Publications (159) View all
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Article: The value of comparative effectiveness research: Projected return on investment of the RxPONDER trial (SWOG S1007).
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ABSTRACT: The objective of this study was to assess the value of research of the RxPONDER study, an ongoing comparative effectiveness RCT designed to evaluate a 21-gene profile in early stage, node-positive breast cancer. We developed a disease-based decision-analytic model to compare use of the 21-gene profile versus standard care. Key clinical data were derived from SWOG-8814, an RCT of chemotherapy in lymph node-positive breast cancer. Other model parameters were obtained from published sources. Probabilistic simulations and value of information calculations were used to assess the expected value of sample information (EVSI) and the expected value of sample parameter information (EVSPI). The cost of the RxPONDER trial is expected to be at least $27million. The expected value of research of the RxPONDER trial ranged from $450million to $1billion, representing a return of 17 to 39 times the projected cost of the trial. The primary objective of RxPONDER, to assess survival, had the largest estimated value relative to other model inputs. The value of RxPONDER increased by $50million to $100million after stakeholder input on additional data collection. The RxPONDER study appears to represent a good investment of public research funds. Stakeholder engagement and assessment of the return on investment should be considered to optimize and quantify the value of comparative effectiveness studies.Contemporary clinical trials 08/2012; 33(6):1117-23. · 1.51 Impact Factor -
Article: Combination anastrozole and fulvestrant in metastatic breast cancer.
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ABSTRACT: The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. We hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)-positive metastatic breast cancer. Postmenopausal women with previously untreated metastatic disease were randomly assigned, in a 1:1 ratio, to receive either 1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed, or anastrozole and fulvestrant in combination (group 2). Patients were stratified according to prior or no prior receipt of adjuvant tamoxifen therapy. Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter. The primary end point was progression-free survival, with overall survival designated as a prespecified secondary outcome. The median progression-free survival was 13.5 months in group 1 and 15.0 months in group 2 (hazard ratio for progression or death with combination therapy, 0.80; 95% confidence interval [CI], 0.68 to 0.94; P=0.007 by the log-rank test). The combination therapy was generally more effective than anastrozole alone in all subgroups, with no significant interactions. Overall survival was also longer with combination therapy (median, 41.3 months in group 1 and 47.7 months in group 2; hazard ratio for death, 0.81; 95% CI, 0.65 to 1.00; P=0.05 by the log-rank test), despite the fact that 41% of the patients in group 1 crossed over to fulvestrant after progression. Three deaths that were possibly associated with treatment occurred in group 2. The rates of grade 3 to 5 toxic effects did not differ significantly between the two groups. The combination of anastrozole and fulvestrant was superior to anastrozole alone or sequential anastrozole and fulvestrant for the treatment of HR-positive metastatic breast cancer, despite the use of a dose of fulvestrant that was below the current standard. (Funded by the National Cancer Institute and AstraZeneca; SWOG ClinicalTrials.gov number, NCT00075764.).New England Journal of Medicine 08/2012; 367(5):435-44. · 53.30 Impact Factor -
Article: Evaluating Components of Dental Utilization among Adults with Diabetes and Matched Controls via Hurdle Models.
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ABSTRACT: BACKGROUND: About one-third of adults with diabetes have severe oral complications. However, limited previous research has investigated dental care utilization associated with diabetes. This project had two purposes: to develop a methodology to estimate dental utilization using claims data and to use this methodology to compare utilization of dental care between adults with and without diabetes. METHODS: Data included secondary enrollment and demographic data from Washington Dental Service (WDS) and Group Health Cooperative (GH), clinical data from GH, and dental-utilization data from WDS claims during 2002-2006. Dental and medical records from WDS and GH were linked for enrolees continuously and dually insured during the study. We employed hurdle models in a quasi-experimental setting to assess differences between adults with and without diabetes in 5-year cumulative utilization of dental services. Propensity score matching adjusted for differences in baseline covariates between the two groups. RESULTS: We found that adults with diabetes had lower odds of visiting a dentist (OR=0.74, p < 0.001). Among those with a dental visit, diabetes patients had lower odds of receiving prophylaxes (OR=0.77), fillings (OR=0.80) and crowns (OR=0.84) (p < 0.005 for all) and higher odds of receiving periodontal maintenance (OR=1.24), non-surgical periodontal procedures (OR=1.30), extractions (OR=1.38) and removable prosthetics (OR=1.36) (p < 0.001 for all). CONCLUSIONS: Patients with diabetes are less likely to use dental services. Those who do are less likely to use preventive care and more likely to receive periodontal care and tooth-extractions. Future research should address the possible effectiveness of additional prevention in reducing subsequent severe oral disease in patients with diabetes.BMC Oral Health 07/2012; 12(1):20. -
Article: Administrative data algorithms to identify second breast cancer events following early-stage invasive breast cancer.
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ABSTRACT: Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993-2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.CancerSpectrum Knowledge Environment 04/2012; 104(12):931-40. · 14.07 Impact Factor -
Article: Breast density, body mass index, and risk of tumor marker-defined subtypes of breast cancer.
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ABSTRACT: Breast density and body mass index (BMI) are correlated attributes and are both potentially modifiable risk factors for breast cancer. However, relationships between these factors and risk of molecularly-defined subtypes of breast cancer have not been established. We used breast density and BMI data collected by the Breast Cancer Surveillance Consortium from 1,054,466 women ages 40 to 84 years receiving mammography, including 13,797 women subsequently diagnosed with breast cancer. Cases were classified into three groups on the basis of expression of the estrogen receptor (ER), progesterone receptor (PR), and HER2:1) ER-positive (ER+, n = 10,026), 2) HER2-expressing (ER-negative/PR-negative/HER2-positive, n = 308), or triple-negative (ER-negative/PR-negative/HER2-negative, n = 705). Using Cox regression, we evaluated subtype-specific associations with breast density and BMI. Breast density was similarly positively associated with risk of all subtypes, especially among women ages 40 to 64 years. BMI was positively associated with risks of ER+ and triple-negative breast cancer in women ages 50 to 84 who were not users of hormone therapy. Breast density is positively associated with breast cancer risk, regardless of disease subtype. Associations with BMI appear to vary more by breast cancer subtype. Additional studies are needed to confirm and further characterize risk factors for HER2-expressing and triple-negative breast cancer.Annals of epidemiology 02/2012; 22(5):340-8. · 2.95 Impact Factor
