Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

BACKGROUND AND OBJECTIVE: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL). METHODS: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration. KEY FINDINGS AND LIMITATIONS: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy. CONCLUSIONS AND CLINICAL IMPLICATIONS: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301. PATIENT SUMMARY: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21.

Systematic Literature Review (SLR) and Network Meta-Analysis (NMA) of First-Line Therapies (1L) for Locally Advanced/Metastatic Urothelial Carcinoma (la/mUC).

To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001-September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator's choice of carbo). Analyses examined comparative efficacy by hazard ratio (HR) for overall survival (OS), and progression-free survival (PFS), and odds ratio (OR) for overall response rate (ORR), with 1L regimens vs. SOC. SOC was gemcitabine + cis (GemCis) or carboplatin (GemCarbo), cis-eligible/mixed network, and GemCarbo cis-ineligible networks. Of 1906 SLR identified citations, 55 trials were selected for data extraction. The NMA comprised 11, 6, and 8 studies in the cis-eligible/mixed, cis-ineligible (strict), cis-ineligible (wide) networks, respectively. In a meta-analysis of SOC control arms, median (95% CI) overall survival (OS) in months varied by network: 13.19 (12.43, 13.95) cis-eligible/mixed, 11.96 (10.43, 13.48) cis-ineligible (wide), and 9.74 (6.71, 12.76) cis-ineligible (strict). Most differences in OS, PFS, and ORR with treatment regimens across treatment networks were not statistically significant compared with SOC. Outcomes with current 1L regimens remain poor, and few significant improvements over SOC have been made, despite inclusion of recent clinical trial data, highlighting an unmet need in the la/mUC patient population.

Oncology Simulation Model: A Comprehensive and Innovative Approach to Estimate and Project Prevalence and Survival in Oncology.

Objective: We demonstrate a new model framework as an innovative approach to more accurately estimate and project prevalence and survival outcomes in oncology. Methods: We developed an oncology simulation model (OSM) framework that offers a customizable, dynamic simulation model to generate population-level, country-specific estimates of prevalence, incidence of patients progressing from earlier stages (progression-based incidence), and survival in oncology. The framework, a continuous dynamic Markov cohort model, was implemented in Microsoft Excel. The simulation runs continuously through a prespecified calendar time range. Time-varying incidence, treatment patterns, treatment rates, and treatment pathways are specified by year to account for guideline-directed changes in standard of care and real-world trends, as well as newly approved clinical treatments. Patient cohorts transition between defined health states, with transitions informed by progression-free survival and overall survival as reported in published literature. Results: Model outputs include point prevalence and period prevalence, with options for highly granular prevalence predictions by disease stage, treatment pathway, or time of diagnosis. As a use case, we leveraged the OSM framework to estimate the prevalence of bladder cancer in the United States. Conclusion: The OSM is a robust model that builds upon existing modeling practices to offer an innovative, transparent approach in estimating prevalence, progression-based incidence, and survival for oncologic conditions. The OSM combines and extends the capabilities of other common health-economic modeling approaches to provide a detailed and comprehensive modeling framework to estimate prevalence in oncology using simulation modeling and to assess the impacts of new treatments on prevalence over time.

Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial.

