Clinical Trials In Older Adults Research Articles

Geriatric assessment for the practicing clinician: The why, what, and how.

Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer-related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 clinical trials in older adults with solid tumors and hematologic malignancies have demonstrated that GAM improves treatment completion, quality of life, communication, and advance care planning while reducing treatment-related toxicity, falls, and polypharmacy. Nonetheless, implementation and uptake of GAM remain challenging. Various strategies have been proposed, including the use of GA screening tools, to identify patients most likely to benefit from GAM, the systematic engagement of the oncology workforce in the delivery of GAM, and the integration of technologies like telemedicine and mobile health to enhance the availability of GA and GAM interventions. Health inequities in minoritized groups persist, and systematic GA implementation has the potential to capture social determinants of health that are relevant to equitable care. Caregivers play an important role in cancer care and experience burden themselves. GA can guide dyadic supportive care interventions, ultimately helping both patients and caregivers achieve optimal health.

Precision medicine and patient-centered outcomes: Learning from APOE for prevention clinical trials in older adults.

This editorial comments on the article by Clocchiatti‐Tuozzo et al.

APOE epsilon variants and composite risk of dementia, disability, and death in the health and retirement study.

Clinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separately, the magnitude of its effect on this composite outcome remains unknown. We tested the hypothesis that APOE ε4 increases, whereas APOE ε2 decreases, the risk of a composite outcome of dementia, disability, and death. We evaluated clinical and genomic data from the Health and Retirement Study collected from 1992 to 2020. We used variants rs429358 and rs7412 to determine APOE genotypes, modeled dominantly (carriers/noncarriers). We conducted survival analysis, using multivariable Cox proportional hazards models with a composite endpoint of dementia, disability, and death. Our primary analysis evaluated participants with genetic data and no previous dementia or disability. In secondary analyses, we focused on persons aged > = 75 years without heart disease or stroke, a subpopulation increasingly important in clinical trials of older adults. We included 14,527 participants in the primary analysis. Over a median of 18 (Interquartile Range [IQR] 12-24) years, 6711 (46%) participants developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.15, 95%CI:1.09-1.22) of the composite outcome, whereas APOE ε2 associated with lower risk (HR:0.92, 95%CI:0.86-0.99). In the secondary analysis, we included 3174 participants. Over a median of 7 (IQR 4-11) years, 1326 participants (42%) developed the composite outcome. In Cox analyses, APOE ε4 associated with higher risk (HR:1.25, 95%CI:1.10-1.41) of the composite outcome, whereas APOE ε2 associated with lower risk(HR:0.84, 95%CI:0.71-0.98). APOE ε variants are linked to the risk of dementia, disability, and death in older adults. By examining these variants in clinical trials, we can better elucidate how they might alter the effectiveness of tested interventions. Importantly, this genetic information could help identify participants who may have greater absolute benefit from such interventions.

Primary outcome reporting in clinical trials for older adults with depression.

Findings from randomised controlled trials (RCTs) are synthesised through meta-analyses, which inform evidence-based decision-making. When key details regarding trial outcomes are not fully reported, knowledge synthesis and uptake of findings into clinical practice are impeded. Our study assessed reporting of primary outcomes in RCTs for older adults with major depressive disorder (MDD). Trials published between 2011 and 2021, which assessed any intervention for adults aged ≥65 years with a MDD diagnosis, and that specified a single primary outcome were considered for inclusion in our study. Outcome reporting assessment was conducted independently and in duplicate with a 58-item checklist, used in developing the CONSORT-Outcomes statement, and information in each RCT was scored as 'fully reported', 'partially reported' or 'not reported', as applicable. Thirty-one of 49 RCTs reported one primary outcome and were included in our study. Most trials (71%) did not fully report over half of the 58 checklist items. Items pertaining to outcome analyses and interpretation were fully reported by 65% or more of trials. Items reported less frequently included: outcome measurement instrument properties (varied from 3 to 30%) and justification of the criteria used to define clinically meaningful change (23%). There is variability in how geriatric depression RCTs report primary outcomes, with omission of details regarding measurement, selection, justification and definition of clinically meaningful change. Outcome reporting deficiencies may hinder replicability and synthesis efforts that inform clinical guidelines and decision-making. The CONSORT-Outcomes guideline should be used when reporting geriatric depression RCTs.

