Cost-Effectiveness Analysis for Therapy Sequence in Advanced Cancer: A Microsimulation Approach with Application to Metastatic Prostate Cancer.

PURPOSE: Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. We developed a general microsimulation framework to study therapy sequence and applied it to metastatic prostate cancer. METHODS: We constructed a discrete-time state transition model to study 2 lines of therapy. Using digitized published survival curves (progression-free survival, time to progression, and overall survival [OS]), we inferred event types (progression or death) and estimated transition probabilities using cumulative incidence functions with competing risks. We incorporated within-patient dependence over time; first-line therapy response informed subsequent event probabilities. Parameters governing within-patient dependence calibrated the model-based results to a target clinical trial. We applied these methods to 2 therapy sequences for metastatic prostate cancer, wherein both docetaxel (DCT) and abiraterone acetate (AA) are appropriate for either first- or second-line treatment. We assessed costs and quality-adjusted life-years (5-y QALYs) for 2 treatment strategies: DCT → AA versus AA → DCT. RESULTS: Models assuming within-patient independence overestimated OS time, which corrected with the calibration approach. With generic pricing, AA → DCT dominated DCT → AA, (higher 5-y QALYs and lower costs), consistent for all values of calibration parameters (including no correction). Model calibration increased the difference in 5-y QALYs between treatment strategies (0.07 uncorrected v. 0.15 with base-case correction). Applying the correction decreased the estimated difference in cost (-$5,360 uncorrected v. -$3,066 corrected). Results were strongly affected by the cost of AA. Under a lifetime horizon, AA → DCT was no longer dominant but still cost-effective (incremental cost-effectiveness ratio: $19,463). CONCLUSIONS: We demonstrate a microsimulation approach to study the cost-effectiveness of therapy sequences for advanced prostate cancer, taking care to account for within-patient dependence. HIGHLIGHTS: We developed a discrete-time state transition model for studying therapy sequence in advanced cancers.Results are sensitive to dependence within patients.A calibration approach can introduce dependence across lines of therapy and closely match simulation outcomes to target trial outcomes.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

An Evaluation of Regional Cardiovascular Disease and Cancer Research Needs Using Conference Abstracts.

Background: Despite cardiovascular diseases and cancer being the leading causes of premature mortality in the Caribbean region, there is limited local research available to guide a comprehensive response to this epidemic. Objective: To evaluate cardiovascular disease and cancer research in the Caribbean using abstracts presented at the Caribbean Public Health Agency's (CARPHA) meeting - the longest running annual research conference in the region. Method: Study data (population, intervention/exposure, comparison and outcome) were extracted from abstracts published for the 2006 to 2018 meetings. Additionally, institutional affiliation and geographic location of the first author, countries involved, sample size, study design and use of specialized testing/biomarkers were also extracted. Data were analysed using STATA version 14. Findings: A total of 1,512 abstracts, 728 posters and 784 oral presentations were reviewed. Research on cancer and cardiovascular disease comprised approximately 15% of all abstracts published annually over the review period. Most of the cardiovascular disease studies had cross sectional or survey designs (46%), with very few laboratory-based studies (<2%) and no intervention studies/clinical trials. For cancer research, 30% were cross-sectional studies/audits, 11% were case control studies, 5% were lab based and there were no clinical trials. Almost a quarter of the cardiovascular disease / cancer abstracts over the period originated from Trinidad and Tobago (26%), with Jamaica and Barbados contributing 18% and 15% respectively. Conclusion: These finding highlight the need for additional studies that can provide evidence for interventions and policy to address the region's high cardiovascular disease and cancer burden. A Regional Centre of Research Excellence could support capacity development to facilitate this process.

A cross-sectional analysis of investigator needs for non-communicable disease research at the University of the West Indies, Mona.

