Methods for Measuring Multiple Medication Adherence: A Systematic Review–Report of the ISPOR Medication Adherence and Persistence Special Interest Group

Background

A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications.

Impact of Interventions on Medication Adherence and Blood Pressure Control in Patients with Essential Hypertension: A Systematic Review by the ISPOR Medication Adherence and Persistence Special Interest Group

ObjectivesTo systematically review the evidence on the impact of interventions to improve medication adherence in adults prescribed antihypertensive medications.MethodsAn electronic search was undertaken of articles published between 1979 and 2009, without language restriction, that focused on interventions to improve antihypertensive medication adherence among patients (≥18 years) with essential hypertension. Studies must have measured adherence as an outcome of the intervention. We followed standard guidelines for the conduct and reporting of the review and conducted a narrative synthesis of reported data.ResultsNinety-seven articles were identified for inclusion; 35 (35 of 97, 36.1%) examined interventions to directly improve medication adherence, and the majority (58 of 97, 59.8%) were randomized controlled trials. Thirty-four (34 of 97, 35.1%) studies reported a statistically significant improvement in medication adherence.Discussion/ConclusionsInterventions aimed at improving patients’ knowledge of medications possess the greatest potential clinical value in improving adherence with antihypertensive therapy. However, we identified several limitations of these studies, and advise future researchers to focus on using validated adherence measures, well-designed randomized controlled trials with relevant adherence and clinical outcomes, and guidelines on the appropriate design and analysis of adherence research.     

Prevalence and Associated Factors of Sarcopenia in Nursing Home Residents: A Systematic Review and Meta-analysis

Objective

To review the prevalence and associated factors of sarcopenia in nursing homes.

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report

ObjectivesThis study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them.MethodsA multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members.ResultsGiven that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level.ConclusionsThere is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.     

Costs of Medication Nonadherence in Patients with Diabetes Mellitus: A Systematic Review and Critical Analysis of the Literature

Objectives:  Information on the health care costs associated with nonadherence to treatments for diabetes is both limited and inconsistent. We reviewed and critically appraised the literature to identify the main methodological issues that might explain differences among reports in the relationship of nonadherence and costs in patients with diabetes.
Methods:  Two investigators reviewed Medline, EMBASE, Cochrane library and CINAHL and studies with information on costs by level of adherence in patients with diabetes published between January 1, 1997 and September 30th 2007 were included.
Results:  A total of 209 studies were identified and ten fulfilled the inclusion criteria. All included studies analyzed claims data and 70% were based on non-Medicaid and non-Medicare databases. Low medication possession ratios were associated with higher costs. Important differences were found in the ICD-9/ICD-9 CM codes used to identify patients and their diagnoses, data sources, analytic window period, definitions of adherence measures, skewness in cost data and associated statistical issues, adjustment of costs for inflation, adjustment for confounders, clinical outcomes and costs.
Conclusions:  Important variation among cost estimates was evident, even within studies of the same population. Readers should be cautious when comparing estimated coefficients from various studies because methodological issues might explain differences in the results of costs of nonadherence in diabetes. This is particularly important when estimates are used as inputs to pharmacoeconomic models.     

Effects of the Medicare Part D Comprehensive Medication Review on Racial and Ethnic Disparities in Medication Adherence

