Landmark survival as an end-point for trials in critically ill patients – comparison of alternative durations of follow-up: an exploratory analysis
1 Department of Intensive care, Austin Hospital, Studley Road, Melbourne 3084, Australia
2 Department of Intensive Care, Royal Perth Hospital, Wellington Street, Perth 6001 Australia
3 Clinical Associate Professor, School of Population Health, University of Western Australia, Stirling Highway, Crawley 6009, Australia
4 ANZICS CORE Group, Australian and New Zealand Intensive Care Society, 10 Ievers St, Carlton 3053, Australia
5 ANZIC-RC, School Public Health & Preventive Medicine, Monash University Alfred Hospital, Commercial Road, Melbourne 3181, Australia
Critical Care 2009, 13:R128 doi:10.1186/cc7988Published: 4 August 2009
Interventional ICU trials have followed up patients for variable duration. However, the optimal duration of follow-up for the determination of mortality endpoint in such trials is uncertain. We aimed to determine the most logical and practical mortality end-point in clinical trials of critically ill patients.
We performed a retrospective analysis of prospectively collected data involving 369 patients with one of the three specific diagnoses (i) Sepsis (ii) Community acquired pneumonia (iii) Non operative trauma admitted to the Royal Perth Hospital ICU, a large teaching hospital in Western Australia (WA cohort). Their in-hospital and post discharge survival outcome was assessed by linkage to the WA Death Registry. A validation cohort involving 4609 patients admitted during same time period with identical diagnoses from 55 ICUs across Australia (CORE cohort) was used to compare the patient characteristics and in-hospital survival to look at the Australia-wide applicability of the long term survival data from the WA cohort.
The long term outcome data of the WA cohort indicate that mortality reached a plateau at 90 days after ICU admission particularly for sepsis and pneumonia. Mortality after hospital discharge before 90 days was not uncommon in these two groups. Severity of acute illness as measured by the total number of organ failures or acute physiology score was the main predictor of 90-day mortality. The adjusted in-hospital survival for the WA cohort was not significantly different from that of the CORE cohort in all three diagnostic groups; sepsis (P = 0.19), community acquired pneumonia (P = 0.86), non-operative trauma (P = 0.47).
A minimum of 90 days follow-up is necessary to fully capture the mortality effect of sepsis and community acquired pneumonia. A shorter period of follow-up time may be sufficient for non-operative trauma.