Quality of Life Analysis in Patients with Retinitis Pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP) is a chronic progressive disease causing loss of visual acuity and ultimately blindness. This visual impairment can contribute to psychiatric comorbidity and worse overall quality of life (QOL). Our goal was to assess the relationship between the severity of disease for people with RP and QOL as it pertains to mental health, social support, disability resources, and financial factors. METHODS: This was a survey study conducted from June 2021 to February 2022 including 38 people with RP. QOL was assessed through a survey questionnaire focusing specifically on demographics, visual function, family, employment, social support, and mental health/well-being. Statistical analysis was conducted using a χ2 test for significance. RESULTS: A best corrected visual acuity (BCVA) of less than 20/200 (p = 0.0285) and living alone (p = 0.0358) were both statistically significant independent risk factors for experiencing depressive symptoms. Highest education level attained and unemployment rate were not found to be related to the development of depressive symptoms. Subjects had a higher unemployment rate (64% vs. US rate of 3.6%) and a high likelihood of reporting depressive symptoms (47.4%). CONCLUSION: People with RP are more likely to be unemployed and to develop depressive symptoms when compared to the general population. Similar to previous studies' findings, those with a BCVA of less than 20/200 were statistically more likely to experience depressive symptoms; living alone is a novel risk factor that is also associated with the presence of depressive symptoms. Contrary to prior findings, highest education level and unemployment status were found not to be related to the development of depressive symptoms. These patients may benefit from regular depression screenings and optional establishment of care with a psychiatrist or psychologist if they live alone or their BCVA is 20/200 or worse.

Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 & 6 inhibitors in patients with HR+, HER2- MBC in the real world.

PURPOSE: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear. METHODS: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression. RESULTS: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2. CONCLUSIONS: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment.

Treatment patterns and health care resource use in patients receiving multiple lines of therapy for metastatic squamous cell carcinoma of the head and neck in the United Kingdom.

This study evaluated the patterns of care and health care resource use (HCRU) in patients with metastatic squamous cell carcinoma of the head and neck (SCCHN) who received ≥3 lines of systemic therapy in the United Kingdom (UK). Oncologists (n = 40) abstracted medical records for patients with metastatic SCCHN who initiated third-line systemic therapy during 1 January 2011-30 August 2014 (n = 220). Patient characteristics, treatment patterns and SCCHN-related HCRU were summarised descriptively for the metastatic period; exploratory multivariable regression analyses were conducted on select HCRU outcomes. At metastatic diagnosis, most patients had an Eastern Cooperative Oncology Group performance status (PS) of 0/1 (95%). For patients with PS 0/1, the most common first-line treatment was cisplatin+5-fluorouracil (5-FU); docetaxel was the most common second- and third-line treatment. For patients with PS ≥ 2, the most common first-, second-, and third-line treatments were carboplatin+5-FU, cetuximab, and methotrexate, respectively. Most patients received supportive care during (85%) and after (89%) therapy. This study provides useful information, prior to the availability of immunotherapy, on patient characteristics, treatment patterns, HCRU, and survival in a real-world UK population with metastatic SCCHN receiving ≥3 lines of systemic therapy. Patterns of care and HCRU varied among patients with metastatic SCCHN; specific systemic therapies varied by patient PS.

Patient-reported pain and other quality of life domains as prognostic factors for survival in a phase III clinical trial of patients with advanced breast cancer.

