Background In the phase III PACIFIC study, durvalumab improved survival versus placebo in patients with unresectable stage III non-small-cell lung cancer (NSCLC) whose disease had not progressed after platinum-based concurrent chemoradiotherapy. The appraisal by the UK's National Institute for Health and Care Excellence (NICE) included a cost-effectiveness analysis based on an early data readout from PACIFIC [March 2018 data cut-off (DCO); median follow-up duration 25.2 months; range 0.2-43.1]. Uncertainties regarding long-term survival outcomes with durvalumab led to some challenges in estimating the cost effectiveness of this therapy. Objective Here, we validate the survival extrapolations used in the original company base-case analysis by benchmarking them against updated survival data from the 4-year follow-up analysis of PACIFIC (i.e. approximately 4 years after the last patient was randomised; March 2020 DCO; median follow-up duration 34.2 months; range 0.2-64.9). Moreover, we update the original analysis with these more mature survival data to examine the consistency of key economic outputs with the original analysis. Methods The original analysis used a semi-Markov (state-transition) approach and was based on patients whose tumours expressed programmed cell death-ligand 1 on ≥ 1% of cells (to reflect the European licence for durvalumab). We benchmarked the survival extrapolations used in the original company base-case analysis against survival data from the 4-year follow-up of PACIFIC and updated the cost-effectiveness analysis with these more mature survival data. Early deaths avoided by the adoption of durvalumab into the UK Cancer Drugs Fund (CDF) in March 2019 were estimated using the 4-year follow-up survival data and an assumed uptake of 125 patients/year (lower estimate) and 367 patients/year (higher estimate). Results The original company base-case analysis had a good visual fit with the observed overall survival (OS) distribution for the durvalumab arm and accurately predicted the 48-month OS rate (predicted 55%; observed 55%); by comparison, the fit was less precise for the placebo arm, for which the analysis underestimated the 48-month OS rate (predicted 32%; observed 38%). In the updated company base-case analysis, durvalumab yielded 2.51 incremental quality-adjusted life-years (QALYs) (− 0.43 vs. the original company base-case analysis), corresponding to an incremental cost-effectiveness ratio of £22,665/QALY (+£3298 vs. the original analysis), which falls within the upper bound of NICE's willingness-to-pay threshold (£30,000/QALY gained). We estimate that between 31 and 91 early patient deaths may have been avoided by the adoption of durvalumab into the CDF. Conclusions These findings reinforce the patient benefit observed with durvalumab in unresectable stage III NSCLC, support the routine use and cost effectiveness of this therapy, and demonstrate how appropriate modelling can inform the early adoption of therapies by payers to achieve patient benefit. Plain Language SummaryBased on the re...

IntroductionDespite advances in endovascular interventions, including the introduction of drug-eluting stents (DES), high target lesion revascularization (TLR) rates still burden the treatment of symptomatic lower-limb peripheral arterial disease (PAD). EluviaTM, a novel, sustained-release, paclitaxel-eluting DES, was shown to further reduce TLRs when compared with the paclitaxel-coated Zilver® PTX® stent, in the IMPERIAL randomized controlled trial. This evaluation estimated the cost-effectiveness of Eluvia when compared with Zilver PTX in Australia, based on 12-month clinical outcomes from the IMPERIAL trial.MethodsA state-transition, decision-analytic model with a 12-month time horizon was developed from an Australian public healthcare system perspective. Cost parameters were obtained from the Australian National Hospital Cost Data Collection Cost Report (2016–17). All costs were captured in Australian dollars (AUD), where AUD 1 = USD 0.69 (June 2020). Complete sets of clinical parameters (primary patency loss, TLR, amputation, and death) and cost parameters from their respective distributions were bootstrapped in samples of 1,000 patients, for each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed.ResultsAt 12 months, modeled TLR rates were 4.5 percent for Eluvia and 8.9 percent for Zilver PTX, and mean total direct costs were AUD 6,537 [USD 4,511] and AUD 6,908 [USD 4,767], respectively (Eluvia average per patient savings; overall cohort=AUD 371 [USD 256]; diabetic cohort=AUD 625 [USD 431]). In probabilistic sensitivity analyses, Eluvia was cost-effective relative to Zilver PTX in 92.0 percent of all simulations at a threshold of $10,000 per TLR avoided. Eluvia was more effective and less costly (dominant) than Zilver PTX in 76.0 percent of simulations.ConclusionsIn the first year after the intervention, Eluvia was more effective and less costly than Zilver PTX, making Eluvia the dominant treatment strategy for treatment of symptomatic lower-limb PAD, from an Australian public healthcare system perspective. These findings should be considered when formulating policy and practice guidelines in the context of priority setting and making evidence-based resource allocation decisions for treatment of PAD in Australia.

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