Competing risks and the clinical community: irrelevance or ignorance?

Abstract

Life expectancy has dramatically increased in industrialized nations over the last 200 hundred years. The aging of populations carries over to clinical research and leads to an increasing representation of elderly and multimorbid individuals in study populations. Clinical research in these populations is complicated by the fact that individuals are likely to experience several potential disease endpoints that prevent some disease-specific endpoint of interest from occurrence. Large developments in competing risks methodology have been achieved over the last decades, but we assume that recognition of competing risks in the clinical community is still marginal. It is the aim of this article to address translational aspects of competing risks to the clinical community. We describe clinical populations where competing risks issues may arise. We then discuss the importance of agreement between the competing risks methodology and the study aim, in particular the distinction between etiologic and prognostic research questions. In a review of 50 clinical studies performed in individuals susceptible to competing risks published in high-impact clinical journals, we found competing risks issues in 70% of all articles. Better recognition of issues related to competing risks and of statistical methods that deal with competing risks in accordance with the aim of the study is needed.

Figure 1

Competing risks as multistate model with cause-specific hazards λ₁(t) and λ₂(t).

Figure 2

Competing risks model with the subdistribution hazards approach α₁(t).

Figure 3

Hypothetical three-arm trial with a competing risks outcome. The top two panels show the assumed cause-specific hazards for placebo (solid black lines) and treatment 1 (dashed gray lines), which affects only the cause-specific hazard of the event of interest and treatment 2 (dotted black lines), which affects both cause-specific hazards. The two bottom panels show the resulting cumulative incidence functions.

Figure 4

Absolute number of articles published on competing risks between 1 January 2000, and 28 October 2010, in the highest ranked clinical journals, biostatistical journals, and core clinical journals.

Figure 5

Critical appraisal for competing risks issues in 50 studies published in high-ranked clinical journals and populations susceptible to competing risks.