BACKGROUND: Patient-reported outcomes have been associated with survival in numerous studies across cancer types, including breast cancer. However, the Brief Pain Inventory-Short Form (BPI-SF) and the Rotterdam Symptom Checklist (RSCL) have rarely been investigated in this regard in breast cancer. METHODS: Here we describe a post hoc analysis of the prognostic effect of baseline scores of these instruments on survival in a phase III trial of patients with advanced breast cancer who received gemcitabine plus paclitaxel or paclitaxel alone after anthracycline-based adjuvant or neoadjuvant therapy. The variables for this analysis were baseline BPI-SF "worst pain" and BPI-SF "pain interference" scores, and four RSCL subscales (each transformed to 0-100). Univariate and multivariate Cox models were used, the latter in the presence of 11 demographic/clinical variables. Kaplan-Meier curves and log-rank tests were used to compare survival for patients by BPI-SF or RSCL scores. RESULTS: Of 529 randomized patients, 286 provided BPI-SF data and 336 provided RSCL data at baseline. Univariate analyses identified BPI-SF worst pain and pain interference (both hazard ratios [HR], 1.07 for a 1-point increase; both p ≤ 0.0061) and three of four RSCL subscales [activity level, physical distress, and health-related quality of life (HRQOL) (HR, 0.86-0.91 for 10-point increase all p ≤ 0.0104)], to have significant prognostic effect for survival. BPI-SF worst pain (p = 0.0342) and RSCL activity level (p = 0.0004) were prognostic in the multivariate analysis. Median survival for patients categorized by BPI-SF worst pain score was 23.8 (n = 91), 17.9 (n = 94) and 14.6 (n = 94) months for scores 0, 1-4, and 5-10, respectively (log-rank p = 0.0065). Median survival was 23.8 and 14.6 months for patients (n = 330) with above- and below-median RSCL activity level scores respectively (log-rank p < 0.0001). CONCLUSION: Pretreatment BPI-SF worst pain and RSCL activity scores provide distinct prognostic information for survival in patients receiving paclitaxel or gemcitabine plus paclitaxel for advanced breast cancer even after controlling for multiple demographic and clinical factors. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00006459.

Impact of caregiver and parenting status on time trade-off and standard gamble utility scores for health state descriptions.

BACKGROUND: The purpose of this study was to examine the effect of caregiver status on time trade-off (TTO) and standard gamble (SG) health state utility scores. Respondents were categorized as caregivers if they reported that either children or adults depended on them for care. METHODS: This study was a secondary analysis of data from three studies in which general population samples rated health state descriptions. Study 1: UK; four osteoarthritis health states. Study 2: UK; three adult ADHD health states. Study 3: US; 16 schizophrenia health states. All three studies included time trade-off assessment. Study 1 also included standard gamble. Descriptive statistics were calculated to examine willingness to trade in TTO or gamble in SG. Utilities for caregivers and non-caregivers were compared using t-tests and ANCOVA models. RESULTS: There were 364 respondents including 106 caregivers (n = 30, 47, and 29 in Studies 1, 2, and 3) and 258 non-caregivers. Most caregivers were parents of dependent children (78.3%). Compared to non-caregivers, caregivers had more responses at the ceiling (i.e., utility = 0.95), indicating less willingness to trade time or gamble. All utilities were higher for caregivers than non-caregivers (mean utility difference between groups: 0.07 to 0.16 in Study 1 TTO; 0.03 to 0.17 in Study 1 SG; 0.06 to 0.10 in Study 2 TTO; 0.11 to 0.22 in Study 3 TTO). These differences were statistically significant for at least two health states in each study (p < 0.05). Results of sensitivity analyses with two caregiver subgroups (parents of dependent children and parents of any child regardless of whether the child was still dependent) followed the same pattern as results of the primary analysis. The parent subgroups were generally less willing to trade time or gamble (i.e., resulting in higher utility scores) than comparison groups of non-parents. CONCLUSIONS: Results indicate that caregiver status, including being a parent, influences responses in time trade-off health state valuation. Caregivers (i.e., predominantly parents) were less willing than non-caregivers to trade time, resulting in higher utility scores. This pattern was consistent across multiple health states in three studies. Standard gamble results followed similar patterns, but with less consistent differences between groups. It may be useful to consider parenting/caregiving status when collecting, interpreting, or using utility data because this demographic variable could influence results.

Comparison of demographics, treatment patterns, health care utilization, and costs among elderly patients with extensive-stage small cell and metastatic non-small cell lung cancers.

