We thank Dr. Karp for his interest in our study (1) and agree of course that randomized controlled trials (RCT) are the ideal approach to eliminate confounding at baseline. But because RCTs to examine harm are unethical, assessment of human cancer risk following use of ranitidine can only be based on nonrandomized studies. The published epidemiologic literature on ranitidine and cancer risk is, however, plagued by risk of reverse causality, confounding by indication, low statistical power, and short follow-up. We therefore undertook a study based on what might be the most informative data currently available worldwide. Without repeating arguments supporting the validity of our study already conveyed in the original publication, it remains enigmatic to us which confounding factor(s) Dr. Karp has in mind that would conceal a positive, causal association between ranitidine and four cancer sites with substantially different etiologies (2). Alcohol, for example, is...

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