Impact of the vaccination against SARS-CoV-2 campaign on disproportionality indicator from the WHO pharmacovigilance database: A competition bias study from case/non-case analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) vaccination campaign has resulted in numerous pharmacovigilance's safety reports which were recorded in the World Health Organization (WHO) pharmacovigilance database (VigiBase) and represent in July 2022 more than 10% of cases recorded. The information component (IC) is a statistical disproportionality measure based on the observed and expected numbers of case reports. A positive value of the lower endpoint of a 95% credibility interval for the information component (IC0.25) suggests a possible causal relationship between the drug and the adverse reaction. This study aimed to evaluate the impact of the wave of COVID-19 vaccines safety declarations on IC0.25 from Vigilyze and thus illustrate with a concrete example the competition bias. METHODS: We arbitrarily selected 21 adverse drug reactions using Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs), divided in two types: PTs known to be related to COVID-19 vaccines ("expected") and others (type "unexpected"). Data were extracted from VigiLyze. We created two groups: V+ (the full database, including COVID-19 vaccines reports) and V- (the same extraction without COVID-19 vaccine reports). IC0.25 was recomputed for the group V- and we compared the positive signal evolution in the two settings of selection (V+ and V- groups). RESULTS: The number of positive potential signals was significantly different in the groups V+ and V- for IC0.25. We observed that most of the "unexpected" PTs lost potential signal after the withdrawal of COVID-19 reports. On the contrary, the majority of 'expected' PTs had potential new signals after the withdrawal of COVID-19 reports. DISCUSSION: This study is one of the first to evaluate the effect of COVID-19 vaccines reporting on Automated Signal Detection of Pharmacovigilance. In this study, we observed that a wave of pharmacovigilance reporting can affect disproportionality estimators such as IC0.25 and then have an impact on automated signal detection; some signals disappear (almost with all PTs related to COVID-19 vaccines) and others appear (mostly with PTs not related to COVID-19 vaccines), illustrating the competition bias. CONCLUSION: We show that a health crisis involving a change in drug use can affect adverse drug reactions reporting and pharmacovigilance databases, leading to competition bias and a change in the disproportionality analyses. For health professionals who use quantitative disproportionality analysis, it is important not only to use the crude values of indicators but also the kind of PTs and the evolution of the signal over time (take into account major events such as crises).

Adverse drug reaction profile of third-generation smallpox vaccines used in France during the 2022 monkeypox epidemic.

Due to the start of the monkeypox epidemic in 2022, we retrospectively analyzed the adverse drug reactions (ADRs) reported in France after monkeypox vaccinations with the third-generation smallpox vaccine. Ninety-eight cases, representing 172 ADRs, were reported. ADRs were mostly expected reactogenicity reactions occurring within days after the first dose of vaccine and having a quick favorable outcome. Unexpected facial palsy and vaccination failure are discussed.

Overview of literature monitoring practice of clinical trials vigilance units in French institutional sponsors - A study from the REVISE working group.

INTRODUCTION: The evaluation of clinical trial (CT) safety is the main task of CT vigilance units. In addition to the management of adverse events, the units must review the literature to identify information that may impact the benefit-risk assessment of studies. In this survey, we investigated the literature monitoring (LM) activity of French Institutional Vigilance Units (IVU) from the working group "REflexion sur la VIgilance et la SEcurite des essais cliniques" (REVISE). MATERIAL AND METHODS: We sent a questionnaire of 26 questions, divided into four themes, to the 60 IVU: (1) Presentation of the IVU and the LM activity; (2) Used sources, queries and criteria for selecting articles; (3) Valuation of the LM and (4) Practical organisation. RESULTS: Of the 27 IVU that responded to the questionnaire, 85% of them carried out LM. This was mainly provided by medical staff to improve general knowledge (83%), to detect Adverse Reactions (AR) not listed in the reference documents (70%) and to detect new safety information (61%). Due to lack of time, staff, available recommendations and sources, only 21% of IVU conducted LM for all CT. On average, units reported four sources: ANSM information (96%), PubMed database (83%), EMA alerts (57%) and the subscription to APM international (48%). The LM had an impact on the CT of 57% of the IVU such as changing the conditions of a study (39%) or suspending a study (22%). DISCUSSION/CONCLUSION: LM is an important but time-consuming activity with heterogeneous practices. According to the results of this survey, we proposed seven ways to improve this practice: (1) Target the highest risk CT; (2) Refine the PubMed queries; (3) Use other tools; (4) Create a decision flowchart for the selection of PubMed articles; (5) Improve training; (6) Value the activity and (7) Outsource the activity.

Real-world safety profiles of pirfenidone and nintedanib in idiopathic pulmonary fibrosis patients.

INTRODUCTION: While pirfenidone and nintedanib have greatly influenced the treatment of idiopathic pulmonary fibrosis (IPF), both drugs have significant early adverse drug reactions (ADRs) and almost nothing is known of their rare and delayed ADRs. We collected and analyzed pirfenidone- or nintedanib-related ADRs identified in a French rare lung disease center, recorded their profiles and identified potential safety signals. METHODS: We analyzed the medical records of IPF patients treated with pirfenidone or nintedanib between January 2011 and January 2020 at the Rennes University Hospital to estimate the incidence of serious and non-serious ADRs cases due to each drug and the incidence of ADRs involving the cardiovascular, hepatobiliary, gastro-intestinal, dermatological, and metabolic/nutritional systems. RESULTS: The 176 patients included 115 (65%) initially treated with pirfenidone and 61 (35%) given nintedanib. ADRs occurred in 78.3% of those given pirfenidone and in 70.5% of those given nintedanib. The incidence of first serious ADRs cases was about 33 per 100 person-years (100 PY) for both drugs; first non-serious pirfenidone ADRs cases were 102 per 100 PY and 130 per 100 PY for nintedanib. The incidence involving each organ system were quite similar, except for the gastro-intestinal and skin disorders. Cardiovascular disorders occurred in about 10 cases per 100 PY in both pirfenidone and nintedanib patients. DISCUSSION: Most ADRs were consistent with the expected antifibrotic drug safety profiles. As arterial and venous thromboembolic events are rare, it is important to assess the risk associated with using antifibrotics by a dedicated pharmacoepidemiological study.