PMID- 33087107
OWN - NLM
STAT- MEDLINE
DCOM- 20210222
LR  - 20240331
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 18
IP  - 1
DP  - 2020 Oct 22
TI  - Identifying frailty in trials: an analysis of individual participant data from 
      trials of novel pharmacological interventions.
PG  - 309
LID - 10.1186/s12916-020-01752-1 [doi]
LID - 309
AB  - BACKGROUND: Frailty is common in clinical practice, but trials rarely report on 
      participant frailty. Consequently, clinicians and guideline-developers assume 
      frailty is largely absent from trials and have questioned the relevance of trial 
      findings to frail people. Therefore, we examined frailty in phase 3/4 
      industry-sponsored clinical trials of pharmacological interventions for three 
      exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), 
      and chronic obstructive pulmonary disease (COPD). METHODS: We constructed a 
      40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 
      42-65 years) using individual-level participant data. Participants with a FI 
      > 0.24 were considered 'frail'. Baseline disease severity was assessed using 
      HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 
      for COPD. Using generalised gamma regression, we modelled FI on age, sex, and 
      disease severity. In negative binomial regression, we modelled serious adverse 
      event rates on FI and combined results for each index condition in a 
      random-effects meta-analysis. RESULTS: All trials included frail participants: 
      prevalence 7-21% in T2DM trials, 33-73% in RA trials, and 15-22% in COPD trials. 
      The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was 
      associated with higher FI in all trials. Increased disease severity was 
      associated with higher FI in RA and COPD, but not T2DM. Frailty was associated 
      with age in T2DM and RA trials, but not in COPD. Across all trials, and after 
      adjusting for age, sex, and disease severity, higher FI predicted increased risk 
      of serious adverse events; the pooled incidence rate ratios (per 0.1-point 
      increase in FI scale) were 1.46 (95% CI 1.21-1.75), 1.45 (1.13-1.87), and 1.99 
      (1.43-2.76) for T2DM, RA, and COPD, respectively. CONCLUSION: The upper limit of 
      frailty in trials is lower than has been described in the general population. 
      However, mild to moderate frailty was common, suggesting trial data may be 
      harnessed to inform disease management in people living with frailty. 
      Participants with higher FI experienced more serious adverse events, suggesting 
      screening for frailty in trial participants would enable identification of those 
      that merit closer monitoring. Frailty is identifiable and prevalent among 
      middle-aged and older participants in phase 3/4 drug trials and has clinically 
      important safety implications.
FAU - Hanlon, Peter
AU  - Hanlon P
AUID- ORCID: 0000-0002-5828-3934
AD  - Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, 
      Glasgow, G12 8RZ, UK.
FAU - Butterly, Elaine
AU  - Butterly E
AD  - Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, 
      Glasgow, G12 8RZ, UK.
FAU - Lewsey, Jim
AU  - Lewsey J
AD  - Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, 
      Glasgow, G12 8RZ, UK.
FAU - Siebert, Stefan
AU  - Siebert S
AD  - Institute of Infection, Immunity and Inflammation, University of Glasgow, 
      Glasgow, UK.
FAU - Mair, Frances S
AU  - Mair FS
AD  - Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, 
      Glasgow, G12 8RZ, UK.
FAU - McAllister, David A
AU  - McAllister DA
AD  - Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, 
      Glasgow, G12 8RZ, UK. David.McAllister@glasgow.ac.uk.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 201492/Z/16/Z/WT_/Wellcome Trust/United Kingdom
GR  - MR/S021949/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201022
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
SB  - IM
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/diagnosis/epidemiology
MH  - Clinical Trials as Topic/*statistics & numerical data
MH  - Data Analysis
MH  - Diabetes Mellitus, Type 2/diagnosis/epidemiology
MH  - Drug Therapy/methods/statistics & numerical data
MH  - Female
MH  - Frailty/diagnosis/*epidemiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/diagnosis/epidemiology
PMC - PMC7579922
OTO - NOTNLM
OT  - Chronic obstructive pulmonary disease
OT  - Diabetes mellitus
OT  - Frailty
OT  - Randomised controlled trials
OT  - Rheumatoid arthritis
COIS- The authors declare no competing interests.
EDAT- 2020/10/23 06:00
MHDA- 2021/02/23 06:00
PMCR- 2020/10/22
CRDT- 2020/10/22 05:26
PHST- 2020/06/08 00:00 [received]
PHST- 2020/08/18 00:00 [accepted]
PHST- 2020/10/22 05:26 [entrez]
PHST- 2020/10/23 06:00 [pubmed]
PHST- 2021/02/23 06:00 [medline]
PHST- 2020/10/22 00:00 [pmc-release]
AID - 10.1186/s12916-020-01752-1 [pii]
AID - 1752 [pii]
AID - 10.1186/s12916-020-01752-1 [doi]
PST - epublish
SO  - BMC Med. 2020 Oct 22;18(1):309. doi: 10.1186/s12916-020-01752-1.