Adherence to human epidermal growth factor receptor-2 testing and adjuvant trastuzumab treatment guidelines in Ontario.

OBJECTIVES: We evaluated adherence of human epidermal growth factor receptor-2 testing using immunohistochemistry and fluorescence in situ hybridization, as well as adjuvant trastuzumab treatment according to Canadian guidelines, and predictors of trastuzumab use in early-stage breast cancer in Ontario. METHODS: Retrospective cohort of early-stage breast cancer patients identified in the Ontario Cancer Registry. Human epidermal growth factor receptor-2 test type, sequence, result(s), tumor grade, and hormone receptor status were abstracted from Ontario Cancer Registry pathology reports. Trastuzumab treatment was determined from provincial cancer agency records. Other variables were determined from administrative data sources. Logistic regression models were used to estimate adjusted odds ratios for factors associated with guideline adherence. RESULTS: The first human epidermal growth factor receptor-2 test result was the strongest predictor of confirmatory testing (p < 0.05). Human epidermal growth factor receptor-2 testing by immunohistochemistry accounted for the majority of documented first tests (94%; n = 8249). Overall, 27% (n = 2360) of tested patients received a second test by fluorescence in situ hybridization (46%) or immunohistochemistry (49%) assay. Most human epidermal growth factor receptor-2 equivocal patients (89%; n = 784) received a confirmatory test. Among human epidermal growth factor receptor-2-positive patients, only 57% (n = 385) received trastuzumab treatment within the study period. Human epidermal growth factor receptor-2 status was the strongest predictor of trastuzumab use. Younger patients (<70 years at diagnosis) and negative hormone receptor status had higher odds of trastuzumab treatment (p < 0.05) compared to older and positive hormone receptor status patients. CONCLUSIONS: Immunohistochemistry use as a first test was largely consistent with Canadian guidelines; however, immunohistochemistry was frequently used as a confirmatory test, which is not guideline-concordant. Monitoring these testing and treating patterns is necessary to optimize health outcomes associated with trastuzumab.

Quality of Life in Individuals with Erythematotelangiectatic and Papulopustular Rosacea: Findings From a Web-based Survey.

OBJECTIVE: The objective of the study was to evaluate the impact of rosacea on self-perception, emotional, social, and overall well-being and quality of life in individuals with erythematotelangiectatic rosacea (ETR) and papulopustular rosacea (PPR). DESIGN: We distributed a cross-sectional email invitation for participants in the United States to fill out a web-based survey. PARTICIPANTS: We included adults who reported having previously received a diagnosis of erythematotelangiectatic rosacea or papulopustular rosacea. MEASUREMENTS: Questionnaires measured the psychosocial aspects of rosacea, including the Satisfaction With Appearance Scale and modified Satisfaction With Appearance Scale questionnaires, Impact Assessment for Rosacea Facial Redness, Rosacea-Specific Quality-of-Life questionnaire, and RAND 36-Item Short Form Health Survey. The Impact Assessment for Rosacea Facial Bumps or Pimples was administered to the papulopustular rosacea cohort. RESULTS: Six hundred participants enrolled and completed the survey, with most rating their rosacea as mild or moderate (ETR: 95.6%; PPR: 93.7%). In the erythematotelangiectatic rosacea and papulopustular rosacea cohorts, respectively, 45 and 53 percent disagreed/strongly disagreed that they were satisfied with their appearance due to rosacea; 42 and 27 percent agreed/strongly agreed that they "worry how people will react when they see my rosacea"; and 43 and 59 percent agreed/strongly agreed that they feel their rosacea is unattractive to others. Rosacea-Specific Quality-of-Life total and domain scores indicated negative impact of rosacea for both cohorts. Both cohorts reported worse 36-item Short Form Health Survey overall and domain scores than population norms in the United States. CONCLUSION: Rosacea had wide-ranging, negative effects on self-perceptions and emotional, social, and overall well-being as well as rosacea-specific quality of life. Overall, both erythematotelangiectatic rosacea and papulopustular rosacea cohorts reported a substantial negative impact of rosacea on quality of life on a range of instruments.

