Background Clostridioides difficile is a Gram-positive anaerobic bacterium, which causes Clostridioides difficile infection (CDI). It has been recognised as a leading cause of healthcare-associated infections and a considerable threat to public health globally. This systematic literature review (SLR) summarises the current evidence on the epidemiology and clinical burden of CDI. Methods A SLR was conducted to identify CDI and recurrent CDI (rCDI) epidemiology studies, to evaluate patient and disease characteristics, incidence rates, epidemiological findings and risk factors. Embase, MEDLINE and the Cochrane Library databases were searched for English articles from 2009 to 2019. Included territories were the United Kingdom, France, Germany, Italy, Spain, Poland, US, Canada, Australia, Japan and China. Results Of 11,243 studies identified, 165 fulfilled the selection criteria. An additional 20 studies were identified through targeted review of grey literature. The most widely reported findings were incidence and risk factors for CDI and rCDI. Among key studies reporting both healthcare-associated (HA-CDI) and community-associated CDI (CA-CDI) incidence rates for each country of interest, incidence rates per 10,000 patient days in the US were 8.00 and 2.00 for HA-CDI and CA-CDI, respectively. The highest incidence in Europe was reported in Poland (HA-CDI: 6.18 per 10,000 patient days, CA-CDI: 1.4 per 10,000 patient days), the lowest from the UK, at 1.99 per 10,000 patient days and 0.56 per 10,000 patient days for HA-CDI and CA-CDI, respectively. No clear trend for incidence over time emerged, with most countries reporting stable rates but some either a decrease or increase. Rates of recurrent CDI varied based on geographical setting. The rate of recurrence was lower in community-associated disease compared to healthcare-associated disease. Independent CDI risk factors identified common to both initial CDI and recurrent CDI included increasing age, antibiotic use, recent hospitalisation, and proton pump inhibitor (PPI) use. In addition, leukocyte count, length of hospital stays, and Charlson comorbidity index score featured as statistically significant risk factors for recurrent CDI, but these are not reported among the most common statistically significant risk factors for initial CDI. Conclusions Despite considerable heterogeneity, evidence suggests substantial incidence of recurrent and primary CDI, even after considerable efforts in the last decade.

Background Parkinson’s disease is a progressive neurodegenerative disease, which significantly impacts patients’ quality of life and is associated with high treatment and direct healthcare costs. In England, levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of levodopa-responsive advanced Parkinson’s disease with troublesome motor fluctuations when available combinations of medicinal products are unsatisfactory. Objective We aimed to determine the cost effectiveness of LCIG compared to the standard of care for patients with advanced Parkinson’s disease in England, using real-world data. Methods A Markov model was adapted from previous published studies, using the perspective of the English National Health System and Personal and Social Services to evaluate the cost effectiveness of LCIG compared to standard of care in patients with advanced Parkinson’s disease over a 20-year time horizon. The model comprised 25 health states, defined by a combination of the Hoehn and Yahr scale, and waking time spent in OFF-time. The base case considered an initial cohort of patients with an Hoehn and Yahr score of ≥ 3, and > 4 h OFF-time. Standard of care comprised standard oral therapies, and a proportion of patients were assumed to be treated with subcutaneous apomorphine infusion or injection in addition to oral therapies. Efficacy inputs were based on LCIG clinical trials where possible. Resource use and utility values were based on results of a large-scale observational study, and costs were derived from the latest published UK data, valued at 2017 prices. The EuroQol five-dimensions-3-level (EQ-5D-3L) instrument was used to measure utilities. Costs and quality-adjusted life-years were discounted at 3.5%. Both deterministic and probabilistic sensitivity analyses were conducted. Results Total costs and quality-adjusted life-years gained for LCIG vs standard of care were £586,832 vs £554,022, and 2.82 vs 1.43, respectively. The incremental cost-effectiveness ratio for LCIG compared to standard of care was £23,649/quality-adjusted life-year. Results were sensitive to the healthcare resource utilisation based on real-world data, and long-term efficacy of LCIG. Conclusions The base-case incremental cost-effectiveness ratio was estimated to be within the acceptable thresholds for cost effectiveness considered for England. Supplementary Information The online version contains supplementary material available at 10.1007/s40273-022-01132-y.

BackgroundAdvocacy around mass treatment for the elimination of selected Neglected Tropical Diseases (NTDs) has typically put the cost per person treated at less than US$ 0.50. Whilst useful for advocacy, the focus on a single number misrepresents the complexity of delivering “free” donated medicines to about a billion people across the world. We perform a literature review and meta-regression of the cost per person per round of mass treatment against NTDs. We develop a web-based software application (https://healthy.shinyapps.io/benchmark/) to calculate setting-specific unit costs against which programme budgets and expenditures or results-based pay-outs can be benchmarked.MethodsWe reviewed costing studies of mass treatment for the control, elimination or eradication of lymphatic filariasis, schistosomiasis, soil-transmitted helminthiasis, onchocerciasis, trachoma and yaws. These are the main 6 NTDs for which mass treatment is recommended. We extracted financial and economic unit costs, adjusted to a standard definition and base year. We regressed unit costs on the number of people treated and other explanatory variables. Regression results were used to “predict” country-specific unit cost benchmarks.ResultsWe reviewed 56 costing studies and included in the meta-regression 34 studies from 23 countries and 91 sites. Unit costs were found to be very sensitive to economies of scale, and the decision of whether or not to use local volunteers. Financial unit costs are expected to be less than 2015 US$ 0.50 in most countries for programmes that treat 100 thousand people or more. However, for smaller programmes, including those in the “last mile”, or those that cannot rely on local volunteers, both economic and financial unit costs are expected to be higher.DiscussionThe available evidence confirms that mass treatment offers a low cost public health intervention on the path towards universal health coverage. However, more costing studies focussed on elimination are needed. Unit cost benchmarks can help in monitoring value for money in programme plans, budgets and accounts, or in setting a reasonable pay-out for results-based financing mechanisms.

Based on the currently available clinical data, this analysis suggests that regorafenib is cost-effective compared with imatinib rechallenge in Germany.