Evaluation of two frailty indices, with practical application in a vaccine clinical trial

Curran, Desmond; Andrew, Melissa K.; Levin, Myron J.; Turriani, Elisa; Matthews, Sean; Fogarty, Charles; Klein, Nicola P.; Grupping, Katrijn; Oostvogels, Lidia; Schmader, Kenneth E.

doi:10.1080/21645515.2019.1622974

Cited by 10 publications

(12 citation statements)

References 30 publications

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“…Despite the lack of pre-specified frailty measure in the parent ZOE studies, it was possible to generate a FI measure based on data collected at baseline in those clinical trials, using an approach that we previously validated. 21 Indeed, the FI could be calculated for 99.5% of participants who were included in the present study. In the case of the ZOE studies, even without specific attempts to recruit frail participants, use of relatively nonrestrictive in/exclusion criteria resulted in a broad range of participants.…”

Section: Discussionmentioning

confidence: 98%

“…Despite the lack of pre‐specified frailty measure in the parent ZOE studies, it was possible to generate a FI measure based on data collected at baseline in those clinical trials, using an approach that we previously validated 21 . Indeed, the FI could be calculated for 99.5% of participants who were included in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] The different aspects of frailty composing the frailty index (FI) were assessed through the medical history and components of the SF-36 and EQ-5D questionnaires recorded before dose one, as previously validated. 21 The SF-36 is a multi-purpose health survey comprising 36 questions, including scales for physical functioning, role physical, bodily pain, general health, vitality, social function, role emotional, and mental health. 22 EQ-5D is a generic measure of health status that defines health in terms of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.…”

Section: Assessmentsmentioning

confidence: 99%

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Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Curran

Kim

Matthews

et al. 2020

J American Geriatrics Society

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BACKGROUND/OBJECTIVES: Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes. DESIGN/SETTING: Data from two previously conducted phase III randomized trials of RZV were pooled. These two parent trials were conducted concurrently at the same study sites using the same methods. PARTICIPANTS/INTERVENTION: In the two parent studies, participants aged ≥50 years (ZOE-50 study) and ≥70 years (ZOE-70 study), respectively, were randomized 1:1 to receive two doses of RZV or placebo. MEASUREMENTS: In the current ZOE-Frailty study (NCT03563183), a frailty index was created using previously validated methods. Clinical outcomes assessed by frailty status included vaccine efficacy, immunogenicity, reactogenicity, and safety. RESULTS: Of 29,305 participants from the pooled ZOE-50 and ZOE-70 total vaccinated cohort, 92% were included in this study. Mean age was 68.8 years; 58.1% were women; 45.6% were pre-frail and 11.3% frail. The percentage of frail participants increased with age from 5.7% aged 50-59 years to 22.7% aged ≥80 years. RZV vaccine efficacy against herpes zoster was >90% for all frailty subgroups (non-frail: 95.8% (95% confidence interval = 91.6-98.2), pre-frail: 90.4% (84.4-94.4), frail: 90.2% (75.4-97.0)). The RZV group demonstrated robust anti-gE antibody and gE-specific CD4 2+ responses, with mean concentrations remaining above pre-vaccination levels at least 3 years post-dose two, in all frailty subgroups. In the RZV group, the percentage of participants reporting solicited adverse events tended to decrease with increasing frailty. CONCLUSION: The relatively nonrestrictive inclusion/ exclusion criteria in the parent ZOE studies resulted in a range of participants that included frail and pre-frail older adults. RZV significantly reduced the risk of herpes zoster across all frailty subgroups.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Assessmentsmentioning

confidence: 99%

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Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Curran

Kim

Matthews

et al. 2020

J American Geriatrics Society

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“…[9][10][11] Even when a measure of frailty has not been included in a study upfront, generation of a robust frailty measure using data already collected is possible. 10,12 A plan for how to consider frailty in COVID-19 vaccine development is important. Involving geriatricians could bring a key lens to assist with planning these ongoing studies focusing on older adults and interpreting the results.…”

