Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II).

PURPOSE: To assess the effect of esketamine nasal spray on patient-reported outcomes (PROs) in patients with major depressive disorder having active suicidal ideation with intent (MDSI). METHODS: Patient-level data from two phase 3 studies (ASPIRE I; ASPIRE II) of esketamine + standard of care (SOC) in patients (aged 18-64 years) with MDSI, were pooled. PROs were evaluated from baseline through end of the double-blind treatment phase (day 25). Outcome assessments included: Beck Hopelessness Scale (BHS), Quality of Life (QoL) in Depression Scale (QLDS), European QoL Group-5-Dimension-5-Level (EQ-5D-5L), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). Changes in BHS and QLDS scores (baseline to day 25) were analyzed using a mixed-effects model for repeated measures (MMRM). RESULTS: Pooled data for esketamine + SOC (n = 226; mean age: 40.5 years, 59.3% females) and placebo + SOC (n = 225; mean age: 39.6 years, 62.2% females) were analyzed. Mean ± SD change from baseline to day 25, esketamine + SOC vs placebo + SOC (least-square mean difference [95% CI] based on MMRM): BHS total score, - 7.4 ± 6.7 vs - 6.8 ± 6.5 [- 1.0 (- 2.23, 0.21)]; QLDS score, - 14.4 ± 11.5 vs - 12.2 ± 10.8 [- 3.1 (- 5.21, - 1.02)]. Relative risk (95% CI) of reporting perceived problems (slight to extreme) in EQ-5D-5L dimensions (day 25) in esketamine + SOC vs placebo + SOC: mobility [0.78 (0.50, 1.20)], self-care [0.83 (0.55, 1.27)], usual activities [0.87 (0.72, 1.05)], pain/discomfort [0.85 (0.69, 1.04)], and anxiety/depression [0.90 (0.80, 1.00)]. Mean ± SD changes from baseline in esketamine + SOC vs placebo + SOC for health status index: 0.23 ± 0.21 vs 0.19 ± 0.22; and for EQ-Visual Analogue Scale: 24.0 ± 27.2 vs 19.3 ± 24.4. At day 25, mean ± SD in domains of TSQM-9 scores in esketamine + SOC vs placebo + SOC were: effectiveness, 67.2 ± 25.3 vs 56.2 ± 26.8; global satisfaction, 69.9 ± 25.2 vs 56.3 ± 27.8; and convenience, 74.0 ± 19.4 vs 75.4 ± 18.7. CONCLUSION: These PRO data support the patient perspective of the effect associated with esketamine + SOC in improving health-related QoL in patients with MDSI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ASPIRE I, NCT03039192 (Registration date: February 1, 2017); ASPIRE II, NCT03097133 (Registration date: March 31, 2017).

Assessment of health-related quality of life and health status in patients with treatment-resistant depression treated with esketamine nasal spray plus an oral antidepressant.

BACKGROUND: Patients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who were treated with esketamine nasal spray and an oral antidepressant (ESK + AD) vs. placebo nasal spray and an AD (AD + PBO). METHODS: Data from TRANSFORM-2, a phase 3, randomized, double-blind, short-term flexibly dosed study, were analyzed. Patients (aged 18-64 years) with TRD were included. The outcome assessments included the European Quality of Life Group, Five Dimension, Five Level (EQ-5D-5L), EQ-Visual Analogue Scale (EQ-VAS), and Sheehan Disability Scale (SDS). The health status index (HSI) was calculated using EQ-5D-5L scores. RESULTS: The full analysis set included 223 patients (ESK + AD: 114; AD + PBO: 109; mean [SD] age: 45.7 [11.89]). At Day 28, a lower percentage of patients reported impairment in the ESK + AD vs. AD + PBO group in all five EQ-5D-5L dimensions: mobility (10.6% vs. 25.0%), self-care (13.5% vs. 32.0%), usual activities (51.9% vs. 72.0%), pain/discomfort (35.6% vs. 54.0%), and anxiety/depression (69.2% vs. 78.0%). The mean (SD) change from baseline in HSI at Day 28 was 0.310 (0.219) for ESK + AD and 0.235 (0.252) for AD + PBO, with a higher score reflecting better levels of health. The mean (SD) change from baseline in EQ-VAS score at Day 28 was greater in ESK + AD (31.1 [25.67]) vs. AD + PBO (22.1 [26.43]). The mean (SD) change in the SDS total score from baseline to Day 28 also favored ESK + AD (-13.6 [8.31]) vs. AD + PBO (-9.4 [8.43]). CONCLUSIONS: Greater improvements in HRQoL and health status were observed among patients with TRD treated with ESK + AD vs. AD + PBO. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02418585.