Predicting cognitive scores from wearable-based digital physiological features using machine learning: data from a clinical trial in mild cognitive impairment

BackgroundContinuous assessment and remote monitoring of cognitive function in individuals with mild cognitive impairment (MCI) enables tracking therapeutic effects and modifying treatment to achieve better clinical outcomes. While standardized neuropsychological tests are inconvenient for this purpose, wearable sensor technology collecting physiological and behavioral data looks promising to provide proxy measures of cognitive function. The objective of this study was to evaluate the predictive ability of digital physiological features, based on sensor data from wrist-worn wearables, in determining neuropsychological test scores in individuals with MCI.MethodsWe used the dataset collected from a 10-week single-arm clinical trial in older adults (50–70 years old) diagnosed with amnestic MCI (N = 30) who received a digitally delivered multidomain therapeutic intervention. Cognitive performance was assessed before and after the intervention using the Neuropsychological Test Battery (NTB) from which composite scores were calculated (executive function, processing speed, immediate memory, delayed memory and global cognition). The Empatica E4, a wrist-wearable medical-grade device, was used to collect physiological data including blood volume pulse, electrodermal activity, and skin temperature. We processed sensors’ data and extracted a range of physiological features. We used interpolated NTB scores for 10-day intervals to test predictability of scores over short periods and to leverage the maximum of wearable data available. In addition, we used individually centered data which represents deviations from personal baselines. Supervised machine learning was used to train models predicting NTB scores from digital physiological features and demographics. Performance was evaluated using “leave-one-subject-out” and “leave-one-interval-out” cross-validation.ResultsThe final sample included 96 aggregated data intervals from 17 individuals. In total, 106 digital physiological features were extracted. We found that physiological features, especially measures of heart rate variability, correlated most strongly to the executive function compared to other cognitive composites. The model predicted the actual executive function scores with correlation r = 0.69 and intra-individual changes in executive function scores with r = 0.61.ConclusionsOur findings demonstrated that wearable-based physiological measures, primarily HRV, have potential to be used for the continuous assessments of cognitive function in individuals with MCI.

Big Data for Geriatric Oncology Research.

Cancer is the second leading cause of death in North Carolina and approximately half of cancers are diagnosed in older adults (≥65 years). Cancer clinical trials in older adults are limited and there is a lack of evidence on optimal care strategies in this population. We highlight how big data can fill in gaps in geriatric oncology research.

Beyond MACE: a multidimensional approach to outcomes in clinical trials for older adults with stable ischemic heart disease.

The global population of older adults is expanding rapidly resulting in a shift towards managing multiple chronic diseases that coexist and may be exacerbated by cardiovascular illness. Stable ischemic heart disease (SIHD) is a predominant contributor to morbidity and mortality in the older adult population. Although results from clinical trials demonstrate that chronological age is a predictor of poor health outcomes, the current management approach remains suboptimal due to insufficient representation of older adults in randomized trials and the inadequate consideration for the interaction between biological aging, concurrent geriatric syndromes, and patient preferences. A shift towards a more patient-centered approach is necessary for appropriately and effectively managing SIHD in the older adult population. In this review, we aim to demonstrate the distinctive needs of older adults who prioritize holistic health outcomes like functional capacity, cognitive abilities, mental health, and quality of life alongside the prevention of major adverse cardiovascular outcomes reported in cardiovascular clinical trials. An individualized, patient-centered approach that involves shared decision-making regarding outcome prioritization is needed when any treatment strategy is being considered. By prioritizing patients and addressing their unique needs for successful aging, we can provide more effective care to a patient population that exhibits the highest cardiovascular risks.

