CSF biomarker concordance with amyloid PET in Phase 3 studies of aducanumab.

INTRODUCTION: We assessed the use of cerebrospinal fluid (CSF) biomarkers as an alternative to positron emission tomography (PET) for brain amyloid beta (Aß) pathology confirmation in the EMERGE and ENGAGE clinical trials. METHODS: EMERGE and ENGAGE were randomized, placebo-controlled, Phase 3 trials of aducanumab in participants with early Alzheimer's disease. Concordance between CSF biomarkers (Aß42, Aß40, phosphorylated tau 181, and total tau) and amyloid PET status (visual read) at screening was examined. RESULTS: Robust concordance between CSF biomarkers and amyloid PET visual status was observed (for Aß42/Aß40, AUC: 0.90; 95% CI: 0.83-0.97; p < 0.0001), confirming CSF biomarkers as a reliable alternative to amyloid PET in these studies. Compared with single CSF biomarkers, CSF biomarker ratios showed better agreement with amyloid PET visual reads, demonstrating high diagnostic accuracy. DISCUSSION: These analyses add to the growing body of evidence supporting CSF biomarkers as reliable alternatives to amyloid PET imaging for brain Aß pathology confirmation. HIGHLIGHTS: CSF biomarkers and amyloid PET concordance were assessed in Ph3 aducanumab trials. Robust concordance between CSF biomarkers and amyloid PET was observed. CSF biomarker ratios increased diagnostic accuracy over single CSF biomarkers. CSF Aß42/Aß40 demonstrated high concordance with amyloid PET. Results support CSF biomarker testing as a reliable alternative to amyloid PET.

Using the MEAT VBP Framework to analyse and understand the value of surgical gloves: an explanatory case study.

BACKGROUND: Value-based healthcare is being extensively piloted, scaled and implemented by healthcare providers and systems around the world. However, the ability of the healthcare supply chain function to strategically contribute to the improvement of value has been held back by a lack of practical tools for turning value-based procurement from concept into action. Two recently developed conceptual models - the American CQO Movement and the European MEAT VBP Framework - have been developed to support the implementation of value-based procurement in healthcare. We demonstrate how the latter of these models can be adapted and applied pragmatically to generate insights into the value of a specific medical device, technology or consumable. METHODS: We undertook an explanatory, qualitative, single-case study focused on a specific consumable - surgical gloves - that provide a critical example of a type of medical device usually procured in high volumes but at risk of commoditisation due to a widespread lack of understanding of their value. Since the global Covid-19 pandemic prevented fieldwork, structured interviews were conducted via Zoom and corroborated by a literature review. RESULTS: We identified ten cost criteria and eight outcome criteria with which the value of surgical gloves can be analysed and understood. For each of these criteria we propose definitions and value impact metrics that decision-makers can use during a procurement exercise to describe, quantify and compare glove value. CONCLUSION: The MEAT VBP Framework provides a highly practical and adaptable means of imposing both structure and rigour on a value analysis process and of qualitatively describing the potential value impact of surgical gloves for patients, professionals, providers and health systems.