Assessing the meaningful change threshold of Quality of Life in Depression Scale using data from two phase 3 studies of esketamine nasal spray.

BACKGROUND: Major depressive disorder (MDD) directly impacts patients' lives including symptoms, functioning and health-related quality-of-life (HRQoL). Patient-reported outcomes can capture these impacts, however interpretation of clinical meaningfulness of these measurements are often not readily available. Meaningful change thresholds (MCTs) can be derived for clinical outcome assessments to quantify the change in symptoms that is meaningful to the patient following pharmacologic treatment or other interventions. The objective of this analysis was to determine the within-patient MCT of the self-reported Quality-of-Life in Depression Scale (QLDS) among patients with MDD and active suicidal ideation with intent (MDSI) using an anchor-based approach. METHODS: Data from 2 randomized phase-3 trials of esketamine nasal spray (ASPIRE I and ASPIRE II) were analyzed. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary anchor with three different severity criteria. Other anchor variables utilized were Clinical Global Impression of Severity of Suicidality-revised version, Clinical Global Impression of Imminent Suicide Risk, and EuroQol Visual Analog Scale [EQ-VAS]. Spearman correlation coefficients between the change in QLDS and anchor variables were calculated. The mean change in QLDS score at Day 25 from baseline was calculated based on the categorical change in the anchor. Coefficient yield from linear regression of the mean changes in EQ-VAS and QLDS, and distribution-based approach with ½ SD of change in QLDS were considered. RESULTS: In ASPIRE I, mean (SD) improvement in QLDS score among patients with one category improvement in MADRS from baseline to Day 25 was - 8.22 (8.87), - 8.30 (9.01), and - 8.20 (8.92) using severity criteria #1, #2, and #3, respectively. Patients who achieved a 7-point improvement (MCT) in EQ-VAS yielded a mean - 9.69-point improvement in QLDS at Day 25. The ½ SD of change in QLDS was 5.63. Similar results were obtained for ASPIRE II. The MCTs identified using multiple anchors across both trials ranged from - 11.4 to - 6.7 and had an overall mean of - 7.90 (ASPIRE I) and - 7.92 (ASPIRE II). Thus, an 8-point change was recommended as the MCT for QLDS. CONCLUSION: The recommended MCT will help quantify within-person changes in HRQoL using patient-reported QLDS and determine meaningful treatment benefit in an MDD patient population with acute suicidal ideation or behavior. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: ASPIRE I (NCT03039192), ASPIRE II (NCT03097133). Date of registration: February 01, 2017; March 31, 2017. URL of trial registry record: https://clinicaltrials.gov/ct2/show/NCT03039192 ; https://clinicaltrials.gov/ct2/show/NCT03097133 .

Psychometric evaluation of the DAILY EATS questionnaire in individuals living with obesity.

