The Importance of Model Structure in the Cost-Effectiveness Analysis of Primary Care Interventions for the Management of Hypertension.

BACKGROUND: Management of hypertension can lead to significant reductions in blood pressure, thereby reducing the risk of cardiovascular disease. Modeling the course of cardiovascular disease is not without complications, and uncertainty surrounding the structure of a model will almost always arise once a choice of a model structure is defined. OBJECTIVES: To provide a practical illustration of the impact on the results of cost-effectiveness of changing or adapting model structures in a previously published cost-utility analysis of a primary care intervention for the management of hypertension Targets and Self-Management for the Control of Blood Pressure in Stroke and at Risk Groups (TASMIN-SR). METHODS: The case study assessed the structural uncertainty arising from model structure and from the exclusion of secondary events. Four alternative model structures were implemented. Long-term cost-effectiveness was estimated and the results compared with those from the TASMIN-SR model. RESULTS: The main cost-effectiveness results obtained in the TASMIN-SR study did not change with the implementation of alternative model structures. Choice of model type was limited to a cohort Markov model, and because of the lack of epidemiological data, only model 4 captured structural uncertainty arising from the exclusion of secondary events in the case study model. CONCLUSIONS: The results of this study indicate that the main conclusions drawn from the TASMIN-SR model of cost-effectiveness were robust to changes in model structure and the inclusion of secondary events. Even though one of the models produced results that were different to those of TASMIN-SR, the fact that the main conclusions were identical suggests that a more parsimonious model may have sufficed.

Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A Systematic Review.

BACKGROUND: Latent tuberculosis infection (LTBI) provides a constant pool of new active tuberculosis cases; a third of the earth's population is estimated to be infected with LTBI. OBJECTIVE: The objective of this systematic review was to assess the quality and summarize the available evidence from published economic evaluations reporting on the cost-effectiveness of tuberculin skin tests (TSTs) compared with interferon gamma release assays (IGRAs) for the screening of LTBI. METHODS: An extensive systematic review of the published literature was conducted. A two-step process was adopted to identify relevant articles: information was extracted into evidence tables and then analyzed. The quality of the publications was assessed using a 10-item checklist specific for economic evaluations. RESULTS: Twenty-eight studies were identified for inclusion in this review. Most of the studies found IGRAs to be more cost-effective than TSTs; however, the conclusions from the studies varied significantly. Most studies scored highly on the checklist although only one fulfilled all the stipulated criteria. A wide variety of methodological approaches were documented; identified differences included the type of economic evaluation and model, time horizon, perspective, and outcomes measures. CONCLUSIONS: The lack of consistent methods across studies makes it difficult to draw any firm conclusions about the most cost-effective option between TSTs and IGRAs. This problem can be solved by improving the quality of economic evaluation studies in the field of LTBI screening, through adherence to quality checklists.

Methods Used in Economic Evaluations of Testing and Diagnosis for Ovarian Cancer: A Systematic Review.

OBJECTIVE: There are multiple tests available that can help diagnose ovarian cancer, and the cost-effective analysis of these diagnostic interventions is essential for making well-informed decisions regarding resource allocation. There are multiple factors that can impact on the conclusions drawn from economic evaluations including test accuracy, the impact of the testing pathway on patient costs and outcomes, and delays along the ovarian cancer test-treat pathway. The objective of this study was to evaluate how test accuracy, the choice of perspective, and delays along the testing and diagnostic pathway have been incorporated in economic evaluations of testing for ovarian cancer. METHODS: A systematic review of published literature was undertaken to identify economic evaluations (eg, cost-effectiveness, cost-utility analysis) focused on testing and diagnosis for ovarian cancer. RESULTS: Seven studies met the inclusion criteria. Six studies incorporated test accuracy and its impact on patients to some extent. Four studies adopted a societal perspective, but only one considered the costs incurred by patients on the testing and diagnosis pathway. Where delays on the testing pathway were incorporated into the analysis, these were frequently due to false-negative test results leading to delays in patients accessing treatment. Any anxiety that patients might experience as a result of a positive test was not considered in these studies. CONCLUSIONS: The impact on patients of receiving a positive test in terms of anxiety and the costs incurred by patients having to attend for testing and diagnosis are rarely considered. Delays along the testing and diagnosis pathway can have a major effect on patient outcomes, and it is important that these are acknowledged in economic evaluations focused on testing. Future economic analysis should incorporate these key determinants in order that diagnostic tests for ovarian cancer can be robustly evaluated.

