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Changes in ethics and expectations are driving the way pharma interacts with medical publishers.


Pharmaceutical Executive

When Jim Dougherty Joined Mcgraw-Hill Almost 30 Years Ago, medical journal publishing was different. The days of the "three-martini lunch" were slowly coming to an end. Yet many companies still determined their ad schedules based on relationships. There was also less competition: without DTC or the Internet, journals garnered larger percentages of pharma's marketing mix. Today, Dougherty is group vice president of McGraw-Hill Healthcare Information and president of the Association of Medical Publications (AMP), an organization of publishing firms in the medical field. Like many of his peers, Dougherty has witnessed—and continues to witness—the transformation of the field. The future is bright, he says, but most certainly uncertain.


Instead of just sending in a manuscript, with clinical trial registries, you might have an opportunity to link to the spreadsheets or other individual case reports to offer a more in-depth review. –Jim Dougherty, group vice president of McGraw-Hill Healthcare Information
Today, with pharma-sponsored research under the microscope, medical journal publishing is faced with sorting out issues of credibility and transparency, not only for themselves, but for pharma. To complicate matters, journals must make these changes in a particularly difficult business climate, with increasing scrutiny of the public and the press. To offer readers insight into how medical journals are handling these challenges—and how they affect pharma—Pharm Exec went inside the world of journal editors and publishers.

No More Ghost Stories The recent changes sweeping the editorial offices at journal publishers might be viewed as an extension of the trend to separate real scientific content from marketing information. Some associate that change with the shift the Office of the Inspector General (OIG) prompted in the world of continuing medical education.


Another way conflict of interest disclosures may evolve is to require not just authors, but the writers and editors with whom they collaborate, to disclose any industry relationships relative to a manuscript's content. –Judy Orvos, editor of Contemporary Ob/Gyn
At the base of it, journal editors are trying to do away with publishing ghostwritten articles. "The issue of guest authors and ghost authors has plagued medical journals forever," says George Lundberg, MD, former editor of the Journal of the American Medical Association (JAMA) and current editor of Medscape General Medicine. "Sometimes they're guests, sometimes they're ghosts. It's the editors' job to flesh out the guests and flush out the ghosts."

Just as physicians at CME events are discouraged from presenting promotional slides handed to them by a sponsoringpharma company, researchers can't just sign their name as anauthor. Editors—certainly at primary research, peer-reviewed publications, but increasingly at other journals—have adopted policies that require authors to disclose their conflicts of interest.


First-to-publish has been the criterion for a long time in terms of who gets credit for certain information. The more you disclose during the research process, the more you open up the opportunity for others to get their own results going earlier. –Tim Bacon, president and CEO of PeerView
"Authors are used to it," says Jordana Bieze Foster, editor of Applied Neurology. "Anybody who's published in an academic journal has done it for years."

Nonetheless, says Diana Mason, RN, editor of the American Journal of Nursing, it's still common to find authors who are unsure about—or try to mask—financial ties to healthcare companies. "I don't think the nurses who write for us understand the issues. At least twice, the authors of manuscripts we accepted for publication told us they had no financial disclosures to make. Then, as we were going into production, we discovered they had very serious financial disclosures.


It is in industry's interest to promote positive data and downplay the negative.The issue is that the general public wants simple answers and industry wants to provide them—even though the simple answer may not be appropriate. –Janice Radak, editor-in-chief of Geriatrics
"We always get the 'Well, I didn't know,' when they probably did know," she says. "We are going to adhere to a standard of honesty and disclosure to make sure the readers know if there are any potential financial conflicts of interest."

Do editors think there need to be additional measures to ensure transparency? Lundberg says that, although they're committed to them, current measures are already onerous.


Authors are used to conflict of interest disclosure statements. Anybody who's published in an academic journal has done it for years. –Jordana Bieze Foster, editor of Applied Neurology.
Janice Radak, editor-in-chief of Geriatrics, offers: "As an editor I don't want to have to examine some author's IRS statements, but neither do I appreciate hearing, 'Oh, maybe should I disclose...?' I think a big part of the evolution of disclosure is making the researchers more aware of their ethical responsibilities."

Judy Orvos, editor of Contemporary Ob/Gyn, says another way conflict of interest disclosures may evolve is to "require not just authors, but also the writers and editors with whom they collaborate, to disclose any industry relationships relative to a manuscript's content."


One of the "rules" of journal editors is to keep various players in healthcare on their toes. At the same time, transparency is an area where we can work more collaboratively. It allows pharmaceutical companies to behave in a way that allows them to be trusted, and for that trust to be built on a background of transparency. –Fiona Godlee, editor of the British Medical Journal
At the same time, journals need to ensure these changes actually increase transparency. "Not all journals provide the ability to acknowledge contributors who may not rate as a full author, but whose contributions materially impacted the research," says Tim Bacon, president and CEO of PeerView, a publication strategy consultancy.

