Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan.


Journal

Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253

Informations de publication

Date de publication:
05 Aug 2019
Historique:
received: 11 12 2018
accepted: 04 07 2019
entrez: 7 8 2019
pubmed: 7 8 2019
medline: 14 2 2020
Statut: epublish

Résumé

The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. The resulting SAP is consistent with best practice and will allow open and transparent reporting. We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias. ANZ Clinical Trials Registry, ACTRN12607000512426 . Registered on 9 October 2007. ClinicalTrials.gov, NCT01503827 . Registered on 4 January 2012. Trial group reference numbers ANZMTG 01.07, TROG 08.05.

Sections du résumé

BACKGROUND BACKGROUND
The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness.
OBJECTIVE OBJECTIVE
The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis.
METHODS METHODS
The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data.
RESULTS RESULTS
The resulting SAP is consistent with best practice and will allow open and transparent reporting.
CONCLUSION CONCLUSIONS
We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias.
TRIAL REGISTRATION BACKGROUND
ANZ Clinical Trials Registry, ACTRN12607000512426 . Registered on 9 October 2007. ClinicalTrials.gov, NCT01503827 . Registered on 4 January 2012. Trial group reference numbers ANZMTG 01.07, TROG 08.05.

Identifiants

pubmed: 31382986
doi: 10.1186/s13063-019-3555-5
pii: 10.1186/s13063-019-3555-5
pmc: PMC6683544
doi:

Banques de données

ClinicalTrials.gov
['NCT01503827']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

477

Subventions

Organisme : Cancer Research UK
ID : 11885
Pays : United Kingdom
Organisme : Cancer Australia
ID : 1084046

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Auteurs

Serigne N Lo (SN)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia.

Angela M Hong (AM)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Mater Hospital, North Sydney, NSW, Australia.
Genesis Care, Mater Radiation Oncology, North Sydney, NSW, Australia.

Lauren E Haydu (LE)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
MD Anderson Cancer Center, Houston, TX, USA.

Tasnia Ahmed (T)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.

Elizabeth J Paton (EJ)

Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Australia and New Zealand Melanoma Trials Group, North Sydney, NSW, Australia.

Victoria Steel (V)

Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Australia and New Zealand Melanoma Trials Group, North Sydney, NSW, Australia.

George Hruby (G)

Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Royal North Shore Hospital, St Leonards, NSW, Australia.
Genesis Care, Sydney, NSW, Australia.

Anh Tran (A)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW, Australia.

Rachael L Morton (RL)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
NHMRC Clinical Trials Centre, The University of Sydney, Camperdown, NSW, Australia.

Anna K Nowak (AK)

Medical School, University of Western Australia, Perth, WA, Australia.

Janette L Vardy (JL)

Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Katharine J Drummond (KJ)

Royal Melbourne Hospital, Parkville, VIC, Australia.

Haryana M Dhillon (HM)

Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Catherine Mandel (C)

Swinburne University of Technology, Melbourne, VIC, Australia.

Richard A Scolyer (RA)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

Mark R Middleton (MR)

University of Oxford, Oxford, UK.

Bryan H Burmeister (BH)

Genesis Care Fraser Coast, Urraween, QLD, Australia.

John F Thompson (JF)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia.
Department of Melanoma and Surgical Oncology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.

Gerald B Fogarty (GB)

Melanoma Institute Australia, The University of Sydney, Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
Mater Hospital, North Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
Genesis Care, Mater Radiation Oncology, North Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
Australia and New Zealand Melanoma Trials Group, North Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
Genesis Care, Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
University of Technology Sydney, Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.
St Vincent's Hospital, Sydney, NSW, Australia. gerald.fogarty@cancer.com.au.

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Classifications MeSH