BACKGROUND: Limited data exist regarding real-world treatment patterns, resource utilization, and costs of extensive-stage small cell lung cancer (esSCLC) among elderly patients in the United States. While abundant data are available on treatment patterns in metastatic non-small cell lung cancer (mNSCLC), to our knowledge no data exist comparing costs and resource use between patients with esSCLC or mNSCLC. METHODS: We retrospectively analyzed administrative claims data (2000-2008) of patients aged ≥65 years from the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database. Patients were selected on the basis of having newly diagnosed esSCLC (n=5,855) or mNSCLC (n=24,090) during 1/1/2000-12/31/2005, and were required to have received cancer-directed therapy. Survival and other measures were compared between esSCLC and mNSCLC patients using Kaplan-Meier log-rank and univariate chi-square and t-tests. Study measures were followed from first diagnosis date of either esSCLC or mNSCLC until the earlier of death or end of the database. RESULTS: Survival between the cohorts did not differ significantly: mean of 10.4 months for esSCLC patients versus 11.1 months for mNSCLC; median survival was 7.4 months versus 5.9 months. A higher percentage of mNSCLC patients (vs. esSCLC) received radiation therapy (75.6% vs. 65.4%; P < 0.001) and surgery (13.6% vs. 7.8%; P < 0.001) during the metastatic disease period. Conversely, a higher percentage of esSCLC patients than mNSCLC patients received chemotherapy (85.5% vs. 60.3%; P < 0.001), red blood-cell transfusion (20.7% vs. 10.9%; P < 0.001), platelet transfusion (5.6% vs. 1.8%; P < 0.001), and growth-factor support (59.0% vs. 39.5%; P < 0.001). esSCLC patients incurred higher lifetime disease-related costs ($44,167 vs. $37,932; P < 0.001) and all-cause costs ($70,549 vs. $67,176; P < 0.001) than mNSCLC patients. CONCLUSIONS: Lifetime total and disease-related costs per patient were high. Increased use of chemotherapy, supportive care therapies (including growth factors), and disease-related hospitalizations were observed in esSCLC patients as compared with mNSCLC patients. Disease-related and all-cause costs for esSCLC also exceeded those of mNSCLC, except for hospice and skilled nursing services. Survival and per-patient costs for both groups underscore the unmet medical need for more effective therapies in patients with esSCLC or mNSCLC.

Using U.S. Medicare records to evaluate the indirect health effects on spouses: a case study in Alzheimer's disease patients.

BACKGROUND: The burden experienced by spouses of patients with Alzheimer's disease (AD) may have negative consequences for their physical health. We describe here a method for analyzing United States Medicare records to determine the changes in health service use and costs experienced by spouses after their marital partner receives an AD diagnosis. METHODS: We initially identified all beneficiaries in the 2001-2005 Medicare 5% sample who had multiple claims listing the ICD-9 diagnostic code for AD, 331.0. The 5% sample includes spouses who share a Medicare account with their marital partners because they lack a sufficient work history for full eligibility on their own. A matched cohort study assessed incremental health costs in the spouses of AD patients versus a control group of spouses of non-AD patients. Longitudinal and cross-sectional analyses tracked the impact of a patient's AD diagnosis on his or her spouse's healthcare costs. RESULTS: Our method located 54,593 AD patients of whom 11.5% had spouses identifiable via a shared Medicare account. AD diagnosis in one member of a couple was associated with significantly higher monthly Medicare payments for the other member's healthcare. The spouses' elevated costs commenced 2 to 3 months before their partners' AD diagnosis and persisted over the follow-up period. After 31 months, the cumulative additional Medicare reimbursements totaled a mean $4,600 in the spouses of AD patients. This excess was significant even after accounting for differences in baseline health status between the cohorts. CONCLUSION: The study methodology provides a framework for comprehensively evaluating medical costs of both chronically ill patients and their spouses. This method also provides monthly data, which makes possible a longitudinal evaluation of the cost effects of specific health events. The observed correlations provide a coherent demonstration of the interdependence between AD patients' and spouses' health. Future research should examine caregiving burden and other possible factors contributing to the AD spouses' health outcomes. It should also extend the method presented here to evaluations of other chronic diseases of the elderly.

Development of a disease-specific version of the EQ-5D-5L for use in patients suffering from psoriasis: lessons learned from a feasibility study in the UK.