BACKGROUND: Physiological and behavioral factors including hunger, satiety, food intake, and cravings are health determinants contributing to obesity. Patient-reported outcome (PRO) measures focused on eating-related factors provide insight into the relationships between food choice and quantity, weight change, and weight-loss treatment for individuals living with obesity. The DAILY EATS is a novel 5-item, patient-reported measure evaluating key eating-related factors (Worst and Average Hunger, Appetite, Cravings, and Satiety). METHODS: Psychometric analyses, consistent with regulatory standards, were conducted to evaluate the DAILY EATS using data from two randomized trials that included individuals with severe obesity without diabetes (NCT03486392) and with severe obesity and type 2 diabetes (NCT03586830). Additional measures included Patient Global Impression of Status (PGIS) and Patient Global Impression of Change items, Impact of Weight on Quality of Life-Lite, Ease of Weight Management, and Patient-Reported Outcomes Measurement Information System Physical Function Short Form 8b and 10a. The reliability, validity, and responsiveness of the DAILY EATS were assessed, and a scoring algorithm and thresholds to interpret meaningful score changes were developed. RESULTS: Item-level analyses of the DAILY EATS supported computation of an Eating Drivers Index (EDI), comprising the related items Worst Hunger, Appetite, and Cravings. Internal consistency (Cronbach's coefficient alphas ≥0.80) and test-retest reliability (coefficients > 0.7) of the EDI were robust. Construct validity correlation patterns with other PRO measures were as hypothesized, with moderate to strong significant correlations between the EDI and PGIS-Hunger (0.30 ≤ r ≤ 0.68), PGIS-Cravings (0.33 ≤ r ≤ 0.77) and PGIS-Appetite (0.52 ≤ r ≤ 0.77). Anchor- and distribution-based analyses support reductions ranging from 1.6 to 2.1 as responder thresholds for the EDI, representing meaningful within-person improvement. CONCLUSIONS: The DAILY EATS individual items and the composite EDI are reliable, sensitive, and valid in evaluating the concepts of hunger, appetite, and cravings for use in individuals with severe obesity with or without type 2 diabetes.

Adult Obesity and Health-Related Quality of Life, Patient Activation, Work Productivity, and Weight Loss Behaviors in the United States.

INTRODUCTION: While it is generally believed that people living with more severe obesity experience greater negative impacts on health-related quality of life (HRQoL), their experience may be impacted by other factors such as age, gender, and type 2 diabetes mellitus (T2DM). METHODS: The 36-Item Short Form Health Survey physical component score and mental component score, Work Productivity and Activity Impairment, and Patient Activation Measure® data from the 2018 National Health and Wellness Survey were analyzed in adults by body mass index (BMI) categories (normal weight: ≥18.5-<25kg/m2, overweight: ≥25-<30kg/m2, class 1 obesity: ≥30-<35kg/m2, class 2 obesity: ≥35-<40kg/m2, class 3 obesity: ≥40kg/m2, combined class 2/3 obesity: ≥35kg/m2). Findings were further stratified across age groups (young: 18-35y, middle-aged: 36-64y, older: ≥65y), by gender, and by T2DM status. RESULTS: Overall, as BMI increased people had greater negative effects on HRQoL, felt less involved with and in control of their healthcare, and had greater work productivity and activity impairments. The largest declines were generally observed between class 2 and 3 obesity categories. Young adults with obesity were more likely to feel less engaged with their health care than middle-aged/older adults with obesity. The effects of obesity on HRQoL and patient activation were generally consistent by gender. People with T2DM and obesity tended to have greater declines in physical functioning and more work and activity impairments than people with obesity without T2DM. The proportion of people trying to lose weight increased with increasing BMI category, and people with T2DM were less likely to exercise and more likely to diet than those without T2DM. CONCLUSION: Increasing levels of obesity tended to have a greater negative impact on HRQoL, patient activation, work productivity, and weight loss behaviors, but some differences in effects by age, gender, and T2DM status were observed.

Real-world impact of glycated hemoglobin reduction on treatment intensification and glycated hemoglobin goal attainment in type 2 diabetes mellitus patients initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).

