Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee
- 1The Queen’s University of Belfast, Belfast, UK
- 2Respiratory Medicine, Barmer Ostseeklinik, Prerow, Germany
- 3GlaxoSmithKline, Greenford, UK
- 4GlazoSmithKline, Research Triangle Park, North Carolina, USA
- 5Johns Hopkins University, Baltimore, Maryland, USA
- Correspondence to:
Dr Lorcan P McGarvey
The Queen’s University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK;
- Received 26 September 2006
- Accepted 21 January 2007
- Published Online First 20 February 2007
Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described.
Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information.
Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (κ = 0.80). COPD-relatedness was reproduced 84% of the time (κ = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases.
Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.
- CEC, Clinical Endpoint Committee
- COPD, chronic obstructive pulmonary disease
- TORCH, Towards a Revolution in COPD Health
Published Online First 20 February 2007
LMcG and MJ were equal contributors to this study and are considered as joint first authors.
Funding for the study described in this article was provided by GlaxoSmithKline.
Competing interests: LMcG, MJ and RAW are paid consultants to GlaxoSmithKline. JAA and MZ are employees of GlaxoSmithKline. RAW’s arrangements are managed by the Johns Hopkins University in accordance with its conflict of interest policies.