Challenges of consolidating evidence collected during a pandemic and lessons for the future.

OBJECTIVE: To illustrate the challenges encountered when gathering rapidly synthesized evidence in response to the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this article, we describe the challenges encountered when we performed a systematic literature review (SLR) of randomized controlled trials (RCTs) on the efficacy and safety of treatments for severe COVID-19. The methods of the SLR are described in full, to show the context of our objectives. Then we use the results of the SLR to demonstrate the problems of producing synthesized evidence in this setting. RESULTS: Various challenges were identified during this SLR. These were primarily a result of heterogeneity in the study methodology of eligible studies. Definitions of the patient populations and outcome measurements were highly variable and the majority of studies demonstrated a high risk of bias, preventing quantitative synthesis of the collated evidence. CONCLUSION: Consolidating evidence from RCTs evaluating COVID-19 interventions was problematic. Guidance is needed for scenarios with high rapid output in primary research.

Development and validation of the Economic Assessment of Glycemic Control and Long-Term Effects of diabetes (EAGLE) model.

BACKGROUND: The Economic Assessment of Glycemic control and Long-term Effects of diabetes (EAGLE) model was developed to provide a flexible and comprehensive tool for the simulation of the long-term effects of diabetes treatment and related costs in type 1 and type 2 diabetes. METHODS: EAGLE simulations are based on risk equations, which were developed using published data from several large studies including the Diabetes Control and Complications Trial, the United Kingdom Prospective Diabetes Study, and the Wisconsin Epidemiological Study of Diabetic Retinopathy. Risk equations for the probability of complications (including hypoglycemia, retinopathy, macular edema, end-stage renal disease, neuropathy, diabetic foot syndrome, myocardial infarction, and stroke) were based on regression analyses, using linear, exponential, and quadratic regression formulae. Subsequent cost calculations are made from the simulated event rates. Internal validation of the EAGLE model was completed by comparing simulated event rates with the published event rates used as the basis for the model. RESULTS: EAGLE provides microsimulations of virtual patient cohorts for type 1 and type 2 diabetes over n years in 1-year cycles. Complications include microvascular and macrovascular events and death, which are calculated over time as cumulative incidences. Glycosylated hemoglobin levels over time are simulated in relation to treatment regimen. Internal validation demonstrated that each mean event rate simulated by EAGLE overlapped with the published mean event (within a range of +/-10%). CONCLUSIONS: The EAGLE model is an evidence-based, internally valid tool for the assessment of the long-term effects of diabetes treatment and related costs.

Influenza treatment with neuraminidase inhibitors: cost-effectiveness and cost-utility in healthy adults in the United Kingdom.

We assessed the cost-effectiveness and cost-utility of treating influenza with neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer's and societal perspective in the United Kingdom. A simulation model was developed to predict morbidity and mortality due to influenza and its specified complications, comparing neuraminidase inhibitors with usual care in an otherwise healthy adult population. Robustness of the results was tested by one-way and multiway as well as probabilistic sensitivity analyses. Treatment with either neuraminidase inhibitor results in reduced morbidity and faster return to normal activities. However, oseltamivir dominates zanamivir in cost-utility analysis due to its lower costs. Comparing oseltamivir with usual care, the costs are pound14.36 per day of normal activity gained and pound5,600 per quality-adjusted life-year gained from the healthcare payer perspective. Oseltamivir dominates usual care from the societal perspective. Treatment with oseltamivir is a cost-effective strategy for otherwise healthy adults in the UK from both the healthcare payer and societal perspective.

Prolonged prophylaxis with valganciclovir is cost effective in reducing posttransplant cytomegalovirus disease within the United States.

BACKGROUND: Cytomegalovirus (CMV) disease in transplant patients is known to have a substantial clinical and economic burden, and its prevention is expected to have long-term benefits. Evidence from the Improved Protection Against CMV in Transplant trial proved that prolonged prophylaxis of 200 days with valganciclovir compared with 100 days significantly reduces the incidence of CMV in high-risk kidney transplant seropositive donors/seronegative recipients. The aim of this study was to develop a cost-effectiveness model to evaluate prolonged prophylaxis of 200 days with valganciclovir and its long-term economic impact. METHODS: An economic model was designed to simulate long-term costs and outcomes of prolonged prophylaxis with valganciclovir (200 vs. 100 days) in a cohort of 10,000 high-risk renal transplant patients over 5 and 10 years. The first year of the model was based on the results of the Improved Protection Against CMV in Transplant trial and the extension to the long-term periods (5 and 10 years); and quality of life data were based on evidence retrieved through a systematic literature search. This analysis was conducted from the US healthcare payer perspective. RESULTS: For the 5-year time horizon, the incremental cost-effectiveness ratio of US $14,859/quality-adjusted life year (QALY) suggests that 200-day valganciclovir prophylaxis is cost effective over the 100-day regimen considering a threshold of US $50,000/QALY. The 10-year analysis revealed the 200-day prophylaxis as cost saving with a 2380 QALY gain and simultaneously lower cost. CONCLUSION: Prolonged prophylaxis with valganciclovir reduces the incidence of events associated with CMV infection in high-risk kidney transplant recipients and is a cost-effective strategy in CMV disease management.

Societal cost savings through bevacizumab-based treatment in non-small cell lung cancer (NSCLC).

Bevacizumab in combination with platinum-based chemotherapy is associated with increased survival outcomes compared to chemotherapy alone in patients with non-squamous metastatic non-small cell lung cancer (mNSCLC). The objective of this study was to estimate potential economic benefits from a societal perspective in patients returning to work when treated with bevacizumab-based combination therapy. These economic benefits were assessed with respect to reduced productivity losses and described in terms of per patient cost savings. The analysis was conducted for France, Germany, Italy and Spain. Clinical outcomes in terms of progression-free survival (PFS) were based on two phase III clinical trials (E4599 and AVAiL) comparing bevacizumab + chemotherapy vs. chemotherapy alone. Potential cost savings due to reduction in productivity losses were assessed in progression-free patients who return back to work (human capital approach). It was assumed that 20% of all progression-free patients with performance status 0 or 1 and below 55 years of age would return back to work after the induction therapy maintaining their prior employment status (60% part-time, 40% full-time). Savings were calculated over 1 and 1.5 year time horizons. Mean savings, per progression-free patient ranged from 12,401 euro in Spain at year 1 to 39,001 euro in France at year 1.5. Respective findings proved to be fairly sensitive to the change of employment patterns and labour costs. This analysis shows that bevacizumab-based treatment can result in substantial cost savings in progression-free patients with mNSCLC.