OBJECTIVE: To describe the needs of academic staff conducting non-communicable disease (NCD) research at the University of the West Indies, Mona Campus in Jamaica. METHODS: Utilizing a cross-sectional design an online survey was created using the research electronic data capture application (REDCap); it was disseminated via email to 708 academic staff members in the Faculties of Medical Sciences and Science & Technology between September and November 2018. Participants were asked to indicate their level of access to expertise, training and equipment for conducting research. Descriptive analysis was conducted using STATA version 14. RESULTS: Most respondents were women (74.2%), predominantly scientists (33.1%) or specialist physicians (22.6%). Less than 2/3 of respondents reported publishing research findings in peer reviewed journals, with a quarter not disseminating their research findings in any medium. Resources for field research/data collection, epidemiological methods and principles, and data management/data analysis were generally available. However, there was limited access to training, expertise and equipment in emerging techniques for NCD research such as metabolomics, bioinformatics/analysis of large-scale data sets and health economics. Additional challenges included limited access to financing for research, inadequate workspace and poor administrative support for conducting research. CONCLUSIONS: There is a need for more local research seed funding, stronger administrative support for researchers, and opportunities for training in cutting edge NCD research techniques. Jamaican researchers could benefit from being part of a regional research centre of excellence with critical research skills and equipment that builds research networks and strengthens the NCD research response.

A cross-sectional analysis of investigator needs for non-communicable disease research at the University of the West Indies, Mona / Análisis transversal de las necesidades de los investigadores de las enfermedades no transmisibles en la Universidad de las Indias Occidentales en Mona / Uma análise transversal das carências dos pesquisadores envolvidos em pesquisa de doenças não transmissíveis na Universidade das Índias Ocidentais, Mona

ABSTRACT Objective. To describe the needs of academic staff conducting non-communicable disease (NCD) research at the University of the West Indies, Mona Campus in Jamaica. Methods. Utilizing a cross-sectional design an online survey was created using the research electronic data capture application (REDCap); it was disseminated via email to 708 academic staff members in the Faculties of Medical Sciences and Science & Technology between September and November 2018. Participants were asked to indicate their level of access to expertise, training and equipment for conducting research. Descriptive analysis was conducted using STATA version 14. Results. Most respondents were women (74.2%), predominantly scientists (33.1%) or specialist physicians (22.6%). Less than 2/3 of respondents reported publishing research findings in peer reviewed journals, with a quarter not disseminating their research findings in any medium. Resources for field research/data collection, epidemiological methods and principles, and data management/data analysis were generally available. However, there was limited access to training, expertise and equipment in emerging techniques for NCD research such as metabolomics, bioinformatics/analysis of large-scale data sets and health economics. Additional challenges included limited access to financing for research, inadequate workspace and poor administrative support for conducting research. Conclusions. There is a need for more local research seed funding, stronger administrative support for researchers, and opportunities for training in cutting edge NCD research techniques. Jamaican researchers could benefit from being part of a regional research centre of excellence with critical research skills and equipment that builds research networks and strengthens the NCD research response.

RESUMEN Objetivo. Describir las necesidades del personal académico que investiga las enfermedades no transmisibles (ENT) en el Campus de Mona de la Universidad de las Indias Occidentales, en Jamaica. Métodos. Mediante un diseño transversal, se elaboró una encuesta en línea con RedCap, una aplicación para la captura de datos electrónicos para la investigación, y se divulgó por correo electrónico a los 708 miembros del personal académico de las Facultades de Ciencias Médicas y Ciencia y Tecnología entre septiembre y noviembre del 2018. Se pidió a los participantes que indicaran su nivel de acceso a conocimientos, capacitación y equipo para llevar a cabo investigaciones. El análisis descriptivo se realizó con STATA, versión 14. Resultados. La mayoría de los entrevistados fueron mujeres (74,2%), predominantemente científicas (33,1%) o médicas especialistas (22,6%). Menos de dos terceras partes de los entrevistados informó que publicaban los resultados de sus investigaciones en revistas arbitradas y una cuarta parte declaró que no divulgaba los resultados de sus investigaciones en ningún medio. Por lo general, tenían a su disposición recursos para la investigación de campo o la recopilación de datos, métodos y principios epidemiológicos, así como para la gestión y el análisis de datos. Sin embargo, tenían poco acceso a conocimientos, capacitación y equipo en las técnicas emergentes para la investigación sobre ENT como la metabolómica, la bioinformática o el análisis de conjuntos de datos a gran escala y economía de la salud. Otros retos incluyeron poco acceso al financiamiento para la investigación, espacios de trabajo inadecuados y un apoyo administrativo deficiente para investigar. Conclusiones. Se necesita más capital inicial destinado a la investigación local, un mayor respaldo administrativo a los investigadores y oportunidades de capacitación en las técnicas más recientes de investigación de ENT. Los investigadores jamaiquinos podrían sacar provecho de formar parte de un centro regional de excelencia para la investigación con el equipo y las capacidades de investigación fundamentales para contribuir a la formación de redes de investigación y fortalecer la respuesta investigadora a las ENT.