BACKGROUND: The EV-201 trial (NCT03219333) demonstrated a clinically meaningful and durable response rate and a tolerable safety profile with enfortumab vedotin (EV) in patients with locally advanced/metastatic urothelial carcinoma (LA/mUC) treated with prior PD-1/PD-L1 inhibitor therapy and platinum-containing chemotherapy (cohort 1). Patient-reported outcome (PRO) measures were included in EV-201 as exploratory endpoints. OBJECTIVE: To evaluate PRO data for cohort 1 of EV-201 to better understand the relationship between EV therapy and health-related quality of life (HRQoL). DESIGN, SETTING, AND PARTICIPANTS: Enrolled patients with LA/mUC who received EV were invited to electronically complete two HRQoL instruments (EORTC QLQ-C30 and EQ-5D-3L) at baseline and day 1 of each cycle until treatment discontinuation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient demographics, completion and compliance rates, and PRO scores were analysed using descriptive statistics. Selected EORTC QLQ-C30 scores were analysed post hoc using a repeated-measures mixed model. RESULTS AND LIMITATIONS: Among treated patients (n = 125), 95% completed both baseline questionnaires. Compliance rates were ≥86% throughout the study. Descriptive analyses showed that global health status, physical functioning, and symptom scores remained stable over time, with average scores similar at each cycle. Lower pain and fatigue scores were observed in responders at cycles following an objective response. Pain was lower at cycle 3 than at baseline in patients with bone metastases. Mean EQ-5D-3L utility score (0.80 at baseline; range from 0.77 at cycle 2 to 0.91 at cycle 10) and visual analogue scale scores (66.9 at baseline; range from 65.5 at cycle 2 to 78.4 at cycle 10) remained similar over time. Variability and the small sample size limited definitive conclusions. CONCLUSIONS: PRO scores remained stable throughout EV treatment, further supporting the overall value of EV in the treatment of patients with LA/mUC. The potential benefit of EV therapy on overall HRQoL and symptoms such as pain and fatigue is currently being explored. PATIENT SUMMARY: In this study of adult patients with advanced cancer of the urinary tract that progressed after previous medications, quality of life, ability to function, and symptoms did not worsen on treatment with enfortumab vedotin, which is an antibody + drug combination. Some improvements in pain and fatigue were reported by patients, but further research needs to be conducted. These data complement the efficacy and safety data from the EV-201 trial.

Real-World Utilization and Safety of Daratumumab IV Rapid Infusions Administered in a Community Setting: A Retrospective Observational Study.

BACKGROUND: Some institutions have implemented a daratumumab intravenous rapid-infusion protocol in which patients with multiple myeloma (MM) receive their third and subsequent infusions within ~ 90 min instead of ≥ 3 h. OBJECTIVE: This study sought to understand the utilization, effectiveness, and infusion reactions (IRs) observed in patients with MM who received daratumumab rapid infusions. METHODS: Electronic medical records from Florida Cancer Specialists & Research Institute were used. Adult patients with MM who received one or more rapid daratumumab infusion (full dose in ≤ 110 min) at their third or later infusion of the first daratumumab-containing regimen (index date: 16 November 2015 to 15 March 2019) were included. IRs included events that (1) occurred ≤ 24 h post-daratumumab infusion or (2) were stated as an IR in the patient charts. Non-IR adverse events (AEs) were events attributed to daratumumab in patient charts that did not meet the IR definition. RESULTS: In total, 147 patients received one or more rapid infusion in their first daratumumab-containing regimen. Median time from initial MM diagnosis to index date was 2.5 years. Non-IR AEs occurred in 10.2% of patients during treatment, and 36.7% experienced one or more IR after receiving a daratumumab infusion. No IRs occurred after a rapid infusion. The overall response rate was 91.1% (after rapid infusions only: 71.3%). CONCLUSIONS: This study provides real-world evidence on the practice patterns of daratumumab rapid infusions in a large community-based oncology clinic system. These results suggest that treatment regimens including daratumumab rapid infusions at the third infusion or later were well-tolerated, and their effectiveness was comparable to that observed in clinical trials.

A concept-wide association study to identify potential risk factors for nonadherence among prevalent users of antihypertensives.

