Signal of potentially protective drug–drug interactions from spontaneous reporting systems: proceed with caution
- 3 Downloads
We do appreciate the letter by Kuss and Rathmann , who re-examined our data with multiplicative and additive models to assess the likelihood of an interaction between DPP4 inhibitors and statins . They calculated confidence intervals to assess the statistical significance of our findings and conclude that a statistically significant negative interaction exists, thus claiming a protective effect of the drug–drug combination on the risk of myopathy.
Their comments on a protective role that was missed in our analysis raise debate on a very controversial aspect of pharmacovigilance: “Are these statistically significant negative disproportionalities really true negatives?” and, more importantly, “Does a drug–drug combination emerging with statistically significant negative disproportionality imply lower risk and protect from an adverse clinical event as compared to each single drug?” .
Pharmacokinetic and pharmacodynamic aspects of the drug–drug combination can indeed be taken into...
Authors at the University of Bologna are supported by Institutional funds (Ricerca Fondamentale Orientata).
Compliance with ethical standards
Conflict of interest
ICA, EP, EF, FS, AP, FDP, ER have no conflicts of interest relevant to the content of the present work. GM reports personal fees and other from Sanofi, personal fees and other from NOVO Nordisk, personal fees and other from Eli-Lilly, other from Astra Zeneca, other from Glaxo, personal fees and other from Janssen, outside the submitted work.