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Trials for new therapeutic agents cost a median of $19 million

The estimated median direct cost of pivotal clinical trials for novel therapeutic agents was $19 million, with costs increasing if more patients were needed to document treatment benefit, active drug comparators were used or clinical outcomes were measured as an end point, according to findings published in JAMA Internal Medicine.

Another study published in JAMA Internal Medicine revealed that clinical trials conducted under the FDA’s pediatric exclusivity program offer significant evidence regarding the effectiveness and safety of drugs used in children, but at a high cost to consumers.

Costs of trials for therapeutic agents

“A critical question in health care is the extent of scientific evidence that should be required to establish that a new therapeutic agent has benefits that outweigh its risks,” Thomas J. Moore, AB, from the Institute for Safe Medication Practices, and colleagues wrote. “Estimating the costs of this evidence of efficacy provides an important perspective.”

Moore and colleagues evaluated the costs and scientific characteristics of pivotal trials that provide evidence of efficacy required by the FDA for approval of novel therapeutic agents from 2015 to 2016.

The researchers reviewed the annual summary reports from the FDA Center for Drug Evaluation and Research and identified 59 new therapeutic agents. They then reviewed data from ClinicalTrials.gov, FDA reviews and peer-reviewed publications, and identified specific characteristics, such as trial design, endpoint, patient enrollment and treatment duration, of each of the 138 clinical trials that provided the basis for approval of the therapeutic agents studied. A global clinical trial cost assessment tool was used to calculate costs.

The results showed that the median estimated cost of the novel therapeutic agents was $19 million (interquartile range, $12.2 million to $33.1 million).

Estimated costs varied among trials, ranging from less than $5 million for trials assessing three orphan drugs that did not have control groups and included fewer than 15 patients each, to $346.8 million for a noninferiority trial with clinical benefit as the endpoint.

Nearly 20% of the trials were uncontrolled and had a mean estimated cost of $13.5 million. The estimated mean cost of trials designed with placebo or active drug comparators was $35.1 million.

Additionally, there was variation in costs by trial endpoint, treatment duration, patient enrollment and therapeutic area, the researchers noted.

“Our study provides a different perspective to the widely held assumption that elaborate and expensive clinical trials are the main reason for the high costs of developing a new drug,” Moore and colleagues concluded. “These data suggest that high-cost trials occur but usually when drug effects are small or a known drug already provides clinical benefit. On the other hand, pivotal trials for novel drugs with substantial clinical benefits can be conducted at a lower cost.”

Costs of trials under pediatric exclusivity extension

In a separate study, Michael S. Sinha, MD, JD, MPH, from Brigham and Women’s Hospital, and colleagues evaluated how the FDA’s pediatric exclusivity program affects drug labeling, the costs of clinical trials and the cost to consumers.

“Pharmaceutical manufacturers can receive 6 additional months of market exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults,” Sinha and colleagues wrote. “Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials.”

The researchers reviewed government records and identified 54 drugs that were included in the pediatric exclusivity incentive between 2007 and 2012. The cost of investment for trials was estimated by assessing industry estimates of trial costs per patient. The cost to consumers during the 6-month exclusivity period and net return were estimated by calculating the additional revenue of the drugs.

Approximately 140 trials totaling 20,240 children were included in the analysis.

Data indicated that the trials resulted in 29 extended indications and three new indications for all drugs and new safety information for 16 drugs. The trials deemed 57% of the drugs as safe and effective in children.

Among the trials, the median cost of investment was $36.4 million (IQR, $16.6 to $100.6 million). The median net return for the 48 drugs with available financial information was $176 million (IQR, $47.0 million to $404.1 million) and a 680% (IQR, 80% to 1,270%) median ratio of net return to cost of investment.

The researchers noted that the costs to consumers exceeded the costs of investment for conducting the trials.

“The pediatric exclusivity extension ... led to substantial rewards to pharmaceutical manufacturers,” Sinha and colleagues concluded. “Over the long term, direct federal funding of pediatric research may be less expensive for consumers and have similar — or greater — public health benefit.” – by Alaina Tedesco

Disclosures: Moore and Sinha report no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.