Patient-reported Outcome Measurement and Reporting for Patients with Advanced Renal Cell Carcinoma: A Systematic Literature Review.

CONTEXT: In the oncology setting, patient-reported outcome measures (PROMs) provide important data that help to ensure patient-relevant endpoints are captured and reported. Use of this information for treatment decision-making by clinicians and patients in real-world settings is facilitated by consistent and transparent reporting of trial methods. OBJECTIVE: To identify and compare PROMs used in advanced renal cell carcinoma (RCC) trials in terms of the rationale for the choice of measure, endpoint hierarchy (primary, secondary, exploratory), assessment time points, statistical methods, and statistical metrics for interpretation. EVIDENCE ACQUISITION: A systematic literature review via searches of four online databases (2016-2021) and recent conference abstracts (2019-2021) identified 2616 articles, of which 33 were included in the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. EVIDENCE SYNTHESIS: Among the 33 clinical studies included, 19 different PROMs were identified: three kidney cancer-specific scales, two cancer-specific scales, two generic scales, and 12 symptom-specific scales. The endpoint hierarchy for patient reported outcome (PRO) assessment was reported in 42% of the studies; one study included PROs as a primary endpoint. Reporting of time points, minimal important differences, and statistical analyses was highly heterogeneous. CONCLUSIONS: A diverse range of PROMs have been included in clinical studies for patients with advanced/metastatic RCC. Prespecified analyses for PRO assessments were generally not stated, while analytical methods and reporting varied. An improvement in alignment across studies would better inform regulatory, market-access, reimbursement, and clinical decision-making to improve patient care. PATIENT SUMMARY: We reviewed how the impact of cancer therapies on health outcomes from the patient's point of view is being measured in clinical trials for kidney cancer. The techniques and reporting varied across trials. Standardisation of how these data are captured and reported may improve care and decision-making for patients with kidney cancer.

Utility value estimates in cardiovascular disease and the effect of changing elicitation methods: a systematic literature review.

OBJECTIVE: Identify the most recent utility value estimates for cardiovascular disease (CVD) via systematic literature review (SLR) and explore trends in utility elicitation methods in the last 6 years. METHODS: This SLR was updated on January 25, 2018, and identified studies reporting utilities for myocardial infarction (MI), stroke, angina, peripheral artery disease (PAD), and any-cause revascularization by searching Embase, PubMed, Health Technology Assessment Database, and grey literature. RESULTS: A total of 375 studies reported CVD utilities (pre-2013 vs post-2013: MI, 38 vs 32; stroke, 86 vs 113; stable angina, 8 vs 9; undefined/unstable angina, 23 vs 8; PAD, 29 vs 13; revascularization, 54 vs 40). Median average utilities for MI, stroke, and revascularization increased over time (pre-2013 vs post-2013: MI, 0.71 vs 0.79; stroke, 0.63 vs 0.64; revascularization, 0.76 vs 0.81); angina and PAD showed a decrease in median values over time (stable angina, 0.83 vs 0.72; undefined/unstable angina, 0.70 vs 0.69; PAD, 0.76 vs 0.71). The proportion of utility estimates from trials increased across health states (pre-2013 vs post-2013: 22.5% vs 37.2%), as did the proportion of trials using the EuroQol Five Dimensions Questionnaire (EQ-5D; pre-2013 vs post-2013: 73.8% vs 91.4%). Use of methods such as the standard gamble, time trade-off, and Health Utilities Index has declined. CONCLUSIONS: Health state utilities for cardiovascular health states have changed in the last 6 years, likely due to changes in the types of studies conducted, the patient populations evaluated, and possibly changing utility elicitation methods. The EQ-5D has been used more frequently.

Achievement of the low-density lipoprotein cholesterol goal among patients with dyslipidemia in South Korea.