BackgroundSubstantial research has documented inequalities between US minorities and whites in meeting the eligibility criteria for the Medicare Part D medication therapy management (MTM) program. Even though the Centers for Medicare & Medicaid Services attempted to relax the eligibility criteria, a critical barrier to effective MTM reform is a lack of stronger evidence about the effects of MTM on minorities'' health outcomes.ObjectiveTo examine the effects of comprehensive medication review (CMR), an MTM core component, on racial and ethnic disparities in adherence to diabetes, hypertension, and hyperlipidemia medications among Medicare beneficiaries aged ≥65 years.MethodsThis study used full-year 2017 Medicare Parts A, B, and D claims data, including MTM data, linked to the Area Health Resources Files. Racial and ethnic disparities in nonadherence to diabetes, hypertension, and hyperlipidemia medications were compared between CMR recipients and nonrecipients matched by their propensity scores. To determine the changes in racial and ethnic disparities after receiving CMR, a difference-in-differences framework was applied, by including in logistic regression analyses interaction terms between dummy variables for CMR receipt and each racial or ethnic minority group.ResultsCompared with CMR nonrecipients, CMR recipients had significantly lower racial and ethnic disparities across the 3 outcome measures, with the exception of the difference between whites and blacks in nonadherence to diabetes medications. For example, compared with CMR nonrecipients, among CMR recipients the differences in the odds of nonadherence to hypertension medications were reduced, respectively, by 8% (95% confidence interval [CI], 0.88–0.96) between whites and blacks; by 18% (95% CI, 0.78–0.86) between whites and Hispanics; by 16% (95% CI, 0.77–0.91) between whites and Asians; and by 9% (95% CI, 0.85–0.98) between whites and other racial and ethnic groups.ConclusionReceiving a CMR reduced the racial and ethnic disparities in adherence to diabetes, hypertension, and hyperlipidemia medications among Medicare beneficiaries aged ≥65 years. These findings provide critical empirical evidence that may inform the future design of the Medicare Part D MTM program, which is valuable for improving pharmacotherapy outcomes and could further realize its potential when additional people from racial and ethnic minorities are enrolled.     

Associated Factors of Sarcopenia in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis

(1) Background: To review the associated factors of sarcopenia in community-dwelling older adults. (2) Methods: PubMed, Embase, Web of Science, and four Chinese electronic databases were searched for observational studies that reported the associated factors of sarcopenia from inception to August 2021. Two researchers independently selected the literature, evaluated their quality, and extracted relevant data. The pooled odds ratio (OR) and its 95% confidence interval (CI) were calculated for each associated factors of sarcopenia using random-effects/fixed-effects models. Publication bias was assessed using funnel plot and the Eggers test. We performed statistical analysis using Stata 15.0 software. (3) Results: A total of 68 studies comprising 98,502 cases were included. Sociodemographic associated factors of sarcopenia among community-dwelling older adults included age (OR = 1.12, 95% CI: 1.10–1.13), marital status (singled, divorced, or widowed) (OR = 1.57, 95% CI: 1.08–2.28), disability for activities of daily living (ADL) (OR = 1.49, 95% CI: 1.15–1.92), and underweight (OR = 3.78, 95% CI: 2.55–5.60). Behavioral associated factors included smoking (OR = 1.20, 95% CI: 1.10–1.21), physical inactivity (OR = 1.73, 95% CI: 1.48–2.01), malnutrition/malnutrition risk (OR = 2.99, 95% CI: 2.40–3.72), long (OR = 2.30, 95% CI: 1.37–3.86) and short (OR = 3.32, 95% CI: 1.86–5.93) sleeping time, and living alone (OR = 1.55, 95% CI: 1.00–2.40). Disease-related associated factors included diabetes (OR = 1.40, 95% CI: 1.18–1.66), cognitive impairment (OR = 1.62, 95% CI: 1.05–2.51), heart diseases (OR = 1.14, 95% CI: 1.00–1.30), respiratory diseases (OR = 1.22, 95% CI: 1.09–1.36), osteopenia/osteoporosis (OR = 2.73, 95% CI: 1.63–4.57), osteoarthritis (OR = 1.33, 95% CI: 1.23–1.44), depression (OR = 1.46, 95% CI: 1.17–1.83), falls (OR = 1.28, 95% CI: 1.14–1.44), anorexia (OR = 1.50, 95% CI: 1.14–1.96), and anemia (OR = 1.39, 95% CI: 1.06–1.82). However, it remained unknown whether gender (female: OR = 1.10, 95% CI: 0.80–1.51; male: OR = 1.50, 95% CI: 0.96–2.34), overweight/obesity (OR = 0.27, 95% CI: 0.17–0.44), drinking (OR = 0.92, 95% CI: 0.84–1.01), hypertension (OR = 0.98, 95% CI: 0.84–1.14), hyperlipidemia (OR = 1.14, 95% CI: 0.89–1.47), stroke (OR = 1.70, 95% CI: 0.69–4.17), cancer (OR = 0.88, 95% CI: 0.85–0.92), pain (OR = 1.08, 95% CI: 0.98–1.20), liver disease (OR = 0.88, 95% CI: 0.85–0.91), and kidney disease (OR = 2.52, 95% CI: 0.19–33.30) were associated with sarcopenia. (4) Conclusions: There are many sociodemographic, behavioral, and disease-related associated factors of sarcopenia in community-dwelling older adults. Our view provides evidence for the early identification of high-risk individuals and the development of relevant interventions to prevent sarcopenia in community-dwelling older adults.     

