Adverse drug reactions (ADRs) are unwanted drug effects that have considerable economic as well as clinical costs as they often lead to hospital admission, prolongation of hospital stay and emergency department visits. Randomized controlled trials (RCTs) are the main premarketing methods used to detect and quantify ADRs but these have several limitations, such as limited study sample size and limited heterogeneity due to the exclusion of the frailest patients. In addition, ADRs due to inappropriate medication use occur often in the real world of clinical practice but not in RCTs. Postmarketing drug safety monitoring through pharmacovigilance activities, including mining of spontaneous reporting and carrying out observational prospective cohort or retrospective database studies, allow longer follow-up periods of patients with a much wider range of characteristics, providing valuable means for ADR detection, quantification and where possible reduction, reducing healthcare costs in the process. Overall, pharmacovigilance is aimed at identifying drug safety signals as early as possible, thus minimizing potential clinical and economic consequences of ADRs. The goal of this review is to explore the epidemiology and the costs of ADRs in routine care.

Introduction: Adverse drug reactions (ADRs) are an important cause of morbidity and mortality worldwide. They are associated with healthcare costs due to hospital admissions or prolonged length of stay, as well as additional interventions. The aim of this study was to conduct a systematic review of observational studies to evaluate the economic impact of preventable ADRs. Areas covered: Published observational research investigating the cost of preventable ADRs in Western countries (limited to the USA and European countries). Expert opinion: Several reviews have been carried out in the field of the ADR epidemiology but fewer reviews have investigated the economic impact of ADRs, and at the time of writing, none has focused on preventable ADRs. The reason why future research should focus on the costs of preventable ADRs is that both the costs and the negative clinical outcomes are preventable, and as such, are a key point of public health policy action. Nevertheless, the present review highlights an important and sobering limitation of published research on the cost of preventable ADRs, of which the major limitation is the heterogeneity in methods and in reporting which limit what can be known through the summarizing work of a systematic review.

Background: Adverse drug reactions (ADRs) are an important public health problem, representing a major cause of morbidity and mortality. However, several countries have no recent studies available. Since 2014, a prospective active pharmacovigilance project, aimed to improve ADRs monitoring in hospital wards (FORWARD) was performed in Sicily. This study, as part of FORWARD project, was aimed to describe ADRs occurred during the hospital stay in Internal Medicine wards. ADRs related to hospital admission, characteristics and preventability of ADRs were also evaluated. Methods: Demographic, clinical, and pharmacological data on patients admitted to six wards of Internal Medicine, from 2014 to 2015, were collected by trained, qualified monitors, who screened all medical records. The rate of ADRs occurred during hospital stay and those leading to hospitalization were analyzed. A descriptive analysis of the reactions, suspected drugs, and associated factors was performed according to the setting analyzed. Results: During the study period, 4,802 admissions were recorded; in 3.2% of them ADRs occurred during hospital stay while in 6.2%, admission was due to ADRs. The duration of hospital stay was longer in patients who experienced ADRs during hospitalization, compared to patients without ADRs [median days 12 (Q1–Q3: 8–17) vs. 9 (6–13)]; p < 0.001). Females [OR1.39 (95% CI 1.03–1.93)] and patients taking ≥ 4 drugs [OR1.46 (95% CI 1.06–2.03)] were more likely to experience ADRs during hospital stay, as well as to be admitted because of ADRs [female: OR1.75 (95% CI 1.37–2.24); ≥ 4 drugs: OR2.14 (95% CI 1.67–2.74)]. The most frequent ADRs occurred during hospital stay were cutaneous (26.8%), general (13.4%), vascular (13.4%), and cardiac (11.5%) disorders and the drug classes mainly involved were anti-bacterials (38.2%) and antithrombotic agents (21.7%). ADRs were serious in 44.6% and probably preventable in 69.4%. Gastrointestinal (27.7%), hematological (26.5%), metabolic (18.1%), and nervous (16.1%) disorders were the main ADRs cause of hospitalization, primarily due to antithrombotic agents (39.0%) RAS-inhibitors (13.9%), NSAIDs (11.9%), and diuretics (9.0%). Only 12.9% of them was not preventable. Conclusion: Adverse drug reactions occurred during hospitalization or contributing to admission to Internal Medicine wards were considerable and most of them were preventable. Females and patients taking many medications were more likely to present ADRs both during hospital stay or as cause of admission.

Introduction As chimeric antigen receptor T-cell therapies are becoming increasingly available in the armamentarium of the hematologist, there is an emerging need to monitor post-marketing safety. Objective We aimed to better characterize their safety profile by focusing on cytokine release syndrome and identifying emerging signals. Methods We queried the US Food and Drug Administration Adverse Event Reporting System (October 2017–September 2020) to analyze suspected adverse drug reactions to tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel). Disproportionality analyses (reporting odds ratio) were performed by comparing chimeric antigen receptor T-cell therapies with (a) all other drugs (reference group 1) and (b) other onco-hematological drugs with a similar indication, irrespective of age (reference group 2), or (c) restricted to adults (reference group 3). Notoriety was assessed through package inserts and risk management plans. Adverse drug reaction time to onset and cytokine release syndrome features were investigated. Results Overall, 3225 reports (1793 axi-cel; 1433 tisa-cel) were identified. The reported toxicities were mainly: cytokine release syndrome (52.2%), febrile disorders (27.7%), and neurotoxicity (27.2%). Cytokine release syndrome and neurotoxicity were often co-reported and 75% of the events occurred in the first 10 days. Disproportionalities confirmed known adverse drug reactions and showed unexpected associations: for example, axi-cel with cardiomyopathies (reporting odds ratio = 2.3; 95% confidence interval 1.2–4.4) and gastrointestinal perforations (2.9; 1.2–7.3), tisa-cel with hepatotoxicity (2.5; 1.1–5.7) and pupil disorders (15.3; 6–39.1). Conclusions Our study confirms the well-known adverse drug reactions and detects potentially emerging safety issues specific for each chimeric antigen receptor T-cell therapy, also providing insights into a stronger role for tisa-cel in inducing some immunodeficiency-related events (e.g., hypogammaglobulinemia, infections) and coagulopathies, and for axi-cel in neurotoxicity.