Measurement properties of the EQ-5D in populations with a mean age of ≥ 75 years: a systematic review.

PURPOSE: Healthcare interventions for middle-old and oldest-old individuals are often (economically) evaluated using the EQ-5D to measure health-related quality of life (HrQoL). This requires sufficient measurement properties of the EQ-5D. Therefore, the current study aimed to systematically review studies assessing the measurement properties of the EQ-5D in this population. METHODS: The databases PubMed, Cochrane library, Web of Science, Embase, and EconLit were searched for studies providing empirical evidence of reliability, validity, and/or responsiveness of the EQ-5D-3L and EQ-5D-5L in samples with a mean age ≥ 75 years. Studies were selected by two independent reviewers, and the methodological quality was assessed using the COSMIN Risk of Bias checklist. Results were rated against updated criteria for good measurement properties (sufficient, insufficient, inconsistent, indeterminate). The evidence was summarized, and the quality of evidence was graded using a modified GRADE approach. RESULTS: For both EQ-5D versions, high-quality evidence for sufficient convergent validity was found. Known-groups validity was sufficient for the EQ-5D-5L (high-quality evidence), whereas the results were inconsistent for the EQ-5D-3L. Results regarding the reliability were inconsistent (EQ-5D-3L) or entirely lacking (EQ-5D-5L). Responsiveness based on correlations of change scores with instruments measuring related/similar constructs was insufficient for the EQ-5D-3L (high-quality evidence). For the EQ-5D-5L, the available evidence on responsiveness to change in (Hr)QoL instruments was limited. CONCLUSION: Since the responsiveness of the EQ-5D in a population of middle-old and oldest-old individuals was questionable, either using additional instruments or considering the use of an alternative, more comprehensive instrument of (Hr)QoL might be advisable, especially for economic evaluations.

Knowledge user survey and Delphi process to inform development of a new risk of bias tool to assess systematic reviews with network meta-analysis (RoB NMA tool).

BACKGROUND: Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted. OBJECTIVES: Conduct (a) a Delphi process to determine expert opinion on an item's inclusion and (b) a knowledge user survey to widen its impact. DESIGN: Cross-sectional survey and Delphi process. METHODS: Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users' views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks. RESULTS: 22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assess both bias in individual NMA results and authors' conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines. CONCLUSIONS: This Delphi process and knowledge user survey informs the development of the RoB NMA tool.

Psychometric Properties of the EQ-5D for the Assessment of Health-Related Quality of Life in the Population of Middle-Old and Oldest-Old Persons: Study Protocol for a Systematic Review.

Introduction: Health care interventions for middle-old and oldest-old individuals (75 years or older) are often economically evaluated using the EuroQol questionnaire (EQ-5D) to measure health-related quality of life. However, the psychometric performance of the EQ-5D in this population has been questioned, as it probably does not adequately capture relevant aspects of quality of life in the older population. Because the results of economic evaluations using the EQ-5D often guide decision-makers, it is important to know whether the EQ-5D has satisfactory psychometric properties in the middle-old and oldest-old population. Therefore, studies assessing the psychometric properties of the EQ-5D in this population should be synthesized by a systematic review. Methods and Analysis: A systematic review of studies providing empirical evidence of reliability, validity, and/or responsiveness of the EQ-5D in a sample with a mean age ≥75 years will be conducted. The databases PubMed, Web of Science, and EconLit will be searched. In addition, reference lists of included studies will be hand-searched. Two independent reviewers will select studies and assess their risk of bias with the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) Risk of Bias checklist. Relevant data will be extracted by one reviewer and cross-checked by a second reviewer. Potential disagreements in any phase will be resolved through discussion with a third person. The guidelines for systematic reviews of measurement properties proposed by the COSMIN group, including criteria of good measurement properties, will guide the synthesis and interpretation of the results. Discussion: The review's results could facilitate the making of recommendations for the use of the EQ-5D in a population of middle-old and oldest-old people and thereby being of interest for decision-makers or for researchers designing new intervention studies for older people. Heterogeneity of individual studies regarding the population under study could limit the possibility of making a synthesized statement on the appropriateness of the EQ-5D for the middle-old to oldest-old population.

A shortened Barnes maze protocol reveals memory deficits at 4-months of age in the triple-transgenic mouse model of Alzheimer's disease.

Alzheimer's disease is a progressive neurodegenerative disease that manifests as memory loss, cognitive dysfunction, and dementia. Animal models of Alzheimer's disease have been instrumental in understanding the underlying pathological mechanism and in evaluation of potential therapies. The triple transgenic (3 × Tg) mouse model of AD is unique because it recapitulates both pathologic hallmarks of Alzheimer's disease--amyloid plaques and neurofibrillary tangles. The earliest cognitive deficits in this model have been shown at 6-m of age by most groups, necessitating aging of the mice to this age before initiating evaluation of the cognitive effects of therapies. To assess cognitive deficits in the 3 × Tg mice, originally we employed a typical Barnes maze protocol of 15 training trials, but found no significant deficits in aged mice. Therefore, we shortened the protocol to include only 5 training trials to increase difficulty. We found cognitive deficits using this protocol using mainly measures from the probe day, rather than the training trials. This also decreased the effort involved with data analysis. We compared 3 × Tg and wild-type mice at 4-m- and 15-m of age using both the original, long training, and the short training paradigms. We found that differences in learning between 3 × Tg and wild-type mice disappeared after the 4(th) training trial. Measures of learning and memory on the probe day showed significant differences between 3 × Tg and wild-type mice following the short, 5-training trial protocol but not the long, 15-training trial protocol. Importantly, we detected cognitive dysfunction already at 4-m of age in 3 × Tg mice using the short Barnes-maze protocol. The ability to test learning and memory in 4-m old 3 × Tg mice using a shortened Barnes maze protocol offers considerable time and cost savings and provides support for the utilization of this model at pre-pathology stages for therapeutic studies.