RESUMO Objetivo. Descrever as carências enfrentadas pelo grupo acadêmico que realiza pesquisa em doenças não transmissíveis (DNT) na Universidade das Índias Ocidentais, campus de Mona, Jamaica. Métodos. Uma pesquisa transversal online foi desenvolvida com o uso da plataforma de captura eletrônica de dados de pesquisa (RedCap) e distribuída por e-mail a 708 integrantes dos grupos acadêmicos nas Faculdades de Ciências Médicas e de Ciência e Tecnologia entre setembro e novembro de 2018. Foi pedido aos participantes que informassem o grau de acesso a conhecimento especializado, capacitação e equipamentos para a realização de pesquisa. Uma análise descritiva foi realizada com o uso do software STATA versão 14. Resultados. Participaram, na sua maioria, mulheres (74,2%), com o predomínio de pesquisadores científicos (33,1%) ou médicos especialistas (22,6%). Menos de 2/3 informaram publicar os resultados de suas pesquisas em periódicos científicos com avaliação por pares e 25% disseram que não divulgavam seus resultados em nenhum veículo. Afirmaram que, em geral, havia recursos para realizar pesquisa de campo/coleta de dados, métodos e procedimentos básicos epidemiológicos e gerenciamento/análise de dados. Porém, era limitado o acesso a capacitação, conhecimentos especializados e equipamentos para empregar métodos emergentes de pesquisa de DNT como metabolômica, bioinformática/processamento em larga escala de grandes conjuntos de dados e economia da saúde. Outras dificuldades citadas foram limitação de financiamento para pesquisa, inadequação dos locais de trabalho e apoio administrativo deficiente à realização de pesquisas. Conclusões. Faz-se necessário mais financiamento para projetos iniciantes locais, firme apoio administrativo aos pesquisadores e oportunidades para capacitação em métodos de ponta de pesquisa de DNT. A situação dos pesquisadores jamaicanos poderia melhorar se fizessem parte de um centro de excelência regional com recursos e equipamentos essenciais para a realização de pesquisa que lhes permitisse formar redes de pesquisadores e fortalecer a resposta da pesquisa de DNT.

Cost-effectiveness of surveillance with CT colonography after resection of colorectal cancer.

OBJECTIVE: Surveillance following colorectal cancer (CRC) resection uses optical colonoscopy (OC) to detect intraluminal disease and CT to detect extracolonic recurrence. CT colonography (CTC) might be an efficient use of resources in this situation because it allows for intraluminal and extraluminal evaluations with one test. DESIGN: We developed a simulation model to compare lifetime costs and benefits for a cohort of patients with resected CRC. Standard of care involved annual CT for 3 years and OC for years 1, 4 and every 5 years thereafter. For the CTC-based strategy, we replace CT+OC at year 1 with CTC. Patients with lesions greater than 6 mm detected by CTC underwent OC. Detection of an adenoma 10 mm or larger was followed by OC at 1 year, then every 3 years thereafter. Test characteristics and costs for CTC were derived from a clinical study. Medicare costs were used for cancer care costs as well as alternative test costs. We discounted costs and effects at 3% per year. RESULTS: For persons with resected stage III CRC, the standard-of-care strategy was more costly (US$293) and effective (2.6 averted CRC cases and 1.1 averted cancer deaths per 1000) than the CTC-based strategy, with an incremental cost-effectiveness ratio of US$55 500 per quality-adjusted life-year gained. Our analysis was most sensitive to the sensitivity of CTC for detecting polyps 10 mm or larger and assumptions about disease progression. CONCLUSION: In a simulation model, we found that replacing the standard-of-care approach to postdiagnostic surveillance with a CTC-based strategy is not an efficient use of resources in most situations.

