Characterization of Serious Adverse Drug Reactions in Hospital to Determine Potential Implications of Mandatory Reporting

ABSTRACT Background: The Protecting Canadians from Unsafe Drugs Act will eventu-ally require institutions to report all serious adverse drug reactions (ADRs), although the proposed regulations do not yet define what will need to be reported and by whom. Knowledge about the occurrence of serious ADRs in the hospital setting is needed to optimize the effectiveness of reporting and to determine the potential implications of mandatory reporting. Objectives: To quantify and characterize suspected serious ADRs in patients admitted to a general medicine service, to assess the likelihood of causality, and to determine inter-rater agreement for identification of ADRs and assessment of their likelihood. Methods: This prospective observational study involved 60 consecutive patients admitted to a general medicine service at a tertiary care teaching centre starting on March 28, 2016. The primary outcome was the number of serious ADRs, defined by Health Canada as ADRs that result in hospital admission, congenital malformation, persistent or significant disability or incapacity, or death; that are life-threatening; or that require significant intervention to prevent one of these outcomes. Medical records were reviewed independently by pairs of pharmacists for serious ADRs, and the likelihood of causality was assessed using the World Health Organization–Uppsala Monitoring Centre system. Inter-rater agreement was calculated using the kappa score, and disagreements were resolved by discussion and consensus. Results: Twenty-three serious ADRs occurred in the sample of 60 patients. The proportion of patients experiencing a serious ADR that contributed to the original hospital admission was 19/60 (32%, 95% confidence interval [CI] 20%–43%), and 4 patients (7%, 95% CI 0%–13%) experienced a serious ADR during their hospital stay. Inter-rater agreement for occurrence of serious ADRs was moderate (kappa 0.58, 95% CI 0.35–0.76). Conclusion: Reportable serious ADRs were common among patients admitted to a general medicine service. Canadian hospitals would face difficulties reporting all serious ADRs because of the frequency of their occurrence and the subjectivity of their identification. RESUME Contexte : La Loi visant a proteger les Canadiens contre les drogues dangereuses obligera eventuellement les etablissements a declarer tout cas de reactions indesirables graves aux medicaments (RIM), quoique les re-glements proposes n’indiquent pas encore ce qui devra etre declare et par qui. Des donnees sur la survenue de RIM graves en milieu hospitalier sont necessaires pour optimiser l’efficacite de la declaration et pour determiner les implications potentielles d’une declaration obligatoire. Objectifs : Quantifier les RIM graves soupconnees chez les patients admis a un service de medecine generale et en offrir un portrait, evaluer la probabilite d’une relation de causalite et determiner l’accord interevalua-teurs pour le reperage des RIM et l’evaluation de leur probabilite. Methodes : La presente etude observationnelle prospective comptait 60 patients admis consecutivement a partir du 28 mars 2016 a un service de medecine generale d’un centre hospitalier universitaire de soins tertiaires. Le principal parametre d’evaluation etait le nombre de RIM graves, definies par Sante Canada comme des RIM qui menent a une hospitalisation, a une malformation congenitale, a une invalidite ou a une incapacite persistante ou importante; qui mettent la vie en danger ou entrainent la mort; ou qui necessitent une intervention significative pour prevenir l’un de ces resultats. Les dossiers medicaux ont ete examines independamment par des paires de pharmaciens a la recherche de RIM graves et la probabilite d’une causalite a ete evaluee a l’aide du systeme du Centre de pharmacovigilance d’Uppsala de l’Organisation mondiale de la Sante. L’accord interevaluateurs a ete mesure a l’aide du coefficient kappa et les desaccords ont ete resolus par la discussion et l’atteinte d’un consensus. Resultats : Vingt-trois RIM graves sont survenues dans l’echantillon compose de 60 patients. La proportion de patients ayant subi une RIM grave qui a contribue a l’hospitalisation initiale etait 19/60 (32 %, intervalle de confiance [IC] de 95 % de 20 %–43 %); de plus, 4 patients (7 %, IC de 95 % de 0 %–13 %) avaient subi une RIM grave au cours de leur sejour a l’hopital. L’accord interevaluateurs sur la survenue de RIM graves etait modere (kappa = 0,58, IC de 95 % de 0,35–0,76). Conclusion : Les RIM graves a declaration obligatoire etaient courantes chez les patients admis a un service de medecine generale. Les hopitaux canadiens auraient de la difficulte a declarer tous les cas de RIM graves a cause de leur frequence et de la subjectivite de leur reperage.