Aptiv Solutions, the US-based provider of biopharmaceutical and medical-device development services, has launched what it says is the first statistical software to enable use of surrogate endpoints in expediting interim-analysis decisions during adaptive clinical trials.
ADDPLAN 6.1 is the latest addition to Aptiv Solutions’ ADDPLAN software range for the design, simulation and analysis of adaptive trials. It employs 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 of the trial.
This approach allows for the use of surrogate endpoints in survival or time-to-event trial designs, spanning the multiple-comparison and population-enrichment settings, Aptiv explains.
As things stand, adaptive designs are not often used in survival-based trials – such as for oncology or cardiovascular therapies – since the primary endpoint is too far off for effective interim analyses and subsequent adaptations, the company notes.
ADDPLAN 6.1 opens up the possibility of using surrogate-based adaptive designs to accelerate trials with long-duration endpoints.
By simulating a multiple-arm adaptive trial and discovering that use of a surrogate does not significantly reduce statistical power, for example, a sponsor may in some cases be able to shave as much as 20 months off the product-development timetable, Aptiv claims.
One unique feature of ADDPLAN 6.1 is that it can simulate the ways in which using surrogate as opposed to primary endpoints affect trial outcomes and operational requirements.
As Aptiv points out, surrogate endpoints are a fundamental component of the US Food and Drug Administration’s (FDA) commitment to widening access to promising new treatments through its Breakthrough Therapy Designation and its Accelerated Approval programme.
Surrogates can also be applied during clinical trials for interim selection of treatment arms or for sub-group selection in population-enrichment designs.
Current users of the ADDPLAN software family, Aptiv says, include regulators at the FDA, the European Medicines Agency and Japan’s Pharmaceuticals and Medical Devices Agency, as well as more than 50 leading pharmaceutical/medical device companies and numerous academic researchers.