BACKGROUND: It is important to achieve the low-density lipoprotein cholesterol (LDL-C) goal recommended by clinical guidelines in managing the risk of cardiovascular (CV) events, however, the current management of LDL-C in actual clinical settings is suboptimal. We examined the LDL-C level among patients with dyslipidemia against the 2015 Korean guidelines, the crude rates of CV events based on LDL-C goal achievement, and the factors associated with LDL-C goal achievement. METHODS: This was a retrospective cohort study using the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from 2006 to 2013. Patients who had a health examination with LDL-C measurement between January 1, 2007, and December 31, 2011 were identified. Patients were required to have at least one diagnosis of dyslipidemia during the 1 year before the index date, defined as the first date of LDL-C measurement. The 2015 Korean guidelines were used to measure LDL-C goal achievement based on the CV risk level. Crude CV event rates were calculated for total and individual CV events as the number of events divided by person-years (PYs) during the follow-up period. CV events included acute coronary syndrome, ischemic stroke, peripheral artery disease, CV death, and all-cause death. Factors associated with LDL-C goal achievement were assessed using logistic regression. RESULTS: In the NHIS-HEALS database, 69,942 patients met the eligibility criteria: 36.7%, 22.5%, 20.1%, and 20.6% were among the very high-, high-, moderate-, and low-risk groups for the CV events, respectively, as defined by the 2015 Korean guidelines. Approximately half of the patients with dyslipidemia (47.6%) achieved their recommended LDL-C goal, but the achievement rates were substantially different across CV risk levels (17.6%, 47.2%, 66.9%, and 82.4% for very high-, high-, moderate-, and low-risk groups, respectively; P<0.0001). The crude event rate of total CV events during the follow-up period in the LDL-C goal non-achievers was higher than that in the LDL-C goal achievers (24.35/100 PYs vs. 11.93/100 PYs; P<0.0001). LDL-C goal achievement was significantly associated with patient characteristics, including age, sex, body mass index, lipid-modifying therapy, and CV risk level. CONCLUSIONS: In South Korea, LDL-C goal achievement among patients with very high or high CV risk was suboptimal. Patients who did not achieve the goal showed a higher rate of CV events during the follow-up period than patients who achieved the goal. LDL-C management strategies should be highlighted in dyslipidemia patients who are less likely to achieve the goal, such as female, overweight or obese patients, patients not adherent to statin, or patients with very high or high CV risk.

Treatment patterns of lipid-lowering therapies and possible statin intolerance among statin users with clinical atherosclerotic cardiovascular disease (ASCVD) or diabetes mellitus (DM) in Taiwan.

OBJECTIVES: To assess treatment patterns of statin and/or ezetimibe and possible statin intolerance among patients initiating statin or statin plus ezetimibe and with clinical atherosclerotic cardiovascular disease (ASCVD) or diabetes mellitus (DM) in Taiwan. METHODS: A retrospective cohort study using Taiwan's 2005 to 2013 National Health Insurance Research Database (NHIRD) was conducted. Patients with history of clinical ASCVD or DM (without previous clinical ASCVD) and initiating statin or statin plus ezetimibe therapy during 2006 to 2012 were identified. The treatment initiation date was defined as index date. Treatment patterns (including discontinuation, reinitiation, subtraction, switching, and augmentation), adherence (medication possession ratio [MPR]), persistence (gap no greater than 60 d) of statin and/or ezetimibe, and possible statin intolerance during 12-month follow-up from the index date were examined. RESULTS: Among patients initiating statin or statin plus ezetimibe, 11 092 patients with history of clinical ASCVD and 31 100 patients with DM but without clinical ASCVD were analysed. The discontinuation, reinitiation, and switching rates among patients with clinical ASCVD were 54.0%, 11.3%, and 25.7% during 12-month follow-up period, respectively. Among patients with DM, the rates were 57.5%, 14.2%, and 28.5%. The MPRs of statin among clinical ASCVD and DM cohorts were 0.62 and 0.60, respectively. As for ezetimibe, the MPRs were 0.56 and 0.59. Persistence to statin treatment was 46.1% among ASCVD patients and 42.6% among DM patients. Among the ASCVD and DM cohorts, possible statin intolerance was observed among 19.9% and 21.4% of patients, respectively. CONCLUSIONS: Large number of patients with either ASCVD or DM discontinued lipid-lowering therapies with suboptimal adherence and persistence among Taiwanese population. There is a large unmet medical need to provide safe and more effective therapies, which can be used in combination with statins or alone, to reduce the risk of CV events and improve outcomes in high-risk patients.

