Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.

BACKGROUND: Chemotherapy improves outcomes for high risk early breast cancer (EBC) patients but is infrequently offered to older individuals. This study determined if there are fit older patients with high-risk disease who may benefit from chemotherapy. METHODS: A multicentre, prospective, observational study was performed to determine chemotherapy (±trastuzumab) usage and survival and quality-of-life outcomes in EBC patients aged ≥70 years. Propensity score-matching adjusted for variation in baseline age, fitness and tumour stage. RESULTS: Three thousands four hundred sixteen women were recruited from 56 UK centres between 2013 and 2018. Two thousands eight hundred eleven (82%) had surgery. 1520/2811 (54%) had high-risk EBC and 2059/2811 (73%) were fit. Chemotherapy was given to 306/1100 (27.8%) fit patients with high-risk EBC. Unmatched comparison of chemotherapy versus no chemotherapy demonstrated reduced metastatic recurrence risk in high-risk patients(hazard ratio [HR] 0.36 [95% CI 0.19-0.68]) and in 541 age, stage and fitness-matched patients(adjusted HR 0.43 [95% CI 0.20-0.92]) but no benefit to overall survival (OS) or breast cancer-specific survival (BCSS) in either group. Chemotherapy improved survival in women with oestrogen receptor (ER)-negative cancer (OS: HR 0.20 [95% CI 0.08-0.49];BCSS: HR 0.12 [95% CI 0.03-0.44]).Transient negative quality-of-life impacts were observed. CONCLUSIONS: Chemotherapy was associated with reduced risk of metastatic recurrence, but survival benefits were only seen in patients with ER-negative cancer. Quality-of-life impacts were significant but transient. TRIAL REGISTRATION: ISRCTN 46099296.

Cost-Effectiveness Modeling of Surgery Plus Adjuvant Endocrine Therapy Versus Primary Endocrine Therapy Alone in UK Women Aged 70 and Over With Early Breast Cancer.

OBJECTIVES: Approximately 20% of UK women aged 70+ with early breast cancer receive primary endocrine therapy (PET) instead of surgery. PET reduces surgical morbidity but with some survival decrement. To complement and utilize a treatment dependent prognostic model, we investigated the cost-effectiveness of surgery plus adjuvant therapies versus PET for women with varying health and fitness, identifying subgroups for which each treatment is cost-effective. METHODS: Survival outcomes from a statistical model, and published data on recurrence, were combined with data from a large, multicenter, prospective cohort study of over 3400 UK women aged 70+ with early breast cancer and median 52-month follow-up, to populate a probabilistic economic model. This model evaluated the cost-effectiveness of surgery plus adjuvant therapies relative to PET for 24 illustrative subgroups: Age {70, 80, 90} × Nodal status {FALSE (F), TRUE (T)} × Comorbidity score {0, 1, 2, 3+}. RESULTS: For a 70-year-old with no lymph node involvement and no comorbidities (70, F, 0), surgery plus adjuvant therapies was cheaper and more effective than PET. For other subgroups, surgery plus adjuvant therapies was more effective but more expensive. Surgery plus adjuvant therapies was not cost-effective for 4 of the 24 subgroups: (90, F, 2), (90, F, 3), (90, T, 2), (90, T, 3). CONCLUSION: From a UK perspective, surgery plus adjuvant therapies is clinically effective and cost-effective for most women aged 70+ with early breast cancer. Cost-effectiveness reduces with age and comorbidities, and for women over 90 with multiple comorbidities, there is little cost benefit and a negative impact on quality of life.

What cost components are relevant for economic evaluations of palliative care, and what approaches are used to measure these costs? A systematic review.

