Development of causality assessment criteria in drug-induced blood dyscrasia at King Chulalongkorn Memorial Hospital

Abstract

Objective: The purposes of this study were to develop a causality assessment scale of drug- induced blood abnormalities for Thai clinical settings, to determine the validity, reliability and diagnostic markers of this scale, and to compare this scale with Naranjo's algorithm in assessing the causality of drug – induced blood dyscrasia cases. Method : The new causality assessment scale comprised six axes of decision strategies such as chronological relationship, alternative causes, concomitant medications,clinical features, rechallenge, and previous reports in medical literatures. The relative importance of each axis was weighted and scoring. The risk probability (i.e.,unlikely, possible. Probable, and highly probable ) og the assessment was expresses as a total score that was summed from each axis. Validity and reliability of the scale were studied by comparing the new clinical scale with experts' opinion. Opinions from two experts were used as a gold standard. Reliability test was performed to determine the agreement between two experts. The agreement was presented as intraclass correlation coefficient (rho [subscrip I]).Rating scale assessment from two pharmacists using the new scale was used to study the reliability that was analyze by weighted kappa coefficients (K[subscript w]).The diagnostic markers (cut-off point, sensitivity, accuracy, predictive value and likelihood ratio) of the new scale were also tested for the appropriateness to diagnose patients with drug-induced blood dyscrasia. Patients with suspected drug-induced blood dyscrasias who was admitted at medical wards at King Chulalongkorn Memorial Hospital were recruited and used as cases for assessing the adverse drug events. Results : During January 1, 2001 to November 30, 2002, forty-one patients with a total of 58 events of suspected drug-induced blood dyscrasias were enrolled in this study. The agreement between two experts when evaluating the case series of drug-induced blood dyscrasias was good relationship (rho [subscript I] 0.685; 95% CI0.515-0.802). Inaddition, this new scale showed the high level of validity when comparing with a gold standard (For pharmacist 1: K[subscript w] 0.712; 95% CI 0.520-0.904 and K[subscript w] 0.683;95%CI 0.495-0.871 for pharmacist 2).As for the inter – rater reliability of the new scale, it had also a very good agreement (K[subscript w] 0.866;95%CI 0.672-1.060).From the ROC curve of both pharmacists, the score of 2 was considered as an appropriate cut-off point. It was shown that our scale could identify the cases of drug- induced blood dyscrasia with the high sensitivity (92.3%), as well as a high level of specificity(94.74% for pharmacist 1 and 84.21% for pharmacist 2). When compared with the Naranjo's algorithm, the weighted kappa coeffieints (K[subscript w]) of the new scale validity were singnificantly higher than those of Naranjo's algorithm(K[subscript w] 0.712; 95% CI 0.520-0.904 vs. K[subscript w] 0.411; 95% CI 0.258-0.564 for pharmacist 1 and K[subscript w] 0.683;95%CI 0.495-0.871 vs. K[subscript w] 0.330;95%CI 0.171-0.489 for pharmacist 2).The reliability of the new scale was also higher than that of Naranjo's algorithm (K[subscript w] 0.866; 95% CI 0.672-1.060 vs. K[subscript w] 0.563; 95% CI 0.367-0.759).Moreover,the disgnosetic markers of this new scale tended to have higher values than those of Naranjo's. Conclusion : This study suggested that the new causality assessment scale had high level of validity and reliability. Clinicians may use this clinical scale as a tool to effectively assess patients who suspected of drug induced blood dyscrasias.