Using Threshold Analysis to Assess the Robustness of Public Health Intervention Recommendations from Network Meta-Analyses: Application to Poison Prevention in Households with Children Under Five

BackgroundIn the appraisal of clinical interventions, complex evidence synthesis methods, such as network meta-analysis (NMA), are commonly used to investigate the effectiveness of multiple interventions in a single analysis. The results from a NMA can inform clinical guidelines directly or be used as inputs into a decision-analytic model assessing the cost-effectiveness of the interventions. However, there is hesitancy in using complex evidence synthesis methods when evaluating public health interventions. This is due to significant heterogeneity across studies investigating such interventions and concerns about their quality. Threshold analysis has been developed to help assess and quantify the robustness of recommendations made based on results obtained from NMAs to potential limitations of the data. Developed in the context of clinical guidelines, the method may prove useful also in the context of public health interventions. In this paper, we illustrate the use of the method in the study investigating the effectiveness of interventions aiming to increase the uptake of poison prevention behaviours in homes with children aged 0-5.MethodsRandom effects NMA was carried out to assess the effectiveness of several interventions for increasing the uptake of poison prevention behaviours, focusing on the safe storage of other household products outcome. Threshold analysis was then applied to the NMA to assess the robustness of the intervention recommendations made based on the NMA.Results15 studies assessing seven interventions were included in the NMA. The results of the NMA indicated that complex intervention, including Education, Free/low-cost equipment, Fitting equipment and Home safety inspection, was the most effective intervention at promoting poison prevention behaviours. However, the threshold analyses highlighted that this intervention recommendation was not robust.Conclusions In our case study, threshold analysis allowed us to demonstrate that the intervention recommendation for promoting poison prevention behaviours was not robust to changes in the evidence due to potential bias. Therefore, caution should be taken when considering such interventions in practice. We have illustrated the potential benefit of threshold analysis and, therefore, encourage the use of the method in practice as a sensitivity analysis for NMA of public health interventions.

Early Treatment with fluvoxamine among patients with COVID-19: a cost-consequence model

ABSTRACT Background Three randomized trials have been conducted indicating a clinical benefit of early treatment with fluvoxamine versus placebo for adults with symptomatic COVID-19. We assessed the cost-consequences associated with the use of this early treatment in outpatient populations. Methods Using results from the three completed trials of fluvoxamine vs. placebo for the treatment of COVID-19, we performed a meta-analysis. We conducted a cost-consequence analysis using a decision-model to assess the health system benefits of the avoidance of progression to severe COVID-19. Outcomes of relevance to resource planning decisions in the US and elsewhere, including costs and days of hospitalization avoided, were reported. We constructed a decision-analytic model in the form of a decision tree to evaluate two treatment strategies for high-risk patients with confirmed, symptomatic COVID-19, from the perspective of a third-party payer: (1) treatment with a 10-day course of fluvoxamine (100mg twice daily); (2) current standard-of-care; (3) molnupiravir 5-day course. We used a time horizon of 28 days. Results Administration of fluvoxamine to symptomatic outpatients with COVID-19 at high-risk of developing progression to severe COVID-19 complications is substantially cost-saving in the US, in the amount of $232 per eligible patient, and saves an average of 0.15 hospital days per patient treated is likely to be similarly beneficial in other settings. Fluvoxamine is cost saving in locations where total hospital costs are >$738. Molnupiravir had an additional cost to the healthcare system of $404 per patient treated. Conclusions Fluvoxamine is cost-saving for COVID-19 outpatient therapy.

The economic impact of rostering junior doctors to triage to assist nursing staff in the early part of the patient journey through the emergency department

Objective This study aims to determine whether redeploying junior doctors to assist at triage represents good value for money and a good use of finite staffing resources. Methods We undertook a cost-minimisation analysis to produce new evidence, from an economic perspective, about the costs associated with reallocating junior doctors in the emergency department. We built a decision-analytic model, using a mix of prospectively collected data, routinely collected administrative databases and hospital costings to furnish the model. To measure the impact of uncertainty on the model’s inputs and outputs, probabilistic sensitivity analysis was undertaken, using Monte Carlo simulation. Results The mean costs for usual care were $27,035 (95% CI $27,016 to $27,054), while the mean costs for the new model of care were $25,474, (95% CI $25,453 to $25,494). As a result, the mean difference was -$1,561 (95% CI -$1,533 to -$1,588), with the new model of care being a less costly approach to managing staffing allocations, in comparison to the usual approach. Conclusion Our study shows that redeploying a junior doctor from the fast-track area of the department to assist at triage provides a modest reduction in cost. Our findings give decision-makers who seek to maximise benefit from their finite budget, support to reallocate personnel within the ED.