BACKGROUND: It is important to understand the costs of palliative and end-of-life care in order to inform decisions regarding cost allocation. However, economic research in palliative care is very limited and little is known about the range and extent of the costs that are involved in palliative care provision. AIM: To undertake a systematic review of the health and social care literature to determine the range of financial costs related to a palliative care approach and explore approaches used to measure these costs. DESIGN: A systematic review of empirical literature with thematic synthesis. Study quality was evaluated using the Weight of Evidence Framework. DATA SOURCES: The databases CINAHL, Cochrane, PsycINFO and Medline were searched from 1995 to November 2015 for empirical studies which presented data on the financial costs associated with palliative care. RESULTS: A total of 38 papers met our inclusion criteria. Components of palliative care costs were incurred within four broad domains: hospital care, community or home-based care, hospice care and informal care. These costs could be considered from the economic viewpoint of three providers: state or government, insurers/third-party/not-for-profit organisations and patient and family and/or society. A wide variety of costing approaches were used to derive costs. CONCLUSION: The evidence base regarding the economics of palliative care is sparse, particularly relating to the full economic costs of palliative care. Our review provides a framework for considering these costs from a variety of economic viewpoints; however, further research is required to develop and refine methodologies.

COMPREHENSIVE ASSESSMENT OF COMPLEX TECHNOLOGIES: INTEGRATING VARIOUS ASPECTS IN HEALTH TECHNOLOGY ASSESSMENT.

OBJECTIVES: Despite recent development of health technology assessment (HTA) methods, there are still methodological gaps for the assessment of complex health technologies. The INTEGRATE-HTA guidance for effectiveness, economic, ethical, socio-cultural, and legal aspects, deals with challenges when assessing complex technologies, such as heterogeneous study designs, multiple stakeholder perspectives, and unpredictable outcomes. The objective of this article is to outline this guidance and describe the added value of integrating these assessment aspects. METHODS: Different methods were used to develop the various parts of the guidance, but all draw on existing, published knowledge and were supported by stakeholder involvement. The guidance was modified after application in a case study and in response to feedback from internal and external reviewers. RESULTS: The guidance consists of five parts, addressing five core aspects of HTA, all presenting stepwise approaches based on the assessment of complexity, context, and stakeholder involvement. The guidance on effectiveness, health economics and ethics aspects focus on helping users choose appropriate, or further develop, existing methods. The recommendations are based on existing methods' applicability for dealing with problems arising with complex interventions. The guidance offers new frameworks to identify socio-cultural and legal issues, along with overviews of relevant methods and sources. CONCLUSIONS: The INTEGRATE-HTA guidance outlines a wide range of methods and facilitates appropriate choices among them. The guidance enables understanding of how complexity matters for HTA and brings together assessments from disciplines, such as epidemiology, economics, ethics, law, and social theory. This indicates relevance for a broad range of technologies.

GENE EXPRESSION PROFILING AND EXPANDED IMMUNOHISTOCHEMISTRY TESTS TO GUIDE SELECTION OF CHEMOTHERAPY REGIMENS IN BREAST CANCER MANAGEMENT: A SYSTEMATIC REVIEW.

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint, and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7,064 citations, of which forty-one citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat, and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomized controlled trial data.

The role of service-user feedback in undergraduate nursing courses.

There is an increasing expectation that service users should contribute in a meaningful way to student nurse education courses. This article describes how service-user feedback on undergraduate student nurses' performance during practice learning opportunities (PLOs) gives an insight into the qualities service users value in student nurses. At Cardiff University, the new Bachelor of Nursing course, launched in September 2012, took into account the Nursing and Midwifery (NMC) standards for preregistration, implementing a mechanism for service users to feed back on students' clinical performance. To facilitate this service, user/carer feedback pages were inserted into the students' bound clinical practice portfolio. A large sample of the clinical portfolios (n=100) from one cohort across adult, child and mental health nursing fields were examined at the end of year 1, year 2 and again at the end of year 3, and service users' comments collated. In considering the words used by service users, the authors propose that they reflected the six fundamental values-or 6Cs-of care, compassion, competence, communication, courage and commitment that underpin the delivery of excellent care. Conclusions drawn from the feedback were that students exhibited the caring and professional qualities that service users value, and indeed showed the dignity and respect for patients and people that the profession demands.

Potential Cross-Reactivity Between Penicillin Derivatives and Cephalosporins.

Allergic reactions to both penicillins and cephalosporins are relatively common. Patients who have had a previous allergic reaction to a penicillin derivative may also be prone to a further reaction if treated with cephalosporins. This case illustrates several important points about potential cross-reactivity between penicillin derivatives and cephalosporins, as well as the benefits of an extended-hours pharmacy service in a longterm care facility.

Economic impact of hospitalisations among patients in the last year of life: an observational study.