Cross-Sectional Survey of the Burden of Illness of Rosacea by Erythema Severity.

Rosacea is a chronic skin condition characterized by persistent central facial erythema. To explore the burden of illness of rosacea in US adults, a cross-sectional web-based survey was conducted. Participants answered questions on sociodemographics, clinical characteristics, bothersome symptoms, coping and avoidance behaviors, self-perceptions, and health care resource utilization, and completed 2 quality of life instruments, the 21-item rosacea-specific quality of life questionnaire (RosaQoL) and the 36-item Short Form Health Survey (SF-36). This paper reports the data from the 409 respondents with erythematotelangiectatic rosacea (ETR), analyzed by erythema severity. Mean age was 53.1 years; mild, moderate, or severe erythema was reported by 63.6%, 32.0%, and 4.4% of participants, respectively. Blushing/flushing and bumps/pustules were the most bothersome symptoms across severity subgroups. Participants in all subgroups coped with rosacea by applying make-up and managing their stress and anxiety, and tried to prevent rosacea flares by avoiding sun exposure, specific skin care products, and other triggers. Self-perceptions differed by severity subgroup: satisfaction with facial appearance significantly decreased, and worrying about how people will react and feelings of unattractiveness to others significantly increased, with greater erythema severity (all P less than 0.01). Treatment or assessment of rosacea was sought by 20% of participants in the past 3 months, most commonly from a dermatologist. Metronidazole was the most frequently prescribed topical product across severity subgroups, whereas doxycycline and other oral antibiotics were prescribed most frequently in the severe erythema subgroup. RosaQoL emotional domain scores increased with erythema severity (P equals 0.0035), but none of the SF-36 domain scores differed significantly by erythema severity. These results demonstrate that rosacea is associated with a substantial burden of illness that spans all levels of erythema severity in patients with ETR. Feelings of unattractiveness and the adverse impact of rosacea on emotional quality of life increased with erythema severity. J Drugs Dermatol. 2018;17(2):150-158.

The Burden of Illness of Erythematotelangiectatic Rosacea and Papulopustular Rosacea: Findings From a Web-based Survey.

Objective: Evaluate patients' perceptions of rosacea symptoms and treatments. Design: Cross-sectional, web-based survey conducted from May 8 to July 1,2015. Setting: E-mail invitation. Participants: Male and female adults in the United States who self-reported having a physician's diagnosis of rosacea. Measurements: Sociodemographic and clinical characteristics were collected for eligible respondents using the Self-Assessment of Rosacea Facial Redness scale and the Symptom Assessment for Rosacea Facial Bumps and Pimples questionnaire. Respondents were instructed how to differentiate erythematotelangiectatic rosacea and papulopustular rosacea. Use of different treatments and satisfaction with treatment were assessed, as were coping mechanisms. Results: More than 4,000 individuals responded and 600 completed the survey. The participants' mean age was 51.7 years and more than 90 percent rated their rosacea severity as mild or moderate. Most practiced stress and/or anxiety management, used makeup to cover rosacea, used sun protection, and changed their exercise regimens to cope with rosacea flare-ups. Participants reported avoiding sun exposure, hot baths and saunas, and specific skin care products to circumvent potential rosacea flare-ups. More than half (55.7%) had used a prescribed topical agent for rosacea in the preceding month, and 26.3 percent had used a prescribed oral antibiotic. Fewer than half were satisfied with treatment outcomes. Conclusion: Despite the chronic nature of rosacea, participants commonly used prescription agents only to treat flare-ups and relied on sun protection and other avoidance mechanisms to reduce their frequency. Education is needed to communicate the long-term nature of rosacea and the need for continued treatment to maintain long-term control.

Closing the personalized medicine information gap: HER2 test documentation practice.

