a novice, Haney was unsure of himself in the technical, jargon-filled world of medicine. He says he would often tape interviews and listen to them several times or even transcribe them. ``A light would go on in my head, and I would begin to understand it,'' he says. The effort paid off; Haney says his Journal stories flew out on the national wire and often got page one play.
About 3,600 manuscripts attempt to make it through the Journal's rigorous editorial gauntlet each year. About 2,500 are scientific research papers. The remaining 1,100 are what Angell calls ``soft articles''--health policy and opinion pieces, of which she is in charge. Kassirer rejects about 100 of the scientific articles right away, he says, because they are about ``cells or mice or something like that'' and not really about medicine. The 2,400 survivors are then sent to the Journal's six part time associate editors, each of whom specializes in an area of medicine--infectious disease, internal medicine and so forth. Those editors reject, on average, another 800 or so papers and then send out the remaining 1,600 for peer review.
A whole mythology surrounds peer review, which is used by most of the large circulation medical and scientific journals. Altman, who believes peer review has been oversold as a Good Housekeeping Seal of Approval, simply calls it editing. Regardless of the label, the essential idea behind peer review is to have outside experts go over a manuscript and recommend whether it should be published. At the Journal, the associate editors pick the reviewers, usually two per manuscript, and ask them to give the manuscript A-through-D letter grades in four different categories, such as accuracy and originality, and recommend acceptance or rejection. They are also invited to offer a short written comment. The reviewers also sometimes anonymously send separate comments directly to the paper's authors.
When researchers complain about peer review they sound a lot like reporters grousing about editors. ``Anybody who has been subjected to peer review can tell you that a lot of it is just random,'' says Ronald E. LaPorte, a University of Pittsburgh disease researcher. Especially in narrow fields where all the qualified experts know each other, the supposed anonymity is pretty transparent. And almost by definition, peer review tends to reward conventional wisdom rather than bold new thinking.
Defenders acknowledge the flaws, blind spots and possible abuses but say those costs are outweighed by the benefits of having research vetted. Noting that the conclusions of a paper often change as a result, Angell believes research isn't finished unless it has been scrutinized by peers.
Whatever its deficiencies, peer review helps cull the herd. The remaining papers are discussed by the Journal's 17-member editorial staff, which meets every Thursday over lunch. Angell says disagreements tend to be about genetic papers, which intrigue some editors but leave others wondering about their practical significance for doctors. And according to Angell, every editor has a limited number of OMDBs--over-my-dead-bodies--at his or her disposal. Over the course of a year, the staff will reject 350 of the 600 papers that got favorable remarks from reviewers. In the end, 250 scientific papers are published.

THERE ARE TWO LONGSTANDING RULES AT The New England Journal of Medicine: a pre-publication embargo date and the Ingelfinger rule. Controversy about both ebbs and flows, but never goes away altogether.
The embargo is a fairly straightforward matter, with Journal-versus-the-press fights flaring up periodically. For $297 a year most medical reporters get their copies of the Journal on the Monday before the official Thursday publication date. Reporters are asked to sign an annual ``embargo contract'' when they send in their check. From the Journal's perspective, an embargo creates a certain orderliness and works to preserve the newsiness of the Journal.
In theory, the embargo is not something that seems to trouble many medical reporters or editors. But when a reporter gets an upcoming Journal story in some other way, there have been problems. That is what Reuters said happened in 1988 when it allegedly broke an embargo on a study that showed that taking aspirin regularly could help people avoid heart attacks. The Journal knocked the wire service off the mailing list for six months. Reuters said it was being punished for a reporter's initiative.
Two years later, a similar situation cropped up when the Washington Times broke a story about an Army AIDS vaccine study. The reporter said he put his piece together through interviews and never saw the Journal's study. And in April 1994, ABC broke an embargo on a Journal study with the contrarian finding that beta carotene might increase the risk of cancer. The National Cancer Institute held a briefing on the study results on a Tuesday, so the network argued that it was legitimate to run with the story that night rather than wait a day. While Kassirer was quoted as saying, ``I am beside myself. It just astonishes me,'' the Journal didn't cancel the network's mail privileges because, it said, the network expressed regret about the decision.
The biggest science story last year--Dolly, the cloned sheep--appeared on the front page of nearly every paper in the country on Sunday, February 23, because Reuters broke an embargo, moving a story on Saturday that, according to the Washington Post's Rob Stein, was triggered by a story in one of the London Sunday papers.