BACKGROUND: Hospital admissions among patients at the end of life have a significant economic impact. Avoiding unnecessary hospitalisations has the potential for significant cost savings and is often in line with patient preference. OBJECTIVE: To determine the extent of potentially avoidable hospital admissions among patients admitted to hospital in the last year of life and to cost these accordingly. DESIGN: An observational retrospective case note review with economic impact assessment. SETTING: Two large acute hospitals in the North of England, serving contrasting socio-demographic populations. PATIENTS: A total of 483 patients who died within 1 year of admission to hospital. MEASUREMENTS: Data were collected across a range of clinical, demographic, economic and service use variables and were collected from hospital case notes and routinely collected sources. Palliative medicine consultants identified admissions that were potentially avoidable. RESULTS: Of 483 admissions, 35 were classified as potentially avoidable. Avoiding these admissions and caring for the patients in alternative locations would save the two hospitals £5.9 million per year. Reducing length of stay in all 483 patients by 14% has the potential to save the two hospitals £47.5 million per year; however, this cost would have to be offset against increased community care costs. LIMITATIONS: A lack of accurate cost data on alternative care provision in the community limits the accuracy of economic estimates. CONCLUSIONS: Reducing length of hospital stay in palliative care patients may offer the potential to achieve higher hospital cost savings than preventing avoidable admissions. Further research is required to determine both the feasibility of reducing length of hospital stay for patients with palliative care needs and the economic impact of doing so.

Principles of health economic evaluations of lipid-lowering strategies.

PURPOSE OF REVIEW: Policy decision-making in cardiovascular disease is increasingly informed by the results generated from decision-analytic models (DAMs). The methodological approaches and assumptions used in these DAMs impact on the results generated and can influence a policy decision based on a cost per quality-adjusted life year (QALY) threshold. Decision makers need to be provided with a clear understanding of the key sources of evidence and how they are used in the DAM to make an informed judgement on the quality and appropriateness of the results generated. RECENT FINDINGS: Our review identified 12 studies exploring the cost-effectiveness of pharmaceutical lipid-lowering interventions published since January 2010. All studies used Markov models with annual cycles to represent the long-term clinical pathway. Important differences in the model structures and evidence base used within the DAMs were identified. Whereas the reporting standards were reasonably good, there were many instances when reporting of methods could be improved, particularly relating to baseline risk levels, long-term benefit of treatment and health state utility values. SUMMARY: There is a scope for improvement in the reporting of evidence and modelling approaches used within DAMs to provide decision makers with a clearer understanding of the quality and validity of the results generated. This would be assisted by fuller publication of models, perhaps through detailed web appendices.

The CHD challenge: comparing four cost-effectiveness models.

OBJECTIVES: To compare four UK models evaluating the cost-effectiveness of interventions in coronary heart disease (CHD), exploring the relative importance of structure and inputs in accounting for differences, and the scope for consensus on structure and data. METHODS: We compared published cost-effectiveness results (incremental cost, quality-adjusted life year, and cost-effectiveness ratio) of three models conforming to the National Institute for Health and Clinical Excellence guidelines dealing with three interventions (statins, percutaneous coronary intervention, and clopidogrel) with a model developed in Southampton. Comparisons were made using three separate stages: 1) comparison of published results; 2) comparison of the results using the same data inputs wherever possible; and 3) an in-depth exploration of reasons for differences and the potential for consensus. RESULTS: Although published results differed by up to 73% (for statins), standardization of inputs (stage 2) narrowed these gaps. Greater understanding of the reasons for differences was achieved, but a consensus on preferred values for all data inputs was not reached. CONCLUSIONS: We found that published guidance on methods was important to reduce variation in important model inputs. Although the comparison of models did not lead to consensus for all model inputs, it provided a better understanding of the reasons for these differences, and enhanced the transparency and credibility of all models. Similar comparisons would be aided by fuller publication of models, perhaps through detailed web appendices.

What supports and constrains the implementation of multifactorial falls risk assessment and tailored multifactorial falls prevention interventions in acute hospitals? Protocol for a realist review.

