Obesity has become a worldwide challenge with significant health and socioeconomic implications. One of the major implications is its impact on drug therapy. In order to gain a better understanding of this impact, we surveyed the regulatory guidances, the newly approved molecular entity drug products, and drug product labels in the Physician's Desk Reference. This review summarizes the findings of the survey along with the existing knowledge on pharmacokinetic and pharmacodynamic changes associated with obesity.

An early detection of functional decline with age is important to start interventions at an early state and to prolong the functional fitness. In order to assure such an early detection, functional assessments must be conducted on a frequent and regular basis. Since the five time chair rise test (5CRT) is a well-established test in the geriatric field, this test should be supported by technology. We introduce an approach that automatically detects the execution of the chair rise test via an inertial sensor integrated into a belt. The system’s suitability was evaluated via 20 subjects aged 72–89 years (78.2 ± 4.6 years) and was measured by a stopwatch, the inertial measurement unit (IMU), a Kinect® camera and a force plate. A Multilayer Perceptrons-based classifier detects transitions in the IMU data with an F1-Score of around 94.8%. Valid executions of the 5CRT are detected based on the correct occurrence of sequential movements via a rule-based model. The results of the automatically calculated test durations are in good agreement with the stopwatch measurements (correlation coefficient r = 0.93 (p < 0.001)). The analysis of the duration of single test cycles indicates a beginning fatigue at the end of the test. The comparison of the movement pattern within one person shows similar movement patterns, which differ only slightly in form and duration, whereby different subjects indicate variations regarding their performance strategies.

Changes that accompany older age can alter the pharmacokinetics (PK), pharmacodynamics (PD), and likelihood of adverse effects (AEs) of a drug. However, older adults, especially the oldest or those with multiple chronic health conditions, polypharmacy, or frailty, are often under‐represented in clinical trials of new drugs. Deficits in the current conduct of clinical evaluation of drugs for older adults and potential steps to fill those knowledge gaps are presented in this communication. The most important step is to increase clinical trial enrollment of older adults who are representative of the target treatment population. Unnecessary eligibility criteria should be eliminated. Physical and financial barriers to participation should be removed. Incentives could be created for inclusion of older adults. Enrollment goals should be established based on intended treatment indications, prevalence of the condition, and feasibility. Relevant clinical pharmacology data need to be obtained early enough to guide dosing and reduce risk for participation of older adults. Relevant PK and PD data as well as patient‐centered outcomes should be measured during trials. Trial data should be analyzed for differences in PK, PD, effectiveness, and safety arising from differences in age or from the presence of conditions common in older adults. Postmarket evaluations with real‐world evidence and drug labeling updates throughout the product lifecycle reflecting new knowledge are also needed. A comprehensive plan is needed to ensure adequate evaluation of the safety and effectiveness of drugs in older adults.

The older population is currently the fastest growing age group in the United States, and this trend is expected to continue for several decades. Older individuals, in general, have a higher disease burden compared with younger adults and are the major users of medications, yet premarketing drug clinical trials have often excluded them even for the drugs that have high utility in this age group. Extrapolation of clinical results from younger to older individuals does not provide adequate benefit-risk estimation, and the frequent need for dose adjustment in older patients from initially approved doses exemplifies the current lack of adequate clinical data in the elderly. Herein, we discuss the information gap for older individuals and the need for a better understanding of the effect of aging on drug responses. We also present cases for future directions, urging the implementation of improved clinical trial designs using new and emerging pharmacokinetic and pharmacodynamic methods to allow the provision of evidence-based individualized treatment to this high drug use group.

Comprehensive and repetitive assessments are needed to detect physical changes in an older population to prevent functional decline at the earliest possible stage and to initiate preventive interventions. Established instruments like the Timed “Up & Go” (TUG) Test and the Sit-to-Stand Test (SST) require a trained person (e.g., physiotherapist) to assess physical performance. More often, these tests are only applied to a selected group of persons already functionally impaired and not to those who are at potential risk of functional decline. The article introduces the Unsupervised Screening System (USS) for unsupervised self-assessments by older adults and evaluates its validity for the TUG and SST. The USS included ambient and wearable movement sensors to measure the user’s test performance. Sensor datasets of the USS’s light barriers and Inertial Measurement Units (IMU) were analyzed for 91 users aged 73 to 89 years compared to conventional stopwatch measurement. A significant correlation coefficient of 0.89 for the TUG test and of 0.73 for the SST were confirmed among USS’s light barriers. Correspondingly, for the inertial data-based measures, a high and significant correlation of 0.78 for the TUG test and of 0.87 for SST were also found. The USS was a validated and reliable tool to assess TUG and SST.