Cost-effectiveness of abiraterone versus docetaxel in the treatment of metastatic hormone naïve prostate cancer.

PURPOSE: Prostate cancer is the second leading cause of cancer death in men in the US. Since 2015, landmark studies have demonstrated improved survival outcomes with the use of docetaxel (DCT) or abiraterone (AA) in addition to androgen deprivation therapy (ADT) in the metastatic hormone-naïve setting. These treatment strategies have not been prospectively compared but have similar overall survival benefits despite differing mechanisms of action, toxicity, and cost. We performed a cost-effectiveness analysis to provide insight into the value of AA vs. DCT in the first-line treatment of metastatic prostate cancer. MATERIALS AND METHODS: We developed Markov models by using a US-payer perspective and a 3-year time horizon to estimate costs (2018 US$) and progression-free quality-adjusted life years (PF-QALYs) for ADT alone, DCT, and AA. Health states were defined as initial state, treatment states according to experience of an adverse event, and progressed disease/death. State transition probabilities were derived from rates for drug discontinuation, frequency of adverse events, disease progression, and death from the randomized phase III trials ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) and LATITUDE. Univariate and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. RESULTS: DCT resulted in an increase of 0.32 PF-QALYs and $16,100 in cost and AA resulted in an increase of 0.52 PF-QALYs and $215,800 in cost compared to ADT alone. The incremental cost-effectiveness ratio for DCT vs. ADT was $50,500/PF-QALY and for AA vs. DCT was $1,010,000/PF-QALY. Probabilistic sensitivity analysis demonstrated that at a willingness-to-pay threshold of $150,000/PF-QALY AA was highly unlikely to be cost-effective. CONCLUSION: DCT is substantially more cost-effective than AA in the treatment of metastatic hormone naïve prostate cancer.

Temporal trends and characteristics of clinical trials for which only one racial or ethnic group is eligible.

BACKGROUND: Increasing diversity in clinical trials may be worthwhile. We examined clinical trials that restricted eligibility to a single race or ethnicity. METHODS: We reviewed 19,246 trials registered on ClinicalTrials.gov through January 2013. We mapped trial ZIP-codes to U.S. Census and American Community Survey data. The outcome was whether trials required participants to be from a single racial or ethnic group. RESULTS: In adjusted analyses, the odds of trials restricting eligibility to a single race/ethnicity increased by 4% per year (95% CI 1.01-1.08, p = .024). Behavioral (5.79% with single race/ethnicity requirements), skin-related (4.49%), and Vitamin D (6.14%) studies had higher rates of single race/ethnicity requirements. Many other trial-specific characteristics, such as funding agency and region of the U.S. in which the trial opened, were associated with eligibility restrictions. In terms of neighborhood characteristics, studies with single race eligibility requirements were more likely to be located in ZIP-codes with greater percentages of those self-reporting the characteristic. For example, 35.2% (SD = 24.9%) of the population self-reported themselves as Black or African American in ZIP-codes with trials requiring participants to be Black/African American, but only 5.9% (SD = 6.9%) self-reported themselves as Black/African American in ZIP-codes with trials that required Asian ethnicity. In ZIP-codes with trials requiring Asian ethnicity, 24.6% (SD = 16.2%) self-reported as Asian. In ZIP-codes with trials requiring Hispanic/Latino ethnicity, 33.3% (SD = 28.5%) self-reported as Hispanic/Latino. Neighborhood level poverty rates and reduced English language ability were also associated with more single race eligibility requirements. CONCLUSIONS: In selected fields, there has been a modest temporal increase in single race/ethnicity inclusion requirements. Some studies may not fall under regulatory purview and hence may be less likely to include diverse samples. Conversely, some eligibility requirements may be related to health disparities research. Future work should examine whether targeted enrollment criteria facilitates development of personalized medicine or reduces trial access.

