Cause-specific mortality adjudication in the UPLIFT ® COPD trial: Findings and recommendations

Lorcan P. McGarvey, Sheldon Magder, Deborah Burkhart, Steven Kesten, Dacheng Liu, Raymond C. Manuel, Denis E. Niewoehner

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT ®) trial, a Mortality Adjudication Committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

Original languageEnglish (US)
Pages (from-to)515-521
Number of pages7
JournalRespiratory Medicine
Volume106
Issue number4
DOIs
StatePublished - Apr 2012

Bibliographical note

Funding Information:
This study was funded by Boehringer Ingelheim International GmbH and Pfizer Inc . All authors contributed to the data analyses, the interpretation of the data and the composition of the manuscript. Dr Kesten contributed to the design and conduct of the UPLIFT ® trial and Dr Liu provided statistical support. The authors would like to thank Natalie Dennis from PAREXEL, who provided editing assistance (which was funded by Boehringer Ingelheim and Pfizer).

Keywords

  • Cause of death
  • Independent
  • Tiotropium
  • UPLIFT

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