Pulmonary and Critical Care, Johns Hopkins Hospital, Baltimore, MD, USA.
Center for Medical Technology Policy, Baltimore, MD, USA.
J Asthma. 2021 Jul;58(7):855-864. doi: 10.1080/02770903.2020.1744641. Epub 2020 Apr 3.
Biologic therapies are emerging as an option to treat a subset of patients with severe asthma, however no direct comparison between these agents has been conducted. Furthermore, heterogeneity of outcomes in clinical trials makes it difficult to compare these agents and traditional therapies. The extent to which this heterogeneity exists has major implications for evidence-based decisions and is yet to be fully reported. We conducted a literature search to examine outcomes currently being used in clinical trials for asthma.
The Cochrane Library and Clinicaltrials.gov were searched for clinical trials of asthma interventions.
We limited our search to phase 2 through 4 clinical trials in adults, as early-phase trials tend to have pharmacodynamic and pharmacokinetic endpoints as primary outcomes. Interventions for acute exacerbations were excluded.
We identified 117 studies and subsequently identified 111 outcomes. The most prevalent outcomes were asthma control and symptom severity, FEV1, and change in ACQ scale. Twenty patient-reported outcomes instruments were identified and de-facto standard asthma outcomes and PROs were under-reported in examined literature. Existing quality of life tools did not capture the day-to-day experience or the unique treatment burden from oral corticosteroids for patient with severe asthma. Compounding the absence of trials directly comparing therapies, the significant variation we identified in outcome definitions and measurement create hurdles to effectively compare traditional and biologic therapies.
With the growing number of clinical trials evaluating advanced therapies such as biologics, a wide range of primary and secondary outcomes are evaluated. A core outcome set created by relevant stakeholders is needed to collectively evaluate pooled outcomes in order to allow more meaningful comparisons of asthma therapies and to incorporate the patient experience.
生物疗法作为治疗严重哮喘患者亚群的一种选择正在出现，然而，尚未对这些药物进行直接比较。此外，临床试验结果的异质性使得难以比较这些药物和传统疗法。这种异质性的程度对基于证据的决策有重大影响，但尚未得到充分报告。我们进行了文献检索，以检查目前在哮喘临床试验中使用的结果。
对 Cochrane 图书馆和 Clinicaltrials.gov 进行了哮喘干预措施的临床试验搜索。
我们将搜索范围限于成人的 2 期至 4 期临床试验，因为早期阶段的试验往往将药效学和药代动力学终点作为主要结果。排除了急性加重的干预措施。
我们确定了 117 项研究，随后确定了 111 项结果。最常见的结果是哮喘控制和症状严重程度、FEV1 和 ACQ 量表的变化。确定了 20 种患者报告的结局工具，并在检查文献中发现，实际上标准的哮喘结局和 PROs 报告不足。现有的生活质量工具无法捕捉严重哮喘患者日常体验或口服皮质类固醇的独特治疗负担。除了缺乏直接比较治疗方法的试验外，我们确定的结果定义和测量的显著差异给有效比较传统和生物疗法带来了障碍。
随着越来越多的临床试验评估生物制剂等先进疗法，评估了广泛的主要和次要结果。需要由相关利益攸关方创建核心结局集，以集体评估汇总结果，以便能够更有意义地比较哮喘疗法，并纳入患者体验。