BACKGROUND: Uncertainty about human epidermal growth factor receptor-2 (HER2) testing practice in Canada continues to hinder efforts to improve personalized medicine. Pathologists routinely perform HER2 assessment for all tumors > 1 cm, and pathology is reported centrally to the provincial cancer registry. OBJECTIVES: To understand patterns of HER2 test documentation for early-stage breast cancer (BC) patients in Ontario's centralized pathology reporting system. STUDY DESIGN: Retrospective cohort study of central HER2 test documentation in early-stage BC patients diagnosed in 2006-2007. METHODS: Cohort and staging information was derived from cancer registry and admissions data. Linkage across administrative databases provided data on surgical and radiologic treatment, sociodemographic factors, diagnosis setting, and comorbidities. Pathology reports from the provincial cancer registry were reviewed for HER2 testing, hormone receptor, and grade. Unadjusted and adjusted odds ratios were calculated to determine factors related to HER2 documentation. RESULTS: A HER2 test was documented for 66% of 13,396 patients. HER2 documentation was associated with stage, hormone receptor, and tumor grade documentation. Higher stage and grade at diagnosis were also associated with HER2 documentation. All models suggested variable regional documentation patterns. Documentation did not differ by sociodemographic factors, presence of comorbidities, or surgical procedure. CONCLUSIONS: Despite a universal testing policy, the rate of centralized HER2 test documentation was lower than expected and related to disease severity. Differences in regional reporting likely reflect ascertainment bias inherent to centralized pathology reporting rather than testing access. Improved HER2 reporting is encouraged for cancer registration, quality-of-care measurement, and program evaluation.

Do economic evaluations of targeted therapy provide support for decision makers?

PURPOSE: Decision makers must make decisions without complete information. That uncertainty can be decreased when economic evaluations use local data and can be quantified by considering the variability of all model inputs concurrently per international evaluation guidelines. It is unclear how these recommendations have been implemented in evaluations of targeted cancer therapy. By using economic evaluations of adjuvant trastuzumab, we have assessed the extent to which decision support recommendations were adopted. STUDY DESIGN: Systematic review. METHODS: Published economic evaluations of adjuvant trastuzumab treatment in early-stage breast cancer were examined as an established example of targeted therapy. Canadian, United Kingdom, and US economic evaluation guidelines were reviewed to establish extraction criteria. Extraction characterized the use of effectiveness evidence and local data sources for model parameters, sensitivity analysis methods (scenario, univariate, multivariate, and probabilistic) and uncertainty representation (ie, cost-effectiveness plane, scatterplot, confidence ellipses, tornado diagrams, cost-effectiveness acceptability curve). RESULTS: Fifteen economic evaluations of adjuvant trastuzumab were identified in the literature. Local data were used to estimate costs (15 of 15) and utilities rarely (two of 15) but not trastuzumab efficacy. Univariate sensitivity analysis was most common (12 of 15), whereas probabilistic analysis was less frequent (10 of 15). Two thirds of all studies provided visual representation of results and decision uncertainty. CONCLUSION: Authors of adjuvant trastuzumab economic evaluations rarely use local data beyond costs. Quantification of uncertainty and its representation also fell short of guideline recommendations. This review demonstrates that economic evaluations of adjuvant trastuzumab, as an example of targeted cancer therapy, can be improved for decision-making support.

Economic evaluation of targeted cancer interventions: critical review and recommendations.