The issues surrounding the Ingelfinger rule are much more complicated. The New York Times' Altman wrote a two-part series on the rule last year for The Lancet. Altman reported that Ingelfinger instituted the rule in 1969 after discovering that the details of a study he had published in the New England Journal had already been written about in two publications distributed free to doctors. ``Rather than conceding a scoop, he retaliated,'' Altman wrote. ``He announced henceforth NEJM's policy would be to reject a paper if it had been published elsewhere, in whole or substance.'' Eventually, most of the major medical journals followed suit.
The Ingelfinger rule has caused all sorts of friction. There is a fundamental difference between medical research findings, which can alter standard treatments and affect thousands of lives, and other kinds of news, which rarely do more than inform or entertain. In 1988, when Reuters broke the embargo with the aspirin story, the Journal came under sharp attack for not disclosing the results of the government-funded study sooner. That the Journal could control when the government made information public set off alarms. The NIH held a conference on embargoes and the stranglehold medical journals have on the release of research findings several years later. The headline on a Time magazine story about the conference read, ``Delays That Can Cause Death.''
In his Lancet article, Altman paraphrases Relman as saying at the conference that if the government reviews a study and decides to release it before publication, the Journal would not object. Later that year, after Kassirer became editor, he and Angell cosigned an editorial about the rule that said they would defer to authorities at NIH and CDC if they felt pre-publication disclosure of a study was necessary ``because of immediate implications for the public health.''
Using that same reasoning, the Journal has waived the rule on its own from time to time. It did so last summer when it allowed the authors of a study documenting the connection between fen-phen diet pills and heart valve disease to go public with their findings in July and still get their research published in the Journal seven weeks later. The early publicity led to more cases being reported to the FDA.
Often researchers are jittery about releasing any information that might ruin their chances of publication in the Journal or elsewhere. For top medical reporters like Altman and Haney, covering scientific meetings where word of new studies, treatments or drugs often first emerges is an important part of their beat. But there are still cases in which researchers hold back because they worry--or have been told directly--that publicity and talking to the press will jeopardize their chances of publication. Altman reported that researcher Nathaniel Landau intended to present an important finding at last year's international AIDS meeting in Vancouver, British Columbia, on how HIV enters white blood cells. According to Altman, Landau decided not to because the editors of Cell, where his research was slated to be published, said he shouldn't.
A handful of researchers resent the Journal and other publications for imposing gag rules. Says Robert Brook, a UCLA health researcher: ``We ought to be able to discuss research with anyone we want to discuss research with without jeopardizing publication.''
Angell notes that some researchers use the Ingelfinger rule to their benefit. ``You have talked to researchers who say they feel chilled. But I have talked to researchers who say they have invoked [the rule] because they don't want to talk to reporters.''
The Post's Stein says he appreciates the position that the research information should flow freely, especially if it has been paid for with taxpayer money. ``But the more important thing is how the public is best served,'' he says.

OF COURSE, ALL THIS MATTERS BECAUSE the Journal is presumed to matter. At least for now, that seems to be a fairly solid presumption. For many medical researchers, the New England Journal is still the major leagues. And for medical and health reporters, the Journal still provides a week-in, week-out view of what is new and important in the diffuse and arcane world of medical research. When Richard Sammon, a reporter with Congressional Quarterly, introduced Angell at the National Press Club last fall, he said the Journal ``is cited so often by mainstream news organizations that its influence on the public's views about health are hard to exaggerate.''
But as with everything else today involving information and the media, the Journal's clout can't be taken for granted. At science desks, infatuation with the ``latest study'' may be waning. The Chicago Tribune's Gorner disparages slavish attention to reporting what is in the week's scientific journals as ``stenography--copying things out of magazines.'' The Tribune, he says, tries to cover science and medicine like it was a brawl. Haney at the AP has also heard grumblings about medical news and ``contradictory bulletins from the medical world.'' At the same time, the appetite for detailed, relevant health and medical news seems to be insatiable, as evidenced by the proliferation of health newsletters and traffic on health- and medicine-oriented Web sites. Clearly people are not waiting to get their dose of medical news delivered from on high, from the Journal, dutifully translated by the press.
So maybe the Journal's influence has peaked? In the best of all worlds, that might mean a bolder, more independent-minded health press. At the same time, with all the hidden agendas and commercial interests in health research, maybe the imprimatur of ``as published in the New England Journal of Medicine'' will become that much more important as the press and its audience struggle to separate the information wheat from the misinformation chaff.