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Reply toWalk et al

TO THE EDITOR—We appreciate Walk et al’s comments [1] regarding our recent publication and welcome the opportunity to clarify the meaning of some terminology regarding the epidemiologic models used in our article [2]. For any factor with >2 levels, several different questions can be asked in one epidemiologic model. The most common is whether there is any evidence of a different impact of one level of a factor compared to the reference/baseline category on the outcome (as in Tables 2 and 3 [2]; eg, the impact on 14-day mortality of polymerase chain reaction [PCR] ribotype 027 Clostridium difficile infection [CDI] vs enzyme immunoassay [EIA]–negative diarrhea [the reference category]). However, different questions can also be asked from the same model, such as “is there any evidence that the effect of clades 1, 2, and 5 versus EIA-negatives are the same as or different from each other?” This is typically termed a heterogeneity test, as we described [2]. The simplest form is to test whether clade 1 and 2 have the same or different effects on mortality versus EIA-negatives, which is identically equal to a pairwise test of whether clades 1 and 2 have the same effect on mortality as each other. Thus, in contrast to Walk et al’s assertion that “head-to-head comparisons (clade 1 vs clade 2 etc) . . . were not conducted,” these tests were performed and were presented by statistical tests throughout our article, albeit within the context of a larger epidemiologic model, rather than by using crude unadjusted head-to-head comparisons. These pairwise tests are illustrated in Figure 3 [2], where we followed standard notation indicating P values corresponding to pairwise comparisons using brackets. In contrast to Walk et al’s assertion, these do not reflect comparisons versus EIA-negatives (which are instead implicit within the 95% confidence interval). The overall test of heterogeneity of mortality impact across the 5 clades is marked by “het” on our Figure 3. We can therefore reassure Walk and colleagues that we definitively have demonstrated that significant between-clade