Letter of Correspondence: Follow-on Rifaximin for the Prevention of Recurrence Following Standard Treatment of Infection with Clostridium difficile: A Competing Risks Analysis Provides a Full Picture of Possible Treatment Effects

“With interest we read the article by Major et al1 on the effect of rifaximin ‘follow-on’ treatment to prevent recurrent Clostridium difficile infection (rCDI).

Major et al point out the advantage of their study sample being composed of elderly patients who represent the frailties and comorbidities of the target population. The frailty of the sample is reflected by the, compared with other trials on new agents, higher mortality rate, which is considered to increase the generalisability of the results to daily clinical practice.

A main statistical challenge when studying a frail patient population using a non-fatal endpoint is dealing with mortality.2

Patients who died without rCDI are no longer at risk of a recurrent infection. Thus, death is a competing risk of rCDI.

In their analysis, Major et al first exclude patients who have died or have withdrawn from the study before end of follow-up by using generalised estimating equations to estimate the risk difference (RD) of rCDI. Second, they treat them equally as randomly censored by using a Kaplan-Meier estimator (K-M) to estimate the risk of rCDI.

However, in contrast to patients who have withdrawn from the study and remain at risk of rCDI after withdrawal, patients who have died will not experience the event of interest at a later time point. Thus, patients who have died differ fundamentally from patients who have withdrawn from the study or are lost to follow-up.”

http://dx.doi.org/10.1136/gutjnl-2018-317839