INTRODUCTION: Falls are the most common type of safety incident reported by acute hospitals and can cause both physical (eg, hip fractures) and non-physical harm (eg, reduced confidence) to patients. It is recommended that, in order to prevent falls in hospital, patients should receive a multifactorial falls risk assessment and be provided with a multifactorial intervention, tailored to address the patient's identified individual risk factors. It is estimated that such an approach could reduce the incidence of inpatient falls by 25%-30% and reduce the annual cost of falls by up to 25%. However, there is substantial unexplained variation between hospitals in the number and type of assessments undertaken and interventions implemented. METHODS AND ANALYSIS: A realist review will be undertaken to construct and test programme theories regarding (1) what supports and constrains the implementation of multifactorial falls risk assessment and tailored multifactorial falls prevention interventions in acute hospitals; and (2) how, why, in what contexts and for whom tailored multifactorial falls prevention interventions lead to a reduction in patients' falls risk. We will first identify stakeholders' theories concerning these two topics, searching Medline (1946-present) and Medline In-Process & Other Non-Indexed Citations, Health Management Information Consortium (1983-present) and CINAHL (1981-present). We will then test these theories systematically, using primary studies to determine whether empirical evidence supports, refutes or suggests a revision or addition to the identified theories. ETHICS AND DISSEMINATION: The study does not require ethical approval. The review will provide evidence for how to implement multifactorial falls risk assessment and prevention strategies in acute hospital settings. This will be disseminated to academic and clinical audiences and will provide the basis for a future multi-site study through which the theories will be further refined. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020184458.

Observational cohort study to determine the degree and causes of variation in the rate of surgery or primary endocrine therapy in older women with operable breast cancer.

BACKGROUND: In the UK there is variation in the treatment of older women with breast cancer, with up to 40% receiving primary endocrine therapy (PET), which is associated with inferior survival. Case mix and patient choice may explain some variation in practice but clinician preference may also be important. METHODS: A multicentre prospective cohort study of women aged >70 with operable breast cancer. Patient characteristics (health status, age, tumour characteristics, treatment allocation and decision-making preference) were analysed to identify whether treatment variation persisted following case-mix adjustment. Expected case-mix adjusted surgery rates were derived by logistic regression using the variables age, co-morbidity, tumour stage and grade. Concordance between patients' preferred and actual decision-making style was assessed and associations between age, treatment and decision-making style calculated. RESULTS: Women (median age 77, range 70-102) were recruited from 56 UK breast units between 2013 and 2018. Of 2854/3369 eligible women with oestrogen receptor positive breast cancer, 2354 were treated with surgery and 500 with PET. Unadjusted surgery rates varied between hospitals, with 23/56 units falling outside the 95% confidence intervals on funnel plots. Adjusting for case mix reduced, but did not eliminate, this variation between hospitals (10/56 units had practice outside the 95% confidence intervals). Patients treated with PET had more patient-centred decisions compared to surgical patients (42.2% vs 28.4%, p < 0.001). CONCLUSIONS: This study demonstrates variation in treatment selection thresholds for older women with breast cancer. Health stratified guidelines on thresholds for PET would help reduce variation, although patient preference should still be respected.

Treatment choices for older women with primary operable breast cancer and cognitive impairment: Results from a prospective, multicentre cohort study.

OBJECTIVES: The presence of dementia co-existing with a diagnosis of breast cancer may render management more challenging and have a substantial impact on oncological outcomes. The aim of this study was to examine the treatment and outcomes of older women with co-existing cognitive impairment and primary breast cancer. MATERIALS AND METHODS: A prospective, multicentre UK cohort study of women aged 70 years or over with primary operable breast cancer. Patients with and without cognitive impairment were compared to assess differences in treatment and survival outcomes. RESULTS: In total, 3416 women were recruited between 2013 and 2018. Of these, 478 (14%) had a diagnosis of dementia or cognitive impairment, subcategorised as mild, moderate and severely impaired. Up to 85% of women with normal cognition underwent surgery compared to 74%, 61% and 40% with mild, moderate, and severe impairment (p = 0.001). Among women at higher risk of recurrence, the uptake of chemotherapy was 25% for cognitively normal women compared to 20%, 22% and 12% for mild, moderate and severe impairment groups (p = 0.222). Radiotherapy use was similar in the subgroups. Although patients with cognitive impairment had shorter overall survival (HR: 2.10, 95% CI: 1.77-2.50, p < 0.001), there were no statistically significant differences in breast cancer specific or progression-free survival. CONCLUSION: Cognitive impairment appears to play a significant part in deciding how to treat older women with breast cancer. Standard treatment may be over-treatment for some women with severe dementia and careful consideration must be given to a more tailored approach in these women.