Characteristics of patients with dyslipidemia treated in routine care setting in China.

Objective: To describe characteristics of patients with dyslipidemia treated in routine care in China overall and stratified by diabetes and atherosclerotic cardiovascular disease (ASCVD). Methods: This study used data from a cross-sectional survey conducted in China in 2017 under the Dyslipidemia Disease Specific Programme (DSP). Each surveyed physician provided information including demographics, dyslipidemia diagnosis and treatment history, lab values on at least 8 patients currently treated for dyslipidemia with oversampling of patients with ASCVD or diabetes mellitus diagnosis at the time of survey. A related patient survey assessed treatment adherence and satisfaction. Results: This study included 195 physicians (40 endocrinologists, 75 internists, 80 cardiologists) who provided data on 1870 patients (852 with diabetes; 1018 patients without diabetes). Among patients with diabetes, 279 had ASCVD and 573 did not (non-ASCVD). In the diabetic population, patients with ASCVD were older (67.3 vs. 62.1 years), more often had caregiver support (34 vs. 14%), and had higher average LDL-C at diagnosis (172.4 vs. 167.4 mg/dL) compared to their non-ASCVD counterparts. Findings were similar for non-diabetic patients (ASCVD: 323 patients; non-ASCVD: 695) patients. In all four subgroups, 46-54% of patients reported low treatment adherence, and fewer than half expressed satisfaction with their cholesterol control, and 2-5% had LDL-C < 70 mg/dL at their most recent assessment. Conclusions: Among patients with dyslipidemia, those with ASCVD had higher LDL-C levels than patients without ASCVD, and many required caregiving. Low levels of treatment adherence, LDL-C control, and patient satisfaction suggest opportunities to improve care for Chinese patients with dyslipidemia.

Understanding the Patient Perception of Statin Experience: A Qualitative Study.

INTRODUCTION: Statin intolerance (SI) occurs in patients with dyslipidemia treated with statins. Statin-associated symptoms have been reported, but the overall patient experience is poorly understood. No instruments are available to collect this patient experience. Our aim is to develop a patient survey to define SI from the patient's perspective, inform clinical practice, and identify potential patient characteristics and barriers associated with discontinuing treatment when statin-related difficulties are encountered. METHODS: We conducted qualitative concept elicitation interviews with 65 patients across 12 European study sites. A semi-structured qualitative interview guide was developed based on literature review and clinician interviews. Concept elicitation interviews with patients were used to describe the patient experience and develop the conceptual framework for the survey. RESULTS: Symptoms experienced by patients included muscle and non-muscle-related pain and discomfort; other muscle-related symptoms; gastrointestinal, cardiovascular, cold-like, fatigue-related, and sensory and systems symptoms; mood changes; and cognitive and memory problems. Impacts included limitations on general physical functioning; physical activities; social functioning; emotional impacts; sleep disturbances; decreased productivity; and increased healthcare use. Conceptual framework elements to support survey goals include demographic and clinical characteristics, health information and beliefs, statin side-effect history, symptom severity, and impact severity. CONCLUSIONS: Symptoms and impacts described by patients showed a wider range of symptoms and impacts than usually discussed clinically. The patient survey is designed to capture information from patients who experience difficulties with statin therapy and may be useful in identifying patients who are at higher risk for giving up or discontinuing their treatment. FUNDING: Amgen Inc.

