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PoliSci: Congress pushes research access

WASHINGTON, Sept. 13 (UPI) -- Members in Congress last week demanded -- amid controversy roiling over the risks of prescribing antidepressants for children -- the release of a dozen unpublished studies on the subject and appeared prepared to mandate all clinical trial results be made public from now on.

The legislation being drafted now could go far beyond the antidepressants controversy and shed light on all drugs being marketed in the United States. It may not reach far enough, however, to capture information from trials done overseas for overseas markets -- trials that could inspire off-label use of legal drugs in the U.S. market. An announcement last week, however, that medical journal editors will use their clout to force more openness, could be enough to tip the balance in favor of patients' access -- no matter where they live.

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It can be extremely difficult for patients or their doctors to become fully informed about the side effects or genuine usefulness of a drug. The pharmaceutical companies, though heavily regulated, are not required to make all their data public. At best, the drug companies play up positive results and downplay negative ones. At worst, they stand accused of suppressing results that could hurt billions of dollars in sales.

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The Food and Drug Administration receives data from all the clinical trials of a drug under consideration in the United States, but the agency often cannot share the information publicly. The results of many -- but not all -- clinical trials are published in medical journals or presented at doctors' conferences. The picture of research painted by the journals, however, often is overly rosy. The journals, by their own admissions, lean toward publishing papers reporting positive results -- that is, news of progress against a disease -- rather than studies showing no new revelations.

Three groups presented proposals to address the problem last week: Congress, medical journal editors and the drug industry. The first two -- particularly if taken together -- really could make a difference.

The members of the International Committee of Medical Journal Editors started the ball rolling by promising to publish only studies based on registered clinical trials. That is, any author with aspirations of being published in one of these 11 journals must file notice of his or her clinical trials in advance in a no-charge, public registry. With a comprehensive, searchable list of clinical trials in hand, the logic goes, missing data from a negative trial would be noticeable and pressure would be brought to bear to report it.

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The ICMJE editors who spoke with United Press International were quite firm on the issue and their action essentially closes debate on whether a central registry will happen.

The strength of the ICMJE plan is it now will go into effect, with deadlines of next summer and fall for registration. The notice must include key information, such as the hypothesis being tested, the start and end date, the name of the principal researcher and who is funding the study. Most important, trials must be registered prior to their start -- well before anyone knows the results and is inclined to hide them. Though no specific registry is required, the ICMJE noted the only registry currently meeting all the requirements is clincaltrials.gov, run by the National Library of Medicine -- a part of the U.S. Department of Health and Human Services.

The ICMJE policy also has teeth. The importance of journal publication cannot be overstated. It is how researchers make their reputations and show their work. Publication in a top journal -- and the ICMJE represents the cream of the crop -- is key to selling a new drug. Anyone serious about their research or pharmaceutical's bottom-line must register their studies.

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There is, however, one huge gap: The ICMJE does not require the results of the trials to be posted.

"We felt that the information we asked for would be sufficient to give researchers the total picture of the research," Harold Sox, editor of the Annuals of Internal Medicine, told UPI.

"The issue with results is a bit complex," added Dr. Gregory Curfman, executive editor of the New England Journal of Medicine. "The way we would prefer to see results posted is that when an article is published in a peer-reviewed journal based on a clinical trial, that there be a link from clinicaltrials.gov to the journal Web site, where the entire article would be accessible."

Curfman added the peer-review function was critical to ensuring the data had been checked and were complete and accurate.

"When they are in a peer-reviewed journal ... they have been checked and seen by statisticians," Curfman told UPI.

Unfortunately, that leaves patients and doctors without access to results that do not appear in journals. It also forces them to pay stiff fees for journal articles, some of which may be difficult to obtain.

The proposed congressional bill, though still very much in progress, would address this gap. It would mandate that all results, whether published in journals or not, be made publicly available. As announced Sept. 9 by Rep. Henry Waxman, D-Calif., and Edward Markey, D-Mass., the bill also would contain enforcement and auditing mechanisms. The ICMJE editors did not include an audit function, relying instead on the integrity and self-policing of the science community.

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A congressional aide, who asked not to be identified, told UPI the bill should be introduced before Congress leaves for its election recess in a few weeks. Legislators still are working out the details, though, including how quickly data would have to be posted and how to address overseas clinical trials.

It is on the issue of international research that the synergy between the ICMJE mandate and the suggested legislation is most clear. The legislation would be more comprehensive and tough, but the ICMJE mandate stretches the registration requirement beyond U.S. borders.

In the global market, where different national standards apply, it is quite possible for a drug to be approved for use for one type of ailment in one country and available, but not approved for the same ailment in another country. Doctors have great latitude to help their patients, however, and may write an "off-label" prescription based on a patient's request or the practices of overseas colleagues. That does not, however, mean physicians have access to all the important information. There may have been a very good reason the drug was not approved for that ailment.

How, then, does one secure access to clinical trials done outside of the United States -- tests that still may be influencing U.S. doctors, but can not be required by Congress to be submitted?

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"That's the beauty of having an international committee of medical journal editors," Curfman said. "These are journals scattered around the world. In terms of the policies set by the editors, (they apply) to research done anywhere in the world, not just in the United States. Congress can do only what they can do. They can deal only with research done in the U.S. but the journals editors have a wider sweep."

What of the registry proposal from the Pharmaceutical Research and Manufacturers of America, the leading association of drug manufacturers? Its plan is much, much more limited. It would provide only information on drugs already approved and being marketed in the United States. That means there would be no additional, advance notice of clinical trials for those seeking to join a test in hopes of being cured.

The PhRMA registry would have a deadline and would mandate that results be provided. Data from trials of approved drugs would have to be posted within a year. This registry could offer data sooner than the others and it will go online in only a few weeks, but participation in the registry is voluntary and there is no enforcement mechanism.

"I think there is still a feeling that legislation is really needed to nail this," Curfman said. "Even short of legislation, I think that what the editors have come out with is very powerful because there is solidarity among the editors and they have said they simply will not publish trials that have not been properly registered. That's a pretty stiff penalty."

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