Observational cohort study in older women with early breast cancer: Use of radiation therapy and impact on health-related quality of life and mortality.

BACKGROUND: Radiotherapy reduces in-breast recurrence risk in early breast cancer (EBC) in older women. This benefit may be small and should be balanced against treatment effect and holistic patient assessment. This study described treatment patterns according to fitness and impact on health-related quality-of-life (HRQoL). METHODS: A multicentre, observational study of EBC patients aged ≥ 70 years, undergoing breast-conserving surgery (BCS) or mastectomy, was undertaken. Associations between radiotherapy use, surgery, clinico-pathological parameters, fitness based on geriatric parameters and treatment centre were determined. HRQoL was measured using the European Organisation for the Research and Treatment of Cancer (EORTC) questionnaires. RESULTS: In 2013-2018 2811 women in 56 UK study centres underwent surgery with a median follow-up of 52 months. On multivariable analysis, age and tumour risk predicted radiotherapy use. Among healthier patients (based on geriatric assessments) with high-risk tumours, 534/613 (87.1%) having BCS and 185/341 (54.2%) having mastectomy received radiotherapy. In less fit individuals with low-risk tumours undergoing BCS, 149/207 (72.0%) received radiotherapy. Radiotherapy effects on HRQoL domains, including breast symptoms and fatigue were seen, resolving by 18 months. CONCLUSION: Radiotherapy use in EBC patients ≥ 70 years is affected by age and recurrence risk, whereas geriatric parameters have limited impact regardless of type of surgery. There was geographical variation in treatment, with some fit older women with high-risk tumours not receiving radiotherapy, and some older, low-risk, EBC patients receiving radiotherapy after BCS despite evidence of limited benefit. The impact on HRQoL is transient.

Bridging the age gap in breast cancer. Impacts of omission of breast cancer surgery in older women with oestrogen receptor positive early breast cancer. A risk stratified analysis of survival outcomes and quality of life.

BACKGROUND: Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET. METHODS: Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET. FINDINGS: A total of 3416 women (median age 77, range 69-102) were recruited from 56 breast units-2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23-0.33, P < 0.001). Unmatched breast cancer-specific survival (BCSS) was also inferior in patients treated with PET (HR: 0.41, CI: 0.29-0.58, P < 0.001 for BCSS). In the matched analysis, PET was still associated with an inferior overall survival (HR = 0.72, 95% CI: 0.53-0.98, P = 0.04) but not BCSS (HR = 0.74, 95% CI: 0.40-1.37, P = 0.34) although at 4-5 years subtle divergence of the curves commenced in favor of surgery. Global health status diverged at certain time points between groups but over 24 months was similar when adjusted for baseline variance. INTERPRETATION: For the majority of older women with early ER+ breast cancer, surgery is oncologically superior to PET. In less fit, older women, with characteristics similar to the matched cohort of this study (median age 81 with higher comorbidity and functional impairment burdens, the BCSS survival differential disappears at least out to 4-5 year follow-up, suggesting that for those with less than 5-year predicted life-expectancy (>90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/). TRIAL REGISTRATION NUMBER: ISRCTN: 46099296.

Bridging the Age Gap in breast cancer: Impact of chemotherapy on quality of life in older women with early breast cancer.