OBJECTIVES: The EuroQol five-dimensional (EQ-5D) questionnaire is a generic measure widely used for the assessment of health status. Research has suggested that it may be insensitive to the burdens associated with particular conditions. This study was designed to explore the feasibility of developing and valuing a disease-specific "bolt-on" version of the EQ-5D questionnaire for use in psoriasis. METHODS: A series of steps were undertaken to develop, test, and evaluate dimensions for a psoriasis-specific version of the EQ-5D questionnaire (hereafter referred to as the EQ-PSO questionnaire). Candidate dimensions were explored through a review of published literature, in-depth qualitative interviews with patients, and consultation with a clinical expert. A psychometric validation exercise was then undertaken to establish how well dimensions functioned. Two dimensions were selected for inclusion in a draft measure alongside the existing EQ-5D questionnaire dimensions: "skin irritation" and "self-confidence." Last, a time trade-off valuation exercise was conducted with 300 members of the UK general public to derive utilities for health states described by the measure. RESULTS: The psychometric analyses indicated that the two new candidate dimensions captured additional variance over and above the existing five dimensions. Data from the valuation exercise were analyzed by using different models. A collapsed random effects model was put forward as a parsimonious and accurate approach. Based on this model, estimated utilities ranged from 0.98 ± 0.02 for state "1111111" to 0.03 ± 0.29 for state "5555555." CONCLUSIONS: This study has developed the EQ-PSO questionnaire to support future psoriasis research and has informed the development of future bolt-on versions of the EQ-5D questionnaire.

Relationship between financial impact and coverage of drugs in Australia.

OBJECTIVES: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). METHODS: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. RESULTS: Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to

Clinical and Genomic Characteristics of Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors.

PURPOSE: We explored the clinical and genomic characteristics of hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (MBC) after progression on cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6i) ± endocrine therapy (ET) to understand potential resistance mechanisms that may aid in identifying treatment options. EXPERIMENTAL DESIGN: Patients in the United States with HR+, HER2- MBC had tumor biopsies collected from a metastatic site during routine care following progression on a CDK4 and 6i ± ET (CohortPost) or prior to initiating CDK4 and 6i treatment (CohortPre) and analyzed using a targeted mutation panel and RNA-sequencing. Clinical and genomic characteristics were described. RESULTS: The mean age at MBC diagnosis was 59 years in CohortPre (n = 133) and 56 years in CohortPost (n = 223); 14% and 45% of patients had prior chemotherapy/ET, and 35% and 26% had de novo stage IV MBC, respectively. The most common biopsy site was liver (CohortPre, 23%; CohortPost, 56%). CohortPost had significantly higher tumor mutational burden (TMB; median 3.16 vs. 1.67 Mut/Mb, P < 0.0001), ESR1 alteration frequency (mutations: 37% vs. 10%, FDR < 0.0001; fusions: 9% vs. 2%, P = 0.0176), and higher copy-number amplification of genes on chr12q15, including MDM2, FRS2, and YEATS4 versus patients in the CohortPre group. In addition, CDK4 copy-number gain on chr12q13 was significantly higher in CohortPost versus CohortPre (27% vs. 11%, P = 0.0005). CONCLUSIONS: Distinct mechanisms potentially associated with resistance to CDK4 and 6i ± ET, including alterations in ESR1 and amplification of chr12q15 and CDK4 copy-number gain, were identified.

Differences among formulary submission guidelines: implications for health technology assessment.

OBJECTIVES: This article provides a detailed understanding of the differences in selected formulary submission guidelines supplied by various health technology assessment (HTA) agencies and indicates how these differences can impact the evidence base used to populate the HTA. METHODS: Detailed summaries of the recommended methods for evidence generation, organized by topic areas relevant for clinical and economic data, for twelve countries in Europe, North America, and Australia where HTA processes are well developed were prepared. Using these summaries, we provide examples of the likely impact these differences in recommended methods could have on the evidence base used to evaluate new health technologies. RESULTS: Areas where recommendations differed included methodologies for systematic literature reviews (e.g., preferred databases and study designs for inclusion); selection of appropriate comparators; guidance on critical appraisal and synthesis of clinical evidence; appropriate sources for health value measures, resource use, and cost data; and approaches to uncertainty analyses. Performing literature searches that capture all relevant studies and then creating subsets of the literature based on a listing of country-specific requirements could allow for direct comparison of the evidence bases associated with the different guidelines. CONCLUSIONS: If the formulary submission guidelines were followed as written, different (although overlapping) bodies of evidence likely would be generated for each country, which could contribute to disparate assessments and recommendations. This comparison of the formulary submission guidelines could contribute to an understanding of why clinical and reimbursement decisions vary across countries.