Yield and Cost-effectiveness of Computed Tomography Colonography Versus Colonoscopy for Post Colorectal Cancer Surveillance.

Purpose. As part of a clinical trial comparing the utility of computed tomographic colonography (CTC) and optical colonoscopy (OC) for post colorectal cancer resection surveillance, we explored the diagnostic yield and costs of a strategy of CTC followed by OC if a polyp is observed (abbreviated CTC_S), versus OC 1 year following curative bowel resection, using the detection of actionable polyps on OC as the criterion. Methods. Using data from 231 patients who underwent same-day CTC followed by OC, we created a decision tree that outlined the choices and outcomes at 1-year clinical follow-up. Colorectal polyp prevalence, sensitivity, and specificity of CTC were compared with five exemplary studies and meta-analyses. Detection criteria were derived for ≥6 mm or ≥10 mm polyps. OC was the gold standard. Costs were gleaned from cataloging components of the cases at the principal investigator's institution. Analyses included marginal cost of the OC strategy to detect additional actionable polyps and number of polyps missed per 10,000 patients. Results. At our prevalence of 0.156 for ≥6 mm (0.043 ≥10 mm), CTC_S would miss 779 ≥6 mm actionable polyps per 10,000 patients (≥10 mm: 173 per 10,000). Cost to detect an additional ≥6 mm polyp in this cohort is $5,700 (≥10 mm: $28,000). Sensitivity analyses demonstrate that any improvement in performance characteristics would raise the cost of OC to detect more actionable polyps. Similar results were seen using Medicare costs, or when literature values were used for performance characteristics. Conclusion. At an action threshold of ≥6 mm, OC costs at least $5,700 per extra polyp detected relative to CTC_S in patients undergoing surveillance after colorectal cancer surgery, on the order of incremental cost-effectiveness ratios found for other clinical problems involving short-term events.

Overtreatment and Cost-Effectiveness of the See-and-Treat Strategy for Managing Cervical Precancer.

BACKGROUND: See-and-treat using loop electrosurgical excision procedure (LEEP) has been recommended as an alternative in managing high-grade cervical squamous intraepithelial lesions, but existing literature lacks evidence of the strategy's cost-effectiveness. We evaluated the overtreatment and cost-effectiveness of the see-and-treat strategy compared with usual care. METHODS: We modeled a hypothetical cohort of 40-year-old females who had not been screened for cervical cancer and followed them through their lifetimes using a Markov model. From a U.S. health-system perspective, the analysis was conducted in 2012 dollars and measured effectiveness in quality-adjusted life-years (QALY). We estimated incremental cost-effectiveness ratios (ICER) using a willingness-to-pay threshold of $50,000/QALY. The robustness of the see-and-treat strategy's cost-effectiveness and its overtreatment rates were further examined in various sensitivity analyses. RESULTS: In the base-case, the see-and-treat strategy yielded an ICER of $70,774/QALY compared with usual care. For most scenarios in the deterministic sensitivity analysis, this strategy had ICERs larger than $50,000/QALY, and its cost-effectiveness was sensitive to the disutility of LEEP treatment and biopsy-directed treatment adherence under usual care. Probabilistic sensitivity analysis showed that the see-and-treat strategy had a 50.1% chance to be cost-effective. It had an average overtreatment rate of 7.1% and a 78.8% chance to have its overtreatment rate lower than the 10% threshold. CONCLUSION: The see-and-treat strategy induced an acceptable overtreatment rate. Its cost-effectiveness, compared with usual care, was indiscriminating at the chosen willingness-to-pay threshold but much improved when the threshold increased. IMPACT: The see-and-treat strategy was reasonable for particular settings, that is, those with low treatment adherence. Cancer Epidemiol Biomarkers Prev; 25(5); 807-14. ©2016 AACR.

High prevalence of discordant human papillomavirus and p16 oropharyngeal squamous cell carcinomas in an African American cohort.