INTRODUCTION: Older patients with early breast cancer (EBC) derive modest survival benefit from chemotherapy but have increased toxicity risk. Data on the impact of chemotherapy for EBC on quality of life in older patients are limited, but this is a key determinant of treatment acceptance. We aimed to investigate its effect on quality of life in older patients enrolled in the Bridging the Age Gap study. MATERIALS AND METHODS: A prospective, multicentre, observational study of EBC patients ≥70 years old was conducted in 2013-2018 at 56 UK hospitals. Demographics, patient, tumour characteristics, treatments and adverse events were recorded. Quality of life was assessed using the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires (EORTC-QLQ) C30, BR23 and ELD 15 plus the Euroqol-5D (eq-5d) over 24 months and analysed at each time point using baseline adjusted linear regression analysis and propensity score-matching. RESULTS: Three thousand and four hundred sixteen patients were enrolled in the study; 1520 patients undergoing surgery and who had high-risk EBC were included in this analysis. 376/1520 (24.7%) received chemotherapy. At 6 months, chemotherapy had a significant negative impact in several EORTC-QLQ-C30 domains, including global health score, physical, role, social functioning, cognition, fatigue, nausea/vomiting, dyspnoea, appetite loss, diarrhoea and constipation. Similar trends were documented on other scales (EORTC-QLQ-BR23, EORTC-QLQ-ELD15 and EQ-5D-5L). Its impact was no longer significant at 18-24 months in unmatched and matched cohorts. CONCLUSIONS: The negative impact of chemotherapy on quality-of-life is clinically and statistically significant at 6 months but resolves by 18 months, which is crucial to inform decision-making for older patients contemplating chemotherapy. TRIAL REGISTRATION NUMBER ISRCTN: 46099296.

Statin therapy in rheumatoid arthritis: a cost-effectiveness and value-of-information analysis.

HMG-CoA reductase inhibitors (statins) are potentially excellent candidate agents for patients with rheumatoid arthritis (RA). They reduce both cardiovascular risks and RA disease activity. To evaluate the potential long-term effects of statin therapy among patients with RA, and to determine their associated cost effectiveness by incorporating both the cardiovascular and the anti-rheumatic benefits. A Markov decision-analytic model was developed to simulate cardiovascular and RA disease profiles over time. The impact of statin therapy was estimated by adjusting the risk of coronary heart disease (CHD) events and changes in the RA Disease Activity Score (DAS28), based on the results of a randomized trial. The benefits (QALYs) and costs (in year 2005 values) were evaluated from a US payer perspective. A full uncertainty analysis, including a value-of-information (VOI) analysis, was undertaken to evaluate the importance of individual parameters. Using a 10-year time horizon, the additional cost and QALYs of statin therapy were estimated to be USD4690 and 0.44 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of USD10 650 per QALY (95% CI 1525, 156 565). The QALY gain associated with statin therapy depended more on the anti-rheumatic effects of statin therapy than on its cardiovascular prevention effect. The VOI analysis found the long-term benefit of statin therapy (i.e. >or=12 months) and the consequent impact on quality of life to be the most uncertain and, therefore, influential parameters. Our analysis indicates that the dual anti-inflammatory/cardiovascular benefits of statins could make this therapy highly cost effective in RA. However, uncertainties remain in the available data, warranting further research on refining the precise RA disease-activity benefits and health-utility changes associated with statin therapy, at least over a 12-month period.

The Expanded Evidence-Centered Design (e-ECD) for Learning and Assessment Systems: A Framework for Incorporating Learning Goals and Processes Within Assessment Design.

Evidence-centered design (ECD) is a framework for the design and development of assessments that ensures consideration and collection of validity evidence from the onset of the test design. Blending learning and assessment requires integrating aspects of learning at the same level of rigor as aspects of testing. In this paper, we describe an expansion to the ECD framework (termed e-ECD) such that it includes the specifications of the relevant aspects of learning at each of the three core models in the ECD, as well as making room for specifying the relationship between learning and assessment within the system. The framework proposed here does not assume a specific learning theory or particular learning goals, rather it allows for their inclusion within an assessment framework, such that they can be articulated by researchers or assessment developers that wish to focus on learning.

Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis.