PURPOSE: We sought to determine whether an association study using information contained in clinical notes could identify known and potentially novel risk factors for nonadherence to antihypertensive medications. METHODS: We conducted a retrospective concept-wide association study (CWAS) using clinical notes to identify potential risk factors for medication nonadherence, adjusting for age, sex, race, baseline blood pressure, estimated glomerular filtration rate, and a combined comorbidity score. Participants included Medicare beneficiaries 65 years and older receiving care at the Harvard Vanguard Medical Associates network from 2010-2012 and enrolled in a Medicare Advantage program. Concepts were extracted from clinical notes in the year prior to the index prescription date for each patient. We tested associations with the outcome for 5013 concepts extracted from clinical notes in a derivation cohort (4382 patients) and accounted for multiple hypothesis testing by using a false discovery rate threshold of less than 5% (q < .05). We then confirmed the associations in a validation cohort (3836 patients). Medication nonadherence was defined using a proportion of days covered (PDC) threshold less than 0.8 using pharmacy claims data. RESULTS: We found 415 concepts associated with nonadherence, which we organized into 11 clusters using a hierarchical clustering approach. Volume depletion and overload, assessment of needs at the point of discharge, mood disorders, neurological disorders, complex coordination of care, and documentation of noncompliance were some of the factors associated with nonadherence. CONCLUSIONS: This approach was successful in identifying previously described and potentially new risk factors for antihypertensive nonadherence using the clinical narrative.

Time to Filling of New Prescriptions for Chronic Disease Medications Among a Cohort of Elderly Patients in the USA.

BACKGROUND: Data on primary nonadherence remains sparse, due to a lack of data resources that combine information on medication prescribing and dispensing. In addition, previous work on primary nonadherence has used follow-up periods ranging from 30 days up to 18 months, making results difficult to compare. OBJECTIVE: To evaluate the prevalence and predictors of primary nonadherence by measuring time until filling in a cohort of elderly patients. DESIGN: Retrospective cohort study of new prescription episodes. PATIENTS: Data comes from a linked database of electronic health records and claims for patients aged ≥ 65 years enrolled in Medicare Parts A, B, and D during 2007-2014. We identified patients receiving a new prescription for a chronic disease medication with continuous Medicare enrollment for 180 days prior to the index prescription order and no fills or orders for the medication during this period. MAIN MEASURES: Time until filling of the index prescription for up to 1 year. KEY RESULTS: In 32,586 new medication orders, the majority (75%; 95% confidence interval [CI] 74-75%) of new prescriptions were filled within 7 days, 81% (81-82%) were filled within 30 days, and 91% (91-92%) were filled within 1 year. The rate and timing of dispensing were similar across therapeutic areas. Timing of initial filling within 7 days or within 30 days could be predicted with moderate accuracy (C-statistics = 0.70-0.74). Patients with > 5 current medications on hand at the time of the index prescription and average out-of-pocket medication costs < $5 filled 89% of prescriptions within 7 days. Patients with no current medications and out-of-pocket costs > $50 filled only 25% of prescriptions within 7 days. CONCLUSIONS: Nearly 20% of patients do not fill a new chronic disease prescription within 30 days. Patients with fewer recent fills and higher out-of-pocket costs are at higher risk of primary nonadherence.

The relative benefits of claims and electronic health record data for predicting medication adherence trajectory.

BACKGROUND: Healthcare providers are increasingly encouraged to improve their patients' adherence to chronic disease medications. Prediction of adherence can identify patients in need of intervention, but most prediction efforts have focused on claims data, which may be unavailable to providers. Electronic health records (EHR) are readily available and may provide richer information with which to predict adherence than is currently available through claims. METHODS: In a linked database of complete Medicare Advantage claims and comprehensive EHR from a multi-specialty outpatient practice, we identified patients who filled a prescription for a statin, antihypertensive, or oral antidiabetic during 2011 to 2012. We followed patients to identify subsequent medication filling patterns and used group-based trajectory models to assign patients to adherence trajectories. We then identified potential predictors from both claims and EHR data and fit a series of models to evaluate the accuracy of each data source in predicting medication adherence. RESULTS: Claims were highly predictive of patients in the worst adherence trajectory (C=0.78), but EHR data also provided good predictions (C=0.72). Among claims predictors, presence of a prior gap in filling of at least 6 days was by far the most influential predictor. In contrast, good predictions from EHR data required complex models with many variables. CONCLUSION: EHR data can provide good predictions of adherence trajectory and therefore may be useful for providers seeking to deploy resource-intensive interventions. However, prior adherence information derived from claims is most predictive, and can supplement EHR data when it is available.

