Projecting event-based analysis dates in clinical trials: An illustration based on the international duration evaluation of adjuvant chemotherapy (IDEA) collaboration. Projecting analysis dates for the IDEA collaboration

Lindsay A. Renfro, Axel F Grothey, James Paul, Irene Floriani, Franck Bonnetain, Donna Niedzwiecki, Takeharu Yamanaka, Ioannis Souglakos, Greg Yothers, Daniel J. Sargent

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose: Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods: In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results: Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions: Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalForum of Clinical Oncology
Volume5
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Adjuvant Chemotherapy
Clinical Trials
Censuses
Colonic Neoplasms
Clinical Protocols
Disease-Free Survival
Meta-Analysis

Keywords

  • Adjuvant therapy
  • Colon cancer
  • Duration of therapy
  • Meta-analysis

ASJC Scopus subject areas

  • Oncology

Cite this

Projecting event-based analysis dates in clinical trials : An illustration based on the international duration evaluation of adjuvant chemotherapy (IDEA) collaboration. Projecting analysis dates for the IDEA collaboration. / Renfro, Lindsay A.; Grothey, Axel F; Paul, James; Floriani, Irene; Bonnetain, Franck; Niedzwiecki, Donna; Yamanaka, Takeharu; Souglakos, Ioannis; Yothers, Greg; Sargent, Daniel J.

In: Forum of Clinical Oncology, Vol. 5, No. 2, 2014, p. 1-7.

Research output: Contribution to journalArticle

Renfro, Lindsay A. ; Grothey, Axel F ; Paul, James ; Floriani, Irene ; Bonnetain, Franck ; Niedzwiecki, Donna ; Yamanaka, Takeharu ; Souglakos, Ioannis ; Yothers, Greg ; Sargent, Daniel J. / Projecting event-based analysis dates in clinical trials : An illustration based on the international duration evaluation of adjuvant chemotherapy (IDEA) collaboration. Projecting analysis dates for the IDEA collaboration. In: Forum of Clinical Oncology. 2014 ; Vol. 5, No. 2. pp. 1-7.
@article{047590fa953d4ec9bb76e2584ab62b09,
title = "Projecting event-based analysis dates in clinical trials: An illustration based on the international duration evaluation of adjuvant chemotherapy (IDEA) collaboration. Projecting analysis dates for the IDEA collaboration",
abstract = "Purpose: Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods: In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results: Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions: Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required.",
keywords = "Adjuvant therapy, Colon cancer, Duration of therapy, Meta-analysis",
author = "Renfro, {Lindsay A.} and Grothey, {Axel F} and James Paul and Irene Floriani and Franck Bonnetain and Donna Niedzwiecki and Takeharu Yamanaka and Ioannis Souglakos and Greg Yothers and Sargent, {Daniel J.}",
year = "2014",
doi = "10.2478/fco-2014-0006",
language = "English (US)",
volume = "5",
pages = "1--7",
journal = "Forum of Clinical Oncology",
issn = "1792-345X",
publisher = "Hellenic Society of Medical Oncology (He.S.M.O.)",
number = "2",

}

TY - JOUR

T1 - Projecting event-based analysis dates in clinical trials

T2 - An illustration based on the international duration evaluation of adjuvant chemotherapy (IDEA) collaboration. Projecting analysis dates for the IDEA collaboration

AU - Renfro, Lindsay A.

AU - Grothey, Axel F

AU - Paul, James

AU - Floriani, Irene

AU - Bonnetain, Franck

AU - Niedzwiecki, Donna

AU - Yamanaka, Takeharu

AU - Souglakos, Ioannis

AU - Yothers, Greg

AU - Sargent, Daniel J.

PY - 2014

Y1 - 2014

N2 - Purpose: Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods: In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results: Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions: Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required.

AB - Purpose: Clinical trials are expensive and lengthy, where success of a given trial depends on observing a prospectively defined number of patient events required to answer the clinical question. The point at which this analysis time occurs depends on both patient accrual and primary event rates, which typically vary throughout the trial's duration. We demonstrate real-time analysis date projections using data from a collection of six clinical trials that are part of the IDEA collaboration, an international preplanned pooling of data from six trials testing the duration of adjuvant chemotherapy in stage III colon cancer, and we additionally consider the hypothetical impact of one trial's early termination of follow-up. Patients and Methods: In the absence of outcome data from IDEA, monthly accrual rates for each of the six IDEA trials were used to project subsequent trial-specific accrual, while historical data from similar Adjuvant Colon Cancer Endpoints (ACCENT) Group trials were used to construct a parametric model for IDEA's primary endpoint, disease-free survival, under the same treatment regimen. With this information and using the planned total accrual from each IDEA trial protocol, individual patient accrual and event dates were simulated and the overall IDEA interim and final analysis times projected. Projections were then compared with actual (previously undisclosed) trial-specific event totals at a recent census time for validation. The change in projected final analysis date assuming early termination of follow-up for one IDEA trial was also calculated. Results: Trial-specific predicted event totals were close to the actual number of events per trial for the recent census date at which the number of events per trial was known, with the overall IDEA projected number of events only off by eight patients. Potential early termination of follow-up by one IDEA trial was estimated to postpone the overall IDEA final analysis date by 9 months. Conclusions: Real-time projection of the final analysis time during a trial, or the overall analysis time during a trial collaborative such as IDEA, has practical implications for trial feasibility when these projections are translated into additional time and resources required.

KW - Adjuvant therapy

KW - Colon cancer

KW - Duration of therapy

KW - Meta-analysis

UR - http://www.scopus.com/inward/record.url?scp=84927622467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927622467&partnerID=8YFLogxK

U2 - 10.2478/fco-2014-0006

DO - 10.2478/fco-2014-0006

M3 - Article

AN - SCOPUS:84927622467

VL - 5

SP - 1

EP - 7

JO - Forum of Clinical Oncology

JF - Forum of Clinical Oncology

SN - 1792-345X

IS - 2

ER -