Clinical Trial Registries In 1978, a group of journal editors met in Vancouver to set guidelines for formatting manuscripts. They suggested authors number pages starting with the title page, leave generous margins, and double-space. But they also set formats for how to describe participants, state conflicts of interest, and discuss results.


One problem is ambiguity over what type of trial should be registered. We don't know enough about this middle ground of trials that fall between those clearly not affecting practice and those that have a primary purpose to affect practice. There's no doubt about Phase III. It's the Phase II and small randomized Phase I trials that are difficult to decide about. So we're going to get our feet wet and formulate what amounts to case law to guide us so each journal will treat articles consistently.–Harold C. Sox, MD, MACP, editor of the Annals of Internal Medicine.
Over the years, the so-called "Vancouver group" evolved into the International Committee of Medical Journal Editors (ICMJE). And it is that organization that put forward a new policy that is changing the way companies handle how they communicate research with professionals: As of July 1, 2005, all clinical trials research must be registered if sponsors want to ever publish their results in a member journal.

The idea for clinical trial registries gained steam in June 2004, when New York State Attorney General Eliot Spitzer sued GlaxoSmithKline (GSK) for withholding negative trial data on the use of Paxil (paroxetine) in children. Soon, journal editors also were demanding a new way to put drug information into context.


This new study will be more well-received because it will show product managers how to optimize their promotional mixes. They can go to the individual product level and see how the brand and its competitors are doing with regard to promotional effectiveness. This could be the best tool for the industry to use its money effectively on promotion—we'll know in the next few months if it's going to happen. –Art Wilschek, director of worldwide ad sales for the New England Journal of Medicine
"It is in industry's interest to promote positive data and downplay the negative," Radak says. "The issue is that the general public wants simple answers and industry wants to provide [them]—even though the simple answer may not be appropriate."

"When only some of the trial results are reported, they tend to be the positive ones," says Harold C. Sox, MD, MACP, editor of the Annals of Internal Medicine. "Then doctors and patients have an inflated view of how good the intervention is."


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In some ways, registries may create a cost-effective repository for negative or insignificant results. "Some physicians would like to see the data even if it didn't come to a conclusion," says Paul Weislogel, executive vice president of publishing for Lippincott Williams & Wilkins. "No journal could support a journal of negative results. That's not in the best interest of pharma and that's not necessarily in the best interests of journals—it's another way that publishing and pharma are closely linked."

Fiona Godlee, editor of the British Medical Journal, sees transparency as a way for pharma and journals—which have traditionally maintained a combative relationship—to work together: "One of the 'rules' of journal editors is to keep various players in healthcare on their toes," Godlee says. "At the same time, transparency is an area where we can work more collaboratively. It allows companies to behave in a way that allows them to be trusted, and for that trust to be built on a background of transparency."


At least twice, the authors of manuscripts we accepted for publication told us they had no financial disclosures to make. Then, as we were going to production we discovered they had very serious financial disclosures. We always get the "Well, I didn't know,' when they probably did know. –Diana Mason, RN, editor of the American Journal of Nursing
Coming out of the GSK case, there was much industry support for the idea of clinical trial registries. Eli Lilly and AstraZeneca, and organizations such as PhRMA—and most recently, the International Federation of Pharmaceutical Manufacturers and Associations—created registries on their Web sites. But that wasn't industry's first experience with the practice. Under the FDA Modernization Act of 1997, FDA established the National Library of Medicine registry (www.clinicaltrials.gov) and required registration of all clinical studies for life-threatening diseases. It was largely designed to make patients more aware of clinical trials they could participate in.

ICMJE doesn't mandate a specific database with which companies must register their trials—so long as registries are publicly accessible and free. But when it talks about registries, it is generally referring to clinicaltrials.gov. Because of that, editors often refer to registries' dual goal of increasing transparency and building a clinical trial patient-recruitment tool.

In reality, that recruitment function may be much more limited. "It will vary by condition," Bacon says. "Most expect that it will prove a useful tool only for those who used it before: patients with orphan or life-threatening diseases who are motivated to get on the Web and seek out clinical trials."


