Musculoskeletal Adaptive Platform Trial (MAPT)

ABSTRACT Over 1 million Americans undergo surgical treatment for a fracture each year. Despite advances in clinical research over the past few decades, poor outcomes remain unacceptably common in this population. The conventional clinical trial design remains slow, inefficient, and unmalleable to a changing clinical landscape. Adaptive platform trials have emerged as a highly efficient alternative, enabling the simultaneous comparison of multiple interventions under the same infrastructure and the addition of new interventions after trial initiation. However, to realize these efficiency gains, substantial pre-trial planning is required. Our trial’s study population will broadly include patients 65 years or older admitted with a fracture of the lower extremity, pelvis, or acetabulum. We will focus on comparative effectiveness interventions and have a roster of comparisons ready to launch once the platform is developed. The comparisons can apply to the entire study population or a specific therapeutic domain, defined as a subpopulation for a decisional dilemma exists, and the interventions will be compared (e.g., plate vs. IM nail in patients with a distal femur fracture). We will assess all comparisons using the win ratio approach four months after randomization based on a common hierarchical composite endpoint of death, ambulation status, and days at home. To successfully initiate this adaptive platform trial, we propose an 18-month planning period. In that time, we will leverage our team’s experience designing, implementing, and conducting multicenter trials in orthopaedics and adaptive trials in other areas of clinical research. During the planning period, we will complete the following three specific aims: 1) perform computer simulations to determine adaptation parameters, 2) establish stakeholder groups and structure for determining the sequence of research comparisons and therapeutic domains, and 3) establish clinical trial infrastructure for the platform.