"Drug research, even from clinical trials sponsored by the federal government, routinely is suppressed, harming patients and increasing health care costs, according to new data highlighting an ethical controversy that continues to plague the field of medicine.
"The current situation is a disservice to research participants, patients, health systems and the whole endeavor of clinical medicine," according to an editorial accompanying the papers published in the British Medical Journal.
Turning up the heat, the journal, in an editorial, posed a remedy that is likely to get the attention of doctors who take part in clinical trial research.
"Concealment of data should be regarded as the serious ethical breach that it is, and clinical researchers who fail to disclose data should be subject to disciplinary action by professional organizations," wrote Richard Lehman of the University of Oxford, and Elizabeth Loder, a BMJ editor.
The BMJ papers are the latest thunderbolts in a gathering storm that has swirled around medicine in recent years. The revelations add to the calls for reform in the field.
"It is grossly unethical and an insult to the integrity of medicine when this is allowed to occur and go unpunished," said orthopedic surgeon Chuck Rosen, president of the Association for Medical Ethics.
From diabetes drugs to spine surgery products, scandals involving concealed data have mounted. Consider the cases of two heart drugs that were the subject of Journal Sentinel stories:
For two years, Schering-Plough, the maker of the popular cholesterol drug Vytorin, sat on the results of a clinical trial showing the drug provided no benefit in improving artery health. During that time the drug was heavily marketed to consumers in TV ads. The situation came to light in 2008 after a congressional investigation was launched.
In 2003, a clinical trial of Multaq, a drug that treated irregular heartbeat, was stopped because more patients who were getting the drug were dying than those who were getting a placebo. However, the study was not published until five years later.
In 2007, an independent analysis of the diabetes drug Avandia found that the drug increased heart attacks and cardiovascular deaths.
Access to evidence
Steve Nissen, the lead author of the analysis, said 35 of the 42 studies he looked at were unpublished and were obtained only because a court case required the drug's maker, GlaxoSmithKline, to turn over the data.
"Had the medical community known about this hazard, Avandia would likely never have become the world's largest selling diabetes drug," said Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. "Our ability to provide the best care for patients is dependent on access to all of the available clinical trial evidence, regardless of whether the study showed favorable results."
While much of the criticism of suppressed medical research has been aimed at drug companies, research data from medical devices also has been delayed, especially when it reflects negatively on a product.
Critics pointed to Medtronic's bone-growth stimulating back surgery product known as Infuse.
Last year, the Journal Sentinel reported that the results of a crucial clinical trial of the product were not published until nearly five years after the trial had to be halted because unwanted bone was growing around the spines of the trial volunteers. The paper was written by surgeons who have received millions of dollars in royalties from other Medtronic spine products.
What's more, the authors of the belated paper downplayed the bone overgrowth, saying it did not harm patients, a claim that was flatly rebutted by a doctor interviewed by the Journal Sentinel.
The doctor, an Oklahoma orthopedic surgeon, said two of his patients who were in the trial had to undergo additional surgery because the bone overgrowth was painfully impinging on nerve roots. One of the patients, a man who was in his 50s at the time, needed three operations - one for the implant, a second to remove the unwanted bone formation, and a third when the additional bone grew back yet again.
Independent research and Journal Sentinel stories since have noted that unpublished data showed that Infuse was linked to a variety of serious complications, including sterility in men and cancer.
'Failure in our field'
The failure of the medical literature to report such findings "has been a major failure in our field," said Eugene Carragee, a Stanford University orthopedic surgeon and editor-in-chief of the Spine Journal. Last year, Carragee spearheaded an unprecedented independent analysis showing that Medtronic and a circle of orthopedic surgeons who have received millions of dollars in royalties from the company systematically have failed to report serious complications with the product.
Carragee said the BMJ analysis and its call for disciplinary action against offending doctors is "an important departure from the historical laissez-faire attitude of the recent past."
A surprising finding in the BMJ analysis was that serious lapses occurred even in clinical trials funded by the National Institutes of Health.
That research showed that less than half of NIH-funded clinical trials were published in a medical journal within 30 months of the completion of the trial and after 51 months, one-third of trials remained unpublished.
While industry-related profit motives may not be a factor in such cases, there are other possible explanations, said senior author Harlan Krumholz, a Yale University professor of medicine and investigative medicine and public health.
Sometimes researchers may get an unexpected finding that contradicts a position they have staked out, he said.
"It is a conflict of their academic beliefs," he said.
At the same time, medical journals may not want to publish negative findings, he said.
A second BMJ paper looked at clinical trials of drugs that already had received at least one Food and Drug Administration approval. In such cases a law requires the reporting within one year of the completion of the trial.
Despite the law, only 163 of 738 such trials, or 22%, had reported the results within a year, the paper found.
Lead author Andrew Prayle, a researcher with the University of Nottingham, said he hoped the finding would spur more researchers to post summaries of the work at the NIH site, ClinicalTrials.gov."
Drug research routinely suppressed, study authors find