Predicting Adherence to Medications Using Health Psychology Theories: A Systematic Review of 20 Years of Empirical Research

ObjectivesThis review sought to identify the empirical evidence for the application of models from sociocognitive theory, self-regulation theory, and social support theory at predicting patient adherence to medications.MethodsA systematic review of the published literature (1990–2010) using MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsychINFO identified studies examining the application of health psychology theory to adherence to medication in adult patients. Two independent reviewers extracted data on medication, indication, study population, adherence measure, theory, model, survey instruments, and results. Heterogeneity in theoretical model specification and empirical investigation precluded a meta-analysis of data.ResultsOf 1756 unique records, 67 articles were included (sociocognitive = 35, self-regulation = 21, social support = 11). Adherence was most commonly measured by self-report (50 of 67). Synthesis of studies highlighted the significance (P ≤ 0.05) of self-efficacy (17 of 19), perceived barriers (11 of 17), perceived susceptibility (3 of 6), necessity beliefs (8 of 9), and medication concerns (7 of 8).ConclusionsThe results of this review provide a foundation for the development of theory-led adherence-enhancing interventions that could promote sustainable behavior change in clinical practice.     

Economic Evaluation of Cognitive Behavioral Therapy for Depression: A Systematic Review

ObjectivesThis study aimed to conduct a systematic review of cost-utility studies of internet-based and face-to-face cognitive behavioral therapy (CBT) for depression from childhood to adulthood and to examine their reporting and methodological quality.MethodsA structured search for cost-utility studies concerning CBT for depression was performed in 7 comprehensive databases from their inception to July 2020. Two reviewers independently screened the literature, abstracted data, and assessed quality using the Consolidated Health Economic Evaluation Reporting Standards and Quality of Health Economic Studies checklists. The primary outcome was the incremental cost-effectiveness ratio (ICER) across all studies. To make a relevant comparison of the ICERs across the identified studies, cost data were inflated to the year 2020 and converted into US dollars.ResultsThirty-eight studies were included in this review, of which 26 studies (68%) were deemed of high methodological quality and 12 studies (32%) of fair quality. Despite differences in study designs and settings, the conclusions of most included studies for adult depression were general agreement; they showed that face-to-face CBT monotherapy or combination therapy compared with antidepressants and usual care for adult depression were cost-effective from the societal, health system, or payer perspective (ICER ?$241 212.4/quality-adjusted life-year [QALY] to $33 032.47/QALY, time horizon 12-60 months). Internet-based CBT regardless of guided or unguided also has a significant cost-effectiveness advantage (ICER ?$37 717.52/QALY to $73 841.34/QALY, time horizon 3-36 months). In addition, CBT was cost-effective in preventing depression (ICER ?$23 932.07/QALY to $26 092.02/QALY, time horizon 9-60 months). Nevertheless, the evidence for the cost-effectiveness of CBT for children and adolescents was still ambiguous.ConclusionsFair or high-quality evidence showed that CBT monotherapy or combination therapy for adult depression was cost-effective; whether CBT-related therapy was cost-effective for children and adolescents depression remains inconclusive.     