Clinical Characteristics, Treatments, and Concurrent Mutations in Non-Small Cell Lung Cancer Patients With NF1 Mutations.

OBJECTIVES: Metastatic non-small cell lung cancer (mNSCLC) is characterized by complex genomic alterations. NF1 mutations may confer distinct clinical characteristics within NSCLC, and real-world evidence on concurrent mutations, treatment patterns, and health outcomes is lacking. MATERIALS AND METHODS: This retrospective study was performed in patients with mNSCLC treated in the Flatiron Health network who underwent the FoundationOne tumor-sequencing. Anticancer therapies, concurrent mutations, real-world progression-free survival (rwPFS), and overall survival (OS) were assessed. RESULTS: Of the 1663 patients, 103 patients were identified with NF1 mutation. Concurrent mutations with Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (16.5%) and epidermal growth factor receptor fusion (6.8%) were the most frequent. In patients with NF1 mutation only (n = 57), 42% were women, 86% patients had smoking history, and 70% had non-squamous cell carcinoma type. Most (51%) of the patients with NF1 mutations received a single line of therapy versus other mutations and the overall treated population (44%). Platinum-based chemotherapy was the predominant first-line therapy, with programmed cell death-1/programmed cell death-ligand-1 inhibitors as subsequent lines of therapy. The NF1 mutation only group had numerically the shortest median rwPFS (82 days) than other mutation groups. Median OS for the NF1 mutation group in first, second, and third lines of therapy was 321, 498, and 210 days, respectively. CONCLUSIONS: NF1 mutations confer distinct clinical characteristics in patients with mNSCLC. These patients may have different trajectories for progression and survival than seen for other mutations, experience less systemic therapy after first-line therapy, and may have shorter survival.

Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer.

OBJECTIVE: This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States. METHODS: De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan-Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS). RESULTS: The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%. CONCLUSIONS: This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy.

Reliability of Conclusions from Early Analyses of Real-World Data for Newly Approved Drugs in Advanced Gastric Cancer in the United States.

BACKGROUND: As real-world data resources expand and improve, there will increasingly be opportunities to study the effectiveness of interventions. There is a need to ensure that study designs explore potential sources of bias and either acknowledge or mitigate them, in order to improve the accuracy of findings. The objective of this study was to understand newly approved drug utilization patterns in real-world clinical settings over time. METHODS: This retrospective study included three sources of real-world data (claims, electronic health records, and recoded data from a quality care program) collected from patients diagnosed with gastric cancer who initiated therapy with either trastuzumab or ramucirumab. Linear regression was used to investigate trends in the use of these drugs for the care of patients with gastric cancer over time from Food and Drug Administration (FDA) approval. RESULTS: Eligible patients (n=1700) had consistent demographic and clinical characteristics over time. After regulatory approval, trastuzumab was used in later lines of therapy and then shifted to earlier lines (p=0.002), while ramucirumab utilization remained consistent over time after FDA approval (p=0.49). Ramucirumab augmentation, defined as the addition of the drug after initiation of a line of therapy, decreased over time (p=0.03), and trastuzumab augmentation remained consistent over time (p=0.58). CONCLUSION: Since treatment effectiveness may change across lines of treatment, bias may arise if there are changes in the use of the drug (such as line migration) during the time period of analysis using real-world data.

The relationship between Eastern Cooperative Oncology Group performance status and healthcare resource utilization among patients with advanced or metastatic colorectal, lung or gastric cancer.