Quantifying the value of older adult-specific clinical trials: Post-lumpectomy irradiation among older adults with early-stage breast cancer

IntroductionAlthough there is increasing interest in conducting cancer clinical trials in older adults, the benefit of such trials is unclear. We aimed to quantify the real-world clinical and economic effects of two phase 3 trials (CALGB 9343 and PRIME II) which showed that post-lumpectomy radiation therapy (RT) improves loco-regional recurrence but makes no improvement in overall survival among older women with early-stage breast cancer (ESBC). Materials and MethodsWe developed a health-transition model to quantify the incremental clinical and economic outcomes between scenarios with vs. without older adult-specific trial results from a societal perspective between 2004 and 2018. The transition probabilities in the model were mainly derived from the 10-year results of CALGB 9343. The total number of the affected patient population in the US and the change in the probability of omitting post-lumpectomy RT due to the CALGB 9343 and PRIME II results were derived from a retrospective analysis of the SEER registry data for patients with ESBC. Sensitivity analyses were conducted to calculate the 95% credible interval (CR) of the incremental clinical and economic outcomes between the two scenarios. ResultsBetween 2004 and 2018, 32,936 (95% CR: 31,512, 34,357) fewer patients received post-lumpectomy RT among those aged 70 years or older diagnosed with ESBC in the US and there was a decrease cost of $419 M USD (95% CR: -$238 M, −$689 M) in scenarios with vs. without older adult-specific trial results. The difference in projected life years (1083 years, 95% CI: −2542, 7985) and QALYs (866 years, 95% CI: −2561, 7780) were not significant. At a willingness-to-pay threshold of $100 k/QALY, the probability of older adult-specific trial results generating a positive net monetary benefit was 98%. DiscussionThe CALGB 9343 and PRIME II trial results were associated with a substantial cost-saving in the US society. Our results suggest that older adult-specific clinical trials that demonstrate no survival benefit of an intervention in older adults could be correlated with a significant monetary benefit. Further case studies are needed for different types of older adult-specific trials to understand the value of older adult-specific trials comprehensively.

How does cumulative evidence from older adult-specific trials influence clinical practice? A difference-in-differences analysis in early-stage breast cancer

BackgroundDespite increasing focus on conducting cancer clinical trials in older adults, it is unclear whether such evidence influences practice patterns. We aimed to estimate the impact of cumulative evidence from older adult-specific trial results from the CALGB 9343 and PRIME II trials that found post-lumpectomy irradiation has little benefit among older adults with early-stage breast cancer (ESBC). MethodsPatients diagnosed with ESBC between 2000 and 2018 were identified from the SEER registry data. We examined the incremental immediate effect, incremental average yearly effect, and cumulative effect of a series of CALGB 9343 and PRIME II results on the utilization level of post-lumpectomy irradiation. We conducted difference-in-differences analyses, comparing those aged 70 or older vs. <65 years old. ResultsThe initial 5-year CALGB 9343 results in 2004 led to a significant immediate (−0.038, 95% CI: −0.064, −0.012) and average yearly decrease (−0.008, 95% CI: −0.013, −0.003) in the probability of irradiation use among those aged 70 or older compared to those below 65 years of age. 11-year CALGB 9343 results in 2010 significantly accelerated the average yearly effect by 1.7 percentage points (95% CI: −0.030, −0.004). The other later results did not significantly change the time trend. The cumulative effect of all results between 2004 and 2018 was −26.3 percentage points (95% CI: −0.29, −0.24). ConclusionCumulative evidence from older adult-specific trials in ESBC led to decreasing use of irradiation over time among elderly patients. The rate of decrease after the initial results was accelerated by long-term follow-up results.

