Master Clinical Trial Protocols Enable New Antibacterial Drug Development

Conducting clinical trials with multiple drug candidates from different manufacturers simultaneously will be key to developing new antibacterial therapies, say experts seeking to address the growing problem of antibiotic resistance.

The use of a master clinical trial protocol provides consistent criteria and endpoints, and lets investigators share results on different pathogens across multiple infection sites, two features that can speed up the regulatory approval process, said Ohad Amit, head of infectious disease clinical statistics at GlaxoSmithKline.

Developing new antibiotics has become a priority of the FDA, as the pipeline for new antibiotics dries up and growing resistance to existing products confounds healthcare providers.

A trial testing four products at once, for example, could identify a candidate that proves to be particularly effective or ineffective, at which point it is either abandoned or moved to the next step in the approval process, Amit said at a July 31 joint meeting held by the FDA and the National Institutes of Health to spur antibiotic development.

Such a trial model may also overcome the problem of having very small patient pools to test therapies addressing multidrug-resistant pathogens.

For example, only 7,000 to 8,000 patients develop Acinetobacter or carbapenemase-resistant infections in the U.S. every year, said Henry Chambers, a professor of infectious diseases at the University of California, San Francisco. You would have to enroll every single one of them in order to reach the traditional sizes of control and active treatment arms, he said.

Because most of these patients are seriously ill and need immediate treatment, placebo-controlled trials are often unethical.

One strategy may be to base analyses on patient outcomes rather than clinical endpoints, which could demonstrate the superiority of one product over another. “If we can figure out a way to rank patients based on how they are treated and what happens to them, there are ways we might be able to incorporate a superiority trial design that will allow you to escape examining endpoints,” Chambers said.

The development of rapid diagnostic tests also will be essential in confirming patients’ infections to determine eligibility in future trials, he added. — Lena Freund

Originally appeared in Drug Industry Daily, the pharmaceutical industry’s number one source for regulatory news and information. Click here for more information.