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Due to a shortage of studies focusing on older adults, clinicians and policy makers frequently rely on clinical trials of the general population to provide supportive evidence for treating complex, older patients.
To examine the inclusion and analysis of complex, older adults in randomized controlled trials.
A PubMed search identified phase III or...
Similar publications
Objective is to explore how multimorbidity is defined in the scientific literature, with a focus on the roles of diseases, risk factors, and symptoms in the definitions. Design: Systematic review. Methods: MEDLINE (PubMed), Embase, and The Cochrane Library were searched for relevant publications up until October 2013. One author extracted the infor...
Citations
... Breast cancer is a common disease among older women, with over 30% of new cases diagnosed in patients aged ≥ 70 years [1]. Yet, they are still underrepresented in pivotal trials investigating novel therapies [2]. Furthermore, previous studies demonstrated that older patients included in breast cancer trials do not represent the general older population, as they have less comorbidities, a better socioeconomic status and less aggressive disease [3,4]. ...
Purpose
Palbociclib has become the standard of care for estrogen receptor-positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer, but real-world evidence in older women remains scarce. Therefore, we investigated tolerability of palbociclib in older women with metastatic breast cancer.
Methods
Consecutive women aged ≥ 70 with ER+/HER2- metastatic breast cancer, treated with palbociclib in any treatment line in six hospitals, were included. Primary endpoint was grade ≥ 3 palbociclib-related toxicity. Predictors of toxicity were identified using logistic regression models. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan Meier.
Results
We included 144 women with a median age of 74 years. Grade 3–4 toxicity occurred in 54% of patients, of which neutropenia (37%) was most common. No neutropenic fever or grade 5 toxicity occurred. Dose reduction during treatment occurred in 50% of patients, 8% discontinued treatment due to toxicity and 3% were hospitalized due to toxicity. Polypharmacy (odds ratio (OR) 2.50; 95% confidence interval (CI) 1.12–5.58) and pretreatment low leukocytes (OR 4.81; 95% CI 1.27–18.21) were associated with grade 3–4 toxicity, while comorbidities were not. In first-line systemic therapy, median PFS was 12 months and median OS 32 months. In second-line, median PFS was 12 months and median OS 31 months.
Conclusion
Although grade 3–4 toxicity and dose reductions occurred frequently, most were expected and managed by dose reductions, showing that palbociclib is generally well tolerated and thus represents a valuable treatment option in the older population.
... For example, the median representation of individuals identifying as Asian in cancer studies in 2021 was 2%; less than 1% each for American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, and individuals indicating more than one race; 8% for Black or African American; and 74% for White; 6% identified as Hispanic or Latino and 87% as not Hispanic or Latino. Disparities in sample representation extend to other segments of the population as 23:297 well, including older adults [9] and adults with less than 12 years of education [10]. Subgroup sample representation plays a role in the generalizability of average treatment effects (ATEs) in experimental and observational studies. ...
Background
Across studies of average treatment effects, some population subgroups consistently have lower representation than others which can lead to discrepancies in how well results generalize.
Methods
We develop a framework for quantifying inequity due to systemic disparities in sample representation and a method for mitigation during data analysis. Assuming subgroup treatment effects are exchangeable, an unbiased sample average treatment effect estimator will have lower mean-squared error, on average across studies, for subgroups with less representation when treatment effects vary. We present a method for estimating average treatment effects in representation-adjusted samples which enables subgroups to optimally leverage information from the full sample rather than only their own subgroup’s data. Two approaches for specifying representation adjustment are offered—one minimizes average mean-squared error for each subgroup separately and the other balances minimization of mean-squared error and equal representation. We conduct simulation studies to compare the performance of the proposed estimators to several subgroup-specific estimators.
Results
We find that the proposed estimators generally provide lower mean squared error, particularly for smaller subgroups, relative to the other estimators. As a case study, we apply this method to a subgroup analysis from a published study.
Conclusions
We recommend the use of the proposed estimators to mitigate the impact of disparities in representation, though structural change is ultimately needed.
... Despite the increasing usage of biomaterials in aged patients, few studies examine the effect of aging on the host response to the material. 26 Given that senescent cells accumulate with increased age, they add another dimension to a large number of other factors which affect the biocompatibility of the introduced material. It is, therefore, imperative to investigate the interaction of senescent cells with biomaterials to engineer implants and tissue scaffolds to promote tissue regeneration in older patients. ...
