Researchers call for using more than surrogate outcomes to approve new antibiotics
Many recent antibiotic approvals from the FDA are based on fewer, smaller and less rigorous pivotal trials, which raises fresh questions about what new incentive programs might do for the antibiotics industry, researchers from Harvard Medical School and George Washington University School of Medicine wrote in the BMJ this week.
The findings highlight the need for not only new antibiotics, but also ones that show clinically relevant evidence of effectiveness and added benefits for the patient, they wrote.
“Bottom line is that of the new antibiotics approved from 2016-2019, nearly all were based on fewer, smaller and non-inferiority pivotal trials that often used surrogate outcome measures but were commonly more costly,” co-author Aaron Kesselheim, a professor at Harvard, told Endpoints News.
He also said the findings suggest that the bipartisan PASTEUR Act, which aims to incentivize new antibiotic development, “is a prescription for wasted money unless it includes a requirement that drug show improvements in clinical outcomes.”
The PhRMA-backed PASTEUR Act would incentivize companies by offering subscription-based contracts under federal health care programs.
Similar critiques of the bill were laid out in a letter to the bill’s sponsors last month from several physicians including Joseph Ross and Reshma Ramachandran of Yale School of Medicine, as the PASTEUR Act may hitch a ride on one of the year-end spending bills.
“Under the PASTEUR Act, taxpayer dollars will be wasted as a blank check to pharmaceutical manufacturers for antimicrobials of limited benefit,” they wrote.
Antimicrobial-resistant infections infect as many as three million Americans every year and kill about 50,000 people, they noted, so the race for a solution is time sensitive.
But the researchers show in their BMJ study that of 15 new antibiotics that recently won approval, more than half of the pivotal trials used an active control non-inferiority design, and all drugs were approved based on surrogate outcome measures.
The value of these new antibiotics “is not always clear based on testing before approval by the FDA,” they wrote, adding:
Efforts like the PASTEUR Act deal with the barrier of low sales potential to new antibiotic development but might not account for whether these drugs provide sufficient added benefit to the patient to justify payment. Increasing the number of agents coming to market should balance the robustness of evidence of improved direct patient outcomes compared with current standards of care, therefore meeting the needs of patients.
Kesselheim added: “I think an important thing to be included in the PASTEUR Act – since the idea behind the Act is to bolster the pipeline of antibiotic development given the need brought on by AMR – is a requirement that for drugs to qualify, they need to be shown in controlled trials to improve actual clinical outcomes in patients with antimicrobial resistant infections.”