and prevailing perspectives on the economic evaluation to inform choice of instrument in future studies. To examine policy options to deny orphan drug exclusivity after drugs exceed a target population of 200 000 across all orphan indications (combined prevalence threshold) or once drugs receive a nonorphan approval (market approval threshold). Retrospective analysis of drugs with 2 or more orphan approvals from 1983 to July 01, 2017 examining prevalence of orphan indications and approval years of orphan and nonorphan indications. Characteristics of drugs crossing either threshold are described. A budget impact analysis of Medicare and Marketscan® claims databases estimated potential savings from generic or biosimilar entry as a result of foregone market exclusivity periods determined by these policies. Out of 86 drugs with 2 or more orphan approvals, 21 drugs would be denied orphan drug exclusivity periods under the prevalence threshold and 18 drugs would be denied orphan drug exclusivity periods under the market approval threshold. Drugs with orphan approvals after 2010 were more likely to be denied orph for drugs that crossed either threshold. Health systems face nonfinancial constraints that can influence the opportunity cost of interventions. Empirical methods to explore their impact, however, are underdeveloped. We develop a conceptual framework for defining health system constraints and empirical estimation methods that rely on routine data. We then present an empirical approach for incorporating nonfinancial constraints in cost-effectiveness models of health benefit packages for the health sector. We illustrate the application of this approach through a case study of defining a package of services for tuberculosis case-finding in South Africa. An economic model combining transmission model outputs with unit costs was developed to examine the cost-effectiveness of alternative screening and diagnostic algorithms. Constraints were operationalized as restrictions on achievable coverage based on (1) financial resources; (2) human resources; and (3) policy constraints around diagnostics purchasing. Cost-effectiveness of the interventions was asse both the importance and feasibility of considering nonfinancial constraints in health sector resource allocation models. A consensus has been reached in The Netherlands that all future medical costs should be included in economic evaluations. Furthermore, internationally, there is the recognition that in countries that adopt a societal perspective estimates of future nonmedical consumption are relevant for decision makers as much as production gains are. The aims of this paper are twofold (1) to update the tool Practical Application to Include Future Disease Costs (PAID 1.1), based on 2013 data, for the estimation of future unrelated medical costs and introduce future nonmedical consumption costs, further standardizing and facilitating the inclusion of future costs; and (2) to demonstrate how to use the tool in practice, showing the impact of including future unrelated medical costs and future nonmedical consumption in a case-study where a life is hypothetically saved at different ages and 2 additional cases where published studies are updated by including future costs. Using the latest published cost of illness data from the year 2017, we model future unrelated medical costs as a function of age, sex, and time to death, which varies per disease. The Household Survey from Centraal Bureau Statistiek is used to estimate future nonmedical consumption by age. The updated incremental cost-effectiveness ratios (ICERs) from the case studies show that including future costs can have a substantial effect on the ICER, possibly affecting choices made by decision makers. This article improves upon previous work and provides the first tool for the inclusion of future nonmedical consumption in The Netherlands. This article improves upon previous work and provides the first tool for the inclusion of future nonmedical consumption in The Netherlands. Given the limited diagnostic accuracy of radiographs on presentation to the emergency department (ED), the management of suspected scaphoid fractures remains clinically challenging and poses an unknown economic burden to healthcare systems. We aimed to evaluate the cost-effectiveness of immediate magnetic resonance imaging (MRI) in the management of patients presenting with suspected scaphoid fracture to an ED in England. A pragmatic, randomized, single-center trial compared the use of immediate MRI in the ED against standard care with radiographs only. Participants' use of healthcare services and costs were estimated from primary care and secondary care databases and questionnaires at baseline, 1, 3, and 6 months postrecruitment. Costs were compared using generalized linear models and combined with quality-adjusted life years (QALYs, based on the EQ-5D-5L) to estimate cost-effectiveness at 6 months postrecruitment. Cost-effectiveness acceptability curves and bootstrapping techniques were used to estimate the probability of cost-effectiveness at different willingness-to-pay (WTP) thresholds. Four deterministic sensitivity scenarios were considered around key parameters. The MRI intervention dominated standard care in the base case and all 4 deterministic sensitivity scenarios, costing less and achieving more QALY gains, with a probability of 100% of being cost-effective at 6 months using the conventional United Kingdom WTP thresholds of £20 000 to £30 000 per QALY. The use of immediate MRI is a cost-effective intervention in the management of suspected scaphoid fractures in a Central Hospital in London. Routine clinical practice at our institution has been changed to include the intervention. The use of immediate MRI is a cost-effective intervention in the management of suspected scaphoid fractures in a Central Hospital in London. Routine clinical practice at our institution has been changed to include the intervention. To conduct a discrete-choice experiment to quantify Americans' acceptance of severe acute respiratory syndrome coronavirus 2 infection risks for earlier lifting of social-distancing restrictions and diminishing the pandemic's economic impact. We designed a discrete-choice experiment to administer 10 choice questions to each respondent representing experimentally controlled pairs of scenarios defined by when nonessential businesses could reopen (May, July, or October 2020), cumulative percentage of Americans contracting coronavirus disease 2019 (COVID-19) through 2020 (2% to 20%), time for economic recovery (2 to 5 years), and the percentage of US households falling below the poverty threshold (16% to 25%). https://www.selleckchem.com/products/AZD2281(Olaparib).html Respondents were recruited by SurveyHealthcareGlobus. A total of 5953 adults across all 50 states completed the survey between May 8 and 20, 2020. Latent-class analysis supported a 4-class model. The largest class (36%) represented COVID-19 risk-minimizers, reluctant to accept any increases in COVID-19 risks.