The result of nearly one in three large clinical trials remain a mystery five years after they end, claims research published this week in the British Medical Journal (BMJ), raising significant questions about the obligations companies have to the hundreds of thousands of patients who participated in these trials.
Researchers looked at 585 "large" clinical trials-trials with 500 or more registered patients-registered with ClinicalTrials.gov as of January 2009. Of the 585, 171 (29%) remain unpublished, researchers said, estimating that approximately 300,000 patients had been involved with the trials.
Per the BMJ article's definition, "publication" was taken to mean in a medical journal or other medium available for public consumption.
Researchers also found that industry-funded trials were more likely to go unpublished (32%) than non-industry funded trials (18%), and that 78% of the unpublished trials also had no results available on the ClinicalTrials.gov website. The average time between the trials' registration and the final literature search for published results was 5 years.
At issue for the BMJ researchers is a core question: Do companies have a responsibility to ensure that trials-and in particular those involving a large number of people-benefit society?
Researchers argued that companies do have that responsibility. "Clinical trials depend on the willingness of participants to expose themselves to the risks of randomization, blinding, and unproven interventions," they wrote in BMJ. "The ethical justification for these risks is that society will eventually benefit from the knowledge gained from the trial. Because the risks involved in trial participation may be significant, and because individual trial participants often do not benefit directly from trial participation, substantial safeguards have been implemented to protect the interests of study participants both prior to and during the trial."
So to ask many patients to participate in a trial but to then hide the results of that trial is akin to both reducing the net benefit of current patients' participation and potentially harming future patients who might unknowingly participate in similar research.
Further, "Publication bias can distort the apparent efficacy of interventions, which complicates the interpretation of the medical literature," researchers added. "When trial data remain unpublished, the societal benefit that may have motivated someone to enroll in a study remains unrealized."
Questions and Reaction
Of course, the study is unable to explain why these trials went unpublished. While some-most, even-may have fallen victim to publication bias, others may have suffered from poor study designs, insufficient blinding or powering, premature shutdowns due to problems obtaining comparator medications, or any number of other issues. Still other studies may have been exempt from reporting, or may have mandated reporting dates yet to come.
Still, the study has already been seized upon by the AllTrials initiative, a prominent voice pushing for the routine publication of clinical trials data.
"There's no excuse for not publishing results but a huge public health benefit to having a complete picture of what was found in trials," AllTrials wrote. "We are facing an opportunity now to make sure this situation doesn't continue."