A typical cellular senescence program involves exposing cells to DNA-damaging agents such as ionization radiation or chemotherapeutic drugs, which cause multipronged changes, including increased cell size and volume, the onset of enhanced oxidative stress, and inflammation. In the present study, we examined if the senescence onset decision is sensitive to the design, porosity, and architecture of the substrate. To address this, we generated a library of polymeric scaffolds widely used in tissue engineering of varied stiffness, architecture, and porosity. Using irradiated A549 lung cancer cells, we examined the differences between cellular responses in these 3D scaffold systems and observed that senescence onset is equally diminished. When compared to the two-dimensional (2D) culture formats, there were profound changes in cell size and senescence induction in three-dimensional (3D) scaffolds. We further establish that these observed differences in the senescence state can be attributed to the altered cell spreading and cellular interactions on these substrates. This study elucidates the role of scaffold architecture in the cellular senescence program.
... The following paragraphs summarize examples of more serious physiological changes observed in older age people according to individual organ systems [37][38][39]. These will significantly influence morbidity in old age -including diabetes [8]. ...
... It brings along several risks not only for the sick seniors but also for their physicians. In essence, it belongs to the characteristics of the geriatric medicine [38]. ...
Diabetes (DM) is a significant risk factor for the onset and development of late diabetic complications at any age. In the elderly, DM often occurs as part of multimorbidity and can contribute to the onset and development of disability. The treatment of DM in old age is based on the same principles as for younger individuals. When choosing therapy for DM, the following should be taken into account: age, life expectancy, the presence of complications, self-sufficiency, economic conditions, eating habits and other handicaps. The authors report their own experience from the outpatient practice of DM type 2 treatment. The authors discuss the growth of the elderly population in relation to organ changes with the ageing process, as well as issues of multimorbidity, the specifics of the clinical picture of diseases in old age and the problem of polypharmacy both from the perspective of ageing and old age and the relationship to diabetes as a comorbidity.
... Sargent et al. combined data from seven randomized controlled trials (RCTs) and found that adjuvant CT had a significant positive effect on both OS and time to tumour recurrence for colon cancer and that age did not appear to affect this result 24 . In general, RCTs have strict eligibility inclusion and exclusion criteria and typically exclude elderly patients with comorbidities and high frailty 25 . Nevertheless, real-world studies, with less restrictive study populations, might be more reflective of the effectiveness of interventions in real settings. ...
Treatment guidelines for colorectal cancer (CRC) in elderly patients remain unclear. This study aimed to investigate whether elderly patients (≥ 70 years) with CRC benefit from surgery and adjuvant therapy. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into a surgery group and a no-surgery group. After being matched by propensity score matching at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan‒Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were utilized to confirm independent prognostic factors for OS and CSS. In age-stratified analysis (70–74; 75–79; 80–84; ≥ 85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Adjuvant therapy was an independent prognostic factor for OS and CSS in elderly patients with CRC (all P < 0.001). Further analysis showed that elderly colon cancer patients with stage III and stage IV disease gained a survival benefit from adjuvant chemotherapy. Adjuvant chemoradiotherapy can significantly improve OS and CSS in elderly rectal cancer patients with stage II, III, and IV disease. In conclusion, among CRC patients aged ≥ 70 years reported in the SEER database, treatment with surgical resection is significantly associated with improved OS and CSS. Moreover, adjuvant therapy led to a significant prognostic advantage for elderly advanced CRC patients who underwent surgery.
... Zudem ist von einer Änderung der Diffusionsbedingungen durch die verminderte Mikrozirkulation im korialen Gewebe auszugehen [37]. Aus praktischer Sicht sollte zudem bedacht werden, dass Personen, die älter als 65 Jahre sind, nahezu regelmäßig aus klinischen Studien zur Testung von Arzneimitteln, Medizinprodukten oder Kosmetika ausgeschlossen werden [38]. Somit gibt es für die Empfehlungen zum Einsatz und zur Sicherheit von Topika bei Senioren eine eher geringe Evidenz [39]. ...
Zusammenfassung
Altersbedingte Veränderungen des Hautorgans beziehen in Abhängigkeit der intrinsischen Gegebenheiten und extrinsischer Einflussfaktoren alle kutanen Schichten ein. Das Ausmaß der seneszenten Veränderungen kann bei Hochaltrigen stark variieren, sodass eine individuelle Bewertung sinnvoll und häufig auch notwendig ist. Von besonderer klinischer Bedeutung sind die Veränderungen der Epidermis, die eine komplexe Reduktion der Barrierefunktion und Minderung der Kompensationskapazität bezüglich exogener Noxen nach sich ziehen. Daraus leitet sich eine erhöhte Suszeptibilität insbesondere gegenüber Infektionen und Tumorerkrankungen ab. Vor diesem Hintergrund ist eine prophylaktische Strategie zur Substitution der physikochemischen und damit auch mikrobiologischen Barriere im Rahmen der Basispflege von großer Bedeutung. Um diese konsequent umsetzen zu können, ist die Empfehlung von explizit für Altershaut konzipierten Präparaten und praktischen Anwendungshinweisen sehr wesentlich. Letztere sollten die Einschränkungen bezüglich der Beweglichkeit sowie mögliche kognitive Defizite von Hochaltrigen berücksichtigen. Dazu sollten sowohl Eincremehilfen als auch bezüglich der Viskosität und Zusammensetzung geeignete Präparationen empfohlen werden. Um die Umsetzung zudem zu erleichtern, können schriftliche oder bildliche Handlungsempfehlungen sowie digitale Assistenzsysteme zur Anwendung kommen. Aufgrund der demografischen Entwicklungen in Deutschland und Europa wird die geriatrische Dermatologie in den nächsten Jahren deutlich an klinischer Relevanz gewinnen.
