Adjudicating Mild Cognitive Impairment Due to Alzheimer's Disease as a Novel Endpoint Event in the TOMMORROW Prevention Clinical Trial.

BACKGROUND: The onset of mild cognitive impairment (MCI) is an essential outcome in Alzheimer's disease (AD) prevention trials and a compelling milestone for clinically meaningful change. Determining MCI, however, may be variable and subject to disagreement. Adjudication procedures may improve the reliability of these determinations. We report the performance of an adjudication committee for an AD prevention trial. METHODS: The TOMMORROW prevention trial selected cognitively normal participants at increased genetic risk for AD and randomized them to low-dose pioglitazone or placebo treatment. When adjudication criteria were triggered, a participant's clinical information was randomly assigned to a three-member panel of a six-member independent adjudication committee. Determination of whether or not a participant reached MCI due to AD or AD dementia proceeded through up to three review stages - independent review, collaborative review, and full committee review - requiring a unanimous decision and ratification by the chair. RESULTS: Of 3494 participants randomized, the committee adjudicated on 648 cases from 386 participants, resulting in 96 primary endpoint events. Most participants had cases that were adjudicated once (n = 235, 60.9%); the rest had cases that were adjudicated multiple times. Cases were evenly distributed among the eight possible three-member panels. Most adjudicated cases (485/648, 74.8%) were decided within the independent review (stage 1); 14.0% required broader collaborative review (stage 2), and 11.1% needed full committee discussion (stage 3). The primary endpoint event decision rate was 39/485 (8.0%) for stage 1, 29/91 (31.9%) for stage 2, and 28/72 (38.9%) for stage 3. Agreement between the primary event outcomes supported by investigators' clinical diagnoses and the decisions of the adjudication committee increased from 50% to approximately 93% (after around 100 cases) before settling at 80-90% for the remainder of the study. CONCLUSIONS: The adjudication process was designed to provide independent, consistent determinations of the trial endpoints. These outcomes demonstrated the extent of uncertainty among trial investigators and agreement between adjudicators when the transition to MCI due to AD was prospectively assessed. These methods may inform clinical endpoint determination in future AD secondary prevention studies. Reliable, accurate assessment of clinical events is critical for prevention trials and may mean the difference between success and failure.

The global impact of the COVID-19 pandemic on clinical radiography practice: A systematic literature review and recommendations for future services planning.

INTRODUCTION: Worldwide, reports and experiences indicate that there has been extensive re-organisation within diagnostic imaging and radiotherapy departments in response to the COVID-19 pandemic. This was necessary due to changes in workload and working practice guidelines that have evolved during the pandemic. This review provides a comprehensive summary of the global impact of the COVID-19 pandemic on radiography practice, service delivery and workforce wellbeing. METHODS: A systematic review methodology was adopted to obtain data from primary studies of qualitative, quantitative, and mixed methods designs from databases (PubMed, Science Direct, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and SCOPUS: all 2020 to present). The included articles were subjected to information extraction and results-based convergent synthesis. RESULTS: The electronic database search yielded 10,420 articles after removal of duplicates. Of these, 31 articles met the final inclusion criteria with some (n = 8) fully focussed on radiotherapy workforce and service delivery. The pandemic impact on radiography practice is broadly themed around: training, communication, and information dissemination; infrastructure, technology, and clinical workflow; and workforce mental health and well-being. CONCLUSION: Globally, most radiographers received inadequate training for managing COVID-19 patients during the initial acute phase of the pandemic. Additionally, there were significant changes to clinical practice, working patterns and perceived increase in workload due to surges in COVID-19 patients and the consequent strict adherence to new infection protocols. These changes, coupled with fear emanating from the increased risk of the workforce to contracting the infection, contributed to anxiety and workplace-related stress during the pandemic. IMPLICATIONS FOR PRACTICE: Local pandemic response strategies must be appropriately developed from standard protocols in readiness for safe clinical practice and well-being management training of practitioners.