Background It is important to identify the relevant parameters of physical performance to prevent early functional decline and to prolong independent living. The aim of this study is to describe the development of physical performance in a healthy community-dwelling older cohort aged 70+ years using comprehensive assessment over two years and to subsequently identify the most relevant predictive tests for physical decline to minimize assessment. Methods Physical performance was measured by comprehensive geriatric assessment. Predictors for the individual decline of physical performance by Principal Component and k-means Cluster Analysis were developed, and sensitivity and specificity determined accordingly. Results 251 subjects (Ø 75.4 years) participated in the study. Handgrip strength was low in 21.1%. The follow-up results of tests were divergent. Handgrip strength [− 16.95 (SD 11.55)] and the stair climb power test (power) [− 9.15 (SD 16.84)] yielded the highest percentage changes. Four most relevant tests (handgrip strength, stair climb power time, timed up & go and 4-m gait speed) were identified. A predictor based on baseline data was determined (sensitivity 82%, specificity 96%) to identify subjects characterized by a high degree of physical decline within two years. Discussion Although the cohort of older adults is heterogeneous, most of the individuals in the study exhibited high levels of physical performance; only a few subjects suffered a relevant decline within the 2-year follow-up. Four most relevant tests were identified to predict relevant decline of physical function. Conclusion In spite of ceiling effects of the geriatric assessment in high-performers, we assume that it is possible to predict an individual's risk of physical decline within 2 years with four tests of a comprehensive geriatric assessment.

ImportanceOlder age may be accompanied by changes in the pharmacokinetics or pharmacodynamics or both of medications that can result in altered safety and efficacy profiles.ObjectiveTo assess representation of older adults in clinical trials of new drug applications (NDAs) and biologics license applications (BLAs).Design, Setting, and ParticipantsThis cross-sectional study analyzed US Food and Drug Administration (FDA) data for NDAs and BLAs approved from 2010 through 2019. Age distribution of clinical trial participants was compared with age distribution of the US population with the disease or disorder (prevalent population). Data were from adults enrolled in registration trials for depression, heart failure, insomnia, non–small cell lung cancer (NSCLC), nonvalvular atrial fibrillation (NVAF) stroke prevention, osteoporosis, and type 2 diabetes or adults sampled from US prevalent population in community-dwelling health data. Data were analyzed from November 2020 to February 2021.ExposuresTrial enrollment.Main Outcomes and MeasuresRepresentativeness of trial populations was assessed by the participation to prevalence ratio (PPR) defined as the percentage of patients by age group among clinical trial participants to the percentage of patients by age group among US prevalent population.ResultsData from 166 clinical trials (229 558 participants) for 44 NDAs and BLAs were analyzed. The most consistent finding was the limited enrollment of the oldest age groups, namely those 75 years and above for type 2 diabetes and NSCLC, and 80 years and above for NVAF stroke prevention, insomnia, heart failure, and osteoporosis. Adults aged 60 to 74 years were enrolled in equal or greater proportion than the US prevalent population.Conclusions and RelevanceIn this cross-sectional study, underrepresentation of the oldest adults existed during evaluation of new drugs and biologics, yet the older adults may represent significant proportions of the treatment population. Closing the representation gap between clinical trial enrollment and potential treatment populations is essential for safe and effective use of new drugs and biologics.

IntroductionIn the context of the COVID-19 pandemic in Germany, governmental restrictions led to the closure of sports facilities for several months. To date, only subjective and fitness-tracking related data on physical activity during the pandemic are available. Using data of a chip-controlled fitness circuit, training data as a measure of physical performance before and after the lockdown during the first wave of the COVID-19 pandemic will show the impact of the training interruption on exercise performance in middle-aged and older adults. The re-training data are analyzed, to extract practical recommendations.MethodsObjective training data of 17,450 participants [11,097 middle-aged (45–64 yrs), 6,353 older (≥65 yrs)] were exported from chip-controlled milon® fitness circuit systems before and after the first COVID-19 related lockdown in Germany. The change in the product of training weight (sum of lifting and lowering the training weight) and repetitions on the leg extension resistance exercise device (leg score) between the last three training sessions before the lockdown and the first ten training sessions after individual training resumption as well as the last training session before the second lockdown in October 2020 was analyzed.ResultsParticipants who trained with high intensity before the lockdown, experienced deleterious effects of the training interruption (middle-aged group: −218 kg, older group: ~−230.8 kg; p &lt; 0.001 for change in leg score from to post-lockdown) with no age effect. Participants training with a leg score of more than 3,000 kg did not resume their leg score until the second lockdown.ConclusionThe interruption of training in a fitness circuit with combined resistance and endurance training due to the lockdown affected mainly those participants who trained at high intensity. Apparently, high-intensity training could not be compensated by home-based training or outdoor activities. Concepts for high-intensity resistance training during closure of sports facilities are needed to be prepared for future periods of high incidence rates of infectious diseases, while especially vulnerable people feel uncomfortable to visit sports facilities.Trial registrationIdentifier, DRKS00022433.