... Numerous barriers have been cited as potentially contributing to the lack of representation of older adults in clinical trials such as poor health status, accessibility issues, social and cultural barriers, decision-making capacity, age discrimination, and lack of family support or agreement. Furthermore, these barriers may be intensified during an acute event such as hospitalization [5,6,16,24]. ...
Background
Heterogenous older adult populations are underrepresented in clinical trials, and their participation is necessary for interventions that directly target them. The purpose of this study was to evaluate reasons why hospitalized older adults declined participation in two deprescribing clinical trials.
Methods
We report enrollment data from two deprescribing trials, Shed-MEDS (non-Veterans) and VA DROP (Veterans). For both trials, inclusion criteria required participants to be hospitalized, age 50 or older, English-speaking, and taking five or more home medications. Eligible patients were approached for enrollment while hospitalized. When an eligible patient or surrogate declined participation, the reason(s) were recorded and subsequently analyzed inductively to develop themes, and a chi-square test was used for comparison (of themes between Veterans and non-Veterans).
Results
Across both trials, 1226 patients (545 non-Veterans and 681 Veterans) declined enrollment and provided reasons, which were condensed into three themes: (1) feeling overwhelmed by their current health status, (2) lack of interest or mistrust of research, and (3) hesitancy to participate in a deprescribing study. A greater proportion of Veterans expressed a lack of interest or mistrust in research (42% vs 26%, chi-square value = 36.72, p < .001), whereas a greater proportion of non-Veterans expressed feeling overwhelmed by their current health status (54% vs 35%, chi-square value = 42.8 p < 0.001). Across both trials, similar proportion of patients expressed hesitancy to participate in a deprescribing study, with no significant difference between Veterans and non-Veterans (23% and 21%).
Conclusions
Understanding the reasons older adults decline participation can inform future strategies to engage this multimorbid population.
... 35 Additionally, guidelines are often based on evidence from RCTs that exclude elderly or multimorbid patients. 36,37 Emphasis therefore should be placed on modifying guidelines to include studies with wider population inclusion criteria to reflect the ever-changing demographic of patients. ...
Objectives:
To summarise the impact of community-based interventions for multimorbid patients on unplanned healthcare use. The prevalence of multimorbidity (co-existence of multiple chronic conditions) is rapidly increasing and affects one-third of the global population. Patients with multimorbidity have complex healthcare needs and greater unplanned healthcare usage. Community-based interventions allow for continued care of patients outside hospitals, but few studies have explored the effects of these interventions on unplanned healthcare usage.
Design:
A systematic review was conducted. MEDLINE, EMBASE, PsychINFO and Cochrane Library online databases were searched. Studies were screened and underwent risk of bias assessment. Data were synthesised using narrative synthesis.
Setting:
Community-based interventions.
Participants:
Patients with multimorbidity.
Main outcome measures:
Unplanned healthcare usage.
Results:
Thirteen studies, including a total of 6148 participants, were included. All included studies came from high-income settings and had elderly populations. All studies measured emergency department attendances as their primary outcome. Risk of bias was generally low. Most community interventions were multifaceted with emphasis on education, self-monitoring of symptoms and regular follow-ups. Four studies looked at improved care coordination, advance care planning and palliative care. All 13 studies found a decrease in emergency department visits post-intervention with risk reduction ranging from 0 (95% confidencec interval [CI]: -0.37 to 0.37) to 0.735 (95% CI: 0.688-0.785).
Conclusions:
Community-based interventions have potential to reduce emergency department visits in patients with multimorbidity. Identification of specific successful components of interventions was challenging given the overlaps between interventions. Policymakers should recognise the importance of community interventions and aim to integrate aspects of these into existing healthcare structures. Future research should investigate the impact of such interventions with broader participant characteristics.
... Age, ethnicity, and preferred language were all found to be significant demographic factors, and insurance and SSN status were found to be significant socioeconomic factors. These results corroborate findings from other clinical trial enrollment studies [13,16,[27][28][29][30][31][32][33][34][35][36][37]. ...