A Systematic Review of Research Guidelines in Decision-Analytic Modeling.

BACKGROUND: Decision-analytic modeling (DAM) has been increasingly used to aid decision making in health care. The growing use of modeling in economic evaluations has led to increased scrutiny of the methods used. OBJECTIVE: The objective of this study was to perform a systematic review to identify and critically assess good practice guidelines, with particular emphasis on contemporary developments. METHODS: A systematic review of English language articles was undertaken to identify articles presenting guidance for good practice in DAM in the evaluation of health care. The inclusion criteria were articles providing guidance or criteria against which to assess good practice in DAM and studies providing criteria or elements for good practice in some areas of DAM. The review covered the period January 1990 to March 2014 and included the following electronic bibliographic databases: Cochrane Library, Cochrane Methodology Register and Health Technology Assessment, NHS Economic Evaluation Database, MEDLINE, and PubMed (Embase). Additional studies were identified by searching references. RESULTS: Thirty-three articles were included in this review. A practical five-dimension framework was developed that describe the key elements of good research practice that should be considered and reported to increase the credibility of results obtained from DAM in the evaluation of health care. CONCLUSIONS: This study is the first to critically review all available guidelines and statements of good practice in DAM since 2006. The development of good practice guidelines is an ongoing process, and important efforts have been made to identify what is good practice and to keep these guidelines up to date.

Cost-effectiveness of a new autoantibody test added to Computed Tomography (CT) compared to CT surveillance alone in the diagnosis of lung cancer amongst patients with indeterminate pulmonary nodules.

Oncimmune's EarlyCDT®-Lung is a simple ELISA blood test that measures seven lung cancer specific autoantibodies and is used in the assessment of malignancy risk in patients with indeterminate pulmonary nodules (IPNs). The objective of this study was to examine the cost-effectiveness of EarlyCDT-Lung in the diagnosis of lung cancer amongst patients with IPNs in addition to CT surveillance, compared to CT surveillance alone which is the current recommendation by the British Thoracic Society guidelines. A model consisting of a combination of a decision tree and Markov model was developed using the outcome measure of the quality adjusted life year (QALY). A life-time time horizon was adopted. The model was parameterized using a range of secondary sources. At £70 per test, EarlyCDT-Lung and CT surveillance was found to be cost-effective compared to CT surveillance alone with an incremental cost-effectiveness ratio (ICER) of less than £2,500 depending on the test accuracy parameters used. It was also found that EarlyCDT-Lung can be priced up to £1,177 and still be cost-effective based on cost-effectiveness acceptance threshold of £20,000 / QALY. Further research to resolve parameter uncertainty, was not found to be of value. The results here demonstrate that at £70 per test the EarlyCDT-Lung will have a positive impact on patient outcomes and coupled with CT surveillance is a cost-effective approach to the management of patients with IPNs. The conclusions drawn from this analysis are robust to realistic variation in the parameters used in the model.

Feasibility randomised controlled trial of a guided workbook intervention to support work-related goals among cancer survivors in the UK.

OBJECTIVES: Employment following illness is associated with better physical and psychological functioning. This study aimed to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support patients with cancer returning to work. DESIGN: Parallel-group randomised controlled trial with embedded qualitative interviews. SETTING: Oncology clinics within four English National Health Service Trusts. PARTICIPANTS: Patients who had received a diagnosis of breast, gynaecological, prostate or colorectal cancer and who had been receiving treatment for a minimum of two weeks. INTERVENTION: A self-guided WorkPlan workbook designed to support patients with cancer to return to work with fortnightly telephone support calls to discuss progress. The control group received treatment as usual and was offered the workbook at the end of their 12-month follow-up. OUTCOME MEASURES: We assessed aspects of feasibility including eligibility, recruitment, data collection, attrition, feasibility of the methodology, acceptability of the intervention and potential to calculate cost-effectiveness. RESULTS: The recruitment rate of eligible patients was 44%; 68 participants consented and 58 (85%) completed baseline measures. Randomisation procedures were acceptable, data collection methods (including cost-effectiveness data) were feasible and the intervention was acceptable to participants. Retention rates at 6-month and 12-month follow-up were 72% and 69%, respectively. At 6-month follow-up, 30% of the usual care group had returned to full-time or part-time work (including phased return to work) compared with 43% of the intervention group. At 12 months, the percentages were 47% (usual care) and 68% (intervention). CONCLUSIONS: The findings confirm the feasibility of a definitive trial, although further consideration needs to be given to increasing the participation rates among men and black and ethnic minority patients diagnosed with cancer. TRIAL REGISTRATION NUMBER: ISRCTN56342476; Pre-results.

