Assessing the opportunities, considerations, and implications of decentralized trials—and why they’re here to stay.
评估去中心化试验的机会、考虑因素和影响——以及为什么它们会存在保留.
For many pharmaceutical organizations, decentralized clinical trials (DCTs) have quickly become a strategic priority, one that is expected to endure long after the COVID-19 pandemic ends. Once viewed as nice-to-have pilot projects, DCTs—trials conducted remotely or through local healthcare providers to improve the patient experience—arrived when Pfizer launched a virtual trial1 in 2011. While drug-based interventional DCTs only experienced a 7% CAGR between 2014 and 2019, they jumped to 77% between the second halves of 2019 and 2020 after the onset of COVID-19, according to ZS’s DCT database, referencing data from more than 1,000 trials.
对于许多制药企业而言，去中心化临床试验 (DCT) 已迅速成为其重点战略，并预计在 COVID-19 大流行结束后仍将持续很长时间。DCT（远程或通过当地医疗保健提供者进行的试验以改善患者体验）在辉瑞于 2011 年启动虚拟试验1时出现时，曾经被视为不错的试点项目。根据 ZS 的 DCT 数据库中参考1,000 多项试验的数据，在 2014 年和 2019 年，基于药物的介入性 DCT 仅有7%CAGR，在 COVID-19 爆发后的 2019 年下半年和 2020 年之间，一跃攀升至 77%。
trials offer a patient-centric approach, addressing various patient needs that often go unmet in traditional designs. DCTs benefit sponsors by accelerating clinical development, enabling more representative patient access and developing a stronger evidence package than traditional trials. Yet, DCT implementation doesn’t have to be all or nothing; trial decentralization can be viewed as a spectrum, with most DCTs combining in-person and remote activities to make clinical trial participation easier for patients. But one thing is certain: COVID-19 has shifted the balance of tradeoffs for the pharma industry, and despite operational challenges that may arise during decentralization, the benefits outweigh the investment. In the era of disruption, now is the time to take the risk.
去中心化临床试验提供了一种以患者为中心的方法，解决了传统设计中经常无法满足的各种患者需求。DCT通过加速临床研发、赋能典型患者接触，并发展比传统试验更有力的证据包，来使申办方受益。然而，DCT的实施并不一定是1或0；试验去中心话可以被视为一个范围，大多数 DCT 结合了面对面和远程活动，使患者更容易参与临床试验。但有一件事是肯定的：COVID-19 改变了制药行业的平衡，尽管去中心化可能会出现运营挑战，但其收益大于投资。在颠覆的时代，现在是承担风险的时候了。
DCTs are here to stay
DCT 将继续存在
Through our work with pharma clients, we have observed four primary drivers that suggest DCTs are here to stay, even in a post-pandemic society:
通过我们与制药客户的合作，我们观察到四个主要驱动因素表明 DCT 将继续存在，即使是在大流行之后的社会：
Regulatory direction: As a result of COVID-19, regulatory agencies including the FDA and European Medicines Agency have clarified their guidance on key decentralized modalities, such as telemedicine across state lines, direct-to-patient investigational product shipments, and more. The FDA’s new Digital Health Center of Excellence2 and legislative direction3 to advance the use of DCTs indicate a smoother regulatory landscape through 2021 and beyond.
• 监管方向：由于 COVID-19，包括 FDA 和欧洲药品管理局在内的监管机构已经明确了他们对关键分散模式的指导，例如跨州远程医疗、直接面向患者的研究产品运输等。FDA 新的数字健康卓越中心和立法方向以推进 DCT 的使用，表明到 2021 年及以后监管环境将更加顺畅。
Technology maturity: Evolving technology—fueled by record-level venture capital investments4 in digital health—is enabling trial decentralization. Furthermore, horizontal and vertical integration among technology solution providers is creating more end-to-end technology solutions to deliver DCTs.
• 技术成熟度：不断发展的技术——在数字健康领域创纪录的风险资本投资的推动下——正在驱动试验去中心化。此外，技术解决方案提供商之间的横向和纵向整合正在创造更多的端到端技术解决方案来实现DCT。
Pharma investment and capability development: Pharma is creating focused DCT capability groups with dedicated leadership and investing in processes and technology to operate DCTs at scale.
• 制药投资和能力开发：制药公司正在创建专注于DCT的小组，具有专门的领导人员，并投入流程和技术以大规模运营DCT。
Patient experience: Patients’ increasing use of digital healthcare, such as telemedicine and digital pharmacies, have enhanced expectations of their clinical trial experience, which we don’t expect to revert moving forward.
• 患者体验：患者越来越多地使用数字医疗保健，例如远程医疗和数字药房，提高了对其临床试验体验的期望，这种情况我们预计未来不会逆转。
Pros and cons of DCTs
DCT的优缺点
DCTs offer patients a more streamlined experience, reduce the burden of time-consuming in-person visits and enable wider patient access, especially in rural and underrepresented communities.