Barriers and Facilitators Associated with the Adoption of and Adherence to a Mediterranean Style Diet in Adults: A Systematic Review of Published Observational and Qualitative Studies

The Mediterranean diet (MedDiet) has been linked with physical and mental health benefits. Previous research, however, suggests that adoption and adherence to a Mediterranean diet might be difficult for people who live outside of the Mediterranean region. The aim of this systematic review was to investigate the factors that influence adoption and adherence to a Mediterranean style diet in adults aged 18 years old and over, as identified in published observational and qualitative studies. Following registration of our protocol on PROSPERO (ID: CRD42018116515), observational and qualitative studies of adults’ perceptions and experiences relevant to following a Mediterranean style diet were identified using systematic searches of databases: MEDLINE, the Cochane Library, CINAHL, Web of Science and Scopus, over all years of records until February 2022. A narrative synthesis was then undertaken. Of 4559 retrieved articles, 18 studies fulfilled our inclusion criteria and were included. Factors influencing adoption and adherence to a MedDiet were identified and categorized as: financial, cognitive, socio-cultural, motivational, lifestyle, accessibility & availability, sensory & hedonic and demographic. Similar barriers and facilitators are often reported in relation to healthy eating or the consumption of specific healthy foods, with a few exceptions. These exceptions detailed concerns with specific components of the MedDiet; considerations due to culture and traditions, and concerns over a cooler climate. Suggestions for overcoming these barriers and facilitators specific to adoption and adherence to the Mediterranean diet are offered. These data will inform the development of future studies of robust methodology in eating behaviour change which offer pragmatic approaches for people to consume and maintain healthy diets.     

Identifying Clusters of Adherence to Cardiovascular Risk Reduction Behaviors and Persistence with Medication in New Lipid-Lowering Drug Users. Impact on Healthcare Utilization

We sought to identify specific profiles of new lipid-lowering drug users based on adherence to a healthy lifestyle and persistence with medication, and to characterize co-morbidities, co-treatments, and healthcare utilization for each of the profiles identified. Observational study in 517 participants in the Aragon Workers’ Health Study (AWHS) without previous cardiovascular disease (CVD) and who initiated lipid-lowering therapy. Data were collected from workplace medical examinations and administrative health databases (2010–2018). Using cluster analysis, we identified distinct patient profiles based on persistence with therapy and lifestyle. We then compared characteristics, morbidity, and healthcare utilization across clusters. Participants were aggregated into four clusters based on persistence with therapy, smoking status, adherence to Mediterranean diet, and physical activity. In cluster 1 (n = 113), comprising those with a healthiest lifestyle (14.2% smokers, 84.0% with medium-high adherence to Mediterranean diet, high physical activity), 16.8% were persistent. In cluster 3 (n = 108), comprising patients with the least healthy lifestyle (100% smokers, poor adherence to the Mediterranean diet, low level of physical activity), all were non-persistent. Clusters 2 (n = 150) and 4 (n = 146) both comprised patients with intermediate lifestyle behaviors, but differed in terms of persistence (100 and 0%, respectively). Compared with other clusters, the burden of morbidity, cardiovascular score, and healthcare utilization were lower in cluster 1. The healthy adherer effect was only observed in new lipid-lowering drug users of certain profiles. Furthermore, we found that differences in adherence to lifestyle and medication recommendations for CVD prevention influenced morbidity burden and healthcare utilization.     

