Algorithm for the evaluation of therapeutic failure reports—proposal and pilot analysis

Purpose To propose and validate an algorithm to analyze the reports of suspected therapeutic failure (TF) received in pharmacovigilance programs. Methods A Delphi consensus method with a group of 12 international experts was used to identify the different causes that prompt TF and to propose an algorithm to analyze reports of suspected lack of efficacy of medicines. A pilot analysis of 50 reports was the basis to evaluate the interrater and intrarater validity of the algorithm. Results A 10‐question algorithm was proposed. The evaluation of 50 reports of suspected TF showed that only 8% could be actually attributed to a manufacturing quality problem, whereas the real reason underlying the alleged TF was the inappropriate use of the prescribed drug in 28%. Minimum information to attribute the cause to a TF was lacking in 31% of these reports. The interrater reliability was “moderate” (kappa coefficient = 0.55), and the intrarater reliability ranged from 0.732 to 0.908 (“substantial” to “almost perfect”). Conclusions The proposed TF algorithm is a valid, reliable, and reproducible analysis tool that can help to disentangle the frequent and complex reports of suspected TF. Copyright © 2012 John Wiley & Sons, Ltd.