DCT 为患者提供了更简化的体验，减少了耗时就诊的负担，并能更广泛地接触患者，尤其是在农村和社区。
Like patients, sponsors also benefit from DCTs. As of 2016, 85% of trials failed to finish on time, financially impacting sponsors by up to $8 million per day, according to Pharmafile.5 Decentralization can reduce these hurdles for sponsors by speeding up recruitment, increasing compliance, and reducing drop-out rates. Additionally, collecting high-quality clinical and real-world data through DCTs can build stronger evidence packages and better reflect the value created for patients. Sponsors can use novel digital endpoints to generate differentiated label claims through DCTs as well.
与患者一样，申办方也受益于DCT。根据 Pharmafile 的数据，截至 2016 年85% 的试验未能按时完成，对申办方每天的财务影响高达 800 万美元。去中心临床试验可以通过加快招募、提高合规性和降低退出率来减少申办方面临的这些障碍. 此外，通过 DCT 收集高质量的临床和现实世界数据，可以构建更强大的证据包，并更好地反映为患者创造的价值。通过DCT,申办方也可以使用新颖的数字端点生成差异化的标签声明。
Still, decentralization—like most new innovations—adds complexity to the clinical trial process. It requires stakeholders to devote time and resources before the benefits can be realized. Sponsors must learn how to effectively and flexibly implement DCTs, as well as support patients and sites on their respective learning journeys. From a regulatory perspective, DCTs are still nascent and without consistent standards, meaning sponsors may have to initially focus on select priority markets. Lastly, while initial proof points to DCTs providing value are emerging—especially for increasing recruitment speed6 and enhancing patient retention7—more work is needed to understand their impact. Sponsors should consider ways to benchmark DCT performance versus traditional trials to understand and capture the value of DCT.
尽管如此，去中心化——与大多数新的创新一样——增加了临床试验过程的复杂性。它需要利益相关者投入时间和资源才能实现收益。申办方必须学习如何有效和灵活地实施 DCT，并在各自的学习过程中支持患者和site。从监管的角度来看，DCT仍处于起步阶段没有一致的标准，这意味着申办方可能必须首先关注特定的优先市场。最后，虽然 DCT提供价值的初步证据正在出现——尤其是在提高招募速度 6 和提高患者保留率方面——但还需要做更多的工作来了解它们的影响。申办方应考虑对 DCT 性能与传统试验进行基准测试的方法，以了解和获取 DCT 的价值。
Key considerations and implications
主要考虑因素和影响
Sponsors considering DCTs must root their approach in a deep understanding of patient needs and experiences. Designing approaches and solutions that reduce the patient burden and provide the right behavioral incentives for patients will lead to better patient engagement and improved trial performance. It’s also important to recognize that sites will remain key to patient experiences: As sponsors develop DCT solutions, providing options that are adaptive to site workflow and capability will be critical.
考虑 DCT 的申办方,必须将他们的方法基于对患者需求和体验的深刻理解。设计减轻患者负担并为患者提供正确行为激励的方法和解决方案将引导更好的患者参与及改进临床试验绩效。意识到site仍是患者体验的关键也很重要：随着申办方开发DCT解决方案，提供适合site工作流程和能力的选择将是至关重要的。
It’s easy to assume solely decentralizing trials and introducing new technology will improve the patient experience, but this isn’t necessarily true. In fact, a multitude of disjointed study apps may even increase the burden, while home nurse visits may be more stressful than visiting a community center. Sponsors must first listen to patients and understand their needs, and then create a more personalized trial experience that meets those needs. It’s important for sponsors with diverse clinical development pipelines to tailor this exercise to specific trial patient populations, endpoints and intervention modalities. Furthermore, within each trial, sponsors should strive to enable optionality for individual patients based on their engagement preferences.
很容易假设仅去中心化临床试验和引入新技术将改善患者体验，但这不一定是真的。事实上，大量杂乱无章的学习应用程序甚至可能会增加负担，而家庭护士访问可能比访问社区中心更具压力。申办方首先必须听取患者的意见并了解他们的需求，然后创建可以满足这些需求的更加个性化的试验体验。对于拥有不同临床开发渠道的申办方来说，根据特定的试验患者群体、终点和干预方式定制这项练习非常重要。此外，在每项试验中，申办方应努力根据个别患者的参与偏好为他们提供选择权。
Beyond the approach itself, sponsors also must ensure that decentralization options are considered early in clinical development planning, allowing sufficient time for patient research, endpoint validation and vendor selection activities. If decentralization is an operational afterthought, the process will be more difficult to incorporate and, moreover, the extent to which the trial can be decentralized will be constrained by traditional, site-centered protocols. Shifting this thinking upstream will enable study teams to assess how decentralization can improve the patient experience.
