Originally founded in the UK, the AllTrials Campaign — a varied group of patient advocates, medical associations, and academia — have brought their crusade for clinical trial transparency to the United States with the July 29, 2015 launch of its website, http://www.alltrials.net/news/usa-launch/.
They begin with the rather stunning but fully referenced assertion that some 50% of all clinical trials, involving hundreds of thousands of patients, have never reported results.1,2 While acknowledging that the situation has improved in recent years, they emphasize there is a veritable iceberg’s bottom of stats and studies that have never seen the light of day.
“We need the results of past trials, and urgently, because these are the trials that were done on the treatments that patients use and will probably continue to use for many years to come,” the group states on the website.
Setting up an advocacy effort in the U.S. was a must, says Trevor Butterworth, BA, MS, MPhil, one of the principals behind U.S. AllTrials and director of Sense About Science USA.
“The U.S. is the world leader in healthcare and medical research, so in order to be successful, the AllTrials campaign had to launch here,” he says. “The number of patients, patient groups, professional societies, and institutions is huge, and they have, collectively, an incredible capacity to actuate change. Much of the research on research integrity — or the lack of it — is being produced in the U.S., so there is considerable awareness within academia that a lack of data transparency is a critical issue, one that must be solved if we are to do scientific research properly.”
Devil in details
Transparency sounds good, but the devil in the details will have to be resolved as issues arise, notes Susan L. Rose, PhD, executive director of the Office for the Protection of Human Subjects at the University of Southern California in Los Angeles. Rose is also a member of the IRB Advisor editorial advisory board.
“I think this is a great idea,” Rose says. “The implementation and operation of it raises questions like how and when is it going to happen? It’s the detail like likelihood of identifiability and meaningfulness of conclusions. The IRB issue would [primarily] be protecting the privacy of the subjects — whether or not their consent allowed this. So that would have to be done on a study level.”
Proprietary issues and the vulnerability of the research subjects could also become issues if previously unpublished clinical trial data are released, she notes. As a practical matter, IRBs do not have the resources or jurisdiction to do literature searches or other methods to track down previously undisclosed data.
“We rely on the principal investigator, sponsor, or the FDA submission to provide needed background information,” she says. “We work with what is provided and expect honesty.”
U.S. AllTrials is not seeking regulation or government mandates for clinical trial data disclosure, Butterworth says. Instead, the group has adopted a strategy of activism, historical inevitably, and coercion that urges the medical industry to get on board because this train is leaving the station. As evidence, some companies have broken ranks and released data, he says.
“The remarkable thing is that GSK, Johnson & Johnson, and Bristol-Myers Squibb have figured out the means to do this and share data,” he says. “There are people in the industry who take this issue very seriously. They know the direction in which history is going.”
As momentum builds, clinical trial transparency will be rewarded in the marketplace, he adds.
“I think there will be enormous pressure on doctors to choose drugs that come from companies with the best records on transparency — and that will spread across academia,” Butterworth says. “There will be an ethical obligation to reify transparency as a good in many different settings. There will be market rewards for those companies that are the most transparent with their data.”
In addition, a robust open data movement exists outside medicine, and the consensus across many fields is that data collaboratives are a better way of solving problems.
“A data collaborative can’t really function if critical data is buried,” he says.
Among the 50 U.S. groups that signed on in support of the U.S. launch of AllTrials — they have 600 globally — is the American Academy of Family Physicians (AAFP), the only medical society devoted solely to primary care.
“If there is data or the results of a test is not favorable or what you expected, maybe you don’t publish it, but that can be useful information, too,” says Robert Wergin, MD, president of the AAFP. “That’s where the transparency comes in. I am a practicing physician in a rural community, so I rely on the outcomes of many of these clinical trials to formulate my best treatment plan for a particular patient. If there are trials or evidence that shows me my treatment plan is not the best, I would certainly like to alter that. So transparency is a useful thing and some of the [medical] discoveries we have made, and some of the bigger changes we’ve made, were almost an indirect outcome of another study [looking for something else]. Transparency results in more evidence to build the best possible treatment plans for patients.”
In addition to a total blackout of trial results, another concern is that data that shows efficacy or benefit in one portion of a trial may be revealed independently.
“We are concerned about [investigators] cherry picking the data and saying, ‘This portion of the study shows this and therefore, this might be a result of this treatment,’” Wergin says. “It’s much better to have full transparency so the physicians and critiquers can look at the exact data that went in and the exact outcomes that came out. I think that was one of the reasons [we joined AllTrials]. We have always been an organization that has been very open and think transparency — [putting data] in the light — is certainly a good thing.”
- Song F, Parekh S, Hooper L, et al. Dissemination and publication of research findings: an updated review of related biases. Health Technology Assessment 2010;14:8:1-93.
- Ross JS, Mulvey GK, Hines EM, et al. Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis. PLoS Medicine 2009;6(9):e1000144. doi:10.1371/journal.pmed.1000144.