mentioning

confidence: 99%

Age and frailty in COVID-19 vaccine development

Andrew

McElhaney

2020

The Lancet

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Age and frailty in COVID-19 vaccine development Older adults, particularly those who are frail or living in long-term care facilities, have been disproportionately affected by the COVID-19 pandemic. 1 Vaccines that are safe and effective in this population have been eagerly anticipated. In The Lancet, Maheshi Ramasamy and colleagues present results of the safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine in older adults (those older than 55 years). 2 Their results are part of a larger single-blind, randomised, controlled, phase 2/3 trial of the ChAdOx1 nCoV-19 vaccine (which is a replication-defective chimpanzee adenovirus-vector vaccine) with a MenACWY menin gococcal vaccine comparison group. The study design was complex, with participants randomly assigned using block randomisation to one of ten different groups, and older adults were only enrolled after initial determination of safety in the youngest age group (aged 18-55 years). Participants in the two older age groups (aged 56-69 and ≥70 years) were further randomly assigned to receive either one dose (day 0) or two doses (day 0 and a boost dose on day 28) of vaccine. The ChAdOx1 nCoV-19 groups were also sequentially recruited to receive either a low dose or (after demonstration of safety) a standard dose of the vaccine. In this immunogenicity subgroup of the larger study, 560 healthy adults were included, distributed among the three age groups (160 participants aged 18-55 years, of whom 100 received the COVID-19 vaccine; 160 aged 56-69 years, of whom 120 received the COVID-19 vaccine, and 240 aged ≥70 years, of whom 200 received the COVID-19 vaccine). 280 (51%) of 552 analysed participants were female and the median age in the 18-55 years group was 43•0 years (IQR 33•6-48•0), in the 56-69 years group was 60•0 years (57•5-63•0), and in the 70 years and older group was 73•0 years (71•0-76•0). For 7 days after each dose, participants completed diary cards for solicited local and systemic adverse events. Serious adverse events were recorded and will be monitored for 1 year. Severity of reactions and adverse events was graded as mild, moderate, or severe, depending on their effect on daily activities. Immune responses were measured using assays of anti-spike protein IgG and neutralising antibody titres for humoral immunity and IFN-γ enzyme-linked immunospot (ELISpot) for cell-mediated immunity.

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“…The EQ-5D utility scores were assessed overall and in post hoc analyses by reactogenicity grade. Details of the development of the frailty assessment are presented elsewhere ( 16 ). The QALY loss was estimated using the area-under-the-curve method, where area under the curve was calculated using the trapezoidal rule ( 17 ).…”

Section: Methodsmentioning

confidence: 99%

Impact of Reactogenicity After Two Doses of Recombinant Zoster Vaccine Upon Physical Functioning and Quality of Life: An Open Phase III Trial in Older Adults

Schmader

Levin

Chen

et al. 2020

The Journals of Gerontology: Series A

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Background Herpes zoster may significantly impact quality of life (QoL) in older adults. The recombinant zoster vaccine (RZV) is efficacious in adults aged ≥50 and older and is associated with increased reactogenicity compared to placebo. We report here on the impact of reactogenicity of the second RZV dose on the QoL and physical functioning (PF) of vaccine recipients, and summarize findings following both doses. Method In this single-arm study, 401 adults aged ≥50 and older were enrolled to receive two RZV doses 2 months apart. Change in mean Short Form Survey-36 (SF-36) PF and EuroQol-5 Dimension (EQ-5D) scores, reactogenicity, safety, productivity loss, and healthcare resource utilization were evaluated. Results In total, 391 (97.5%) participants received dose 2. Post-dose 2, the most common solicited local symptoms were injection site pain (75.1%), erythema (22.4%), and swelling (13.9%), and the most common systemic symptoms were fatigue (46.3%), headache (37.5%), and myalgia (32.9%). Grade 3 solicited (local and systemic) adverse events were reported by 61 (15.6%) participants and were associated with a transient clinically significant decrease in SF-36 PF score on Days 1–2 post-dose 2 that recovered by Day 3. Overall, no clinically important reduction in mean SF-36 PF scores was observed from baseline to post-dose 2 (mean change −0.4), and no quality-adjusted-life-year loss was recorded. Conclusions Overall, QoL and PF of RZV vaccinees were not affected by vaccine-related reactogenicity. A transient reduction was observed in the first 2 days after RZV vaccination in individuals with Grade 3 adverse events. No safety concerns were identified.

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Evaluation of two frailty indices, with practical application in a vaccine clinical trial

Cited by 10 publications

References 30 publications

Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals

Age and frailty in COVID-19 vaccine development

Impact of Reactogenicity After Two Doses of Recombinant Zoster Vaccine Upon Physical Functioning and Quality of Life: An Open Phase III Trial in Older Adults

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