除了方法本身，申办方还必须确保在临床开发计划的早期考虑去中心化的选择，为患者研究、终点验证和供应商选择活动留出足够的时间。如果去中心化是事后的想法，则该过程将更难以纳入，而且，试验的去中心化程度将受到传统的、以site为中心的协议的限制。将这种想法向上游转移将使研究团队能够评估去中心化如何改善患者体验。
Developing the digital capabilities needed for DCTs is also critical. There are new types of data collected in DCTs and oftentimes new insight generation opportunities from continuous data collection. Digital solutions must enable a unified user experience and one source of truth for data integration. Additionally, while the infrastructure can be gradually built—with numerous digital solutions and providers in the market—sponsors must have an enterprise architecture blueprint to guide the development to enable connectivity and optionality. Developing the DCT infrastructure without a plan would lead to future challenges with technological integration and agility.
发展DCT所需的数字能力也很关键。在 DCT 中收集了新类型的数据，并且经常从连续数据收集中获得新的视角及机会。数字解决方案必须支持统一的用户体验和数据集成的一个真实来源。此外，虽然基础设施可以逐步构建——市场上有许多数字解决方案和供应商——但申办方必须有一个企业架构蓝图来指导开发以实现连接性和可选性。在没有计划的情况下开发 DCT 基础设施将导致未来的技术集成和敏捷性挑战。
Finally, since DCTs are cross-functional in nature, they require collaboration across sponsors’ trial design, trial operations, regulatory, digital health and innovation functions. These teams must overcome functional silos and establish new ways of working to successfully drive DCTs. Sponsors must also establish consistent processes to facilitate scaling DCTs from a proof-of-concept to an organizational capability. One key step here is organizational knowledge sharing: applying learnings rapidly and efficiently across study teams.
最后，由于 DCT 本质上是跨职能的，因此它们需要在申办方的试验设计、试验运营、监管、数字健康和创新职能之间进行协作。这些团队必须克服功能孤岛并建立新的工作方式以成功推动 DCT。申办方还必须建立统一的流程，以促进 DCT 从概念验证到组织能力的扩展。这里的一个关键步骤是组织知识共享：跨研究团队快速有效地应用学习。
Where to start?
从哪里开始？
For sponsors wondering where to begin or focus DCT efforts across a portfolio, a combination of their business needs and the feasibility of decentralization between therapy areas can act as a guide. Some therapy areas are a better fit for decentralized trials, based on factors such as the investigational medicinal product’s administration route (e.g., oral vs. infusion), type of assessment procedure (e.g., non-invasive vs. invasive biopsy), and whether the condition being studied is chronic or acute. Although ZS’s DCT database found cardiovascular, neurology, and diabetes as the most common therapy areas for DCTs, they can also be applied in other therapeutic areas. In fact, oncology and infectious diseases makeup 5% and 4%, respectively, of all DCTs historically. That said, for many therapy areas, full decentralization may not be feasible or right for patients; instead, identifying specific procedures that can be decentralized or combined into a single visit can drive valuable improvements to the patient experience.
对于想知道从哪里开始或在整个投资组合中集中 DCT工作的发起人来说，他们的业务需求和治疗领域之间去中心化的可行性的组合可以作为指导。一些治疗领域更适合分散试验，这取决于研究药物的给药途径（例如，口服与输注）、评估程序类型（例如，非侵入性与侵入性活检）以及病情是否正在研究的是慢性的或急性的。尽管 ZS 的 DCT 数据库发现心血管、神经病学和糖尿病是 DCT 最常见的治疗领域，但它们也可以应用于其他治疗领域。事实上，肿瘤学和传染病历来分别占所有 DCT 的 5% 和 4%。也就是说，对于许多治疗领域，完全分散对患者来说可能不可行或不正确。相反，确定可以分散或合并到单次访问中的特定程序可以推动对患者体验的宝贵改进。
As DCTs become more common, they will raise the bar for patient experience and patient data collection. They offer an opportunity to fundamentally change how we perform clinical research. As pharma companies embark on this journey, they can’t do it alone. The good news is that patients, investigators, sites and regulators are prepared to make the change and unlock the value of moving clinical trials closer to patients.
随着 DCT变得越来越普遍，它们将提高患者体验和患者数据收集的标准。它们提供了从根本上改变我们进行临床研究的方式的机会。随着制药公司踏上这一旅程，他们无法独自完成。好消息是，患者、研究人员、研究中心和监管机构已准备好做出改变并释放让临床试验更贴近患者的价值。
Fan Gao is a Principal; Maurice Solomon is a Principal; Arnab Roy is a Manager; and William Chaplin is a Consultant, all with ZS
