Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience

Bridget-Anne Kirwan; Jacobus Lubsen; Sophie de Brouwer; Nicolas Danchin; Alexander Battler; Antonio Bayes de Luna; Peter H. J. M. Dunselman; Stephen Glasser; Peter J. Koudstaal; George Sutton; Frederik J. van Dalen; Philip A. Poole-Wilson; null, null

doi:10.1016/j.cct.2007.04.001

Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience

Bridget-Anne Kirwan, Jacobus Lubsen^*, Sophie de Brouwer, Nicolas Danchin, Alexander Battler, Antonio Bayes de Luna, Peter H. J. M. Dunselman, Stephen Glasser, Peter J. Koudstaal, George Sutton, Frederik J. van Dalen, Philip A. Poole-Wilson, null, null

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

24 Citations (Scopus)

Abstract

Objective: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria.

Methods: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC.

Results: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228).

Conclusion: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. (c) 2007 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	720-729
Number of pages	10
Journal	Contemporary Clinical Trials
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.cct.2007.04.001
Publication status	Published - Nov-2007

Keywords

clinical trials
critical events committee
diagnostic classification
event-rates
diagnostic adjudication procedures
CARDIOVASCULAR MORBIDITY
CLINICAL-TRIAL
END-POINTS
MORTALITY
HYPERTENSION
NIFEDIPINE
COMMITTEE

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Kirwan, B.-A., Lubsen, J., de Brouwer, S., Danchin, N., Battler, A., de Luna, A. B., Dunselman, P. H. J. M., Glasser, S., Koudstaal, P. J., Sutton, G., van Dalen, F. J., Poole-Wilson, P. A., & null, null (2007). Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience. Contemporary Clinical Trials, 28(6), 720-729. https://doi.org/10.1016/j.cct.2007.04.001

@article{19d54ad057d34bc3b20474f12bb86b19,

title = "Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience",

abstract = "Objective: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria.Methods: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC.Results: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228).Conclusion: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. (c) 2007 Elsevier Inc. All rights reserved.",

keywords = "clinical trials, critical events committee, diagnostic classification, event-rates, diagnostic adjudication procedures, CARDIOVASCULAR MORBIDITY, CLINICAL-TRIAL, END-POINTS, MORTALITY, HYPERTENSION, NIFEDIPINE, COMMITTEE",

author = "Bridget-Anne Kirwan and Jacobus Lubsen and {de Brouwer}, Sophie and Nicolas Danchin and Alexander Battler and {de Luna}, {Antonio Bayes} and Dunselman, {Peter H. J. M.} and Stephen Glasser and Koudstaal, {Peter J.} and George Sutton and {van Dalen}, {Frederik J.} and Poole-Wilson, {Philip A.} and {null, null}",

year = "2007",

month = nov,

doi = "10.1016/j.cct.2007.04.001",

language = "English",

volume = "28",

pages = "720--729",

journal = "Contemporary Clinical Trials",

issn = "1551-7144",

publisher = "ELSEVIER SCIENCE INC",

number = "6",

}

Kirwan, B-A, Lubsen, J, de Brouwer, S, Danchin, N, Battler, A, de Luna, AB, Dunselman, PHJM, Glasser, S, Koudstaal, PJ, Sutton, G, van Dalen, FJ, Poole-Wilson, PA & null, null 2007, 'Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience', Contemporary Clinical Trials, vol. 28, no. 6, pp. 720-729. https://doi.org/10.1016/j.cct.2007.04.001

TY - JOUR

T1 - Diagnostic criteria and adjudication process both determine published event-rates

T2 - The ACTION trial experience

AU - Kirwan, Bridget-Anne

AU - Lubsen, Jacobus

AU - de Brouwer, Sophie

AU - Danchin, Nicolas

AU - Battler, Alexander

AU - de Luna, Antonio Bayes

AU - Dunselman, Peter H. J. M.

AU - Glasser, Stephen

AU - Koudstaal, Peter J.

AU - Sutton, George

AU - van Dalen, Frederik J.

AU - Poole-Wilson, Philip A.

AU - null, null

PY - 2007/11

Y1 - 2007/11

N2 - Objective: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria.Methods: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC.Results: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228).Conclusion: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. (c) 2007 Elsevier Inc. All rights reserved.

AB - Objective: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria.Methods: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC.Results: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228).Conclusion: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. (c) 2007 Elsevier Inc. All rights reserved.

KW - clinical trials

KW - critical events committee

KW - diagnostic classification

KW - event-rates

KW - diagnostic adjudication procedures

KW - CARDIOVASCULAR MORBIDITY

KW - CLINICAL-TRIAL

KW - END-POINTS

KW - MORTALITY

KW - HYPERTENSION

KW - NIFEDIPINE

KW - COMMITTEE

U2 - 10.1016/j.cct.2007.04.001

DO - 10.1016/j.cct.2007.04.001

M3 - Article

SN - 1551-7144

VL - 28

SP - 720

EP - 729

JO - Contemporary Clinical Trials

JF - Contemporary Clinical Trials

IS - 6

ER -

Diagnostic criteria and adjudication process both determine published event-rates: The ACTION trial experience

Abstract

Keywords

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