GSK, Wavre, Belgium.
Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Hum Vaccin Immunother. 2019;15(12):2960-2968. doi: 10.1080/21645515.2019.1622974. Epub 2019 Jun 21.
Frail older adults are at increased risk of poor clinical outcomes. Frailty assessment is therefore important in clinical trials to understand the benefits and harms of interventions. However, consensus is lacking on how frailty should be assessed.We developed a prospectively specified index using a battery of formal tests and instruments and a retrospectively generated index using medical comorbidities and patient reported outcomes (PROs) within an adjuvanted recombinant zoster vaccine (RZV) trial (NCT02979639). For both frailty indices (FIs), a total deficit score was calculated as the accumulation of deficits and participants were categorized as non-frail, pre-frail and frail. We assessed (1) the feasibility and validity of both FIs; (2) the impact of RZV vaccine reactogenicity by frailty status on Short Form-36 [SF-36] physical functioning (PF) scores.Of 401 participants, aged ≥50 years, 236 (58.9%) were categorized non-frail, 143 (35.7%), pre-frail, and 22 (5.5%) frail using the prospective FI. Corresponding numbers for the retrospective FI were 192 (47.9%), 169 (42.1%) and 40 (10.0%), respectively. Strong concordance was observed between the frailty status assessments ( < .001). The proportion defined as frail increased from 1.5%, to 10.4% in participants aged 50-59, and ≥70 years, respectively, for the prospective FI. Corresponding numbers for the retrospective FI were 3.7%, and 17.2%, respectively. RZV vaccination was associated with a transient, non-clinically meaningful, decrease on the SF-36 PF score in frail participants.Both frailty indices provided similar results. The retrospectively generated FI offers the advantage of being easier to incorporate into vaccine clinical trials of older adults.
虚弱的老年人发生不良临床结局的风险增加。因此，在临床试验中，虚弱评估对于了解干预措施的获益和危害很重要。然而，目前对于如何进行虚弱评估尚无共识。我们在佐剂重组带状疱疹疫苗（RZV）试验（NCT02979639）中，使用一系列正式的测试和工具前瞻性地制定了一个指数，同时也使用医疗合并症和患者报告的结局（PRO）回顾性地制定了一个指数。对于这两个虚弱指数（FI），我们计算了总缺陷评分，即缺陷的累积，参与者被分为非虚弱、虚弱前期和虚弱。我们评估了（1）这两个 FI 的可行性和有效性；（2）根据 FI 评估的虚弱状态和 RZV 疫苗的反应原性对 SF-36 （PF）评分的影响。在 401 名年龄≥50 岁的参与者中，根据前瞻性 FI，236 名（58.9%）被归类为非虚弱，143 名（35.7%）为虚弱前期，22 名（5.5%）为虚弱；对应的回顾性 FI 的数字分别为 192 名（47.9%）、169 名（42.1%）和 40 名（10.0%）。两种 FI 的虚弱状态评估之间存在很强的一致性（<0.001）。根据前瞻性 FI，50-59 岁和≥70 岁参与者中被定义为虚弱的比例从 1.5%分别增加到 10.4%和 10.4%；对应的回顾性 FI 的数字分别为 3.7%和 17.2%。RZV 疫苗接种与虚弱参与者的 SF-36 PF 评分短暂、无临床意义的下降有关。两种 FI 提供了相似的结果。回顾性生成的 FI 具有更容易纳入老年人群疫苗临床试验的优势。
