Supplementary file 1_Outcome observability in evidence on proton pump inhibitor-associated clostridioides difficile outcomes: a result-specific methodological audit.docx

Codes were not summed, weighted, or dichotomized. Meta-analytic reports were described as aggregate evidence, and odds ratios, risk ratios, and hazard ratios were not treated as quantitatively interchangeable.</p>Results<p>Eleven evidence sources contained an eligible PPI exposure contrast for a CDI-related outcome after one report was excluded during result-level reassessment. Eight addressed incident CDI, one addressed C. difficile detection without uniform confirmation of clinical CDI, one addressed severity among patients with established CDI, and one addressed mortality among patients with established CDI.

Nine estimates were odds ratios, one was a risk ratio, and one was a hazard ratio. Temporal alignment and outcome ascertainment varied across original reports, while three meta-analytic reports combined heterogeneous component definitions. Two Swedish registry reports were treated as one overlapping data-source cluster.</p>Conclusions<p>The included estimates did not represent one common PPI-CDI estimand.

A result-specific outcome-observability profile can identify methodological non-comparability, but it is not a score of study quality, causal validity, statistical power, or likelihood of a positive result. The framework should be interpreted as a descriptive methodological audit rather than evidence that observability conditions explain the direction of reported associations.</p>