BACKGROUND: Most studies on human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) have been performed on white Americans. Our study examined the incidence of HPV in an African American oropharyngeal SCC cohort and its survival. METHODS: African American patients with oropharyngeal SCC in a combined tumor registry were identified. HPV16 testing was performed by polymerase chain reaction (PCR) from DNA extracted from tumor blocks. The p16 staining was performed using standard immunohistochemistry. RESULTS: Forty-four patients were identified for analysis. Seventy-three percent of the tumors were HPV-positive. Only 39% of the patients who were HPV-positive were also p16-positive. Survival between all 3 tumor types, patients who tested HPV-positive/p16, HPV-positive/p16-positive, and HPV-negative/p16-negative was significantly different (p = .03). HPV/p16 status was significant on univariate and multivariate analysis. CONCLUSION: HPV oropharyngeal SCC is strongly present in this African American cohort. Two thirds of the patients who were HPV-positive were p16-negative. Greater study is needed to explain the high p16 negativity among this HPV-positive oropharyngeal SCC African American cohort. © 2015 Wiley Periodicals, Inc. Head Neck 38: E867-E872, 2016.

Time to Surgery and Breast Cancer Survival in the United States.

IMPORTANCE: Time to surgery (TTS) is of concern to patients and clinicians, but controversy surrounds its effect on breast cancer survival. There remains little national data evaluating the association. OBJECTIVE: To investigate the relationship between the time from diagnosis to breast cancer surgery and survival, using separate analyses of 2 of the largest cancer databases in the United States. DESIGN, SETTING, AND PARTICIPANTS: Two independent population-based studies were conducted of prospectively collected national data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database and the National Cancer Database (NCDB). The SEER-Medicare cohort included Medicare patients older than 65 years, and the NCDB cohort included patients cared for at Commission on Cancer-accredited facilities throughout the United States. Each analysis assessed overall survival as a function of time between diagnosis and surgery by evaluating 5 intervals (≤30, 31-60, 61-90, 91-120, and 121-180 days) and disease-specific survival at 60-day intervals. All patients were diagnosed with noninflammatory, nonmetastatic, invasive breast cancer and underwent surgery as initial treatment. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival as a function of time between diagnosis and surgery, after adjusting for patient, demographic, and tumor-related factors. RESULTS: The SEER-Medicare cohort had 94 544 patients 66 years or older diagnosed between 1992 and 2009. With each interval of delay increase, overall survival was lower overall (hazard ratio [HR], 1.09; 95% CI, 1.06-1.13; P < .001), and in patients with stage I (HR, 1.13; 95% CI, 1.08-1.18; P < .001) and stage II disease (HR 1.06; 95% CI, 1.01-1.11; P = .01). Breast cancer-specific mortality increased with each 60-day interval (subdistribution hazard ratio [sHR], 1.26; 95% CI, 1.02-1.54; P = .03). The NCDB study evaluated 115 790 patients 18 years or older diagnosed between 2003 and 2005. The overall mortality HR was 1.10 (95% CI, 1.07-1.13; P < .001) for each increasing interval, significant in stages I (HR, 1.16; 95% CI, 1.12-1.21; P < .001) and II (HR, 1.09; 95% CI, 1.05-1.13; P < .001) only, after adjusting for demographic, tumor, and treatment factors. CONCLUSIONS AND RELEVANCE: Greater TTS is associated with lower overall and disease-specific survival, and a shortened delay is associated with benefits comparable to some standard therapies. Although time is required for preoperative evaluation and consideration of options such as reconstruction, efforts to reduce TTS should be pursued when possible to enhance survival.

Characteristics of clinical trials that require participants to be fluent in English.