Scientific advances have improved our ability to target cancer interventions to individuals who will benefit most and spare the risks and costs to those who will derive little benefit or even be harmed. Several approaches are currently used for targeting interventions for cancer risk reduction, screening, and treatment, including risk prediction algorithms for identifying high-risk subgroups and diagnostic tests for tumor markers and germline genetic mutations. Economic evaluation can inform decisions about the use of targeted interventions, which may be more costly than traditional strategies. However, assessing the impact of a targeted intervention on costs and health outcomes requires explicit consideration of the method of targeting. In this study, we describe the importance of this principle by reviewing published cost-effectiveness analyses of targeted interventions in breast cancer. Few studies we identified explicitly evaluated the relationships among the method of targeting, the accuracy of the targeting test, and outcomes of the targeted intervention. Those that did found that characteristics of targeting tests had a substantial impact on outcomes. We posit that the method of targeting and the outcomes of a targeted intervention are inextricably linked and recommend that cost-effectiveness analyses of targeted interventions explicitly consider costs and outcomes of the method of targeting.

Do economic evaluations of targeted therapy provide support for decision makers?

OBJECTIVE: Decision makers must make decisions without complete information. That uncertainty can be decreased when economic evaluations use local data and can be quantified by considering the variability of all model inputs concurrently per international evaluation guidelines. It is unclear how these recommendations have been implemented in evaluations of targeted cancer therapy. By using economic evaluations of adjuvant trastuzumab, we have assessed the extent to which decision support recommendations were adopted. STUDY DESIGN: Systematic review. METHODS: Published economic evaluations of adjuvant trastuzumab treatment in early-stage breast cancer were examined as an established example of targeted therapy. Canadian, United Kingdom, and US economic evaluation guidelines were reviewed to establish extraction criteria. Extraction characterized the use of effectiveness evidence and local data sources for model parameters, sensitivity analysis methods (scenario, univariate, multivariate, and probabilistic), and uncertainty representation (ie, cost-effectiveness plane, scatterplot, confidence ellipses, tornado diagrams, cost-effectiveness acceptability curve). RESULTS: Fifteen economic evaluations of adjuvant trastuzumab were identified in the literature. Local data were used to estimate costs (15 of 15) and utilities rarely (2 of 15) but not trastuzumab efficacy. Univariate sensitivity analysis was most common (12 of 15), whereas probabilistic analysis was less frequent (10 of 15). Two-thirds of all studies provided visual representation of results and decision uncertainty. CONCLUSION: Authors of adjuvant trastuzumab economic evaluations rarely use local data beyond costs. Quantification of uncertainty and its representation also fell short of guideline recommendations. This review demonstrates that economic evaluations of adjuvant trastuzumab, as an example of targeted cancer therapy, can be improved for decision-making support.

Health technology assessment for radiologists: basic principles and evaluation framework.

Decision makers are faced with the task of allocating health resources to maximize patients' health under budget constraints. To offer structure to the complexity of the decision-making process, the field of health technology assessment (HTA) was developed. This paper offers an introduction to the fundamental aspects of HTA and acts as a guide to the conduct of HTA for radiologists. First, the authors define HTA and describe how it is linked to the field of diagnostics. Second, a basic 11-step framework for the conduct of an HTA is outlined. The framework begins with the identification of the problem and proceeds through to the dissemination and impact of an HTA. Third, the authors provide a real-world example of an HTA in the field of diagnostics. Last, they describe the challenges and barriers faced in HTA.

Approaches for economic evaluations of health care technologies.

Economic evaluations involve the comparison of alternative courses of action in terms of both their costs and their consequences. In response to increasing health care costs, economic evaluations of competing technologies, including radiologic interventions, are increasingly used to inform resource allocation decisions. It is therefore crucial that radiologists have a thorough understanding of the methods. The objective of this paper is to present a detailed overview of the principles and methods of economic evaluations of health technologies, including recent methodologic developments. For the purpose of this paper, the key elements of an economic evaluation are divided into 5 broad sections: 1) types of economic evaluations (eg, cost-effectiveness analysis, cost-utility analysis), 2) study perspectives (ie, temporal and cost perspectives), 3) analysis of costs and effects (eg, incremental cost-effectiveness ratios, cost-effectiveness planes), 4) conducting economic evaluations alongside trials or using decision-analytic models, and 5) dealing with the different forms of uncertainty in economic evaluations (eg, sampling uncertainty in trials, parameter uncertainty in models). Examples from the recent radiology literature are used to explain the key concepts. This review improves upon the previous educational papers published in radiologic journals, as it covers recent methodologic advances regarding the treatment of uncertainty.