... The mean age of the Enrolled patients was found to be significantly lower than that of the Declined patients (p < 0.05). While findings from ophthalmology-specific clinical trials were relatively limited, clinical trial data from other fields similarly found that older adults were consistently underrepresented [27][28][29][30]. Cancer clinical trial data have shown that, despite two-thirds of cancer patients being over 65 years of age, only a quarter of trial participants are of this age cohort, and the gap between the median age of the clinical trial and general populations has widened over time [27,28]. ...
... Cancer clinical trial data have shown that, despite two-thirds of cancer patients being over 65 years of age, only a quarter of trial participants are of this age cohort, and the gap between the median age of the clinical trial and general populations has widened over time [27,28]. Other reviews of randomized clinical trials have reported that adults over the age of 65 were disproportionately excluded, particularly from phase 3 and phase 4 trials [29,30]. The discrepancy in the age of patients who enrolled in retina-focused clinical trials could be at least partially related to the age requirements in clinical trial protocols, as age has been used as an exclusion criterion in some studies [30]. ...
Historically marginalized populations are disproportionately affected by many diseases that commonly affect the retina, yet they have been traditionally underrepresented in prospective clinical trials. This study explores whether this disparity affects the clinical trial enrollment process in the retina field and aims to inform future trial recruitment and enrollment. Age, gender, race, ethnicity, preferred language, insurance status, social security number (SSN) status, and median household income (estimated using street address and zip code) for patients referred to at least one prospective, retina-focused clinical trial at a large, urban, retina-based practice were retrospectively extracted using electronic medical records. Data were collected for the 12-month period from 1 January 2022, through 31 December 2022. Recruitment status was categorized as Enrolled, Declined, Communication (defined as patients who were not contacted, were contacted with no response, were waiting for a follow-up, or were scheduled for screening following a clinical trial referral.), and Did Not Qualify (DNQ). Univariable and multivariable analyses were used to determine significant relationships between the Enrolled and Declined groups. Among the 1477 patients, the mean age was 68.5 years old, 647 (43.9%) were male, 900 (61.7%) were White, 139 (9.5%) were Black, and 275 (18.7%) were Hispanic. The distribution of recruitment status was: 635 (43.0%) Enrolled, 232 (15.7%) Declined, 290 (19.6%) Communication, and 320 (21.7%) DNQ. In comparing socioeconomic factors between the Enrolled and Declined groups, significant odds ratios were observed for age (p < 0.02, odds ratio (OR) = 0.98, 95% confidence interval (CI) [0.97, 1.00]), and between patients who preferred English versus Spanish (p = 0.004, OR = 0.35, 95% CI [0.17, 0.72]. Significant differences between the Enrolled and Declined groups were also observed for age (p < 0.05), ethnicity (p = 0.01), preferred language (p < 0.05), insurance status (p = 0.001), and SSN status (p < 0.001). These factors may contribute to patient participation in retina-focused clinical trials. An awareness of these demographic and socioeconomic disparities may be valuable to consider when attempting to make clinical trial enrollment an equitable process for all patients, and strategies may be useful to help address these challenges.
... Sargent et al. combined data from seven randomized controlled trials (RCTs) found that adjuvant CT had a signi cant positive effect on both OS and time to tumor recurrence for colon cancer, and age didn't appear to affect this result 24 . Generally, RCTs have strict eligibility inclusion and exclusion criteria and typically exclude the elderly with comorbidity and high frailty 25 . However, real-world studies, with less restrictive in the study populations, could more re ective the effectiveness of interventions in real settings. ...
Currently, the treatment guidelines for colorectal cancer (CRC) in elder patients remained unclear. This study aims to investigate whether elder patients (≥70 years) with CRC benefit from surgery and different therapeutic patterns. A total of 90,347 eligible CRC patients older than 70 years were collected from the Surveillance, Epidemiology, and End Results(SEER) database. All the patients were divided into the surgery group and the no-surgery group. After being matched by propensity score matching (PSM) at a 1:1 ratio, 23,930 patients were included in our analysis. The Kaplan-Meier method and log-rank test were applied to compare overall survival (OS) and cancer-specific survival (CSS). In the age-stratified analysis (70–74; 75–79; 80–84; ≥85), the OS and CSS rates of patients in the surgery group were significantly higher than those of patients in the no-surgery group (all P < 0.001). Further analysis showed that surgery plus chemotherapysignificantly improved OS and CSS in elder colon cancer patients with III stage and IV stage compared to surgery alone. Surgery plus chemoradiotherapy significantly improved OS and CSS in elder rectal cancer patients with II stage, III stage and IV stage compared to other therapeutic patterns. Among these CRC patients with aged ≥70 years reported in the SEER database, treatment with surgical resection is significantly associated with an improved OS and CSS. Moreover, adjuvant therapyshowed a significant prognostic advantage for elder advanced CRC patients underwent surgery.
