Supplementary Material for: Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease. This poses a major challenge for the development of new therapies and is compounded by the considerable heterogeneity in clinical manifestations across patients and the fluctuating nature of many signs and symptoms of PD. Digital health technologies (DHT), such as smartphone applications, wearable sensors, and digital diaries, have the potential to address many of these gaps by enabling the objective, remote, and frequent measurement of PD signs and symptoms in natural living environments. The current climate of the COVID-19 pandemic creates a heightened sense of urgency for effective implementation of such strategies. In order for these technologies to be adopted in drug development studies, a regulatory-aligned consensus on best practices in implementing appropriate technologies, including the collection, processing, and interpretation of digital sensor data, is required. A growing number of collaborative initiatives are being launched to identify effective ways to advance the use of DHT in PD clinical trials. The Critical Path for Parkinson’s Consortium of the Critical Path Institute is highlighted as a case example where stakeholders collectively engaged regulatory agencies on the effective use of DHT in PD clinical trials. Global regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency, are encouraging the efficiencies of data-driven engagements through multistakeholder consortia. To this end, we review how the advancement of DHT can be most effectively achieved by aligning knowledge, expertise, and data sharing in ways that maximize efficiencies.

亟需创新工具，以加速可减缓、阻断或逆转帕金森病（Parkinson disease, PD）进展的新型疗法的评估与后续获批流程。针对疾病进程早期进行干预的疗法，是当前药物开发管线中众多候选药物的优先研发方向。目前尚缺乏敏感客观且具备临床可解读性、能够捕捉疾病关键特征的评估手段，这给新型疗法的开发带来了重大挑战；而患者临床表现的显著异质性，以及PD诸多体征与症状的波动性，进一步加剧了这一困境。数字健康技术（Digital health technologies, DHT），如智能手机应用、可穿戴传感器、数字日记等，有望填补上述诸多空白——其可在自然生活环境中，实现对PD体征与症状的客观、远程且高频次测量。当前新冠疫情的大环境，进一步提升了此类策略有效落地的紧迫性。若要让这些技术在药物开发研究中得到应用，需围绕适宜技术的实施最佳实践形成符合监管要求的共识，涵盖数字传感器数据的采集、处理与解读等环节。目前已有越来越多的协作倡议陆续启动，旨在探索推进DHT在PD临床试验中应用的有效路径。作为典型案例，关键路径研究所（Critical Path Institute）旗下的帕金森病关键路径联盟，便是利益相关方与监管机构共同探讨DHT在PD临床试验中有效应用的合作范例。包括美国食品药品监督管理局（US Food and Drug Administration）、欧洲药品管理局（European Medicines Agency）在内的全球监管机构，均鼓励通过多利益相关方联盟提升数据驱动合作的效率。为此，本文综述了如何通过整合知识、专业技能与数据共享，以最大化效率的方式，最有效地推动DHT的发展。