Cost-Effectiveness of Nutrient Supplementation in Cancer Survivors

Cancer patients are at risk for malnutrition; the aim of this study was to provide a cost-effectiveness analysis of dietary supplementation in cancer survivors. We estimated prevalence of supplementation, hospitalization rates, quality of life (QOL), cost of care and mortality among cancer survivors. We built a decision analytic model to simulate life-long costs of health care and supplementation and QOL among cancer survivors with and without supplementation. Cost of supplements was derived from national pharmacy databases including single- and multivitamin formularies. One-way and probabilistic sensitivity analysis were performed to evaluate the robustness of the incremental cost-effectiveness ratio (ICER) to changes in supplementation costs and duration. The study cohort represented the national cancer survivor population (average age 61 years, 85% white, 52% male, and 94% insured). Hospitalization rates for supplement users and non-users were 12% and 21%, respectively. The cost of hospitalization was $4030. Supplementation was associated with an additional 0.48 QALYs (10.26 vs. 9.78) at the incremental cost of $2094 ($236,933 vs. $234,839) over the remaining lifetime of survivors (on average 13 years). Adequate nutrition provides a cost-effective strategy to achieving potentially optimum health. Further studies are needed to determine the effects of specific nutrient doses and supplementation on long-term outcomes per cancer type.

Cost-effectiveness of cryptococcal antigen screening at CD4 counts of 101–200 cells/µL in Botswana

Background: Cryptococcal antigen (CrAg) screening in individuals with advanced HIV reduces cryptococcal meningitis (CM) cases and deaths. The World Health Organization recently recommended increasing screening thresholds from CD4 ≤100 cells/µL to ≤200 cells/µL. CrAg screening at CD4 ≤100 cells/µL is cost-effective; however, the cost-effectiveness of screening patients with CD4 101–200 cells/µL requires evaluation. Methods: Using a decision analytic model with Botswana-specific cost and clinical estimates, we evaluated CrAg screening and treatment among individuals with CD4 counts of 101–200 cells/µL. We estimated the number of CM cases and deaths nationally and treatment costs without screening. For screening we modeled the number of CrAg tests performed, number of CrAg-positive patients identified, proportion started on pre-emptive fluconazole, CM cases and deaths. Screening and treatment costs were estimated and cost per death averted or disability-adjusted life year (DALY) saved compared with no screening. Results: Without screening, we estimated 142 CM cases and 85 deaths annually among individuals with CD4 101–200 cells/µL, with treatment costs of $368,982. With CrAg screening, an estimated 33,036 CrAg tests are performed, and 48 deaths avoided (1,017 DALYs saved). While CrAg screening costs an additional $155,601, overall treatment costs fall by $39,600 (preemptive and hospital-based CM treatment), yielding a net increase of $116,001. Compared to no screening, high coverage of CrAg screening and pre-emptive treatment for CrAg-positive individuals in this population avoids one death for $2440 and $114 per DALY saved. In sensitivity analyses assuming a higher proportion of antiretroviral therapy (ART)-naïve patients (75% versus 15%), cost per death averted was $1472; $69 per DALY saved. Conclusions: CrAg screening for individuals with CD4 101–200 cells/µL was estimated to have a modest impact, involve additional costs, and be less cost-effective than screening populations with CD4 counts ≤100 cells/µL. Additional CrAg screening costs must be considered against other health system priorities.

PP219 Combining Healthcare Solutions For Cataract Surgery. An Incremental Benefit Analysis From The Perspective Of The Russian Healthcare System

IntroductionRising health expenditures lead to increasing budgetary pressures, which often manifest in budget managers seeking more for the same resources or trying to maintain the status quo with less. Consequently, enablers that drive efficiencies throughout the entire care pathway have come under increasing focus. This is particularly true in the operating room (OR) setting where considerations around operational efficiency, clinical excellence, and patient-centered care pose challenging questions. While a comprehensive solution set should be formulated, small parts of the solution can be applied now to prime systems for easy integration into future solutions. The objective of this analysis was to estimate the impact of combining custom healthcare solutions for cataract surgery from the perspective of a Russian hospital.MethodsA decision-analytic model was developed to assess the aggregated impact of combining the following products or services for cataract surgery: an intraocular lens delivery-system; process-redesign; a phacoemulsification machine; and a phaco tip. The model and underlying assumptions were validated by clinical experts. OR time-savings was chosen as the variable of efficiency underpinning the analysis. Inputs were estimated from the literature, expert opinion, and the local cost databases. Two scenarios were defined that reflected technologies commonly used in surgical practice. The model scenarios assumed that a hospital performs 2,000 cataract procedures per year, with 100 percent adoption and equal acquisition costs.ResultsChoosing a combination of healthcare solutions for cataract surgery was associated with an incremental benefit of RUB5,935,982 per year (EUR71,364) and generated an OR time saving of approximately 237 cataract procedures.ConclusionsThis analysis highlighted that, compared with treating technologies on an individual level, combining healthcare solutions commonly used for cataract surgery has the potential to drive efficiencies and cost savings for hospitals and to reduce surgical wait lists.

