Cargando…

Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review

BACKGROUND: Traditionally, within dose-finding clinical trials, treatment toxicity and tolerability are assessed by clinicians. Research has shown that clinician reporting may have inadequate inter-rater reliability, poor correlation with patient reported outcomes, and under capture the true toxicit...

Descripción completa

Detalles Bibliográficos
Autores principales: Alger, Emily, Minchom, Anna, Lee Aiyegbusi, Olalekan, Schipper, Matthew, Yap, Christina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541462/
https://www.ncbi.nlm.nih.gov/pubmed/37781154
http://dx.doi.org/10.1016/j.eclinm.2023.102228
_version_ 1785113910136799232
author Alger, Emily
Minchom, Anna
Lee Aiyegbusi, Olalekan
Schipper, Matthew
Yap, Christina
author_facet Alger, Emily
Minchom, Anna
Lee Aiyegbusi, Olalekan
Schipper, Matthew
Yap, Christina
author_sort Alger, Emily
collection PubMed
description BACKGROUND: Traditionally, within dose-finding clinical trials, treatment toxicity and tolerability are assessed by clinicians. Research has shown that clinician reporting may have inadequate inter-rater reliability, poor correlation with patient reported outcomes, and under capture the true toxicity burden. The introduction of patient-reported outcomes (PROs), where the patient can assess their own symptomatic adverse events or quality of life, has potential to complement current practice to aid dose optimisation. There are no international recommendations offering guidance for the inclusion of PROs in dose-finding trial design and analysis. Our review aimed to identify and describe current statistical methods and data visualisation techniques employed to analyse and visualise PRO data in published early phase dose-finding oncology trials (DFOTs). METHODS: DFOTs published from June 2016–December 2022, which presented PRO analysis methods, were included in this methodological review. We extracted 35 eligible papers indexed in PubMed. Study characteristics extracted included: PRO objectives, PRO measures, statistical analysis and visualisation techniques, and whether the PRO was involved in interim and final dose selection decisions. FINDINGS: Most papers (30, 85.7%) did not include clear PRO objectives. 20 (57.1%) papers used inferential statistical techniques to analyse PROs, including survival analysis and mixed-effect models. One trial used PROs to classify a clinicians’ assessed dose-limiting toxicities (DLTs). Three (8.6%) trials used PROs to confirm the tolerability of the recommended dose. 25 trial reports visually presented PRO data within a figure or table within their publication, of which 12 papers presented PRO score longitudinally. INTERPRETATION: This review highlighted that the statistical methods and reporting of PRO analysis in DFOTs are often poorly described and inconsistent. Many trials had PRO objectives which were not clearly described, making it challenging to evaluate the appropriateness of the statistical techniques used. Drawing conclusions based on DFOTs which are not powered for PROs may be misleading. With no guidance and standardisation of analysis methods for PROs in early phase DFOTs, it is challenging to compare study findings across trials. Therefore, there is a crucial need to establish international guidance to enhance statistical methods and graphical presentation for PRO analysis in the dose-finding setting. FUNDING: EA has been supported to undertake this work as part of a PhD studentship from the 10.13039/501100000650Institute of Cancer Research within the 10.13039/501100000265MRC/10.13039/501100000272NIHR Trials Methodology Research Partnership. AM is supported by the 10.13039/501100000272National Institute for Health Research (NIHR) 10.13039/100014461Biomedical Research Centre at the 10.13039/100012139Royal Marsden NHS Foundation Trust, the 10.13039/501100000650Institute of Cancer Research and Imperial College.
format Online
Article
Text
id pubmed-10541462