Variation in adherence to medications across the healthcare system in two comparative effectiveness research cohorts.

AIM: To assess heterogeneity in adherence to medications in two example comparative effectiveness research studies. PATIENTS & METHODS: We analyzed data from commercially insured patients initiating a statin or anticoagulant during 2005-2012. We calculated the cross-validated R2 from a series of hierarchical linear models to assess variation in 1-year adherence. RESULTS: There was less heterogeneity in adherence in the statin cohort compared with the anticoagulant cohort, where patient characteristics explained 7.2% of variation in adherence, and adding therapy and provider characteristics increased the proportion of variation explained to 8.0 and 8.5%, cumulatively. Random effects provided essentially no explanatory power, even in the statin cohort with large numbers of patients clustered within each pharmacy, prescriber and provider. CONCLUSION: The dependence of adherence on the healthcare system was stronger when the healthcare system influenced treatment choice and patient access to medication and when indications for treatment were strong.

Real-world first-line treatment and overall survival in non-small cell lung cancer without known EGFR mutations or ALK rearrangements in US community oncology setting.

PURPOSE: To establish a baseline for care and overall survival (OS) based upon contemporary first-line treatments prescribed in the era before the introduction of immune checkpoint inhibitors, for people with metastatic non-small cell lung cancer (NSCLC) without common actionable mutations. METHODS: Using a nationally representative electronic health record data from the Flatiron dataset which included 162 practices from different regions in US, we identified patients (≥18 years old) newly diagnosed with stage IV NSCLC initiating first-line anticancer therapy (November 2012- January 2015, with follow-up through July 2015). Patients with documented epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) translocation were excluded. Anti-cancer drug therapy and overall survival were described overall, and by histology. RESULTS: A total of 2,014 patients with stage IV NSCLC without known EGFR or ALK genomic tumor aberrations initiated systemic anticancer therapy, 22% with squamous and 78% with nonsquamous histology. Their mean (SD) age was 67 (10) years, 55% were male, and 87% had a smoking history. In nonsquamous NSCLC, carboplatin plus pemetrexed either without (25.7%) or with bevacizumab (16%) were the most common regimens; 26.6% of nonsquamous patients receiving induction therapy also received continuation maintenance therapy. In squamous NSCLC, carboplatin plus paclitaxel (37.6%) or nab-paclitaxel (21.1%) were the most commonly used regimens. Overall median OS was 9.7 months (95% CI: 9.1, 10.3), 8.5 months (95% CI: 7.4, 10.0) for squamous, and 10.0 months (95% CI: 9.4, 10.8) for nonsquamous NSCLC. CONCLUSION: The results provide context for evaluating the effect of shifting treatment patterns of NSCLC treatments on patient outcomes, and for community oncology benchmarking initiatives.

Treatment Patterns for Advanced Non-Small-cell Lung Cancer After Platinum-containing Therapy in U.S. Community Oncology Clinical Practice.