Defining Patient Engagement in Research: Results of a Systematic Review and Analysis: Report of the ISPOR Patient-Centered Special Interest Group

ObjectivesLack of clarity on the definition of “patient engagement” has been highlighted as a barrier to fully implementing patient engagement in research. This study identified themes within existing definitions related to patient engagement and proposes a consensus definition of “patient engagement in research.”MethodsA systematic review was conducted to identify definitions of patient engagement and related terms in published literature (2006-2018). Definitions were extracted and qualitatively analyzed to identify themes and characteristics. A multistakeholder approach, including academia, industry, and patient representation, was taken at all stages. A proposed definition is offered based on a synthesis of the findings.ResultsOf 1821 abstracts identified and screened for eligibility, 317 were selected for full-text review. Of these, 169 articles met inclusion criteria, from which 244 distinct definitions were extracted for analysis. The most frequently defined terms were: “patient-centered” (30.5%), “patient engagement” (15.5%), and “patient participation” (13.4%). The majority of definitions were specific to the healthcare delivery setting (70.5%); 11.9% were specific to research. Among the definitions of “patient engagement,” the most common themes were “active process,” “patient involvement,” and “patient as participant.” In the research setting, the top themes were “patient as partner,” “patient involvement,” and “active process”; these did not appear in the top 3 themes of nonresearch definitions.ConclusionDistinct themes are associated with the term “patient engagement” and with engagement in the “research” setting. Based on an analysis of existing literature and review by patient, industry, and academic stakeholders, we propose a scalable consensus definition of “patient engagement in research.”     

Factors Associated With Social Isolation in Older Adults: A Systematic Review and Meta-Analysis

ObjectiveSocial isolation is a global health issue that affects older adults throughout their lives. This study aimed to identify the factors associated with social isolation in older adults.DesignSystematic review and meta-analysis.Setting and ParticipantsAdults aged 60 years and older.MethodsWe searched for observational studies without language restrictions in 11 databases from inception to August 2022. Pooled odds ratio (OR) and 95% CI were calculated using the R software (version 4.2.1). The modified Newcastle-Ottawa Scale was used to evaluate the risk of bias.ResultsEighteen factors were grouped into 5 themes. The following 13 factors were statistically significant: (1) demographics theme: aged 80 years and older (OR: 2.41; 95% CI: 1.20–4.85), less than or equal to a high school degree (OR: 1.68; 95% CI: 1.44–1.97), smoking (OR: 1.43; 95% CI: 1.18–1.73), and male (OR: 1.38; 95% CI: 1.01–1.89); (2) environment theme: low social support (OR: 7.77; 95% CI: 3.45–17.50) and no homeownership (OR: 1.38; 95% CI: 1.25–1.51); (3) role theme: no social participation (OR: 3.18; 95% CI: 1.30–7.80) and no spouse (OR: 2.61; 95% CI: 1.37–4.99); (4) physical health: hearing loss (OR: 2.78; 95% CI: 1.54–5.01), activities of daily living impairment (OR: 2.38; 95% CI: 1.57–3.61), and poor health status (OR: 1.52; 95% CI: 1.32–1.74); and (5) mental health: cognitive decline (OR: 1.85; 95% CI: 1.40–2.45) and depression (OR: 1.72; 95% CI: 1.21–2.44).Conclusions and ImplicationsSocial isolation in older adults is associated with various factors. Hence, focused intervention should be adopted for older adults. In addition, further longitudinal studies are required to confirm a direct link between multiple factors and social isolation.     

