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Roughly 20% of trials involving pediatric participants are discontinued early, and another 30% go unpublished after completion, according to a new report.
Studies involving pediatric patients are already few and far between in comparison with adult studies, and now a new report claims that up to half of children who participate in clinical trials do so for no purpose because the trials are ended early or results are never published.
Florence Bourgeois, MD, MPH, associate physician in medicine at Boston Children’s Hospital in Massachusetts, assistant professor of pediatrics and emergency medicine at Harvard Medical School, and scientific director of Biobank at Boston Children’s Hospital, co-authored the study, published in Pediatrics, and says there are vast consequences associated with wasted pediatric trials.
“First, limited and precious resources are not being utilized to their fullest to inform our scientific knowledge-all children participating in research should be contributing to the information available to us on treatments. Secondly, the nonpublication of trials is frequently related to the types of results obtained. Studies have shown that trials with negative findings are the ones most often not published,” she says. “This results in a scientific literature that is incomplete and biased, and may be misrepresentative of the true safety and efficacy of an intervention.”
Incomplete or unpublished trials also equate to a “breach of contract” for participants who volunteered for the studies, Bourgeois says.
“Many participants do not benefit directly from enrolling in trials-and might even be exposed to harm. The only way to justify this is if their participation benefits our greater knowledge and contributes to improved care to patients down the line,” she says. “These patients deserve to be assured that their sacrifice will contribute to our scientific knowledge and benefit future patients.”
Randomized clinical trials provide a wealth of information, particularly as healthcare providers increasingly rely on evidence-based practices to treat their patients. These evidence-based practices, however, require trials with volunteer participants who may not end up receiving any benefit from the study.
Because of this, sponsors of these trials owe it to participants to conduct research that is held to the highest standards and that minimizes the potential harms to the participants.
“The nonpublication of trial findings compromises the available medical evidence by distorting the apparent safety and efficacy of interventions, and undermining clinical guidelines and evidence-based clinical practice,” the report states.
In 1997, the passage of the US Food and Drug Administration Modernization Act mandated public access to clinical trial information for patients with serious or life-threatening illnesses. Since then, registration of trials on ClinicalTrials.gov has become standard even when not required, and results are sometimes available for review.
However, waste still happens, and clinical trials are still frequently discontinued or remain unpublished, the study says. This is particularly damaging for pediatric research results because there is already limited funding allotted to pediatric research.
A total of 559 trials were reviewed for the report, and 19%-involving a total of 8369 pediatric participants-ended early. Of the 104 trials that were discontinued, 36 were stopped before any participants were even recruited. Another 5 trials were suspended and 63 were terminated completely after enrolling participants.
Difficulty recruiting participants was cited as the most common reason studies were halted, with 36.5% ended for this reason. Conduct problems were blamed for 12.5% of trial discontinuations, and just 4.8% were ended because of funding problems. However, of those that were cancelled for funding problems, 39.4% were funded by industry compared with 54.8% funded by academia. Larger-scale trials also were more likely to be discontinued, according to the report.
The researchers also reviewed 455 studies that were completed, but not published. Thirty percent of these studies went unpublished, they wrote, representing the efforts of 165 pediatric patients. Another 42 unpublished trials at least posted results on ClinicalTrials.gov.
Trials that were funded by academic institutions were more likely to be discontinued early than those funded by industry, the study found, but trials funded by industry were more than twice as likely to go unpublished at 24 and 36 months compared with those funded by academia.
The report reviewed only studies registered with ClinicalTrials.gov, and focused on trials involving children aged 0 to 17 years.
Roughly 25% of the trials were initiated to study childhood vaccines, and another 8% examined interventions-mostly drugs and biologics-for common childhood infectious diseases. Funding for the studies was split nearly evenly, with 43.8% funded by academic institutions and 48.7% funded by industry.
The type of intervention studied and the primary funding source were found to be associated with nonpublication at 24 months, according to the researchers, and the primary funding source was associated with nonpublication at 36 months. They also found that after an average of 58 months following the completion of the study, 30% of trials remain unpublished, meaning that more than 69,000 children were exposed to interventions and study without the results being published.
Bourgeois says it’s important for physicians to weigh evidence of various interventions carefully when making decisions with families of pediatric patients, and abandoned or unpublished trials not only waste resources, but cause caregivers to lose an opportunity to learn more about pediatric care options.
“Children have historically been referred to as ‘therapeutic orphans’ because of the dearth of research that has been conducted in pediatric populations and the resultant lack of robust knowledge on therapeutic options,” she explains. “Despite tremendous progress in increasing awareness of this critical issue and huge progress in increasing the amount of research being conducted in children, pediatric trials continue to face substantial barriers. The high rate of trials that aren’t completed or aren’t published means that the information available to primary care physicians to guide clinical decision making isn’t as complete as it could or should be.”
The study authors request that additional efforts be made to ensure that all participation of pediatric patients in clinical trials be applied to increasing scientific knowledge.