Objective: To evaluate the impact of a 0.2% reduction in glycated hemoglobin (HbA1c) on treatment intensification, poor HbA1c control and HbA1c goal attainment in patients with type 2 diabetes mellitus (T2DM) initiated on a sodium glucose co-transporter 2 (SGLT2) inhibitor (SGLT2i).Methods: IQVIATM Health Plan Claims Data - US and IQVIATM Ambulatory EMR Data - US databases (29 October 2012-31 March 2016) were used to identify adults with T2DM initiated on an SGLT2i (index date) who had HbA1c measurements pre- and post-index, and ≥6 months of eligibility pre-index (baseline). HbA1c change was defined as the difference between the first post-index and the last pre-index measurements. Cox regression models were used to assess treatment intensification, poor HbA1c control (i.e. HbA1c > 9%, among patients <9% at baseline) and goal attainment (HbA1c < 7%, <8%; among patients with HbA1c above goal at baseline) adjusting for HbA1c change and baseline characteristics. Patients were observed up to one year after the first HbA1c measurement or end of eligibility. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported.Results: A total of 938 patients (mean age 54.9, 42.5% female, mean HbA1c 8.5%) were selected. Following SGLT2i initiation, each 0.2% reduction in HbA1c levels was associated with a decreased risk of treatment intensification (HR [95% CI] = 0.90 [0.86-0.92]), a decreased likelihood of reaching HbA1c > 9% (HR [95% CI] = 0.85 [0.79-0.88]) and higher likelihoods of achieving a treatment goal of HbA1c < 7% (HR [95% CI] = 1.17 [1.12-1.21]) and HbA1c < 8% (HR [95% CI] = 1.08 [1.04-1.10]).Conclusions: In T2DM patients, each HbA1c reduction of 0.2% following the initiation of an SGLT2i was associated with a significant positive impact on treatment intensification and HbA1c goal attainment.

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE (n = 1,340) and those with MB (n = 3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively (p < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively (p < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

Comparison of real-world outcomes in patients with nonvalvular atrial fibrillation treated with direct oral anticoagulant agents or warfarin.

PURPOSE: To compare patients with atrial fibrillation (AF) initiating direct oral anticoagulants (DOACs) versus warfarin on clinical outcomes including stroke, systemic embolism (SE), bleeding events, and cost of care. METHODS: This retrospective observational study used Medicare Advantage Prescription Drug and fully insured commercial claims from the Humana Research Database. Patients with AF who initiated a DOAC or warfarin from January 1, 2012, through September 30, 2015, were included. Date of the first prescription of DOAC or warfarin was the index date. Patients in the DOAC and warfarin groups were matched on propensity scores. Patients were censored at end of enrollment or study period, discontinuation, or switch of index medication. Clinical outcomes were compared in the matched groups using Cox proportional hazards models. Annualized costs and costs adjusted for censoring using Lin's interval method were also compared between the two cohorts. RESULTS: Patients on DOACs had a significantly lower risk of ischemic stroke (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98), hemorrhagic stroke (HR, 0.65; CI, 0.46-0.92), SE (HR, 0.53; 95% CI, 0.43-0.65), and composite outcome of stroke or SE (HR, 0.78; 95% CI, 0.71-0.86) compared with patients on warfarin. Bleeding risk was not statistically significant (HR, 0.85; 95% CI, 0.71-1.01). While annualized pharmacy costs were higher, annualized medical and total costs were lower in the DOAC group compared with the warfarin group. CONCLUSION: The results of the study indicated that patients on DOACs had lower rates of ischemic stroke, hemorrhagic stroke, SE, and composite outcome of stroke or SE compared with patients on warfarin. No significant differences in bleeding rates between the DOAC and warfarin groups were observed, while total cost of care was lower in the DOAC group.

Did death certificates and a death review process agree on lung cancer cause of death in the National Lung Screening Trial?

