FDA releases new guidelines for cancer clinical trials in response to President Biden’s anti-cancer initiative.
Earlier this year, President Biden set a goal to cut cancer deaths in half when he announced plans to reinstitute the Cancer Moonshot program he originally led as vice president. The program promises investments in science and technology to reach the ambitious goal over the next 25 years.
This latest Cancer Moonshot program has the same research initiatives as the earlier program, but with two new goals and an “all-hands-on-deck approach” to call upon the scientific community, medical and public health communities, and even individuals with personal experience with cancer, for any ideas for improvement.
The U.S. Food and Drug Administration (FDA) recently responded to the new initiative by releasing three guidance documents related to cancer clinical trials. One calls for including more older adults in cancer clinical trials. A second identifies clinical trial protocols intended to speed up approval of cancer-fighting drugs. And a third eases some of the submission process requirements for additional protocols as a drug trial moves through approval phases. Each of the three guidance documents focuses on providing information about designing trials that could facilitate fast-track approval by FDA and help eliminate delays in the process.
The guidance on including older adults applies to both of the other guidances released. This guidance acknowledges the under-representation of adults 75 and older in clinical trials and provides recommendations on enrolling more of these older adults. The guidance stands in stark contrast to the FDA’s existing guidance for pediatric trial development, as the older adult guidance is comparatively shorter.
This first new guidance offers recommendations on enrolling older adults early in trial development and designing trials to compare older adult data against other age groups. It also suggests marketing strategies to enroll more older adults in clinical trials, and it considers separate safety reporting geared to this older population. Unlike the pediatric trial guidance, the guidance for including older adults requires no substantial additional design changes, but simply offers suggestions on best practices to incorporate more members of a different age group into the current protocol.
The second new guidance for clinical trial set-up applies to first-in-human investigational new drugs (INDs) and the creation of these INDs under different clinical trial designs. This guidance does not provide any new information about trial design. Instead, it summarizes previously released guidance documents over the last 25 years. It does, though, provide some considerations for evaluating the changes of a chosen therapy to help manufacturers identify FDA foci to approve a therapy for the next phase of the trial.
After IND sponsors narrow down the therapy-specifics of safety, efficacy, and potency in an earlier trial phase, sponsors can then develop a more robust master protocol and clinical trial design. A master protocol describes the therapy’s dosing strategy, safety reporting, and more, all in great detail.
Previously, sponsors submitted master protocols under one IND to evaluate the therapy. For example, if the sponsor used the same biomarker but wanted to see the effects on a different disease, the sponsor would submit a new master protocol under a new IND with all the same information except the details of the new disease application.
The third recent cancer-related guidance document builds on one that FDA issued for exploratory drugs in 2006. At that time, FDA intended the exploratory IND to allow for the evaluation of new applications as long as it was “conducted early in phase 1, involves very limited human exposure, and has no therapeutic or diagnostic intent.”
FDA adopted these conditions with safety in mind, but in practice, they worked against the goal of exploring the bounds of the therapy. As a result, industry leaders collaborated on a paper recognizing the FDA’s intent but explaining the shortcomings of the 2006 guidance. The paper proposed a “parent-child” IND: that is, a primary “parent” IND with subsequent IND “children” that refer to the “parent” but describe the differences from the “parent .”
The new guidance on ease of submission moving through phases applies a similar concept to the parent-child proposal but separates the reasons for the “children”—essentially, creating options based on the intent of a therapy’s use.
The new guidance defines these intentions as a basket, an umbrella, or a combination protocol.
A basket is a protocol design with a drug applied to different types of cancer; an umbrella design compares different treatment options to a single cancer type, and a combination assesses different drugs for different cancer types. In addition to defining each of these novel design options, FDA also describes the safety and regulatory specifics to consider before a drug company or research organization adopts one of these designs.
FDA recognizes the opportunity for the flexibility for trial sponsors to use the new protocol design. But also cautions about the difficulty of assessing and attributing safety reporting that can follow from applying the same protocol for multiple uses. For this reason, the agency encourages multiple meetings throughout the pre-IND and IND process to communicate with FDA and increase the likelihood of a therapy moving to the next phase.
With these efforts, FDA hopes that the approval process for cancer treatments can be more streamlined not only for those in industry but also for FDA reviewers to meet the goals of the President’s Cancer Moonshot.
