Time toxicity associated with early phase clinical trial participation.

early phase clinical trials phase 1 risk versus benefit shared decision making time toxicity

Journal

ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685

Informations de publication

Date de publication:
16 Nov 2023
Historique:
received: 25 08 2023
revised: 27 09 2023
accepted: 28 09 2023
medline: 19 11 2023
pubmed: 19 11 2023
entrez: 18 11 2023
Statut: aheadofprint

Résumé

Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Sections du résumé

BACKGROUND BACKGROUND
Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation.
PATIENTS AND METHODS METHODS
A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work.
RESULTS RESULTS
A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy.
CONCLUSIONS CONCLUSIONS
Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Identifiants

DOI: 10.1016/j.esmoop.2023.102046 PMID: 37979324
pubmed: 37979324
pii: S2059-7029(23)01287-5
doi: 10.1016/j.esmoop.2023.102046
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102046

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure The authors have declared no conflicts of interest.

Auteurs

U Nindra (U)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney. Electronic address: udit.nindra@health.nsw.gov.au.

G Shivasabesan (G)

Department of Medical Oncology, Liverpool Hospital, Liverpool.

S Childs (S)

Department of Medical Oncology, Liverpool Hospital, Liverpool.

R Yoon (R)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney; Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown Hospital, Campbelltown.

S Haider (S)

Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney; Department of Medical Oncology, Northern Cancer Service, Burnie.

M Hong (M)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney.

A Cooper (A)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney.

A Roohullah (A)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney; Department of Medical Oncology, Macarthur Cancer Therapy Centre, Campbelltown Hospital, Campbelltown.

K Wilkinson (K)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney.

A Pal (A)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Department of Medical Oncology, Bankstown-Lidcombe Hospital, Bankstown, Australia.

W Chua (W)

Department of Medical Oncology, Liverpool Hospital, Liverpool; Ingham Institute for Applied Medical Research, Liverpool; School of Medicine, Western Sydney University, Sydney.

Classifications MeSH