BACKGROUND: Knowledge of the real-world treatment patterns for non-small-cell lung cancer (NSCLC) can identify quality-of-care gaps and guide resource allocation needs. Our objective was to describe the treatment patterns for advanced NSCLC after first-line chemotherapy in the era before the approval of immunotherapeutic agents. MATERIALS AND METHODS: The present was a retrospective observational study of adult patients with advanced NSCLC (stage IIIB/IV or metastatic recurrence) who had completed a platinum-containing regimen, with an appropriate tyrosine kinase inhibitor if positive for epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Eligible patients initiated second-line chemotherapy from November 2012 through October 2014, recorded in an oncology record system for U.S. community clinics. RESULTS: Of 6867 patients with advanced NSCLC, 4188 (61%) initiated and 2707 (39%) completed platinum therapy, with a tyrosine kinase inhibitor, if appropriate. Subsequently 1889 of 2707 (70%) received second-line chemotherapy, including 1173 within the study period (844 [72%] nonsquamous, 275 [23%] squamous, and 54 [5%] not otherwise specified). The mean ± standard deviation patient age was 66 ± 10 years; 54% were male. Of the 94 different second-line regimens, docetaxel was the most common, prescribed to 14% of the patients overall and 14% and 16% of the nonsquamous and squamous cohorts, respectively. The median duration was 64 days (range, 1-455 days) and 48 days (range, 1-210 days) for the nonsquamous and squamous cohorts, respectively. The median duration by regimen category was 15 to 85 days (overall range, 1-953 days). CONCLUSION: These findings show the diversity, short treatment duration, and lack of efficacy of second-line chemotherapy regimens for NSCLC in the community oncology setting.

Self-Reported Medication Adherence Barriers Among Ambulatory Older Adults with Mild Cognitive Impairment.

STUDY OBJECTIVE: To compare the frequencies of barriers to medication adherence reported by ambulatory older adults with a diagnosis of mild cognitive impairment (MCI) and ambulatory older adults with normal cognition. DESIGN: Cross-sectional study. SETTING: Outpatient clinics within a safety-net health care system. PARTICIPANTS: Ambulatory older adults (≥ 65 yrs) with a diagnosis of MCI (96 participants) or normal cognition (104 participants). MEASUREMENTS AND MAIN RESULTS: Self-reported beliefs and barriers to medication nonadherence were assessed by items from the Morisky Medication Adherence Survey, the Adherence Estimator, and barriers derived from a systematic review of studies in older adults with cognitive impairment. Participants with a diagnosis of MCI had a mean age of 72 years, 77% were female, and 37% were African-American. Participants with normal cognition had a mean age of 76 years, 79% were female, and 47% were African-American. Among all participants, 83% reported the presence of at least one barrier to medication adherence, and 62.5% reported two or more barriers to medication adherence. The most commonly reported barriers were difficulty remembering the amount or time of each medication to take (49%), difficulty opening or reading prescription bottles (42%), feeling worse when taking medications (29%), and trouble affording medications (26%). Considering the multiple comparisons made in this analysis, few significant differences in barrier frequencies were identified between the groups with MCI and normal cognition. CONCLUSION: Multiple medication adherence barriers were identified among all participants, including cognitive, physical, and financial barriers, although few significant differences were identified between those with and without MCI. Interventions capable of addressing multiple barriers are required to improve medication adherence in older adults with and without MCI.

Development of an early nurse led intervention to treat children referred to secondary paediatric care with constipation with or without soiling.

BACKGROUND: Constipation is a common chronic childhood condition referred to secondary care. Effective treatment requires early intervention, prolonged medication to soften stools and behavioural support to achieve a regular habit of sitting on the toilet to pass a stool. The purpose of this audit and service development was to assess routine consultant paediatrician-led care against minimum standards and if appropriate to develop a nurse-led intervention. The new care package could then be tried out within general paediatric clinics in Glasgow as a service evaluation. NICE guideline (CG99) has a research recommendation to compare nurse-led care with routine consultant-led care. METHODS: Design was an audit then development of a nurse-led intervention followed by a service evaluation. Participants were children (age 0-13 years), referred by their General Practitioner (GP) to the Royal Hospital for Sick Children Glasgow, with constipation the main problem in the GP letter. The audit covered appointment waiting times, intervention provided, initial follow-up and parental satisfaction with routine consultant-led practice. The nurse-led intervention focused on self-help psychology practice with NICE guideline medical support. This was compared with routine consultant paediatrician care in a service evaluation. RESULTS: The audit found consultant-led care had long waiting times, delayed initial follow-up and variable intervention. The new nurse-led intervention is described in detail. The nurse-led intervention performed well compared with consultant-led care. Less 'nurse-led' children, 3/45 (7%), were still constipated passing less than 3 stools per week compared with 8/58 (14%) receiving consultant-led care. Less 'nurse-led' parents, 10/45 (22%), reported their child having pain passing stools in the previous week compared with consultant-led care, 26/58 (45%). The proportion of children, over 4 years, free from soiling accidents was similar, 15/23 (65%) in the nurse-led group and 18/29 (62%) with consultant-led care. Parental satisfaction was slightly better in the nurse-led group. CONCLUSION: It is difficult to achieve minimum standards using routine consultant-led care for children referred by their GP with constipation. Nurse-led early intervention is feasible and has produced promising results in a service evaluation. An exploratory trial is planned to develop a teaching module, robust outcomes including costs and benefits, and methodology for a definitive trial recommended by NICE.

