In Reply We appreciate the interest in our work1 and the opportunity to discuss its interpretation. Van der Linden et al raise a lot of issues, but we will focus primarily on the interpretation of the findings for drug-related vs non–drug-related hospital admissions. Van der Linden et al point out the somewhat counterintuitive finding that while hospitalization in general seemed to show a statistically significant reduction, drug-related hospitalizations did not. We interpret this as a matter of power; the hazard ratio point estimate for extended vs basic intervention was 0.77 for the main end point compared to 0.80 and 0.65 for drug-related hospitalization within 180 and 30 days, respectively. These figures are obviously of the same magnitude, but because there were fewer of the drug-related outcomes, they did not reach statistical significance. There are 2 counterexamples mentioned: Gillespie et al2 and Pellegrin et al.3 The trial by Gillespie et al2 was considerably smaller than ours, and the apparent strong benefit for drug-related admissions (relative risk, 0.20) was offset by other admissions, so that overall readmission rates were identical in the 2 groups. The study by Pellegrin et al3 is not randomized, but is instead a macroanalysis using interrupted time series. As we pointed out in our discussion,1 it is conceivable that our intervention could have an effect on non–drug-related admission, as well as on drug-related admission. For example, a patient who is hospitalized because of nonadherence would manifest as someone hospitalized because of a disease exacerbation and not necessarily because of a drug problem. If our intervention improved adherence, such hospitalization could possibly be prevented. We fully agree that it would have been desirable to present data on adherence, and we had planned to do so. Unfortunately, our adherence data were not of sufficient quality to allow for it.
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Hallas J, Ravn-Nielsen LV, Pottegård A. Enough Power to Build a Strong Case for Clinical Pharmacy Services?—Reply. JAMA Intern Med. 2018;178(6):864–865. doi:10.1001/jamainternmed.2018.1709
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