Remotely Administered Resilience- and Wisdom-Focused Intervention to Reduce Perceived Stress and Loneliness: Pilot Controlled Clinical Trial in Older Adults

Older adults are vulnerable to perceived stress and loneliness, exacerbated by the COVID-19 pandemic. We previously reported inverse relationships between loneliness/perceived stress and wisdom/resilience. There are few evidence-based tele-health interventions for older adults. We tested a new remotely-administered manualized resilience- and wisdom-focused behavioral intervention to reduce perceived stress and loneliness in older adults. This pilot controlled clinical trial used a multiple-phase-change single-case experimental design, with three successive 6-week phases: control, intervention, and follow-up periods. The intervention included six once-a-week one-hour sessions. Participants were 20 adults >65 years, without dementia. All 20 participants completed every session. The study indicated feasibility and acceptability of the intervention. While the sample was too small for demonstrating efficacy, there was a reduction (small-to-medium effect size) in perceived stress and loneliness, and increase in resilience, happiness, and components of wisdom and positive perceptions of aging. These preliminary data support feasibility, acceptability, and possible efficacy of a remotely-administered resilience- and wisdom-focused intervention in older adults to reduce stress and loneliness.

Management of Hyperglycemia in Older Adults with Type 2 Diabetes.

The increasing incidence of type 2 diabetes in the general population as well as enhanced life expectancy has resulted in a rapid rise in the prevalence of diabetes in the older population. Diabetes causes significant morbidity and impairs quality of life. Managing diabetes in older adults is a daunting task due to unique health and psychosocial challenges. Medical management is complicated by polypharmacy, cognitive impairment, urinary incontinence, injurious falls, and persistent pain. Health care providers now have several traditional and contemporary pharmacologic agents to manage diabetes. Avoidance of hypoglycemia is critical; however, evidence-based guidelines are lacking due to the paucity of clinical trials in older adults. For many in this population, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goal of diabetes care in older adults is to enhance the quality of life without subjecting these patients to intrusive and complicated interventions. Recent technological advancements such as continuous glucose monitoring systems can have crucial supplementary benefits in the geriatric population.

ESPO and Health Sciences Section Symposium: Conducting Clinical Trial Research During the COVID-19 Pandemic: Transforming Research Practice for the Future

The COVID-19 pandemic caused significant disruptions for people and institutions across healthcare settings. Clinical trials are an important research tool to test interventions in real-world healthcare settings and provide high quality evidence that supports older adults’ longevity and wellness. Clinical trialists must consider how to account for unpredictable and ever-changing environmental contexts. The COVID-19 pandemic is a specific example of a changing context that impacted all stages of the clinical trials process from planning, to administration, and outcomes. Reflecting on ways clinical trialists navigated their studies during the COVID-19 pandemic may unlock opportunities to design flexible clinical trials that meet the needs of older adults in real-world environments. This symposium highlights five clinical trials for older adults that occurred during the COVID-19 pandemic. Dr. Carpenter will discuss lessons learned in implementing a palliative care intervention in nursing homes. Brianna Morgan will describe the pivots needed to complete a clinical trial testing an advance care planning website for nursing home residents with dementia. Dr. Nuckols will describe obstacles and opportunities to implementing a randomized controlled trial on hospital nursing units, including implications for medication safety. Dr. Pevnick will highlight barriers and facilitators to implementing a pharmacist-led intervention to reduce hospital readmissions. Dr. Stark will share novel procedures for conducting clinical trials in the community that reduce burden for older adult participants while maintaining fidelity. Presenters will address practice transformations that researchers can bring forward to design flexible clinical trials that meet the needs of older adults in different healthcare contexts.

Effectiveness of the Mobility Rehab System for Mobility Training in Older Adults: A Pragmatic Clinical Trial.