Risk Factors for Agricultural Injury: A Systematic Review and Meta-analysis

ABSTRACT

The objective of this study was to identify significant risk factors for agricultural injury based on the literature. The authors conducted a systematic review of commonly reported risk factors. Studies that reported adjusted odds ratio (OR) or relative risk (RR) estimates for the selected risk factors were identified from PubMed and Google Scholar. Pooled risk factor estimates were calculated using meta-analysis. A total of 441 (PubMed) and 285 (Google Scholar) studies were found in the initial searches; of these, 132 and 78 studies, respectively, met the selection criteria for injury outcomes, and 32 of these reported adjusted OR or RR estimates. One study was excluded because it did not meet the set Newcastle-Ottawa Scale quality criteria. Finally, 31 studies were used for meta-analysis. The pooled ORs for the risk factors were as follows: male gender (vs. female) 1.68, full-time farmer (vs. part-time) 2.17, owner/operator (vs. family member or hired worker) 1.64, regular medication use (vs. no regular medication use) 1.57, prior injury (vs. no prior injury) 1.75, health problems (vs. no health problems) 1.21, stress or depression (vs. no stress or depression) 1.86, and hearing loss (vs. no hearing loss) 2.01. All selected factors except health problems significantly increased the risk of injury, and they should be (a) considered when selecting high-risk populations for interventions, and (b) considered as potential confounders in intervention studies.     

The Association of Potentially Inappropriate Medication at Older Age With Cardiovascular Events and Overall Mortality: A Systematic Review and Meta-Analysis of Cohort Studies

Objective

The aim of this systematic review was to identify, evaluate, and meta-analyze cohort studies reporting the association of potentially inappropriate medication (PIM) intake with mortality and cardiovascular events.

Relation between Attachment and Obesity in Preschool Years: A Systematic Review of the Literature

Increasing evidence suggests that attachment plays an important role in obesity. However, few studies examined this relationship in preschool children. This study aimed to systematically examine the empirical, peer-reviewed evidence regarding the relationship between attachment quality and obesity in the preschool years. Using established guidelines, relevant peer-reviewed literature published between 2000 and July 2021 was searched through EBSCO. This yielded a total of 1124 records for review. Established inclusion criteria comprised: empirical studies published in peer-review journals; include at least one anthropometric measure and/or food consumption measure. Exclusion criteria comprised: attachment measures not following Bowlby-Ainsworth conceptualization of the construct; children in institutionalized settings; context of severe mental illness, documented substance use disorders, or eating disorders; include only a measure of the psychological aspects of eating; intervention programs. After exclusions, eight studies with a total of 9225 participants met the inclusion criteria. Results support the role of attachment in weight-related outcomes, suggesting that considering attachment in the risk of obesity could contribute to the elaboration of effective prevention and intervention programs. Limitations included the small number of studies, predominately cross-sectional designs, the diversity of methodologies, most samples not including fathers, and lack of evidence about the developmental mechanisms underlying the association between attachment and obesity. More evidence is needed to determine how attachment and obesity are linked, and the potential underlying mechanisms accounting for this relationship.     

我国老年人健康自评状况相关社会经济因素的系统评价

[目的]评价社会健康功能和经济状况与我国老年人健康自评的相关性及其人群归因危险度。[方法]检索1960—2009年4月发表的有关社会健康功能和经济状况对我国老年人健康自评影响的中文和英文文献。计算有关因素的合并比值比（odds ratio,OR）值及其95%可信区间（confidence interval,CI）;结合人群暴露率,估计人群归因危险度。[结果]共纳入4篇横断面研究。与我国老年人健康自评较差密切相关的社会健康功能主要是生活不满意[OR 2.98,95%CI（1.82,4.87）],家庭关系不和谐[OR 2.71,95%CI（2.10,3.51）],没有人关心[OR 1.68,95%CI（1.16,2.43）];其经济状况主要是收支不平衡[OR 2.02,95%CI（1.19,3.43）],支付医疗费用困难[OR 1.94,95%CI（1.41,2.68）],家庭月收入少于100元[OR 1.77,95%CI（1.46,2.15）];其人群归因危险度分别为24.19%、19.65%和14.18%。对我国老年人健康自评影响最大的前三位经济状况依次为支付医疗费用困难、家庭月收入少于100元及收入不是来自自己,其人群归因危险度分别为24.83%、18.42%和18.05%。[结论]积极防治老年人慢性病和提倡老年人参加社会活动是社区保健和卫生行政部门的工作重点。但由于纳入的研究较少,论证强度较低,目前尚缺乏高质量证据证明各种影响因素与老年人健康自评的相关性。