AIMS: The ability of a patient to receive anti-cancer treatment depends on a variety of factors, including performance status (PS), which is typically measured using the Eastern Cooperative Oncology Group (ECOG) scale. This study hypothesized that there would be a strong and positive correlation between ECOG PS values and healthcare resource utilization (HCRU) and a strong and negative correlation with the use of anti-cancer therapy. MATERIALS AND METHODS: Patients with colorectal, lung or gastric cancer were included in this retrospective analysis of administrative claims data linked to electronic medical records (EMR). All-cause HCRU (hospitalization/inpatient care, emergency room visits, systemic anti-cancer therapy, radiation therapy, outpatient physician visits, hospice, home health care and key supportive care treatments such as anti-emetics, hematopoietic treatments, transfusions, and durable medical equipment) was evaluated by baseline ECOG PS value and PS over time. Adjusted multivariable regression analysis was used to assess the relationship between baseline ECOG PS and HCRU. Regression analyses were conducted to explore the relationship between other baseline variables and HCRU. RESULTS: There were 1311 patients included in this study. There was low correlation between PS and any HCRU variable or receipt of anti-cancer therapy (correlation coefficients all <0.10). In regression analyses, the proportion of patients with poor PS (PS = 2+) who were hospitalized was not significantly different from those with good PS (PS = 0/1) (28.9% versus 19.3%, p = .07). LIMITATIONS: The low rate of reporting of PS and the small sample size of patient groups in this study. CONCLUSIONS: There is very little evidence of a relationship between ECOG PS and HCRU, ECOG PS, or anti-cancer therapy in this study, in part due to low rates of and lack of variability in reported PS. There is some evidence that baseline comorbidities were significantly associated with HCRU and should be accounted for in future research evaluating HCRU.

A simple and reliable method for determination of optimum pH in coupled enzyme assays.

Determination of the optimum pH in a coupled enzyme assay poses significant challenges because altering the pH of the reaction mixture can affect the performance of both enzymes. Here, we demonstrate a simple and reliable method to determine the pH optimum for pyruvate kinase using the pyruvate kinase/lactate dehydrogenase coupled enzyme assay. This simple and reliable method can be broadly adapted to determine the pH optimum for various enzymes that are assayed using a coupled enzyme assay.

Value of clinical trial narrative data to estimate the costs of adverse event management: a feasibility study.

Aims: The objective of this feasibility study was to determine the extent to which data from randomized controlled trials (RCTs) may serve as a useful source for collecting health care resource use (HCRU) for the purposes of estimating costs of managing adverse events (AEs), specifically, grade 3-4 nausea and thrombocytopenia, which may be experienced during chemotherapy treatment.Materials and Methods: The feasibility study was conducted in four steps: (1) HCRU data were extracted from patient narratives in four phase 3 RCTs in non-small cell lung cancer; (2) missing HCRU data were imputed; (3) unit costs were applied to the resulting HCRU data set and costs of managing AEs were estimated; and (4) the overall utility of using RCT data as a source for estimating costs of AEs was evaluated.Results: 33 nausea and 68 thrombocytopenia AEs met eligibility criteria and were evaluated in this study. Medication usage was recorded as a treatment in 76% of nausea AEs, although only 14% of the instances of medication usage included the minimum data elements required for costing. Platelet transfusions were provided in 24% of thrombocytopenia AEs; however, in only one instance were the minimum data elements recorded. Of nausea and thrombocytopenia AEs, 18% and 72%, respectively, required no missing data assumptions or imputation.Limitations: Only two AEs were considered, and they may not be representative of all AEs in terms of suitability for use in estimating HCRU and costs of managing AEs. Not all grade 3-4 AEs met the criteria for requiring a patient narrative. HCRU data in the narratives were incomplete.Conclusions: The usefulness of RCTs for estimating the costs of AEs may be improved by using a standardized form to collect HCRU data for key AEs, including an appropriate level of detail required to estimate costs of managing the AEs.

Occurrence and Characteristics of Hospitalizations During First-Line Chemotherapy Among Individuals with Metastatic Colorectal Cancer.