Subsyndromal posttraumatic stress disorder symptomatology in primary care military veterans: treatment implications.

Subsyndromal posttraumatic stress disorder (PTSD) is highly prevalent in Veterans Affairs Medical Centers' primary-care clinics and is associated with significant impairment. We used a cross-sectional design to examine PTSD symptoms and depressive disorders endorsed by two cohorts of Veterans meeting less than full PTSD criteria who presented to primary care at the Philadelphia VA Medical Center (i.e., those from Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) and non-OEF/OIF/OND Veterans). The Philadelphia VA Behavioral Health Lab (BHL) assessed 141 Veterans who screened positive for subsyndromal PTSD. Avoidance was endorsed significantly less often than arousal in the total group. When the groups were split by cohort era, higher levels of avoidance and lower levels of arousal were reported in the non-OEF/OIF/OND group than the OEF/OIF/OND group. Comorbid depression was present in 43.9% of the total group with no significant differences between groups. Exposure-based treatments for PTSD offered in specialty mental health clinics target avoidance symptoms. Because the endorsement of avoidance symptoms was low in both of the cohorts that were studied this may not be the most effective treatment target for Veterans with subsyndromal PTSD receiving treatment in primary care settings. For these Veterans, treatments that target reexperiencing and arousal symptoms and/or comorbid depression may be more effective.

A multilevel study of the associations between economic and social context, stage of adolescence, and physical activity and body mass index.

OBJECTIVE: Prevention efforts targeting adolescent risk behavior have had limited effectiveness, partly because of the reliance on individual-level interventions that do not consider the context within which behavior occurs. In addition, the role of development has not been well studied regarding its possible moderating effects on contextual influences on behavior. The purpose of this study was to examine the influence of economic and social context on the odds of being inactive or having above-normal weight and whether the influence differed on the basis of stage of adolescence. METHODS: Analysis used a subset of adolescents aged 10 to 17 years from the National Survey of Children's Health (n = 37930) from all states and the District of Columbia (n = 51). Dependent variables included physical activity and BMI. State-level economic context was measured by the proportion of families living below 200% of the federal poverty level. Social context was measured by aggregated means of responses to 2 indicators of social capital: mutual aid and social trust. Multilevel modeling was conducted to investigate associations between state-level economic and social context and physical activity and BMI, while controlling for individual sociodemographic characteristics, and whether these associations were dependent on an individual's stage of adolescence. RESULTS: Both state-level mutual aid and social trust were significantly related to the odds of an adolescent not meeting current physical activity recommendations, yet state-level poverty was not. For BMI, all 3 state-level variables were significant predictors of having an above-normal BMI. Evidence was found of the moderating influence of stage of adolescence for both outcomes. CONCLUSIONS: These findings point to the need for the inclusion of contextual-level data in surveillance systems assessing risk behavior in adolescents and consideration of the multilevel nature of the growing problem of inactivity and above-normal weight when focusing public health prevention efforts.