Katie Breheny

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing — A Systematic Review

Background The prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression. Aims This systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur. Methods Articles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies. Results The initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model. Conclusion Future economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.

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 earths 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.