A patient-centered composite endpoint weighting technique for orthopaedic trauma research

Abstract

BackgroundThis study aimed to address the current limitations of the use of composite endpoints in orthopaedic trauma research by quantifying the relative importance of clinical outcomes common to orthopaedic trauma patients and use those values to develop a patient-centered composite endpoint weighting technique.MethodsA Best-Worst Scaling choice experiment was administered to 396 adult surgically-treated fracture patients. Respondents were presented with ten choice sets, each consisting of three out of ten plausible clinical outcomes. Hierarchical Bayesian modeling was used to determine the utilities associated with the outcomes.ResultsDeath was the outcome of greatest importance (mean utility = − 8.91), followed by above knee amputation (− 7.66), below knee amputation (− 6.97), severe pain (− 5.90), deep surgical site infection (SSI) (− 5.69), bone healing complications (− 5.20), and moderate pain (− 4.59). Mild pain (− 3.30) and superficial SSI (− 3.29), on the other hand, were the outcomes of least importance to respondents.ConclusionThis study revealed that patients’ relative importance towards clinical outcomes followed a logical gradient, with distinct and quantifiable preferences for each possible component outcome. These findings were incorporated into a novel composite endpoint weighting technique.

Aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis in orthopaedic trauma patients: A patient-centered randomized controlled trial

“…The experiment surveyed 232 orthopaedic trauma patients to quantify the relative importance of the included endpoints. Using the methods described by Udogwu et al [ 26 ], the relative importance of the component outcomes was used to calculate the outcome weights ( Table 1 ) and determined a hierarchy of severity for the observed combination of events experienced during the first 90 days from injury. The weights of the component outcomes are reported relative to death, which has been weighted as 1.00.…”

“…We also analyzed the data using a time to event model that weighted each event and then adjusted the patient’s health state based on that event for their remaining person-time [ 26 ]. Each patient was able to incur an unlimited number of events prior to 90-days post-injury or death, at which point they were censored in the analysis.…”

Composite endpoint to evaluate complement inhibition therapy in patients with paroxysmal nocturnal hemoglobinuria

“…In accordance with previous research in other therapeutic areas, development of a composite endpoint as a primary endpoint for PNH can provide insight into meaningful PNH research endpoints for stakeholders such as clinicians, patients, investigators, and policy‐makers 24 . Composite endpoints have previously been developed for use in several therapeutic areas including diabetes, heart failure, multiple sclerosis, rheumatoid arthritis, chronic obstructive pulmonary disease, oncology, orthopedics, and allogeneic hematopoietic cell transplantation 34–41 …”

“…24 Composite endpoints have previously been developed for use in several therapeutic areas including diabetes, heart failure, multiple sclerosis, rheumatoid arthritis, chronic obstructive pulmonary disease, oncology, orthopedics, and allogeneic hematopoietic cell transplantation. [34][35][36][37][38][39][40][41] This novel, exploratory composite endpoint offers a more comprehensive evaluation of PNH treatment effect than any individual endpoint in the clinical trial, which can potentially allow for improved assessment of clinical benefit of PNH treatments. 24 The composite endpoint for PNH enables evidence generation of sufficient validity and generalizability for translation into practice and policy to improve health outcomes in patients with PNH.…”

Using a Patient-Centered Composite Endpoint in a Secondary Analysis of the Control of Hypertension in Pregnancy Study (CHIPS) Trial

“…While integrating preferences into composites has been considered in cardiology 3,13 and other elds, 15 this is the rst study to integrate patient weights with individual event data from a high-quality RCT in pregnancy. Our ndings show that specifying outcome weights may change interpretation of trial results when applied to individual women.…”