Commercial impact of adding real-world evidence to clinical trials at regulatory approval: a Markovian-like transition model

Regulatory use of real-world evidence (RWE) has been recognized as a useful supplement to clinical trial evidence and could benefit patients by reducing time to treatment. However, commercial benefits have not been documented. The aim was to determine commercial impact of regulatory RWE, using ambrisentan as an illustrative example.
A Markovian-like transition model was constructed to simulate the drug development workflow across a simulation time of t = 20 years. RWE was assumed to be incorporated at pII–pIII and pII–pIII–pIV, and its multiplicative median transition rate was determined by biopharma expert opinion. Each model was subjected to “with” and “without” RWE rates. Commercial impact was estimated using potential decrease in time to launch. Time to first medicine adoption and potential lives saved were also estimated.
Based on cumulative first prescriptions for ambrisentan among pulmonary arterial hypertension patients (N = 487), in comparison to standard drug development, RWE incorporation has the potential to expedite first medicine adoption by 10.4 weeks. The duration of market launch was estimated at 2.5–3.0 years earlier than standard, and approximately 9% of patients would benefit in survival. Potential earnings for an earlier launch would be GBP £43,597.86 per patient, with launch being brought forward from 2009 to 2007.
Regulatory RWE has the potential to increase overall survival rates and potential earnings by reducing time to launch. This study provides further support for industry efforts to generate RWE in time for regulatory approval.

真实世界证据（real-world evidence, RWE）的监管应用已被公认为临床试验证据的有益补充，可通过缩短患者治疗等待时间使其获益，但目前尚未有其商业价值的相关研究报道。本研究以安立生坦（ambrisentan）为示例案例，旨在评估监管用途真实世界证据的商业影响。
本研究构建了类马尔可夫转换模型，在t=20年的模拟周期内复现药物开发全流程。研究假设真实世界证据分别在Ⅱ期-Ⅲ期（pII-pIII）与Ⅱ期-Ⅲ期-Ⅳ期（pII-pIII-pIV）阶段纳入研发管线，其倍增中位转换率由生物制药行业专家意见确定。所有模型均分别设置“纳入RWE”与“未纳入RWE”两种对比场景。商业影响通过预估的上市时间潜在缩短幅度进行量化评估，同时还估算了首款药物首次临床应用时间及潜在挽救的生命数量。
基于肺动脉高压患者（N=487）的安立生坦首处方累积数据，与标准药物开发流程相比，纳入RWE可将首款药物首次临床应用时间缩短10.4周。预估上市时间较标准流程提前2.5~3.0年，约9%的患者可获得生存获益。若将上市时间从2009年提前至2007年，每位患者可带来43597.86英镑的潜在收益。
监管用途的真实世界证据可通过缩短上市时间，提升患者总体生存率与潜在商业收益。本研究为行业开展及时生成真实世界证据以支持监管审批的工作提供了进一步的证据支持。