Illustrating economic evaluation of diagnostic technologies: comparing Helicobacter pylori screening strategies in prevention of gastric cancer in Canada.

OBJECTIVE: The aim of this paper is to present an economic evaluation of diagnostic technologies using Helicobacter pylori screening strategies for the prevention of gastric cancer as an illustration. METHODS: A Markov model was constructed to compare the lifetime cost and effectiveness of 4 potential strategies: no screening, the serology test by enzyme-linked immunosorbent assay (ELISA), the stool antigen test (SAT), and the (13)C-urea breath test (UBT) for the detection of H. pylori among a hypothetical cohort of 10,000 Canadian men aged 35 years. Special parameter consideration included the sensitivity and specificity of each screening strategy, which determined the model structure and treatment regimen. The primary outcome measured was the incremental cost-effectiveness ratio between the screening strategies and the no-screening strategy. Base-case analysis and probabilistic sensitivity analysis were performed using the point estimates of the parameters and Monte Carlo simulations, respectively. RESULTS: Compared with the no-screening strategy in the base-case analysis, the incremental cost-effectiveness ratio was $33,000 per quality-adjusted life-year (QALY) for the ELISA, $29,800 per QALY for the SAT, and $50,400 per QALY for the UBT. The probabilistic sensitivity analysis revealed that the no-screening strategy was more cost effective if the willingness to pay (WTP) was <$20,000 per QALY, while the SAT had the highest probability of being cost effective if the WTP was >$30,000 per QALY. Both the ELISA and the UBT were not cost-effective strategies over a wide range of WTP values. CONCLUSION: Although the UBT had the highest sensitivity and specificity, either no screening or the SAT could be the most cost-effective strategy depending on the WTP threshold values from an economic perspective. This highlights the importance of economic evaluations of diagnostic technologies.

Health technology assessment from a Canadian device industry perspective.

Health technology assessment has significantly improved the decision-making process via the thorough and systematic evaluation of the clinical utility and cost-effectiveness of new drugs and health technologies. However, the device industry faces a significant challenge in meeting the evidentiary demands of the health technology assessment process, particularly given the small size of the Canadian market and device manufacturers. This is further compounded by the somewhat short-sighted nature of health care budgets, which see medical devices as a cost-driver given the sometimes significant upfront investment required to implement a technology producing downstream benefits in the long-term. Industry is the research and development of the health care system, but innovative development could be stifled unless the health technology assessment process recognizes the risk of manufacturers. The authors propose that health technology assessment can be improved by recognizing the challenges that device manufacturers face and by sharing the risk associated with evaluations of effectiveness. Health technology assessment is a powerful tool that can be used to evaluate new and potentially obsolete technologies alike, with the goal of meeting the needs of patients as customers of both the device industry and the health care system.

Looking back at 10 years of trastuzumab therapy: what is the role of HER2 testing? A systematic review of health economic analyses.

Trastuzumab is a targeted therapy for human EGF receptor-2 (HER2)-positive breast cancer. The effectiveness and cost-effectiveness of trastuzumab hinges not only on its clinical efficacy in responding patients, but on the ability to accurately identify appropriate therapeutic candidates. We sought to systematically review the cost-effectiveness of trastuzumab with a focus on the impact of the test(s) used for HER2 diagnosis. Our review included 17 economic evaluations or health technology assessments of trastuzumab therapy or HER2 testing. Trastuzumab was considered cost-effective in all early-stage disease studies, while one author concluded that trastuzumab was not cost-effective for metastatic disease. Only two papers considered the joint effects of test accuracy and sequencing with trastuzumab therapy. These demonstrated that trastuzumab cost-effectiveness is sensitive to HER2-test properties.