BACKGROUND/AIMS: Randomized controlled trials frequently use death review committees to assign a cause of death rather than relying on cause of death information from death certificates. The National Lung Screening Trial, a randomized controlled trial of lung cancer screening with low-dose computed tomography versus chest X-ray for heavy and/or long-term smokers ages 55-74 years at enrollment, used a committee blinded to arm assignment for a subset of deaths to determine whether cause of death was due to lung cancer. METHODS: Deaths were selected for review using a pre-determined computerized algorithm. The algorithm, which considered cancers diagnosed during the trial, causes and significant conditions listed on the death certificate, and the underlying cause of death derived from death certificate information by trained nosologists, selected deaths that were most likely to represent a death due to lung cancer (either directly or indirectly) and deaths that might have been erroneously assigned lung cancer as the cause of death. The algorithm also selected deaths that might be due to adverse events of diagnostic evaluation for lung cancer. Using the review cause of death as the gold standard and lung cancer cause of death as the outcome of interest (dichotomized as lung cancer versus not lung cancer), we calculated performance measures of the death certificate cause of death. We also recalculated the trial primary endpoint using the death certificate cause of death. RESULTS: In all, 1642 deaths were reviewed and assigned a cause of death (42% of the 3877 National Lung Screening Trial deaths). Sensitivity of death certificate cause of death was 91%; specificity, 97%; positive predictive value, 98%; and negative predictive value, 89%. About 40% of the deaths reclassified to lung cancer cause of death had a death certificate cause of death of a neoplasm other than lung. Using the death certificate cause of death, the lung cancer mortality reduction was 18% (95% confidence interval: 4.2-25.0), as compared with the published finding of 20% (95% confidence interval: 6.7-26.7). CONCLUSION: Death review may not be necessary for primary-outcome analyses in lung cancer screening trials. If deemed necessary, researchers should strive to streamline the death review process as much as possible.

Revisiting the Surveillance Epidemiology and End Results Cancer Registry and Medicare Health Outcomes Survey (SEER-MHOS) Linked Data Resource for Patient-Reported Outcomes Research in Older Adults with Cancer.

Researchers and clinicians are increasingly recognizing the value of patient-reported outcome (PRO) data to better characterize people's health and experiences with illness and care. Considering the rising prevalence of cancer in adults aged 65 and older, PRO data are particularly relevant for older adults with cancer, who often require complex cancer care and have additional comorbid conditions. A data linkage between the Surveillance Epidemiology and End Results (SEER) cancer registry and the Medicare Health Outcomes Survey (MHOS) was created through a partnership between the National Cancer Institute and the Centers for Medicare and Medicaid Services that created the opportunity to examine PROs in Medicare Advantage enrollees with and without cancer. The December 2013 linkage of SEER-MHOS data included the linked data for 12 cohorts, bringing the number of individuals in the linked data set to 95,723 with cancer and 1,510,127 without. This article reviews the features of the resource and provides information on some descriptive characteristics of the individuals in the data set (health-related quality of life, body mass index, fall risk management, number of unhealthy days in the past month). Individuals without (n=258,108) and with (n=3,440) cancer (1,311 men with prostate cancer, 982 women with breast cancer, 689 with colorectal cancer, 458 with lung cancer) were included in the current descriptive analysis. Given increasing longevity, advances in effective therapies and earlier detection, and population growth, the number of individuals aged 65 and older with cancer is expected to reach more than 12 million by 2020. SEER-MHOS provides population-level, self-reported, cancer registry-linked data for person-centered surveillance research on this growing population.

Participants' Views of Retention Materials Used in the PLCO Cancer Screening Trial.

OBJECTIVE: To obtain information from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial regarding their perception of the retention materials employed by the screening centers. Also, to determine the viability of using email or the internet as a data collection tool with an older population. DESIGN: Three of ten PLCO screening centers queried participants towards the end of the study (2010) as to their opinions of the various retention materials and whether they would have been willing to use electronic communication for study activities, had the option been available. SETTING: The questionnaires were administered by mail, and responses were returned to the originating screening center. PARTICIPANTS: The participants in this study consisted of all the active participants at three PLCO screening centers: the University of Colorado Anschutz Medical Campus, the University of Utah, and Henry Ford Health System. METHODS: A short, self-administered questionnaire was mailed to all active participants at three PLCO centers (n=41,482). This was a one-time mailing with no follow-up, as the responses were designed to be anonymous in order to obtain the most honest responses. RESULTS: The response rate was 62%. Of respondents, 97% reported their PLCO experience was good or excellent. Nearly 50% of respondents indicated that receipt of an annual newsletter made them more likely to participate; newsletter features they reported as most important were those that conveyed information on cancer, study findings, and how their data were being used. Results did not support study coordinators' suppositions that receipt of a token gift or birthday card by participants was important for retention. Fewer than 30% of respondents indicated that they would have been unwilling to use a secure website to complete study forms. CONCLUSION: These data indicate the importance of querying participants rather than relying on impressions of study staff, and also indicate that the internet will be a viable means of data collection in future prevention studies that include older Americans.