BACKGROUND: Breast cancer and its treatment can have an impact on health-related quality of life and survival. Tumour profiling tests aim to identify whether or not women need chemotherapy owing to their risk of relapse. OBJECTIVES: To conduct a systematic review of the effectiveness and cost-effectiveness of the tumour profiling tests oncotype DX® (Genomic Health, Inc., Redwood City, CA, USA), MammaPrint® (Agendia, Inc., Amsterdam, the Netherlands), Prosigna® (NanoString Technologies, Inc., Seattle, WA, USA), EndoPredict® (Myriad Genetics Ltd, London, UK) and immunohistochemistry 4 (IHC4). To develop a health economic model to assess the cost-effectiveness of these tests compared with clinical tools to guide the use of adjuvant chemotherapy in early-stage breast cancer from the perspective of the NHS and Personal Social Services. DESIGN: A systematic review and health economic analysis were conducted. REVIEW METHODS: The systematic review was partially an update of a 2013 review. Nine databases were searched in February 2017. The review included studies assessing clinical effectiveness in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I or II cancer with zero to three positive lymph nodes. The economic analysis included a review of existing analyses and the development of a de novo model. RESULTS: A total of 153 studies were identified. Only one completed randomised controlled trial (RCT) using a tumour profiling test in clinical practice was identified: Microarray In Node-negative Disease may Avoid ChemoTherapy (MINDACT) for MammaPrint. Other studies suggest that all the tests can provide information on the risk of relapse; however, results were more varied in lymph node-positive (LN+) patients than in lymph node-negative (LN0) patients. There is limited and varying evidence that oncotype DX and MammaPrint can predict benefit from chemotherapy. The net change in the percentage of patients with a chemotherapy recommendation or decision pre/post test ranged from an increase of 1% to a decrease of 23% among UK studies and a decrease of 0% to 64% across European studies. The health economic analysis suggests that the incremental cost-effectiveness ratios for the tests versus current practice are broadly favourable for the following scenarios: (1) oncotype DX, for the LN0 subgroup with a Nottingham Prognostic Index (NPI) of > 3.4 and the one to three positive lymph nodes (LN1-3) subgroup (if a predictive benefit is assumed); (2) IHC4 plus clinical factors (IHC4+C), for all patient subgroups; (3) Prosigna, for the LN0 subgroup with a NPI of > 3.4 and the LN1-3 subgroup; (4) EndoPredict Clinical, for the LN1-3 subgroup only; and (5) MammaPrint, for no subgroups. LIMITATIONS: There was only one completed RCT using a tumour profiling test in clinical practice. Except for oncotype DX in the LN0 group with a NPI score of > 3.4 (clinical intermediate risk), evidence surrounding pre- and post-test chemotherapy probabilities is subject to considerable uncertainty. There is uncertainty regarding whether or not oncotype DX and MammaPrint are predictive of chemotherapy benefit. The MammaPrint analysis uses a different data source to the other four tests. The Translational substudy of the Arimidex, Tamoxifen, Alone or in Combination (TransATAC) study (used in the economic modelling) has a number of limitations. CONCLUSIONS: The review suggests that all the tests can provide prognostic information on the risk of relapse; results were more varied in LN+ patients than in LN0 patients. There is limited and varying evidence that oncotype DX and MammaPrint are predictive of chemotherapy benefit. Health economic analyses indicate that some tests may have a favourable cost-effectiveness profile for certain patient subgroups; all estimates are subject to uncertainty. More evidence is needed on the prediction of chemotherapy benefit, long-term impacts and changes in UK pre-/post-chemotherapy decisions. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017059561. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Breast cancer is the most commonly diagnosed cancer in women in England and Wales. Breast cancer, and its treatment, can have an impact on a person's health-related quality of life and survival. Tumour profiling tests are used before chemotherapy. They test small samples of a patient's tumour (removed during surgery) to find out whether the genes in it mean that a person has a high or low risk of the disease returning (relapse). If the risk is low, the patient may be able to avoid having chemotherapy and, therefore, avoid its side effects. Some tests might also be able to identify which patients will respond to chemotherapy. This study looked at the evidence for five tumour profiling tests. A total of 153 studies were identified. This study considered the results and the quality of the studies to find out if the tests are helpful. Most studies had design flaws (e.g. some patients had already had chemotherapy) that meant that the studies were of low quality overall. The results suggest that all of the tests can give information on the risk of relapse; however, some tests may be less useful in patients whose disease has spread to the lymph nodes (lymph node-positive disease). There was limited and varying evidence about whether or not two of these tests can also predict which patients will respond to chemotherapy. This study also looked at whether or not these tests represent good value for money for the NHS through cost-effectiveness analyses. The analyses showed that some of the tests may represent a good use of NHS resources for some patient groups; however, there was still a lot of uncertainty about this.