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.

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.

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.

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.

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.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy.

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost-effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92-1.00] and an estimated specificity of 0.71 [95% CI = 0.62-0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81-0.89). The per-patient and per-site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

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.

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.

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.

Integration of prostate cancer clinical data using an ontology.

It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO.

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.

The performance of human papillomavirus high-risk DNA testing in the screening and diagnostic settings.

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. RESULTS: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR- were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR- were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. CONCLUSIONS: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older.

Accuracy of colposcopy in the diagnostic setting compared with the screening setting.

OBJECTIVE: To estimate the accuracy of colposcopy to identify cervical precancer in screening and diagnostic settings. METHODS: As part of a larger clinical trial to evaluate the diagnostic accuracy of optical spectroscopy, we recruited 1,850 patients into a diagnostic or a screening group depending on their history of abnormal findings on Papanicolaou tests. Colposcopic examinations were performed and biopsies specimens obtained from abnormal and normal colposcopic sites for all patients. The criterion standard of test accuracy was the histologic report of biopsies. We calculated sensitivities, specificities, likelihood ratios, receiver operating characteristic curves, and areas under the receiver operating characteristic curves. RESULTS: The prevalence of high-grade squamous intraepithelial lesions (HSIL) or cancer was 29.0% for the diagnostic group and 2.2% for the screening group. Using a disease threshold of HSIL, colposcopy had a sensitivity of 0.983 and a specificity of 0.451 in the diagnostic group when the test threshold was low-grade squamous intraepithelial lesions (LSIL), and a sensitivity of 0.714 and a specificity of 0.813 when the test threshold was HSIL. Using the same HSIL disease threshold, in the screening group, colposcopy had a sensitivity of 0.286 and a specificity of 0.877 when the test threshold was LSIL, and a sensitivity of 0.191 and a specificity of 0.961 when the threshold was HSIL. The colposcopy area under the receiver operating characteristic curve was 0.821 (95% confidence interval 0.79-0.85) in the diagnostic setting compared with 0.587 (95% confidence interval 0.56-0.62) in the screening setting. Changing the disease threshold to LSIL demonstrated similar patterns in the tradeoff of sensitivity and specificity and measure of accuracy. CONCLUSION: Colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used to screen for cervical intraepithelial neoplasia. LEVEL OF EVIDENCE: II.

The accuracy of the Papanicolaou smear in the screening and diagnostic settings.

OBJECTIVE: We evaluated the performance of the Papanicolaou smear in screening and diagnostic settings. STUDY DESIGN: We analyzed Papanicolaou smear results of 1,850 women recruited into a clinical trial to evaluate an emerging technology for the detection of cervical cancer. Screening and diagnosis groups were based on the history of previous Papanicolaou smear results. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic curves, and areas under the receiver operating characteristic curve (AUC). RESULTS: In the screening group, by defining disease as cervical intraepithelial neoplasia (CIN) 2,3/cancer or worse and using high-grade squamous intraepithelial lesion (HSIL) as the test cutpoint, the AUC was 0.689, and the LR+ and LR- were 39.25 and 0.67, respectively. In the diagnosis group, the AUC was 0.764, and the LR+ and LR- were 3.79 and 0.56, respectively. By defining disease as human papillomavirus/CIN 1 or worse and HSIL as the test cutpoint, the AUC was 0.586, and the LR+ and LR- were 17.01 and 0.92 in the screening group; in the diagnosis group, the AUC was 0.686, and the LR+ and LR- were 2.77 and 0.75, respectively. CONCLUSIONS: In a screening setting, a Papanicolaou smear result of HSIL or worse is 39 times more likely in a patient with CIN 2,3/cancer than in a patient without it. This compares to 4 times more likely in the diagnostic setting. The magnitude of the positive likelihood ratio observed in the screening group indicated that abnormal Papanicolaou smear results obtained in the screening setting should have more impact on clinical decision making than those from results obtained in the diagnostic setting.

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.

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.

Using decision analysis to determine the cost-effectiveness of intensity-modulated radiation therapy in the treatment of intermediate risk prostate cancer.

BACKGROUND: The specific aim of this study is to evaluate the cost-effectiveness of intensity-modulated radiation therapy (IMRT) compared with three-dimensional conformal radiation therapy (3D-CRT) in the treatment of a 70-year-old with intermediate-risk prostate cancer. METHODS: A Markov model was designed with the following states; posttreatment, hormone therapy, chemotherapy, and death. Transition probabilities from one state to another were calculated from rates derived from the literature for IMRT and 3D-CRT. Utility values for each health state were obtained from preliminary studies of preferences conducted at Fox Chase Cancer Center. The analysis took a payer's perspective. Expected mean costs, cost-effectiveness scatterplots, and cost acceptability curves were calculated with commercially available software. RESULTS: The expected mean cost of patients undergoing IMRT was $47,931 with a survival of 6.27 quality-adjusted life years (QALYs). The expected mean cost of patients having 3D-CRT was $21,865 with a survival of 5.62 QALYs. The incremental cost-effectiveness comparing IMRT with CRT was $40,101/QALYs. Cost-effectiveness acceptability curve analysis revealed a 55.1% probability of IMRT being cost-effective at a $50,000/QALY willingness to pay. CONCLUSION: Intensity-modulated radiation therapy was found to be cost-effective, however, at the upper limits of acceptability. The results, however, are dependent on the assumptions of improved biochemical disease-free survival with fewer patients undergoing subsequent salvage therapy and improved quality of life after the treatment. In the absence of prospective randomized trials, decision analysis can help inform physicians and health policy experts on the cost-effectiveness of emerging technologies.

Collecting direct non-health care and time cost data: application to screening and diagnosis of cervical cancer.

BACKGROUND: Data on direct non-health care and time costs are rarely collected, though the incorporation of such data is essential for performing cost-effectiveness analyses according to established guidelines. OBJECTIVES: To explore the challenges involved in collecting and analyzing these data from patients enrolled in a clinical trial. METHODS: Through the use of a pilot study, the authors designed a questionnaire to collect these costs. They used this questionnaire in a clinical trial conducted at a comprehensive cancer center and a public community hospital. Patients in the trial were undergoing screening or diagnostic procedures through a clinical protocol designed to measure the effectiveness of fluorescence and reflectance spectroscopy for detecting cervical precancers. Direct non-health care costs were adjusted to 2003 constant dollars. RESULTS: The authors successfully collected direct non-health care and time cost data, thus demonstrating the feasibility of acquiring such data. Compared to patients receiving diagnostic services for cervical cancer, those receiving screening services for the same condition in both settings incurred lower direct non-health care costs and time costs, as defined in the questionnaire. Compared to patients receiving either service at the comprehensive cancer center, those seeking either service at the public community hospital incurred lower direct non-health care costs and time costs. When outliers were removed, total direct non-health care costs and time costs substantially decreased for diagnostic patients in the comprehensive cancer center; total direct non-health care costs and time costs for other subgroups remained essentially unchanged. CONCLUSIONS: Direct non-health care and time cost data can be collected within a large-scale clinical trial. The setting (community v. specialty hospital) and population (patients receiving screening v. diagnostic examination) makes a difference regarding the cost totals. The order of magnitude of the final result depends on the context in which the non-health care and time cost data will be used.

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.