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-105414622023-10-01 Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review Alger, Emily Minchom, Anna Lee Aiyegbusi, Olalekan Schipper, Matthew Yap, Christina eClinicalMedicine Articles BACKGROUND: Traditionally, within dose-finding clinical trials, treatment toxicity and tolerability are assessed by clinicians. Research has shown that clinician reporting may have inadequate inter-rater reliability, poor correlation with patient reported outcomes, and under capture the true toxicity burden. The introduction of patient-reported outcomes (PROs), where the patient can assess their own symptomatic adverse events or quality of life, has potential to complement current practice to aid dose optimisation. There are no international recommendations offering guidance for the inclusion of PROs in dose-finding trial design and analysis. Our review aimed to identify and describe current statistical methods and data visualisation techniques employed to analyse and visualise PRO data in published early phase dose-finding oncology trials (DFOTs). METHODS: DFOTs published from June 2016–December 2022, which presented PRO analysis methods, were included in this methodological review. We extracted 35 eligible papers indexed in PubMed. Study characteristics extracted included: PRO objectives, PRO measures, statistical analysis and visualisation techniques, and whether the PRO was involved in interim and final dose selection decisions. FINDINGS: Most papers (30, 85.7%) did not include clear PRO objectives. 20 (57.1%) papers used inferential statistical techniques to analyse PROs, including survival analysis and mixed-effect models. One trial used PROs to classify a clinicians’ assessed dose-limiting toxicities (DLTs). Three (8.6%) trials used PROs to confirm the tolerability of the recommended dose. 25 trial reports visually presented PRO data within a figure or table within their publication, of which 12 papers presented PRO score longitudinally. INTERPRETATION: This review highlighted that the statistical methods and reporting of PRO analysis in DFOTs are often poorly described and inconsistent. Many trials had PRO objectives which were not clearly described, making it challenging to evaluate the appropriateness of the statistical techniques used. Drawing conclusions based on DFOTs which are not powered for PROs may be misleading. With no guidance and standardisation of analysis methods for PROs in early phase DFOTs, it is challenging to compare study findings across trials. Therefore, there is a crucial need to establish international guidance to enhance statistical methods and graphical presentation for PRO analysis in the dose-finding setting. FUNDING: EA has been supported to undertake this work as part of a PhD studentship from the 10.13039/501100000650Institute of Cancer Research within the 10.13039/501100000265MRC/10.13039/501100000272NIHR Trials Methodology Research Partnership. AM is supported by the 10.13039/501100000272National Institute for Health Research (NIHR) 10.13039/100014461Biomedical Research Centre at the 10.13039/100012139Royal Marsden NHS Foundation Trust, the 10.13039/501100000650Institute of Cancer Research and Imperial College. Elsevier 2023-09-21 /pmc/articles/PMC10541462/ /pubmed/37781154 http://dx.doi.org/10.1016/j.eclinm.2023.102228 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Alger, Emily
Minchom, Anna
Lee Aiyegbusi, Olalekan
Schipper, Matthew
Yap, Christina
Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title_full Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title_fullStr Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title_full_unstemmed Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title_short Statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
title_sort statistical methods and data visualisation of patient-reported outcomes in early phase dose-finding oncology trials: a methodological review
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541462/
https://www.ncbi.nlm.nih.gov/pubmed/37781154
http://dx.doi.org/10.1016/j.eclinm.2023.102228
work_keys_str_mv AT algeremily statisticalmethodsanddatavisualisationofpatientreportedoutcomesinearlyphasedosefindingoncologytrialsamethodologicalreview
AT minchomanna statisticalmethodsanddatavisualisationofpatientreportedoutcomesinearlyphasedosefindingoncologytrialsamethodologicalreview
AT leeaiyegbusiolalekan statisticalmethodsanddatavisualisationofpatientreportedoutcomesinearlyphasedosefindingoncologytrialsamethodologicalreview
AT schippermatthew statisticalmethodsanddatavisualisationofpatientreportedoutcomesinearlyphasedosefindingoncologytrialsamethodologicalreview
AT yapchristina statisticalmethodsanddatavisualisationofpatientreportedoutcomesinearlyphasedosefindingoncologytrialsamethodologicalreview