Aptiv Solutions, a global biopharmaceutical and medical device development services company, has released ADDPLAN 6.1, the first statistical software to enable the use of surrogate endpoints to expedite interim analysis decisions in adaptive clinical trials. With this tool, survival trials for cancer therapeutics and other trials with long-duration endpoints can now utilize adaptive designs to a far greater extent.
ADDPLAN 6.1 is the latest enhancement to the ADDPLAN family of innovative software for the design, simulation and analysis of adaptive clinical trials. Current ADDPLAN users include industry regulators at the FDA, the EMA and Japan’s Pharmaceuticals Medical Devices Agency (PMDA), more than 50 pharmaceutical and medical device companies and academic researchers.
Surrogate endpoints, which include biomarkers that substitute for a clinical endpoint, are instrumental in the FDA’s commitment to “speeding access to important new therapies.” Drugs that show clinical benefit on certain types of surrogate endpoints can receive a Breakthrough Therapy Designation from the FDA that expedites development and review. As part of its Accelerated Approval program, the FDA may approve drugs for serious conditions with unmet medical needs on the basis of a surrogate endpoint.
Surrogate endpoints also can be used for interim selection of treatment arms or sub-group selection in population enrichment designs. Specifically, seamless phase II/III adaptive designs often use surrogate endpoint analysis to increase the speed of decision-making. Selecting phase II treatment arms based on a surrogate endpoint can not only accelerate phase II, but also benefit phase III because patients in the treatment arm can continue on to the confirmatory analysis.
“Trials utilizing surrogate endpoint analysis to select treatment arms require a different statistical method than those using the clinical endpoint. ADDPLAN 6.1 is the first software to include the appropriate statistical methods for the use of surrogates in interim analysis decisions,” said Gernot Wassmer, Ph.D., senior vice president and chief software architect at Aptiv Solutions. “ADDPLAN 6.1 is a powerful tool for implementing innovative designs for survival based trials, such as those in oncology or cardiovascular disease, to improve drug development decision-making.”
ADDPLAN 6.1 utilizes a variant of the p-value combination method in a closed test procedure to account for repetition of patients in the exploratory and confirmatory phases. The approach enables the use of surrogates in survival (or time-to-event) designs in both the multiple comparison and the population enrichment settings. As a unique feature, ADDPLAN 6.1 simulates how the use of surrogate versus primary endpoints impacts trial outcomes and operational requirements.