Some subscribers are taking the online-only subscription. That leads us to an interesting situation for advertising because, so far, companies have not embraced the Web as an ad vehicle. –Lenne P. Miller, senior director of publications for the Endocrine Society.
Most stakeholders agree that clinical trial registries are a good idea—they just don't agree on specifics. ICMJE wants companies to register all "clinically-directive trials"—those whose primary purpose is to affect clinical practice—before they enroll their first patient. And they're not the only ones. The Fair Access to Clinical Trials Act introduced to Congress in October 2004, requires companies to register research at clinicaltrials.gov. In addition, the World Health Organization (WHO) has designated a registration advisory group to establish a clinically meaningful trial registration process.

However, some say medical journal editors aren't the most appropriate gatekeepers: "Publishers certainly have cause for concern if they feel the flow of manuscript submissions is being biased based on interference from grantors," says John Carter, vice president of publishing operations for Slack. "But I'm not sure that a new entity formed by a group of publishers is the most appropriate body to address these issues."


If an article comes out of a registry so it is possible to trace the trial through its various stages, it would make the review a lot easier. In theory, it would even make it faster and better. But we're a long way from having that. –George Lundberg, MD, editor of Medscape General Medicine.
No nonsense ICMJE recently published an editorial updating the specifics of working with trial registries. Among other changes, the group has adopted WHO's 20-item questionnaire to collect the basic information companies must provide to register a trial. Editors emphasized that authors must fill out items completely and with relevant information.

"Trial sponsors don't always enter useful information into the field called 'intervention,'" Sox says. "They say 'investigational new drug' instead of Vioxx, for example. That's contrary to the spirit of the registry—it deliberately misleads people. Eventually, authors and sponsors will get the word that if they don't input useful information into each field, we'll refuse to consider the trial."


We know a large percentage of authors are willing and able to pay publication charges for open access. It's possible there will be a general perception that costs will create more reliance on pharma companies for dollars to sponsor studies. However, the solution to this is to adopt a policy of transparency. –Martin Richardson, director of Oxford Journals
Peer review "Peer review is where the rubber meets the road in journal publishing," Bacon says. But the question remains: Can the peer review process use registries to make pharma-sponsored research truly transparent?

At the very least, editors say registries will keep scientists on track for reporting what they said they set out to prove. Those initial trial plans will be traced by a registry number that authors receive when they first register the trial. "That number allows the editor to look at the trial information in the registry and make sure that the submitted article agrees with what the authors said the trial is going to do when they first registered," Sox says. "We want authors to report the primary result they intended in the beginning of the trial rather than picking a result that happens to suit their purposes." Sox says peer reviewers will also use registries to ensure that when authors describe other work that's been done, they describe both published and unpublished studies, so readers get a balanced view.

The hope is clinical trial registries will make the peer review process better. "Instead of just sending a manuscript, with clinical trial registries, you might have an opportunity to link to the spreadsheets or other individual case reports to offer a more in-depth review," says Dougherty.

"If an article comes out of a registry so it is possible to trace the trial through its various stages, it would make the review a lot easier," Lundberg says. "In theory, it would even make it faster and better. But we're a long way from having that."

There are still issues to sort out. "One problem is ambiguity over what type of trial should be registered," Sox says. "We don't know enough about this middle ground of trials that fall between those clearly not affecting practice and those that have a primary purpose to affect practice. There's no doubt about Phase III. It's the Phase II and small randomized Phase I trials that are difficult to decide about. So we're going to get our feet wet and formulate what amounts to case law to guide us so each journal will treat articles consistently."

Another issue of concern is how registries will affect intellectual property and innovation. "First-to-publish has been a criterion for a long time in terms of who gets the credit for certain information," Bacon says. "The more you disclose during the research process, the more you open up the opportunity for others to get their own results running earlier."

Either way, it's sure to be a long road ahead. "If trial registries function as they should, they would answer the problem of transparency—but only for research that's funded by industry," Lundberg says. "Government also funds large numbers of trials, and their transparency hasn't been all that great either. It's a tough nut to crack because there are so many organizations, trials, and funding agencies."

Ad Support The two customers of medical journals—readers and advertisers—have one thing in common: They tend to change their behavior only after careful analysis of the benefits of what's "new."

Because of that, several medical journals have been slow to translate their businesses online. "Pharma is being dragged kicking and screaming into the online arena," Weislogel says. "We who do electronic products think, 'Why wouldn't a pharma company want to be in something that is going to physicians?' And then you look at the way decisions are made and the information and metrics out there, which are very much in support of print products."

Most banner ads on journal Web sites are ineffective, says William Kelly, president of marketing consultancy Bioinformatics and author of the report "Scientific and Medical Journals on the Web." Instead, journals are developing more formats and metrics to get pharma executives over the hump in moving dollars online. "It is difficult to point to proven stickiness and proven ROI," says David Marshall, senior publisher of The Neurologist. "So we are seeing interesting discussions going on over what works, draws eyeballs, and provides stickiness. Now we are starting to see some interest in hot-linking, which allows someone to double-click on the name of a drug in a published article and be taken to a site where they could get information about that particular drug."

