Improving Methodology Improves Timing: Reply to Thombs et al.

CORRESPONDENCE Improving Methodology Improves Timing: Reply to Thombs et al. To the Editor: e thank Thombs and colleagues for their close reading of our article, which has identified an issue related to the inclusion and coding of “dummy” variables for certain effects. By prompting a reexamination of our data, their letter has helped to clarify further the role of post–acute coronary syndrome (ACS) depression. The covariates in the analysis included 10 demographic and cardiac risk factors plus three dummy variables related to the onset of depression. The coding of these dummy variables needed to address (in some way) the effects of whether patients were depressed or not pre-ACS; if they were, whether they remained depressed; and if they were not, whether post-ACS they developed a first episode of depression (incident) or a recurrent episode (nonincident). There are various constraints and dependencies among these questions (hence the issue raised by Thombs and colleagues), and not all questions are necessarily answerable in a single analysis. As the letter notes, the reported analyses (Table 2) included a dummy variable for any post-ACS depression (new depression onset postbaseline) and one for an incident-type post-ACS depression (incident depression). These are strongly associated (the basis for multicollinearity) and resulted in the effect (odds ratio) for incident depression switching direction when adjusted for the risk factors and the other dummy variables. The odds ratio (OR) for any post-ACS episode also increased. However, a large increase occurred when adjusting for the risk factors alone, and that increase does not appear to be attributable to multicollinearity. Different coding schemes are possible. We have now examined an analysis using the following four dummy variables: incident depression, recurrent depression, prebaseline depression that continued, and prebaseline depression that ceased. These variables show no evidence of multicollinearity. The results (consistent in direction with the respective unadjusted effects) were as follows: incident depression OR ⫽ 4.06 (95%

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confidence interval [CI] ⫽ 1.44 –11.4); recurrent depression OR ⫽ 7.07 (95% CI ⫽ 2.22–22.48); prebaseline depression that continued OR ⫽ 1.30 (95% CI ⫽ .42– 4.20); and prebaseline depression that ceased OR ⫽ .49 (95% CI ⫽ .11–2.25). These ORs support the view that any new episode post-ACS is a nonprotective risk factor, but the precise size of that risk and the relative risks of incident and recurrent depression are much less clear: the power of the study is too low for that purpose, and the concerns about power expressed in the letter are appropriate. Thombs and colleagues contemplate whether our findings would generalize “beyond this particular group of patients.” In the second paragraph of our Discussion, we reference two articles reporting that a first-ever episode of depression commencing post-ACS (incident depression) predicted a poorer cardiac outcome, whereas non-incident depression did not. The reexamination of our data concurs with those studies regarding incident depression and refines nonincident depression by distinguishing between nonincident episodes that are new (and for which the OR was significant) and those that are continuing (and for which the OR was not significant). Replication of a finding across quite differing samples is generally encouraging in suggesting a valid “signal” or true finding. Gordon Parker Dusan Hadzi-Pavlovic School of Psychiatry, University of New South Wales and Black Dog Institute, Prince of Wales Hospital Hospital Road Randwick NSW 2031 Australia E-mail: [email protected] Professor Parker has received research support from Pfizer International and Servier. He serves on the advisory boards of Astra Zeneca, Eli Lilly, Lundbeck, and Janssen. The other author reports no biomedical financial interests or potential conflicts of interest. doi:10.1016/j.biopsych.2009.02.006

BIOL PSYCHIATRY 2009;66:e3 © 2009 Society of Biological Psychiatry