Ferris Bueller and the Cost of Pivotal Clinical Trials

It turns out asking what a pivotal phase 3 clinical trial costs is a little like asking, “What does a car cost?”

The answer will depend on whether the car in question is a $12,000 Nissan Versa, or a $13 million Rolls-Royce Sweptail. Like cars, not all clinical trials are equal. The one difference, perhaps, is that either of those cars will get you to where you are going. In the case of clinical trials, thought, that’s not the case.

A new study in JAMA estimates the cost of pivotal trials for novel therapeutic agents the U.S. Food and Drug Administration approved between 2015 and 2016. The study, led by Thomas Moore of the Institute for Safe Medication Practices, looked at 138 pivotal trials that formed the basis for an approval of 59 new therapies. The authors used clinical trials software that is widely used by clinical research organizations and pharmaceutical companies and considered 52 specific items for each trial.

The authors found that the mean cost of a pivotal trial had an estimated cost of $19 million. Estimated costs ranged from $5 million for trials without a control group for three orphan drugs with fewer than 15 patients each to $346.8 million for a noninferiority trial with endpoints assessing clinical benefit.

The study does show how various factors affect the costs of a pivotal trials. Not surprisingly, the larger the trial and the longer it lasts, the more it will cost. Costs also varied by trial endpoint, treatment duration, patient enrollment, and therapeutic area.

• Trials with less than 100 patients cost $5.9 million compared to trials with more than 1,000 patients, which cost $77.2 million.
• A total of 26 studies in the sample group were without a control arms and had a mean cost of $13.5 million. That compared to trials designed with placebo or active drug comparators had an estimated cost of $35.1 million.
• The cost of trials that ran for 26 weeks or less costs $19.7 million, compared to trials longer than 26 weeks, which costs $51.7 million.
• And using a surrogate endpoint is a lot less expensive than a clinical endpoint ($19.7 million vs. $51.7 million)

All of that should be good news for developers of rare disease therapies, suggesting that from a cost basis there is a relatively low barrier to funding pivotal trials.

The question of what it costs to produce a drug is an issue of great debate and studies can produce wide variations in results. Methodologies vary widely and often they can be colored by the purpose of a study. The drug industry wants to make the case that drug development is a costly and high-risk venture to justify the prices it charges for drugs. Industry critics who think drug prices are too high, will counter with a considerably lower figure.

One problem is that drug companies do not report the actual R&D costs associated with a product. In the absence of such numbers, the public is reliant on methodologies that may be based on confidential information provided by drug companies to researchers (often small samples). These numbers are very pliable and can be easily moved in one direction or the other by altering the methodology. Including the cost of drug failures, or doing such things as considering the cost of capital will significantly increase the number. Considering all drug approvals, and not just new molecular entities, will drive the costs down.

The authors think they addressed a common misperception about why drugs are so expensive to develop.

“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 development a new drug, the authors write. “These data suggest that high-cost trail 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 lower cost.”

But then there is the issue of cars.

Joseph Ross, associate editor of JAMA in an accompanying editorial noted that the study had limits, including a narrow sample of approved drugs, and an estimation tool not available for public scrutiny, and a distinct piece of the work that needs to be done to win approval.

“Nevertheless, it suggests that the stronger the evidence that is generated, which is most useful to inform clinical practice, the more it costs,” writes Ross. “We get what we pay for, and high-quality clinical trial data are well worth the investment to be sure that we prioritize spending our health care resources on therapies that have been shown to benefit patients.”

As Ferris Bueller says, “If you have the means, I highly recommend it.”

There’s something to be said for that. But not everyone needs a Rolls. For most people, the issue is getting to where you need to go as economically as possible.

September 25, 2018