Figuring out the online model is all the more important given that subscriptions for print medical journals are declining. "We find that some subscribers are dropping the print and taking the online-only subscription," says Lenne P. Miller, senior director of publications for the Endocrine Society. "That leads us to an interesting situation for advertising. So far, companies have not embraced the Web as an ad vehicle the way they have embraced tabloids, journals, and medical magazines driven by print circulation."

Of course, some journals are doing online well, particularly those that were electronic-only from inception. Medscape General Medicine, for example, uses Internet capabilities to enhance the reader experience. "We use multimedia so readers can see how important the content is to the author presenting it—and that really engages our audience," says Steve Zatz, MD, EVP of Professional Information Services and Chief Medical Officer for WebMD.

New formats Journal advertising still remains largely driven by product launches. Because of that, the products FDA approves in 2005 will drive the success of some journals—and the struggles of others. "Specialty publications continue to be stronger than multi-specialty journals," says Art Wilschek, director of worldwide ad sales for the New England Journal of Medicine (NEJM).

Dougherty also notes there is a change in companies' ad mixes. "In eliminating waste, they are doing more advertorials and other projects, because those programs tend to be more targeted in terms of editorial content and distribution."

The search for ROI makes it more important than ever for journal publishers to inform pharma about the value of journal advertising. To that end, Wilschek says AMP is looking into new research that will model hundreds of products' promotional mixes over five years.

"This will be better received [than the RAPP and ARP studies] because it will show product managers how to optimize their promotional mix," Wilschek says. "They can go to the individual product level and see how the brand and its competitors are doing with regard to promotional effectiveness. This could be the best overall tool for the industry to put together its promotion and use its money effectively—we'll know in the next few months if it's going to happen."

Open Access Clinical trial registries, new online models, and NIH's new policy requesting that government-funded researchers publish their results in PubMedCentral.gov, point to the expansion of access to research for physicians, researchers, and the public. Those kinds of initiatives, coupled with libraries being stretched to pay for the high-priced specialty journals, have heightened the demand for open access journals. However, the groundswell of support for that model comes not from readers, but from the research community and government, according to Jennifer Kilpatrick, Slack's editorial director of journals. And pharma needs to understand the potential implications.

"The idea behind journals is that they are subsidized on prepaid subscriptions," Weislogel says. "If people get whatever they want without paying for it, it totally undermines the subscription model."

To get more data on how open access can work, Oxford Journals, a division of Oxford University Press, announced it will experiment with an open-access model that shifts the cost of publishing to authors. "It must achieve the dual goals of maximizing access to research without undermining the quality and integrity of the journals themselves," says Martin Richardson, director of Oxford Journals.

"From three questionnaires, we know a large percentage of authors are willing and able to pay publication charges for open access," Richardson says. "It's possible there will be a general perception that [costs will create more reliance on pharma companies for dollars to sponsor studies]. However, the solution to this is to adopt a policy of transparency, using clear declarations within the published articles about who has written them, and who has sponsored the research, and the publication charges."

Other journals are looking at their policies on what is made available online and when. "Some journals put all, while others put part, of the content online," Lundberg says. "Some put it up immediately, others after six months. We go beyond that—not only is it free to the user, it's free to the author."

Other journals are moving toward posting peer-reviewed but unedited information free, while making the final version of clinical studies and review articles available only to subscribers—at least for a time.

That's the case with the Endocrine Society's journals. "It is not the copy-edited, formatted, final version, but it is the accepted, peer-reviewed version," Miller says. With our journals, we are not as worried as, say, NEJM or JAMA, that unedited material could have severe implications on the public in terms of there being incorrect dosing information."

On one level, pharma doesn't care whether articles are open access or not. "What they do care about is if their research is published in a credible form," says Bacon. "It also raises some questions for what constitutes a reprint, and what sales reps may take into physicians' offices." He also notes that pharma will have to consider if they continue to order reprints from societies and journal companies or if they print them on their own.

Clearly, the traditional ways pharma uses to distribute research are changing. And it's up to companies to understand the evolving role of journals.

"We're going down the route of just publishing trials in a database, and using journals for analysis and context setting," Godlee says. "That's one direction that journals might be going. But I think it is quite a long way off, given the way academic research is rewarded, and given that granting is attached to the place where you are published rather than the impact of that research."

In particular, companies must study the potential wildcards—disclosure, clinical trial registries, evolving formats, and open access—that can change the way they communicate with professionals.

Additional reporting done by Natasha Metzler.

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