The FDA announced two new draft guidances for industry on Sept 28. The first document, “Master Protocols—Efficient Clinical Trial Design Strategies to Expedite Development of Cancer Drugs and Biologics,” addresses master protocol design. This includes a discussion of the information sponsors should submit to the FDA as part of these approaches, and how sponsors should interact with FDA to facilitate efficient review and mitigate risks to patients.
The second draft guidance, “Adaptive Designs for Clinical Trials of Drugs and Biologics,” discusses principles for designing, conducting and reporting the results from an adaptive clinical trial. An adaptive design is a type of clinical trial design that allows for planned modifications to one or more aspects of the design based on data collected from the study’s subjects while the trial is ongoing. The advantage of an adaptive design is the ability to use information that was not available at the start of the trial to improve efficiency. An adaptive design can provide a greater chance to detect the true effect of a product, often with a smaller sample size or in a shorter timeframe.
An adaptive design can reduce the number of patients exposed to an unnecessary risk of an ineffective investigational treatment. Patients may even be more willing to enroll in these types of trials, as they can increase the probability that subjects will be assigned to the more effective treatment. These guidance documents are part of the FDA’s science-based mission to modernize clinical trials and advance the development of safe and effective drugs and biologics for the American public.
“By modernizing our approach to the design of clinical trials, we can make drug development more efficient and less costly while also increasing the amount of information we can learn about a new product’s safety and benefits,” says FDA Commissioner Scott Gottlieb, M.D. “Using more modern approaches to clinical trials, we can lower the cost of developing new drugs and increase the amount of competition in the market.
“This can improve patient access. We’ve found that it’s taking much longer after a new drug is approved to get a second or third drug to the market that’s in the same class as the original medicine. That means that new drugs are enjoying monopolies for longer periods of time, and consumers aren’t benefiting from price competition. Also, patients aren’t getting the benefits from a choice between different drugs in a new class of medicines, where each drug is similar but might have slightly different profiles, and where one drug may work better for an individual patient.”
Gottlieb continues, “One of the most promising ways to make drug development more efficient—while enabling providers and patients to get better information about how a new medicine works—is through the use of more modern approaches to the design of clinical trials. One such approach are master protocol designs. These are clinical trials that allow the evaluation of more than one investigational drug or biologic, more than one disease type, or more than one patient population in parallel, under a single clinical trial structure.
“The standard approach to generating evidence—a series of clinical trials, each investigating one or two interventions in a single disease—has become more expensive and challenging to execute. As a result, important clinical questions can go unanswered. Instead, well-designed master protocols that look at multiple therapies in a single disease, a single therapy in multiple diseases, or multiple therapies across multiple diseases or disease subtypes, can provide answers more quickly and efficiently than traditional clinical trials.
“These approaches allow the evaluation of how different drugs, often developed by different manufacturers, affect a common biomarker or genetic mutation that might be a measure of response to treatment. Because of the complexity of these trials and the potential regulatory impact, it’s important that we’re providing adequate guidance on how to conduct well-designed trials that protect patient safety and obtain quality data needed to support drug approval.”
Gottlieb notes that with today’s issuance of these two draft guidance documents the agency “is proposing important principles for modernizing clinical trials through these and similar approaches. Adaptive clinical trials can give sponsors the flexibility to react to clinical evidence as it’s being collected and modify the design and enrollment in trials by including more patients with characteristics that help predict that they’re more likely to derive a benefit—or exclude patients with characteristics that suggest that they’re more likely to suffer a side effect.
“By enriching the enrollment in the trial for patients with characteristics that are likely to predict clinical success, it has the potential to make the development process more efficient. This approach also allows us to potentially learn much more about the characteristics that can inform safer prescribing. All of these efforts are part of our broader program to modernize the FDA’s science-based framework for making clinical trials more efficient and lower cost while strengthening the agency’s gold standard for safety and efficacy.”
FDA has published a 60-day notice requesting public comment on these guidances by using the following links: