Photo: Lydia Polimeni, National Institutes of Health via Flickr
A Stat investigation has found that “prestigious medical research institutions have flagrantly violated a federal law requiring public reporting of study results, depriving patients and doctors of complete data to gauge the safety and benefits of treatments.”
The violations have left gaping holes in a federal database used by millions of patients, their relatives, and medical professionals, often to compare the effectiveness and side effects of treatments for deadly diseases such as advanced breast cancer.
Efforts to increase the transparency and accessibility of clinical trial data kicked into a higher gear last week.
Some of the major stakeholders in these efforts emerged wearing white hats, while others had more shadowy motives revealed.
First, the good news: GlaxoSmithKline (GSK) announced, in the New England Journal of Medicine, that it has begun to release de-identified patient-level data from its clinical trials.
So far, 200 studies have been added to a new website, with another 200 coming by year’s end, according to the report. And there will be further updates beyond that.
To access the raw data, GSK is asking researchers to submit a proposal, which will also be published on the website. They’re also asking researchers who want access to their data to post summary results on the website and seek publication of their work, “in line with standard scientific practice.” Continue reading
Medical reporters are likely familiar with ClinicalTrials.gov, the U.S. government-run registry of clinical trials. The site became available in 2000, three years after Congress passed the Food and Drug Administration Modernization Act of 1997 (FDAMA), which, as the site notes,
required the U.S. Department of Health and Human Services, through NIH, to establish a registry of clinical trials information for both federally and privately funded trials conducted under investigational new drug applications (IND) to test the effectiveness of experimental drugs for serious or life-threatening diseases or conditions.
The site – and others around the world – really took off in 2005 after the International Committee of Medical Journal Editors began requiring that researchers register their trials when they started if they wanted to publish the results. Publishing in the peer-reviewed literature is the coin of the realm in academia and also vital for FDA approval, so the carrot worked, according to a 2007 update:
Before the ICMJE policy, ClinicalTrials.gov, the largest trial registry at the time, contained 13 153 trials; this number climbed to 22 714 one month after the policy went into effect (3). In April 2007, the registry contained over 40 000 trials, with more than 200 new trial registrations occurring weekly (Zarin D. Personal communication).
Registration of a trial’s plans – what researchers plan to test, and how – also means there’s a pixel trail if reporters, or any member of the public, wants to see if scientists changed the goalposts to make their results look better, or buried negative results. (Also see Ghost protocols: Scientists propose a way to plug major holes in the medical literature)
Like professional sports, cancer trials can be competitive, for both patients and researchers. And, also like professional sports, the competitors are apparently doing anything they can to get an edge, as MedPage Today’s Crystal Phend writes in a story about patients using “blood doping” to get into clinical trials.
Phend points to a NEJM letter which references three different patients who relied on blood transfusions to become eligible for trials of new chemotherapy agents. Naturally, Phend writes, this is not advisable.
Clinicians should try to correct the underlying laboratory value through other treatments first, such as treating anemia, they urged. Explore all possible other options, including looking for other trials at other institutions for patients who don’t meet eligibility criteria, they added.
“Patient safety must trump all decisions for such patients,” the group concluded. “There should be few situations, if any, in which a patient receives a transfusion solely for the purpose of temporarily altering a laboratory value to gain admittance to a clinical trial.”
The authors also recommend that publications disclose the number of patients in each trial who required blood transfusions to meet eligibility requirements.
An observational study published in PLoS Medicine finds that not all trial results in New Drug Applications for new drugs submitted to the FDA are published in medical journals. Researchers from the University of California, San Francisco, examined efficacy trials between 2001 and 2002, and searched for discrepancies between trial data included in NDAs and in published articles between July 2006 and June 2007.
New drug applications
They found that “only three-quarters of the efficacy trials in the NDAs were published; trials with favorable outcomes were nearly five times as likely to be published as those without favorable outcomes. Although 155 primary outcomes were in both the papers and NDAs, 41 outcomes were only in the NDAs.
Just the same, they offered some optimism: “The recent introduction in the US and elsewhere of mandatory registration of all clinical trials before they start and of mandatory publication in trial registers of the full results of all the predefined primary outcomes should reduce publication bias over the next few years and should allow clinicians and patients to make fully informed treatment decisions.”
But in an accompanying editorial, An-Wen Chan, who previously worked as a scientist with the World Health Organization’s International Clinical Trials Registry Platform and is now at the Mayo Clinic, writes that “much remains to be done – not only to establish reliable, comprehensive registration and results disclosure processes worldwide, but also to start heeding the calls for increased access to full protocols and regulatory agency submissions….”