Introduction: Mobility impairments are among the main causes of falls in older adults and patients with neurological diseases, leading to functional dependence and substantial health care costs. Feedback-based interventions applied in controlled, laboratory environments have shown promising results for mobility rehabilitation, enhancing the benefits of standard therapy. However, the effectiveness of sensor-based feedback to improve gait in actual outpatient physical therapy settings is unknown. The proposed trial examines the effectiveness of a physical therapist-assisted, visual feedback system using wearable inertial sensors, Mobility Rehab, for mobility training in older adults with gait disturbances in an outpatient clinic.Methods: The study is a single site, pragmatic clinical trial in older adults with gait disturbances. Two hundred patients undergoing their outpatient rehabilitation program are assigned, by an independent assistant, for screening by one of four therapists, and assigned to either a standard physical therapy or therapist-assisted feedback therapy. Both groups train twice a week for 6 weeks. Four physical therapists were randomized and stratified by years of experience to deliver standard therapy or therapist-assisted feedback rehabilitation. Each session is 45 min long. Gait is trained for 30 min. The additional 15 min include exercises for endurance, strength, and static and dynamic balance in functional tasks. Mobility Rehab uses unobtrusive, inertial sensors on the feet and belt with real-time algorithms to provide real-time feedback on gait metrics (i.e., gait speed, double support time, foot clearance, angle at foot strike, and arm swing), which are displayed on a hand-held monitor. Blinded assessments are carried out before and after the intervention. The primary outcome measure is subjects' perception of balance as measured by the Activities-specific Balance Confidence scale. Gait speed, as measured with wearable inertial sensors during walking, is the secondary outcome measure.Discussion: We hypothesize that therapist-assisted feedback rehabilitation will be more effective than standard rehabilitation for gait. Feedback of motor performance plays a crucial role in rehabilitation and objective characterization of gait impairments by Mobility Rehab has the potential to improve the accuracy of patient-specific gait feedback.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03869879.

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

ObjectivesOlder adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake. Materials and MethodsWe conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005–2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis. ResultsOur study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%). ConclusionMore than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.

Weight management intervention identifies association of decreased DNA methylation age with improved functional age measures in older adults with obesity

BackgroundAssessing functional ability is an important component of understanding healthy aging. Objective measures of functional ability include grip strength, gait speed, sit-to-stand time, and 6-min walk distance. Using samples from a weight loss clinical trial in older adults with obesity, we examined the association between changes in physical function and DNA-methylation-based biological age at baseline and 12 weeks in 16 individuals. Peripheral blood DNA methylation was measured (pre/post) with the Illumina HumanMethylationEPIC array and the Hannum, Horvath, and PhenoAge DNA methylation age clocks were used. Linear regression models adjusted for chronological age and sex tested the relationship between DNA methylation age and grip strength, gait speed, sit-to-stand, and 6-min walk.ResultsParticipant mean weight loss was 4.6 kg, and DNA methylation age decreased 0.8, 1.1, and 0.5 years using the Hannum, Horvath, and PhenoAge DNA methylation clocks respectively. Mean grip strength increased 3.2 kg. Decreased Hannum methylation age was significantly associated with increased grip strength (β = −0.30, p = 0.04), and increased gait speed (β = 0.02, p = 0.05), in adjusted models. Similarly, decreased methylation age using the PhenoAge clock was associated with significantly increased gait speed (β = 0.02, p = 0.04). A decrease in Horvath DNA methylation age and increase in physical functional ability did not demonstrate a significant association.ConclusionsThe observed relationship between increased physical functional ability and decreased biological age using DNA methylation clocks demonstrate the potential utility of DNA methylation clocks to assess interventional approaches to improve health in older obese adults.Trial registration: National Institute on Aging (NIA), NCT03104192. Posted April 7, 2017, https://clinicaltrials.gov/ct2/show/NCT03104192

Challenges in Obtaining and Assessing Salivary Cortisol and α-Amylase in an Over 60 Population Undergoing Psychotherapeutic Treatment for Complicated Grief: Lessons Learned.

Biomarkers may serve as objective measures in complicated grief (CG) potentially capturing responses to stress reduction treatment. This paper reports challenges in obtaining and assessing salivary cortisol and α-amylase (sAA) for a recent randomized clinical trial. Within-session changes in salivary cortisol and sAA for 54 older adults with CG who received Accelerated Resolution Therapy were compared with perceived stress measured by Subjective Units of Distress Scale. Bivariate correlations and multiple regressions examined changes in biomarkers. Protocols, study logs, and audit reports identified challenges. Challenges included obtaining unstimulated passive drool salivary samples and their analyses. Our sample of older females on multiple medications may have resulted in a perfect storm of moderating and intervening variables which affected the stress response. This paper contributes to the discussion on designing clinical trials for older adults which must account for physiologic changes, multimorbidity, and polypharmacy common in this population and makes recommendations moving forward.

Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma

The novel coronavirus (SARS-CoV-2, COVID-19) was first identified in the province of Wuhan, China in December 2019 [1], following the emergence of new cases of pneumonia of unknown etiology. Since then, the manifestations of COVID-19 infections have ranged from asymptomatic to severe respiratory infections, with increased morbidity in older adults including those with co-morbidities and cancer [2,3]. Presently, global mortality is reported at 4.7%, but this varies widely by location, from 0.7% in Germany to 10.8% in Italy [4]. As of April 13, 2020, the number of infections continues to rise well beyond the 1.9 million cases, and approximately 120,000 COVID-19-related deaths that have already occurred globally [5]. Multiple myeloma (MM) is a malignant plasma cell dyscrasia which predominantly affects older and often frail adults. Although tremendous gains have been made for older adults with MM, infections, including respiratory infections, significantly impact the rate of early mortality in these patients [6,7]. Furthermore, older adults with MM have age-associated vulnerabilities leading to heterogeneity in outcomes [8]. The complexity of caring for older patients have increased substantially during this pandemic, due to concern about their risk of severe morbidity of COVID19 infection. Optimal strategies for these patients will involve staging the malignancy/aging, while simultaneously considering the local prevalence of COVID-19 infection. Herein, we discuss strategies for the risk reduction of COVID-19 transmission, treatment stratification of anti-myeloma therapy and discussion regarding goals of care for older adults with MM during the COVID-19 pandemic.

Implementation of the Goal-directed Medication review Electronic Decision Support System (G-MEDSS)\xa9 into home medicines review: a protocol for a cluster-randomised clinical trial in older adults

BackgroundOlder people living in the community have a high prevalence of polypharmacy and are vulnerable to adverse drug events. Home Medicines Review (HMR) is a collaborative medication review service involving general practitioners (GPs), accredited clinical pharmacists (ACPs) and patients, which aims to prevent medication-related problems. This study aims to evaluate the implementation of a Computerised Clinical Decision Support System (CCDSS) called G-MEDSS© (Goal-directed Medication Review Electronic Decision Support System) in HMRs to deprescribe anticholinergic and sedative medications, and to assess the effect of deprescribing on clinical outcomes.MethodsThis study consists of 2 stages: Stage I – a two-arm parallel-group cluster-randomised clinical trial, and Stage II – process evaluation of the CCDSS intervention in HMR. Community-dwelling older adults living with and without dementia who are referred for HMR by their GP and recruited by ACPs will be included in this study. G-MEDSS is a CCDSS designed to provide clinical decision support for healthcare practitioners when completing a medication review, to tailor care to meet the patients’ goals and preferences. The G-MEDSS contains three tools: The Goals of Care Management Tool, The Drug Burden Index (DBI) Calculator©, and The revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire. The G-MEDSS produces patient-specific deprescribing reports, to be included as part of the ACPs communication with the patient’s GP, and patient-specific reports for the patient (or carer). ACPs randomised to the intervention arm of the study will use G-MEDSS to create deprescribing reports for the referring GP and for their patient (or carer) when submitting the HMR report. ACPs in the comparison arm will provide the usual care HMR service (without the G-MEDSS).OutcomesThe primary outcome is reduction in DBI exposure 3 months after HMR ± G-MEDSS intervention between comparison and intervention groups. The secondary outcomes include changes in clinical outcomes (physical and cognitive function, falls, institutionalisation, GP visits, medication adherence and mortality) 3-months after HMR.DiscussionThis study is expected to add to the evidence that the combination of CCDSS supporting medication review can improve prescribing and clinical outcomes in older adults.Trial registrationThe trial was registered on the Australian New Zealand Clinical Trials Registry ACTRN12617000895381 on 19th June 2017.

Continuous Digital Monitoring of Walking Speed in Frail Elderly Patients: Noninterventional Validation Study and Longitudinal Clinical Trial.