Data Processing and Analytic Support in the PLCO Cancer Screening Trial.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was a large, randomized controlled trial of cancer screening that also evolved over time into a unique epidemiologic cohort. Vast quantities of data have been collected since the beginning of the trial in 1993. Screening data was obtained through 2006. Questionnaire-based risk factor data (collected at baseline and at other points in the trial), vital status, cancer diagnoses and treatment, biospecimen data and additional ancillary efforts continue to be collected. Accurate data collection and efficient management methods are required to ensure high-quality data and valid and consistent analyses of trial outcomes. Information Management Services (IMS) was and continues to be responsible for processing and converting the collected raw PLCO data into comprehensive and accessible datasets. IMS also continues to provide a wide spectrum of analytic support including support for trial monitoring, data sharing, and epidemiologic research. In this paper, we describe the data processing and management requirements from the analytic team perspective, highlighting the various data sources and their complexity. We also illustrate the construction of usable analytic data files and discuss the wide range of analytic support provided. Instructions for accessing PLCO data also are provided.

Participation rates for organized colorectal cancer screening programmes: an international comparison.

OBJECTIVE: Participation, an indicator of screening programme acceptance and effectiveness, varies widely in clinical trials and population-based colorectal cancer (CRC) screening programmes. We aimed to assess whether CRC screening participation rates can be compared across organized guaiac fecal occult blood test (G-FOBT)/fecal immunochemical test (FIT)-based programmes, and what factors influence these rates. METHODS: Programme representatives from countries participating in the International Cancer Screening Network were surveyed to describe their G-FOBT/FIT-based CRC screening programmes, how screening participation is defined and measured, and to provide participation data for their most recent completed screening round. RESULTS: Information was obtained from 15 programmes in 12 countries. Programmes varied in size, reach, maturity, target age groups, exclusions, type of test kit, method of providing test kits and use, and frequency of reminders. Coverage by invitation ranged from 30-100%, coverage by the screening programme from 7-67.7%, overall uptake/participation rate from 7-67.7%, and first invitation participation from 7-64.3%. Participation rates generally increased with age and were higher among women than men and for subsequent compared with first invitation participation. CONCLUSION: Comparisons among CRC screening programmes should be made cautiously, given differences in organization, target populations, and interpretation of indicators. More meaningful comparisons are possible if rates are calculated across a uniform age range, by gender, and separately for people invited for the first time vs. previously.

Non-compliance with the initial screening exam visit in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

OBJECTIVE: Identify predictors of non-compliance with first round screening exams in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. METHOD: The PLCO was conducted from 1993 to 2011 at 10 US institutions. A total of 154,897 healthy men and women ages 55-74 years were randomized. Intervention arm participants were invited to receive gender-appropriate screening exams for prostate, lung, colorectal and ovarian cancer. Using intervention-arm data (73,036 participants), non-compliance percentages for 13 covariates were calculated, as were unadjusted and adjusted odds ratios (ORs), and 95% confidence intervals. Covariates included demographic factors as well as factors specific to PLCO (e.g., method of consent, distance from screening center). RESULTS: The rate of non-compliance was 11% overall but varied by screening center. Significant associations were observed for most covariates but indicated modest increases or decreases in odds. An exception was the use of a two-step consent process (consented intervention arm participants for exams after randomization) relative to a one-step process (consented all participants prior to randomization) (OR: 2.2, 95% CI: 2.0-2.5). Non-compliance percentages increased with further distance from screening centers, but ORs were not significantly different from 1. CONCLUSIONS: Many factors modestly influenced compliance. Consent process was the strongest predictor of compliance.

