Returning research results that indicate risk of Alzheimer disease (AD) dementia—a disease for which no meaningful treatments or cure exist—to cognitively normal participants is controversial. AD is thought to begin many years before clinical signs and symptoms begin. During this time, individuals are cognitively normal but have biomarkers that indicate pathophysiological changes in the brain. With this study, we aim to evaluate the impact of returning research results on cognitively normal participants recruited from a longitudinal observational cohort on ageing at the Knight Alzheimer Disease Research Centre (Knight ADRC) at Washington University in St. Louis.

Our study uses a 2-year, delayed-start randomised clinical trial design. Participants are randomised to receive their research results either 2 weeks or 1 year after informed consent. This study was approved to recruit up to 450 participants with existing genetic and biomarker testing results from the Knight ADRC. During the study period, 260 individuals were eligible and approached for entry into the study. The primary cognitive outcomes are 1-year change in subjective cognitive score on the clinical dementia rating sum of box scores and the objective cognitive score on cognitive composite score. The primary psychosocial outcome is change in geriatric depression scale score 1 year after return of research results. The study was powered to answer primary outcomes with 140 participants (70 per study arm).

This study has been approved by the Washington University School of Medicine (WUSM) Institutional Review Board and the Human Research Protection Office. Results from these trials are shared through conferences and publications.

NCT04699786.

Lymphoma is a haematologic malignancy affecting cells of the immune system. With numerous treatment options available, clinicians and patients frequently face difficulty in selecting the most appropriate therapy. Patient-reported Outcome (PRO) offers valuable patients’ insight that may support treatment differentiation. A PRO measure (PROM) is a questionnaire or survey measuring a PRO. Despite many efforts to guide the selection of PROMs in clinical trials, choosing the appropriate ones remains a challenge. This study aims to develop a pragmatic paradigm for selecting PROMs in clinical trials involving adult patients with lymphoma through the collaboration and communication between clinical investigators involved in trials and Health Economics and Outcomes Research (HEOR) scientists specialised in research methodologies.

A rapid review was conducted to identify existing PROMs for adult patients with lymphoma in clinical trials and guidelines supporting PROM selection.

PubMed, Google Scholar and websites for regulatory and health technology assessment (HTA) bodies in eight countries of interest were searched from 2009 to July 2024.

Publications with PROMs were identified for adult patients in lymphoma trials. The most relevant guidelines supporting the development of the pragmatic paradigm were selected.

The initial search and data extraction were conducted by one author. All authors participated in an in-depth review process.

We categorise 31 applicable PROMs for lymphoma into four distinct groups, streamlining the PROM selection process to facilitate effective communication among clinical investigators, HEOR scientists, patients and others. Additionally, a five-step pragmatic paradigm is developed for identifying appropriate PROM(s).

The pragmatic paradigm presents a practical approach for selecting PROM(s) in lymphoma clinical trials. An appropriate PROM should conceptually align with the treatment goals and be acceptable to regulatory and HTA bodies. Thus, lymphoma clinical trials can generate more patient-focused data, contributing to improving patients’ quality of life and advancing lymphoma care.