BackgroundDigital technologies and advanced analytics have drastically improved our ability to capture and interpret health-relevant data from patients. However, only limited data and results have been published that demonstrate accuracy in target indications, real-world feasibility, or the validity and value of these novel approaches.ObjectiveThis study aimed to establish accuracy, feasibility, and validity of continuous digital monitoring of walking speed in frail, elderly patients with sarcopenia and to create an open source repository of raw, derived, and reference data as a resource for the community.MethodsData described here were collected as a part of 2 clinical studies: an independent, noninterventional validation study and a phase 2b interventional clinical trial in older adults with sarcopenia. In both studies, participants were monitored by using a waist-worn inertial sensor. The cross-sectional, independent validation study collected data at a single site from 26 naturally slow-walking elderly subjects during a parcours course through the clinic, designed to simulate a real-world environment. In the phase 2b interventional clinical trial, 217 patients with sarcopenia were recruited across 32 sites globally, where patients were monitored over 25 weeks, both during and between visits.ResultsWe have demonstrated that our approach can capture in-clinic gait speed in frail slow-walking adults with a residual standard error of 0.08 m per second in the independent validation study and 0.08, 0.09, and 0.07 m per second for the 4 m walk test (4mWT), 6-min walk test (6MWT), and 400 m walk test (400mWT) standard gait speed assessments, respectively, in the interventional clinical trial. We demonstrated the feasibility of our approach by capturing 9668 patient-days of real-world data from 192 patients and 32 sites, as part of the interventional clinical trial. We derived inferred contextual information describing the length of a given walking bout and uncovered positive associations between the short 4mWT gait speed assessment and gait speed in bouts between 5 and 20 steps (correlation of 0.23) and longer 6MWT and 400mWT assessments with bouts of 80 to 640 steps (correlations of 0.48 and 0.59, respectively).ConclusionsThis study showed, for the first time, accurate capture of real-world gait speed in slow-walking older adults with sarcopenia. We demonstrated the feasibility of long-term digital monitoring of mobility in geriatric populations, establishing that sufficient data can be collected to allow robust monitoring of gait behaviors outside the clinic, even in the absence of feedback or incentives. Using inferred context, we demonstrated the ecological validity of in-clinic gait assessments, describing positive associations between in-clinic performance and real-world walking behavior. We make all data available as an open source resource for the community, providing a basis for further study of the relationship between standardized physical performance assessment and real-world behavior and independence.

Evaluation of two frailty indices, with practical application in a vaccine clinical trial

ABSTRACT Frail older adults are at increased risk of poor clinical outcomes. Frailty assessment is therefore important in clinical trials to understand the benefits and harms of interventions. However, consensus is lacking on how frailty should be assessed. We developed a prospectively specified index using a battery of formal tests and instruments and a retrospectively generated index using medical comorbidities and patient reported outcomes (PROs) within an adjuvanted recombinant zoster vaccine (RZV) trial (NCT02979639). For both frailty indices (FIs), a total deficit score was calculated as the accumulation of deficits and participants were categorized as non-frail, pre-frail and frail. We assessed (1) the feasibility and validity of both FIs; (2) the impact of RZV vaccine reactogenicity by frailty status on Short Form-36 [SF-36] physical functioning (PF) scores. Of 401 participants, aged ≥50 years, 236 (58.9%) were categorized non-frail, 143 (35.7%), pre-frail, and 22 (5.5%) frail using the prospective FI. Corresponding numbers for the retrospective FI were 192 (47.9%), 169 (42.1%) and 40 (10.0%), respectively. Strong concordance was observed between the frailty status assessments (P < .001). The proportion defined as frail increased from 1.5%, to 10.4% in participants aged 50–59, and ≥70 years, respectively, for the prospective FI. Corresponding numbers for the retrospective FI were 3.7%, and 17.2%, respectively. RZV vaccination was associated with a transient, non-clinically meaningful, decrease on the SF-36 PF score in frail participants. Both frailty indices provided similar results. The retrospectively generated FI offers the advantage of being easier to incorporate into vaccine clinical trials of older adults.