In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and... Show moreIn September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inact i v i t y against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but wi l l not eliminate the disease as a public health problem. The potential for Schistosoma to develop resistance towards PZQ , as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments. Show less
Due to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomised studies when considering new... Show moreDue to uncertainty regarding the potential impact of unmeasured confounding, health technology assessment (HTA) agencies often disregard evidence from nonrandomised studies when considering new technologies. Quantitative bias analysis (QBA) methods provide a means to quantify this uncertainty but have not been widely used in the HTA setting, particularly in the context of cost-effectiveness modelling (CEM). This study demonstrated the application of an aggregate and patient-level QBA approach to quantify and adjust for unmeasured confounding in a simulated nonrandomised comparison of survival outcomes. Application of the QBA output within a CEM through deterministic and probabilistic sensitivity analyses and under different scenarios of knowledge of an unmeasured confounder demonstrates the potential value of QBA in HTA. Show less
Evidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence,... Show moreEvidence generated from nonrandomized studies (NRS) is increasingly submitted to health technology assessment (HTA) agencies. Unmeasured confounding is a primary concern with this type of evidence, as it may result in biased treatment effect estimates, which has led to much criticism of NRS by HTA agencies. Quantitative bias analyses are a group of methods that have been developed in the epidemiological literature to quantify the impact of unmeasured confounding and adjust effect estimates from NRS. Key considerations for application in HTA proposed in this article reflect the need to balance methodological complexity with ease of application and interpretation, and the need to ensure the methods fit within the existing frameworks used to assess nonrandomized evidence by HTA bodies. Show less