BACKGROUND/AIMS: Diverse samples in clinical trials can make findings more generalizable. We sought to characterize the prevalence of clinical trials in the United States that required English fluency for participants to enroll in the trial. METHODS: We randomly chose over 10,000 clinical trial protocols registered with ClinicalTrials.gov and examined the inclusion and exclusion criteria of the trials. We compared the relationship of clinical trial characteristics with English fluency inclusion requirements. We merged the ClinicalTrials.gov data with US Census and American Community Survey data to investigate the association of English-language restrictions with ZIP-code-level demographic characteristics of participating institutions. We used Chi-squared tests, t-tests, and logistic regression models for analyses. RESULTS: English fluency requirements have been increasing over time, from 1.7% of trials having such requirements before 2000 to 9.0% after 2010 (p < 0.001 from Chi-squared test). Industry-sponsored trials had low rates of English fluency requirements (1.8%), while behavioral trials had high rates (28.4%). Trials opening in the Northeast of the United States had the highest regional English requirement rates (10.7%), while trials opening in more than one region had the lowest (3.3%, p<0.001). Since 1995, trials opening in ZIP codes with larger Hispanic populations were less likely to have English fluency requirements (odds ratio=0.92 for each 10% increase in proportion of Hispanics, 95% confidence interval=0.86-0.98, p=0.013). Trials opening in ZIP codes with more residents self-identifying as Black/African American (odds ratio=1.87, 95% confidence interval=1.36-2.58, p<0.001 for restricted cubic spline term) or Asian (odds ratio=1.16 for linear term, 95% confidence interval=1.07-1.25, p<0.001) were more likely to have English fluency requirements. ZIP codes with higher poverty rates had trials with more English-language restrictions (odds ratio=1.06 for a 10% poverty rate increase, 95% confidence interval=1.001-1.11, p=0.045). There was a statistically significant interaction between year and intervention type, such that the increase in English fluency requirements was more common for some interventions than for others. CONCLUSION: The proportion of clinical trials registered with ClinicalTrials.gov that have English fluency requirements for study inclusion has been increasing over time. English-language restrictions are associated with a number of characteristics, including the demographic characteristics of communities in which the sponsoring institutions are located.

Why Summary Comorbidity Measures Such As the Charlson Comorbidity Index and Elixhauser Score Work.

BACKGROUND: Comorbidity adjustment is an important component of health services research and clinical prognosis. When adjusting for comorbidities in statistical models, researchers can include comorbidities individually or through the use of summary measures such as the Charlson Comorbidity Index or Elixhauser score. We examined the conditions under which individual versus summary measures are most appropriate. METHODS: We provide an analytic proof of the utility of comorbidity summary measures when used in place of individual comorbidities. We compared the use of the Charlson and Elixhauser scores versus individual comorbidities in prognostic models using a SEER-Medicare data example. We examined the ability of summary comorbidity measures to adjust for confounding using simulations. RESULTS: We devised a mathematical proof that found that the comorbidity summary measures are appropriate prognostic or adjustment mechanisms in survival analyses. Once one knows the comorbidity score, no other information about the comorbidity variables used to create the score is generally needed. Our data example and simulations largely confirmed this finding. CONCLUSIONS: Summary comorbidity measures, such as the Charlson Comorbidity Index and Elixhauser scores, are commonly used for clinical prognosis and comorbidity adjustment. We have provided a theoretical justification that validates the use of such scores under many conditions. Our simulations generally confirm the utility of the summary comorbidity measures as substitutes for use of the individual comorbidity variables in health services research. One caveat is that a summary measure may only be as good as the variables used to create it.

A Simple Method for Evaluating Within Sample Prognostic Balance Achieved by Published Comorbidity Summary Measures.

OBJECTIVE: To demonstrate how a researcher can investigate the appropriateness of a published comorbidity summary measure for use with a given sample. DATA SOURCE: Surveillance, Epidemiology, and End Results linked to Medicare claims data. STUDY DESIGN: We examined Kaplan-Meier estimated survival curves for four diseases within strata of a comorbidity summary measure, the Charlson Comorbidity Index. DATA COLLECTION: We identified individuals with early-stage kidney cancer diagnosed from 1995 to 2009. We recorded comorbidities present in the year before diagnosis. PRINCIPAL FINDINGS: The use of many comorbidity summary measures is valid under appropriate conditions. One condition is that the relationships of the comorbidities with the outcome of interest in a researcher's own population are comparable to the relationships in a published algorithm's population. The original comorbidity weights from the Charlson Comorbidity Index seemed adequate for three of the diseases in our sample. We found evidence that the Charlson Comorbidity Index might underestimate the impact of one disease in our sample. CONCLUSION: Examination of survival curves within strata defined by a comorbidity summary measure can be a useful tool for determining whether a published method appropriately accounts for comorbidities. A comorbidity score is only as good as those variables included.