Annual patient time costs associated with medical care among cancer survivors in the United States.

BACKGROUND: Although patient time costs are recommended for inclusion in cost-effectiveness analyses, these data are not routinely collected. We used nationally representative data and a medical service-based approach to estimate the annual patient time costs among cancer survivors. METHODS: We identified adult 6699 cancer survivors and 86,412 individuals without a cancer history ages 18 years or more from 2008-2011 Medical Expenditure Panel Survey (MEPS). Service use was categorized as hospitalizations, emergency room use, provider visits, ambulatory surgery, chemotherapy, and radiation therapy. Service time estimates were applied to frequencies for each service category and the US median wage rate in 2011 was used to value time. We evaluated the association between cancer survivorship and service use frequencies and patient time costs with multivariable regression models, stratified by age group (18-64 and 65+ y). Sensitivity analyses evaluated different approaches for valuing time. RESULTS: Cancer survivors were more likely to have hospitalizations, emergency room visits, ambulatory surgeries, and provider visits in the past year than individuals without a cancer history in adjusted analyses (P<0.05). Annual patient time was higher for cancer survivors than individuals without a cancer history among those aged 18-64 years (30.2 vs. 13.6 h; P<0.001) and 65+ years (55.1 vs. 36.6 h; P<0.001), as were annual patient time costs (18-64 y: $500 vs. $226; P<0.001 and 65+ y: $913 vs. $607; P<0.001). CONCLUSIONS: Cancer survivors had greater annual medical service use and patient time costs than individuals without a cancer history. This medical service-based approach for estimating annual time costs can also be applied to other conditions.

Culturally sensitive approaches to recruitment and retention of Hispanics in the national lung screening trial.

Hispanics are underrepresented in medical research. At the National Lung Screening Trial's University of Colorado Denver screening center, traditional recruitment methods resulted in enrollment of few Hispanics. In response, the center adopted culturally sensitive recruitment techniques, including use of carefully-crafted bilingual materials. Bilingual interviewers were hired, and persons familiar with culture and language of groups of different Hispanic origin were consulted. Representation of Hispanics among participants enrolled at the Colorado center increased nearly threefold, from 3.3 to 9.4 %, after adoption of these methods. In this manuscript, we report on the specialized recruitment methods that were developed and how they were used to address known barriers to Hispanic recruitment.

Access to preventive health care for cancer survivors.

BACKGROUND: Access to health care, particularly effective primary and secondary preventive care, is critical for cancer survivors, in order to minimize the adverse sequelae of cancer and its treatment. PURPOSE: The goal of the study was to evaluate the association between cancer survivorship and access to primary and preventive health care. METHODS: Cancer survivors (n=4960) and individuals without a cancer history (n=64,431) aged ≥ 18 years, from the 2008-2010 Medical Expenditure Panel Survey (MEPS), were evaluated. Multiple measures of access and preventive services use were compared. The association between cancer survivorship and access and preventive services was evaluated with multivariate logistic regression models, stratified by age group (18-64 years and ≥ 65 years), controlling for the effects of age, gender, race/ethnicity, education, marital status, and comorbidities. Data were analyzed in 2013. RESULTS: Cancer survivors aged ≥ 65 years had equivalent or greater access and preventive services use than individuals without a cancer history, in adjusted analyses. However, among those aged 18-64 years with private health insurance, cancer survivors were more likely than other individuals to have a usual source of care and to use preventive services, whereas uninsured or publicly insured cancer survivors were generally less likely to have a usual source of care and to use preventive services than were uninsured or publicly insured adults without a cancer history. CONCLUSIONS: Although access and preventive care use in cancer survivors is generally equivalent or greater compared to that of other individuals, disparities for uninsured and publicly insured cancer survivors aged 18-64 years suggest that improvements in survivor care are needed.