David Perlman, Science Editor San Francisco Chronicle Sunday, December 14, 2008
San Francisco -- What are the pills in your medicine cabinet, and how do you know they're best for you?
When drug companies seek approval to market new medicines, they must show the U.S. Food and Drug Administration the results of all the tests they've run on volunteer patients - at first on only a few, then on dozens, and finally on hundreds or sometimes thousands.
After winning approval, the companies typically sponsor reports of those tests in medical journal publications, which many doctors often rely on to determine whether to prescribe new drugs for their patients.
Now a skeptical team of medical investigators at UCSF has accused the major drug companies of bias by distorting the results of their trials in those publications, making it hard for doctors to judge for themselves the pros and cons of prescribing the new drugs.
As a result, say the researchers, patients may sometimes be taking medicines they don't need - or with unwanted side effects - that their doctors have prescribed on the basis of inadequate information.
Negative findings omitted The UCSF team, led by Lisa A. Bero of the medical center's Institute for Health Policy Studies, probed the details of 164 drug trials involving as many as 1,500 patients over a two-year period and then examined reports on those trials that were published in medical journals, as well as those that remained unpublished.
Their conclusions are published in the current issue of PLoS Medicine, an online medical journal.
"We found really important information from the official trial reports that were either not published at all or that stressed mostly the positive results of trials in the published versions," said Kristin Rising, a physician at the institute who did the major investigation and has now moved to the Boston University Medical Center.
"Doctors who prescribe new drugs - or even older ones - for their patients should have complete and unbiased information on those medicines before prescribing them," she said.
According to Bero, doctors frequently complain that they're left to rely on incomplete data from the drug companies.
"I do think our findings are important for patients because their physicians may not have full and accurate information about the drugs they prescribe," she said.
Conclusions disputed In response to questions from The Chronicle, a pharmaceutical industry leader disagreed with the researchers' conclusions.
Doctors who seek to make "appropriate prescribing decisions" on new drugs can find all the critical information they need in the detailed drug labels that the FDA has approved based on all the trials every drug has undergone, said Ken Johnson, senior vice president of the Pharmaceutical Research and Manufacturers of America.
A policy statement from the industry also says its member companies "have a long-standing commitment to ensure that physicians and patients have access to all relevant information about the medicines we discover, consistent with regulatory requirements, so that our products can be used safely and effectively."
According to Johnson, drug companies are required by law to post "a broad range of ongoing clinical trials and comprehensive information about those trials" on a registry maintained by the National Institutes of Health. The registry is at www.clinicaltrials.gov.
But in a commentary on the study published in the same issue of PLoS Medicine, An-Wen Chan, a Mayo Clinic physician who studies drug approval policies, said the UCSF investigators' findings show "bias, spin and misreporting" by the industry.
If this sounds like an in-house controversy, far removed from the bedside or the medicine cabinets of sick folks taking their prescriptions, it isn't. According to Rising, many doctors get their information about new drugs they prescribe either during visits from drug company representatives known in the trade as "detail men," or from articles published in major medical journals.
Drug companies may call on specialized companies to prepare articles for medical journals on new medicines that have won FDA approval, with the articles emphasizing the trials' positive reports, and bearing the names of physicians who have participated in the trials as the authors, researchers say. The journal articles may also be written by drug company physicians involved in developing the new medicines.
"I'm just amazed at how many doctors will prescribe a new drug right away and depend only on what they read in the company's own summaries of trial results or on articles in medical journals that may be incomplete," said Thomas Bodenheimer, a physician at San Francisco General Hospital who was previously in private practice for 23 years:
"Practicing docs are not getting all the information about new drugs we need, and the information we are getting favors the new drug, with the studies almost always funded and controlled by the company making the drug," he said.
Long-term controversy The issue has long been controversial and has been raised before in studies of individual drugs and how doctors prescribe them, but this is a detailed look at that the issue, involving a large number of new drugs tested and a large number of patients.
According to the study by Bero, Rising and Peter Bacchetti, UCSF director of biostatistics, not all trial results that were submitted to the FDA by drug companies were published in medical journals. When they were published, there were often many discrepancies between the results the FDA received and the published data.
In fact, one-quarter of the trial results testing the effectiveness of new drugs were not published at all within five years after the FDA approved them, the researchers found.
Furthermore, drug trials showing "favorable" results were five times more likely to be published than trial results that showed "unfavorable results," the UCSF team said. In other words, the publication of drug trial results can often give doctors a more favorable view of a new drug's safety and effectiveness than information the drug manufacturer has submitted to the FDA, according to the researchers.
Even information on new drugs that doctors can find in the journals they read is often "incomplete and potentially biased," the UCSF team concluded.
http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2008/12/14/MNKF14GTLO.DTL&t sp=1
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