Prevalence and incidence of atherosclerotic cardiovascular disease and its risk factors in Korea: a nationwide population-based study.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in Korea. According to a report of published by Statistics Korea in 2014, cerebrovascular disease and cardiovascular disease were the major/leading causes of mortality. However, it is more difficult to identify prevalence and incidence of a disease than the mortality owing to the lack of national-level statistics. Few studies have examined the prevalence and incidence of ASCVD and its risk factors since 2012. This study aimed to estimate the prevalence and incidence of ASCVD and its risk factors in Korea using national claims data. METHODS: We conducted a retrospective analysis using the national claims data of the Health Insurance Review and Assessment Service. Patients aged ≥18 years with ASCVD (defined as myocardial infarction, angina, coronary revascularization, peripheral artery disease, ischemic stroke, and transient ischemic attack) were identified between January 1, 2014 and December 31, 2015. Patients at high risk for ASCVD (defined as hypertension, diabetes mellitus, and dyslipidemia without ASCVD during the baseline period) were identified between January 1, 2015 and December 31, 2015. We estimated the prevalence, cumulative incidence, and incidence density. These were further stratified by age and sex. The respective denominators for prevalence and incidence were the census population and the at-risk population (defined as the population without respective disease 1 year prior to the respective disease identification). RESULTS: Among the included Korean adult patients, the overall prevalence of clinical ASCVD per 1000 individuals was 98.25 in 2014 and 101.11 in 2015. The respective cumulative incidence and incidence density rates of ASCVD per 1000 individuals were 65.30 and 68.03 in 2014, and 67.05 and 69.94 in 2015, respectively. Peripheral artery disease seemed to drive the increase in the total prevalence and incidence of ASCVD. The prevalence and incidence of ASCVD continued to increase with age until 79 years. CONCLUSIONS: This national population-based study confirmed the high prevalence and incidence of ASCVD and its risk factors in the adult population of South Korea. We suggest that more intensive treatment and prevention are needed to prevent ASCVD.

A Systematic Review of Direct Cardiovascular Event Costs: An International Perspective.

INTRODUCTION: There is a lack of comprehensive cost information for cardiovascular events since 2013. OBJECTIVE: A systematic review on the contemporary cost of cardiovascular events was therefore undertaken. METHODS: Methods complied with those recommended by the Cochrane Collaboration and the Centre for Reviews and Dissemination. Studies were unrestricted by language, were from 2013 to 23 December 2017, and included cost-of-illness data in adults with the following cardiovascular conditions: myocardial infarction (MI), stroke, transient ischaemic attack (TIA), heart failure (HF), unstable angina (UA), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), or peripheral artery disease (PAD). Seven electronic databases were searched, namely Embase (Ovid), MEDLINE (Ovid), MEDLINE In-Process Citations and Daily Update (Ovid), NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) database, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed. The included studies reported data from a variety of years (sometimes prior to 2013), so costs were inflated and converted to $US, year 2018 values, for standardization. RESULTS: After de-duplication, 29,945 titles and abstracts and then 403 full papers were screened; 82 studies (88 papers) were extracted. Year 1 average cost ranges were as follows: MI ($11,970 in Sweden to $61,864 in the USA), stroke ($10,162 in Spain to $46,162 in the USA), TIA ($6049 in Sweden to $25,306 in the USA), HF ($4456 in China to $49,427 in the USA), UA ($11,237 in Sweden to $31,860 in the USA), PCI ($17,923 in Italy to $45,533 in the USA), CABG ($17,972 in the UK to $76,279 in the USA). One Swedish study reported PAD costs in a format convertible to $US, 2018 values, with a mean annual cost of $15,565. CONCLUSIONS: There was considerable unexplained variation in contemporary costs for all major cardiovascular events. One emerging theme was that average costs in the USA were considerably higher than anywhere else.

Estimating Years of Life Lost Due to Cardiovascular Disease in Japan.

BACKGROUND: In Japan, the burden associated with myocardial infarction (MI) and ischemic stroke as well as atherosclerotic cardiovascular disease (ASCVD) generally is high. One key element in measuring disease burden is years of life lost (YLL). The aim of this study was to understand the burden of these diseases by estimating YLL at an overall disease level and average person-YLL (PYLL), a measure of disease burden also used in prior studies. Methods and Results: Because calculation of YLL and PYLL involves inputs such as disease prevalence, disease-related mortality by age, and general population mortality by age and sex, we searched public databases of disease surveillance to identify comprehensive Japanese-specific inputs. For our reference analysis, disease-specific prevalence and mortality were taken from the Institute for Health Metrics and Evaluation Global Disease Burden study, and background mortality data were from the Japanese life tables published by the Ministry of Health, Labour and Welfare. The average age of patients with MI or stroke was 74 and 70 years, respectively. On average, men comprised 59% and 54% of the MI and stroke population, respectively. The disease-level burden of ASCVD (inclusive of MI, stroke, and peripheral artery disease) was 2,703,711 YLL in 2017. The patient-level burden was 11.99 PYLL for MI and 9.39 PYLL for stroke. CONCLUSIONS: The burden of ASCVD, MI, and stroke in terms of premature mortality is substantial in Japan, both on a population disease level and an individual patient level.

