Digital medicine is an interdisciplinary field, drawing together stakeholders with expertize in engineering, manufacturing, clinical science, data science, biostatistics, regulatory science, ethics, patient advocacy, and healthcare policy, to name a few. Although this diversity is undoubtedly valuable, it can lead to confusion regarding terminology and best practices. There are many instances, as we detail in this paper, where a single term is used by different groups to mean different things, as well as cases where multiple terms are used to describe essentially the same concept. Our intent is to clarify core terminology and best practices for the evaluation of Biometric Monitoring Technologies (BioMeTs), without unnecessarily introducing new terms. We focus on the evaluation of BioMeTs as fit-for-purpose for use in clinical trials. However, our intent is for this framework to be instructional to all users of digital measurement tools, regardless of setting or intended use. We propose and describe a three-component framework intended to provide a foundational evaluation framework for BioMeTs. This framework includes (1) verification, (2) analytical validation, and (3) clinical validation. We aim for this common vocabulary to enable more effective communication and collaboration, generate a common and meaningful evidence base for BioMeTs, and improve the accessibility of the digital medicine field.

Rationale: A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements.Objectives: To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH.Methods: Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH (nadir epiglottic pressure before arousal). The ArTH was measured from up to 20 non-REM and REM respiratory events selected randomly. Multiple linear regression was used to determine the independent predictors of the ArTH. Logistic regression was used to develop a clinical scoring system.Measurements and Main Results: Nadir oxygen saturation as measured by pulse oximetry, apnea-hypopnea index, and the fraction of events that were hypopneas (F hypopneas ) were independent predictors of the ArTH (r 2 = 0.59; P , 0.001). Using this information, we used receiver operating characteristic analysis and logistic regression to develop a clinical score to predict a low ArTH, which allocated a score of 1 to each criterion that was satisfied: (apnea-hypopnea index, ,30 events per hour) 1 (nadir oxygen saturation as measured by pulse oximetry .82.5%) 1 (F hypopneas .58.3%). A score of 2 or above correctly predicted a low arousal threshold in 84.1% of participants with a sensitivity of 80.4% and a specificity of 88.0%, a finding that was confirmed using leaveone-out cross-validation analysis.Conclusions: Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.Keywords: sleep apnea; respiratory-induced arousals; arousal threshold; phenotype traits; lung Obstructive sleep apnea (OSA) is a common disease with major neurocognitive and cardiovascular sequelae (1-3). Despite its high prevalence and well-recognized consequences, treatment of OSA remains unsatisfactory because of poor adherence (e.g., continuous positive airway pressure) and variable efficacy of existing therapies (e.g., surgery, oral appliances) (4), creating a need for further research into underlying mechanisms to identify new therapeutic targets.

values remains an area of debate based on evidence from single studies.In 2007, a number of meta-analyses were published investigating the effect of PAP on BP, each adopting different study selection criteria, with confl icting results. An analysis of ten studies did not fi nd any signifi cant difference in either systolic or diastolic BP (SBP, DBP) between PAP and control groups when 24-h ambulatory blood pressure monitoring (ABPM) and offi ce BP measurements were combined.1 Twenty-four hour mean arterial BP declined signifi cantly by 1.7 mm Hg in a meta-analysis of 12 trials, and meta-regression analyses of these data found that a greater reduction in BP occurred with increasing OSA severity, greater frequency of arousals during diagnosis of OSA, and greater adherence to treatment, with no signifi cant effect of subjective sleepiness reported at baseline. 2In the largest meta-analysis to date which included 16 studies representing 818 subjects, PAP use was associated with mean decreases in SBP of 2.5 mm Hg, DBP of 1.8 mm Hg, and mean arterial pressure of 2.2 mm Hg, all of which reached statistical signifi cance.3 Thus, these previously published meta-analyses suggest that a small but signifi cant reduction in SBP and DBP Study Objectives: We sought to provide an updated systematic review and meta-analysis of studies investigating the effect of positive airway pressure (PAP) treatment for obstructive sleep apnea (OSA) on systolic and diastolic blood pressure (SBP, DBP). Methods: Two independent investigators undertook a systematic search of the PubMed database to identify randomized controlled trials comparing therapeutic PAP to sham-PAP, pill placebo, or standard care over at least one week in adult OSA patients without major comorbidities. The mean, variance, and sample size for diurnal and nocturnal SBP and DBP data were also extracted independently from each study. Random effects meta-analyses were conducted, followed by pre-specifi ed subgroup and meta-regression analyses. Results: 32 studies were identifi ed, with data available from 28 studies representing n = 1,948 patients. The weighted mean difference in diurnal SBP (−2.58 mm Hg, 95% CI −3.57 to −1.59 mm Hg) and DBP (−2.01 mm Hg, 95% CI −2.84 to −1.18 mm Hg) both signifi cantly favored PAP treatment over control arms, with similar results seen in nocturnal readings. Statistically signifi cant reductions in BP were seen in studies whose patients were younger, sleepier, had more severe OSA, and exhibited greater PAP adherence. Meta-regression indicated that the reductions in DBP with PAP were predicted by mean baseline BP (β = −0.22, p = 0.02) and Epworth Sleepiness Scale scores (β = −0.27, p = 0.04). Conclusions: PAP treatment for OSA is associated with modest but signifi cant reductions in diurnal and nocturnal SBP and DBP. Future research should be directed towards identifying subgroups likely to reap greater treatment benefi ts as well as other therapeutic benefi ts provided by PAP therapy. O bstructive sleep apnea (OSA) is a disorder characterized...