Oncologists' response to new data regarding the use of epidermal growth factor receptor inhibitors in colorectal cancer.

PURPOSE: Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice. METHODS: Commercially insured patients with mCRC who received second-line therapy between 2004 and 2010 were identified by dusing the LifeLink Health Plan Claims Database. We calculated the fraction of patients receiving anti-EGFR antibody in 2-month intervals. χ(2) tests were used to compare treatment rates at four time points: time 1: June 2008, ASCO presentation of clinical data; time 2: February 2009, ASCO guidelines publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8 months after FDA label change. RESULTS: Five thousand eighty-nine patients received second-line therapy; of these, 2,599 patients received an anti-EGFR antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The majority of patients (59.4%) received an anti-EGFR antibody at time 1, with significant decrease at each of the subsequent time points (time 2: 46.2% [P = .019]; time 3: 35.2% [P < .001]; Time 4: 16.2% [P < .001]). Multivariable logistic regression did not show any affect of age, sex, comorbidities, or region of the country on this pattern. CONCLUSIONS: The use of anti-EGFR antibodies for mCRC decreased after the presentation of clinical trial data, ASCO guidelines publication, and FDA label change. These data suggest that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice.

Cost concerns of patients with cancer.

PURPOSE: Health care providers are accustomed to identifying populations for whom cost-related concerns may be a significant barrier, such as the poor, but few empiric data have been collected to substantiate such assumptions, particularly among insured patients. METHODS: Patients with cancer from academic and community hospitals completed a questionnaire that included closed-ended items concerning demographic variables, optimism, numeracy, and concerns about present and future medical costs. In addition, they answered open-ended questions regarding cost concerns and medical expenses. RESULTS: Nearly all (99%) participants were insured. In response to the closed-ended questions, 30.3% of patients reported concern about paying for their cancer treatment, 22.3% reported that their family had made sacrifices to pay for their care, and 8.3% stated that their insurance adequately covered their current health care costs, and 17.3% reported concerns about coverage for their costs in the future. On open-ended questions, 35.3% reported additional expenses, and 47.5% reported concerns about health care costs. None of the assessed patient characteristics proved to be a robust predictor across all cost-related concerns. There was a strong association between the identification of concerns or expenses on the open-ended questions and concerns on closed-ended questions. CONCLUSION: Cost concerns are common among patients with cancer who have health insurance. Health care providers may alleviate concerns by discussing cost-related concerns with all patients, not only those of lower socioeconomic status or those without insurance. A closed-ended screening question may help to initiate these conversations. This may identify potential resources, lower distress, and enable patients to make optimal treatment decisions.

Optical technologies and molecular imaging for cervical neoplasia: a program project update.

There is an urgent global need for effective and affordable approaches to cervical cancer screening and diagnosis. In developing nations, cervical malignancies remain the leading cause of cancer-related deaths in women. This reality may be difficult to accept given that these deaths are largely preventable; where cervical screening programs have been implemented, cervical cancer-related deaths have decreased dramatically. In developed countries, the challenges of cervical disease stem from high costs and overtreatment. The National Cancer Institute-funded Program Project is evaluating the applicability of optical technologies in cervical cancer. The mandate of the project is to create tools for disease detection and diagnosis that are inexpensive, require minimal expertise, are more accurate than existing modalities, and can be feasibly implemented in a variety of clinical settings. This article presents the status and long-term goals of the project.

Exploring the potential of Web 2.0 to address health disparities.

This article addresses use of the Internet and Web 2.0 technologies by racial and ethnic minorities and explores the potential opportunities and challenges in leveraging Web 2.0 approaches to impact health disparities. These opportunities and challenges include developing approaches and methods to (a) identify strategies for integrating social media into health promotion interventions focused on major health-related issues that affect members of medically underserved groups; (b) amalgamate techniques to leverage and connect social-media technologies to other evidence-informed online resources; (c) integrate health communication best practices, including addressing health literacy issues; (d) capitalize on social networking to enhance access and communication with health care providers; and (e) advance current efforts and ongoing expansion of research participation by individuals from underserved communities.