Utilization Patterns of Lipid-lowering Therapies in Patients With Atherosclerotic Cardiovascular Disease or Diabetes: A Population-based Study in South Korea.

PURPOSE: We aimed to study the utilization patterns of lipid-lowering treatment (LLT), including treatment modification, adherence, and possible statin intolerance, in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes using national claims data in South Korea. METHODS: A retrospective cohort study was conducted using data from the Korean Health Insurance Review & Assessment Service claims database. Patients aged ≥18 years with >1 outpatient pharmacy claim for a statin and/or ezetimibe dated January 1, 2012, to December 31, 2014, were identified and categorized into the following cohorts: patients with ASCVD, and patients with diabetes mellitus without ASCVD. LLT modification, adherence to index LLT, and possible statin intolerance were explored during the 12 months after the date of first prescription for a statin and/or ezetimibe. FINDINGS: Among 1,399,872 patients who met the eligibility criteria, 807,547 (57.7%) were patients with ASCVD and 592,325 (42.3%) were patients with diabetes without ASCVD. About half of the patients had no modification in their index treatment (46.2% in the ASCVD cohort and 48.9% in the diabetes cohort), and the most common modification was permanent discontinuation (19.6% in the ASCVD cohort and 21.4% in the diabetes cohort). The mean medication possession ratios were 0.77 in the ASCVD cohort and 0.73 in the diabetes cohort and showed a decreasing trend during the 12-month follow-up period. Among patients who initiated a statin and/or ezetimibe, possible statin intolerance was observed in 53,921 patients (6.7%) in the ASCVD cohort and 42,172 patients (7.1%) in the diabetes cohort. IMPLICATIONS: In South Korea, a high rate of permanent discontinuation of statin therapy in patients with ASCVD or diabetes places these patients at high risk for cardiovascular events in the future. A decreasing trend of adherence to LLT implies that more intensive education and management are required to improve therapeutic effect and reduce the risk for ASCVD. The high rate of possible statin intolerance highlights an unmet need in the prevention and management of ASCVD in South Korea.

Treatment Patterns, Statin Intolerance, and Subsequent Cardiovascular Events Among Japanese Patients With High Cardiovascular Risk Initiating Statin Therapy.

BACKGROUND: This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months' pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months' post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort. CONCLUSIONS: High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.

Prevalence and predictors of non-evidence based proton pump inhibitor use among elderly nursing home residents in the US.

BACKGROUND: Proton pump inhibitors (PPIs) can lead to several adverse effects among the elderly, particularly when used inappropriately or in contrast to evidence suggested protocols. OBJECTIVE: The aim of this study was to examine the prevalence and predictors of non-evidence based PPI use in elderly nursing home residents. METHODS: A cross-sectional study was conducted using data from the 2004 National Nursing Home Survey (NNHS). The study sample included nursing home residents 65 years and older. Descriptive statistics were used to examine the prevalence of non-evidence based PPI use. Multivariable logistic regression was used to evaluate the patient and facility-level factors associated with non-evidence based PPI use among the elderly nursing home residents. RESULTS: A total of 355,600 elderly nursing home residents received at least one PPI for an overall prevalence of 26.99%. Among those elderly receiving PPIs, 48.59% of the use was not evidence based. Multivariable logistic regression revealed that residents with osteoporosis (Odds Ratio (OR): 0.55, 95% CI: 0.45-0.68), SSRI users (OR: 0.81, 95% CI: 0.68-0.97) and those residing in micropolitan area (OR: 0.79, 95% CI: 0.63-0.98) were negatively associated with prescription of PPIs without an indication. Patients with chronic cough (OR: 2.10, 95% CI: 1.12-3.96) and Medicare insurance (OR: 1.23, 95% CI: 1.01-1.50) were positively associated with prescription of PPIs without an indication. CONCLUSIONS: The current study found that almost half of the elderly nursing home residents used PPIs for non-evidence based indications. Given the safety concerns and high non-evidence based use of PPIs in nursing homes, there is an urgent need to optimize PPI use in the elderly.