OBJECTIVE: Choosing chemotherapy for metastatic colorectal cancer (mCRC) requires balancing clinical effectiveness and risk of complications. This study characterized real-world inpatient/emergency department (ED) hospitalizations during first-line chemotherapy among individuals with mCRC. METHODS: This retrospective cohort study used data from medical and pharmacy claims. All patients had mCRC with ≥1 claim for ≥1 of the 5 most frequently utilized first-line chemotherapy agents (fluorouracil, oxaliplatin, bevacizumab, irinotecan, capecitabine). The main outcome was all-cause hospitalizations (inpatient or ED setting) identified from claims via ICD-9/10-CM coding from index date until 30 days after the end of first-line chemotherapy or last available data. RESULTS: A total of 717 individuals (mean age 55 years; 58% male; ECOG 0/1/2+/missing in 44%/39%/6%/11%; median follow-up 116 days) met study criteria. Thirty-four distinct chemotherapy regimens were used. Overall, 40% of patients had ≥1 hospitalization (n=285; total 415 hospitalizations); 12% (n=85) had ≥2 hospitalizations. The median time to first hospitalization was 52 days; median inpatient length of stay was 4 days; infections/neutropenia (21%) and bowel-related complications (17%) were the most common issues associated with inpatient hospitalizations. In univariate analyses, insurance plan type, geographical location, ECOG, and renal disease were associated with hospitalization. In multivariable analyses, ECOG ≥1 was associated with a 67% increase (p<0.01) in the odds of hospitalization vs ECOG= 0. CONCLUSION: Approximately 40% of patients with mCRC were hospitalized during the study period. Hospital stays were typically short. Further research is needed to determine how many of these hospitalizations may be avoidable. We also observed a large amount of variation in regimens used in the first-line setting.

Ramucirumab in the second-line for patients with hepatocellular carcinoma and elevated alpha-fetoprotein: patient-reported outcomes across two randomised clinical trials.

BACKGROUND: Symptoms of advanced hepatocellular carcinoma (HCC) represent a substantial burden for the patient and are important endpoints to assess when evaluating treatment. Patient-reported outcomes were evaluated in subjects with advanced HCC and baseline alpha-fetoprotein (AFP) ≥400 ng/mL treated with second-line ramucirumab. PATIENTS AND METHODS: Patients with AFP≥400 ng/mL enrolled in the REACH or REACH-2 phase 3 studies were used in this analysis. Eligible patients had advanced HCC, Child-Pugh A, Eastern Cooperative Oncology Group performance status 0/1 and prior sorafenib. Patients received ramucirumab 8 mg/kg or placebo once every 2 weeks. Disease-related symptoms and health-related quality of life (HRQoL) were assessed with the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL-5-Dimensions (EQ-5D) instruments, respectively. Time to deterioration (TTD) (≥3-point decrease in FHSI-8 total score;≥0.06-point decrease in EQ-5D score, from randomisation to first date of deterioration) was determined using Kaplan-Meier estimation and the Cox proportional hazards model. Both separate and pooled analyses for REACH AFP≥400 ng/mL and REACH-2 patients were conducted. RESULTS: In the pooled population with AFP ≥400 ng/mL (n=542; ramucirumab, n=316; placebo, n=226), median TTD in FHSI-8 total score was prolonged with ramucirumab relative to placebo (3.3 vs 1.9 months; HR 0.725; (95% CI 0.559 to 0.941); p=0.0152), including significant differences in back pain (0.668; (0.497 to 0.899); p=0.0044), weight loss (0.699; (0.505 to 0.969); p=0.0231) and pain (0.769; (0.588 to 1.005); p=0.0248) symptoms. TTD in EQ-5D score was not significantly different between ramucirumab and placebo groups (median 2.9 vs 1.9 months). Results in the individual trials were consistent with these findings. CONCLUSIONS: Ramucirumab in second-line treatment of advanced HCC demonstrates consistent benefit in the delay of deterioration in disease-related symptoms with no worsening of HRQoL. Taken with previously demonstrated ramucirumab-driven survival benefits in this setting, these data may inform patient-clinician discussions about the benefit-risk profile of this therapy. TRIAL REGISTRATION NUMBER: NCT01140347; NCT02435433, NCT02435433.