Target Trial Emulation to Incorporate Real-World Data in the Estimation of the Clinical and Cost-Effectiveness of Biologic Treatment

目标试验模拟将真实世界数据纳入生物制剂治疗临床疗效和成本效益评估

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Abstract

IntroductionIn the health technology assessment (HTA) of biologic treatments for rheumatoid arthritis (RA), there is limited randomized evidence on treatment effectiveness after first-line treatment failure. We demonstrate how real-world data (RWD) could fill this evidence gap.MethodsTarget trial emulation (TTE) minimizes biases in the causal analysis of RWD by prespecifying a protocol for a hypothetical randomized clinical trial (RCT) that would estimate the effect of interest. The application of TTE for HTA was illustrated using RWD from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis to estimate the effectiveness of rituximab versus nonbiologic therapy (NBT) after first-line biologic failure, in terms of European Alliance of Associations for Rheumatology response achievement. The effectiveness estimates from RWD were combined with RCT estimates in a meta-analysis. The pooled estimates were entered into an economic model to estimate the incremental cost-effectiveness ratio (ICER) comparing biologic versus NBT strategies.ResultsBased on RWD, rituximab was associated with higher probabilities of achieving a moderate or good response (0.215 v. 0.174) and a good response (0.090 v. 0.066) as compared with NBT. These probabilities were lower than those estimated from RCT data (moderate or good 0.650; good 0.150). The economic model estimated less time on treatment and lower costs associated with biologics when based on RWD compared with RCT data (mean £63,500 v. £70,000). This resulted in a higher ICER based on RWD compared with RCT data (mean £46,800 v. £34,700 per quality-adjusted life-year gained).ConclusionsRWD can provide supplemental evidence on treatment effectiveness where randomized evidence is limited. This can make a meaningful difference to cost-effectiveness estimates. Our results are not intended to inform current RA management.HighlightsIn health technology assessment, real-world data (RWD) can provide supplemental evidence on treatment effectiveness where there is limited randomized evidence.Target trial emulation was applied using RWD to estimate the clinical effectiveness of biologic treatment; these estimates were combined with estimates from an RCT in a meta-analysis, and the pooled estimates were entered into an economic model for rheumatoid arthritis.Treatment effect estimates based on combining RWD and RCT data were more modest compared with the effectiveness estimates from the RCT data alone, leading to a difference in the estimate of cost-effectiveness comparing biologics with nonbiologic therapy.

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