Usefulness and engagement with a guided workbook intervention (WorkPlan) to support work related goals among cancer survivors.

BACKGROUND: Returning to work after cancer is associated with improved physical and psychological functioning, but managing this return can be a challenging process. A workbook based intervention (WorkPlan) was developed to support return-to-work among cancer survivors. The aim of this study was to explore how participants using the workbook engaged with the intervention and utilised the content of the intervention in their plan to return-to-work. METHODS: As part of a feasibility randomised controlled trial, 23 participants from the intervention group were interviewed 4-weeks post intervention. Interviews focussed on intervention delivery and data was analysed using Framework analysis. RESULTS: Participants revealed a sense of empowerment and changes in their outlook as they transitioned from patient to employee, citing the act of writing as a medium for creating their own return-to-work narrative. Participants found the generation of a return-to-work plan useful for identifying potential problems and solutions, which also served as a tool for aiding discussion with the employer on return-to-work. Additionally, participants reported feeling less uncertain and anxious about returning to work. Timing of the intervention in coordination with ongoing cancer treatments was crucial to perceived effectiveness; participants identified the sole or final treatment as the ideal time to receive the intervention. CONCLUSIONS: The self-guided workbook supports people diagnosed with cancer to build their communication and planning skills to successfully manage their return-to-work. Further research could examine how writing plays a role in this process. TRIAL REGISTRATION: Current Controlled Trials ISRCTN56342476 . Retrospectively registered 14 October 2015.

Should we screen for the sexually-transmitted infection Mycoplasma genitalium? Evidence synthesis using a transmission-dynamic model.

There is increasing concern about Mycoplasma genitalium as a cause of urethritis, cervicitis, pelvic inflammatory disease (PID), infertility and ectopic pregnancy. Commercial nucleic acid amplification tests (NAATs) are becoming available, and their use in screening for M. genitalium has been advocated, but M. genitalium's natural history is poorly-understood, making screening's effectiveness unclear. We used a transmission-dynamic compartmental model to synthesise evidence from surveillance data and epidemiological and behavioural studies to better understand M. genitalium's natural history, and then examined the effects of implementing NAAT testing. Introducing NAAT testing initially increases diagnoses, by finding a larger proportion of infections; subsequently the diagnosis rate falls, due to reduced incidence. Testing only symptomatic patients finds relatively little infection in women, as a large proportion is asymptomatic. Testing both symptomatic and asymptomatic patients has a much larger impact and reduces cumulative PID incidence in women due to M. genitalium by 31.1% (95% range:13.0%-52.0%) over 20 years. However, there is important uncertainty in M. genitalium's natural history parameters, leading to uncertainty in the absolute reduction in PID and sequelae. Empirical work is required to improve understanding of key aspects of M. genitalium's natural history before it will be possible to determine the effectiveness of screening.

Do Economic Evaluations in Primary Care Prevention and the Management of Hypertension Conform to Good Practice Guidelines? A Systematic Review.

Background: Results of previous research have identified the need for further investigation into the compliance with good practice guidelines for current decision-analytic modeling (DAM). Objective: To identify the extent to which recent model-based economic evaluations of interventions focused on lowering the blood pressure (BP) of patients with hypertension conform to published guidelines for DAM in health care using a five-dimension framework developed to assess compliance to DAM guidelines. Methods: A systematic review of English language articles was undertaken to identify published model-based economic evaluations that examined interventions aimed at lowering BP. The review covered the period January 2000 to March 2015 and included the following electronic bibliographic databases: EMBASE and Medline via Ovid interface and the Centre for Reviews and Dissemination's (CRD) NHS-EED. Data were extracted based on different components of good practice across five dimensions utilizing a framework to assess compliance to DAM guidelines. Results: Thirteen articles were included in this review. The review found limited compliance to good practice DAM guidelines, which was most frequently justified by the lack of data. Conclusions: The assessment of structural uncertainty cannot yet be considered common practice in primary prevention and management of hypertension, and researchers seem to face difficulties with identifying sources of structural uncertainty and then handling them correctly. Additional guidelines are needed to aid researchers in identifying and managing sources of potential structural uncertainty. Adherence to guidelines is not always possible and it does pose challenges, in particular when there are limitations due to data availability that restrict, for example, a validation process.