PIPELINEs: Creating Comparable Clinical Knowledge Efficiently by Linking Trial Platforms

Abstract

Adaptive, seamless, multisponsor, multitherapy clinical trial designs executed as large scale platforms, could create superior evidence more efficiently than single‐sponsor, single‐drug trials. These trial PIPELINEs also could diminish barriers to trial participation, increase the representation of real‐world populations, and create systematic evidence development for learning throughout a therapeutic life cycle, to continually refine its use. Comparable evidence could arise from multiarm design, shared comparator arms, and standardized endpoints—aiding sponsors in demonstrating the distinct value of their innovative medicines; facilitating providers and patients in selecting the most appropriate treatments; assisting regulators in efficacy and safety determinations; helping payers make coverage and reimbursement decisions; and spurring scientists with translational insights. Reduced trial times and costs could enable more indications, reduced development cycle times, and improved system financial sustainability. Challenges to overcome range from statistical to operational to collaborative governance and data exchange.

Adaptive Design for a Confirmatory Basket Trial in Multiple Tumor Types Based on a Putative Predictive Biomarker

“…Our proposed adaptive confirmatory basket trial design has the potential to lead to considerable resource savings, either utilized alone or as part of an overall PIPELINE of platform trials . It can facilitate development in molecular niche indications in which accrual for a standalone confirmatory trial is challenging, resulting in earlier and enhanced patient access to effective therapy in these settings.…”

“…Confirmatory basket trials are potentially a very valuable component of an organized pipeline of adaptive platform trials . The greatest expense in current clinical development programs is in the confirmatory trial stage.…”

Late translational research: putting forward a new model for developing new anti‐cancer treatments that addresses the needs of patients and society

“…However, clinical research still uses classical approaches in the development of a protocol, for a specific drug addressing a certain target, and therefore searching for relatively rare subsets of patients who may benefit from the intervention. Moving into patient‐centred clinical research requires the implementation of integrated and collaborative molecular screening platforms, integrating curated biologically annotated clinical data (Meric‐Bernstam et al ., ; Trusheim et al ., ). Screening platforms can provide solutions to bring translational research to patients not only at a certain point in time for access to a specific matched treatment, but also over time as the disease evolves, for optimal subsequent treatment decisions.…”

On strategic choices faced by large pharmaceutical laboratories and their effect on innovation risk under fuzzy conditions

“…At this point, it should be highlighted that there are several alternative paths for achieving valuable and sustainable innovation. Some innovators at the frontier have a preference for creating knowledge inside the organization while others to look outside in order to push innovation (Lowman et al, 2012;Macher and Boerner 2012;Schuhmacher et al, 2013;Honig and Hirsch, 2016;Schuhmacher et al, 2016;Trusheim et al, 2016;Gascón et al, 2017). Whatever organizational alternatives are selected, there will be innovation risks that need to be quantified and managed.…”