Development and validation of ester impregnated pH strips for locating nasogastric feeding tubes in the stomach—a multicentre prospective diagnostic performance study

Background NG (nasogastric) tubes are used worldwide as a means to provide enteral nutrition. Testing the pH of tube aspirates prior to feeding is commonly used to verify tube location before feeding or medication. A pH at or lower than 5.5 was taken as evidence for stomach intubation. However, the existing standard pH strips lack sensitivity, especially in patients receiving feeding and antacids medication. We developed and validated a first-generation ester-impregnated pH strip test to improve the accuracy towards gastric placements in adult population receiving routine NG-tube feeding. The sensitivity was improved by its augmentation with the action of human gastric lipase (HGL), an enzyme specific to the stomach. Methods We carried out a multi-centred, prospective, two-gate diagnostic accuracy study on patients who require routine NG-tube feeding in 10 NHS hospitals comparing the sensitivity of the novel pH strip to the standard pH test, using either chest X-rays or, in its absence, clinical observation of the absence of adverse events as the reference standard. We also tested the novel pH strips in lung aspirates from patients undergoing oesophageal cancer surgeries using visual inspection as the reference standard. We simulated health economics using a decision analytic model and carried out adoption studies to understand its route to commercialisation. The primary end point is the sensitivity of novel and standard pH tests at the recommended pH cut-off of 5.5. Results A total of 6400 ester-impregnated pH strips were prepared based on an ISO13485 quality management system. A total of 376 gastric samples were collected from adult patients in 10 NHS hospitals who were receiving routine NG-tube feeding. The sensitivities of the standard and novel pH tests were respectively 49.2% (95% CI 44.1‑54.3%) and 70.2% (95% CI 65.6‑74.8%) under pH cut-off of 5.5 and the novel test has a lung specificity of 89.5% (95% CI 79.6%, 99.4%). Our simulation showed that using the novel test can potentially save 132 unnecessary chest X-rays per check per every 1000 eligible patients, or direct savings of £4034 to the NHS. Conclusions The novel pH test correctly identified significantly more patients with tubes located inside the stomach compared to the standard pH test used widely by the NHS. Trial registration http://www.isrctn.com/ISRCTN11170249, Registered 21 June 2017—retrospectively registered

Cost effectiveness of screening for intracranial aneurysms among patients with bicuspid aortic valve: a Markov modelling study

ObjectiveBicuspid aortic valve (BAV) is common and 7.7%–9.8% of patients with BAV have intracranial aneuryms (IAs) which might lead to a devastating subarachnoid haemorrhage (SAH). We aimed to evaluate different screening and follow-up strategies using magnetic resonance angiography for IAs among patients with BAV.MethodsA decision-analytic model was built to evaluate the costs and effectiveness of different management strategies from the Chinese healthcare payer’s perspective. The evaluated strategies included natural history without screening for possible IAs, regular screening and no follow-up for detected IAs, and regular screening with regular follow-up (Screen strategy/Follow-up strategy). Base case calculation, as well as probabilistic, one-way, and two-way sensitivity analyses, were performed.ResultsAccording to the base case calculation, natural history had the least cost and effectiveness while Every 5 years (y)/Annual gained the highest cost and effectiveness. Every 10y/Biennial was cost effective when compared with Every 10y/Every 5y under the willingness-to-pay threshold of ¥211 743 (US$30 162). Probabilistic sensitivity analysis showed that Every 10y/Biennial was superior in 88.3% of the cases when compared with Every 10y/Every 5y. One-way and two-way sensitivity analyses proved that Every 10y/Biennial was the dominant strategy under most circumstances.ConclusionsScreening for possible IAs among patients with BAV and follow-up for detected IAs would increase the effectiveness. Every 10y/Biennial was the optimal strategy from the Chinese healthcare payer’s perspective.