What place for intelligent automation and artificial intelligence to preserve and strengthen vigilance expertise in the face of increasing declarations?

In 2018, the "Ateliers de Giens" (Giens Workshops) devoted a workshop to artificial intelligence (AI) and led its experts to confirm the potential contribution and theoretical benefit of AI in clinical research, pharmacovigilance, and in improving the efficiency of care. The 2022 workshop is a continuation of this reflection on AI and intelligent automation (IA) by focusing on its contribution to pharmacovigilance and the applications and tasks could be optimized to preserve and strengthen medical and pharmacological expertise in pharmacovigilance. The evolution of pharmacovigilance work is characterized by many tasks with low added value, a growing volume of pharmacovigilance reporting of suspected side effects, and a scarcity of medical staff with expertise in clinical pharmacology and pharmacovigilance and human resources to support this growing need. Together, these parameters contribute to an embolization of the pharmacovigilance system at risk of missing its primary mission: to identify and characterize a risk or even a health alert on a drug. The participants of the workshop (representatives of the Regional Pharmacovigilance Centres (CRPV), the French National Agency for Safety of Medicinal Products (ANSM), patients, the pharmaceutical industry, or start-ups working in the development of AI in the field of medicine) shared their experiences, their pilot projects and their expectations on the expected potential, theoretical or proven, AI and IA. This work has made it possible to identify the needs and challenges that AI or IA represent, in the current or future modes of organization of pharmacovigilance activities. This approach led to the development of a SWOT matrix (strengths, weaknesses, opportunities, threats), a basis for reflection to identify critical points and consider four main recommendations: (1) preserve and develop business expertise in pharmacovigilance (including research and development in methods) with the integration of new technologies; (2) improve the quality of pharmacovigilance reports; (3) adapt technical and regulatory means; (4) implement a development strategy for AI and IA tools at the service of expertise.

Emergency department admissions induced by drug-drug interactions in the elderly: A cross-sectional study.

The elderly people are increasingly exposed to polymedication and therefore to the risks of drug-drug interactions (DDIs). However, there are few data available on the clinical consequences of these drug combinations. We investigated the impact of the various DDIs classified as severe in terms of emergency admissions in the elderly. A cross-sectional study was conducted using information from the emergency department admissions of Bordeaux University Hospital between September 2016 and August 2017. Events of interest were frequency of concomitant uses of interacting drugs that are contraindicated or warned against and frequency of emergency admissions due to contraindicated or warned against concomitant uses of interacting drugs. Five thousand, eight hundred sixty (5860) admissions to the emergency department were analyzed. A total of 375 (6.4%) contraindicated or warned against concomitant uses were identified, including 163 contraindicated (43.5%) and 212 warned against (56.5%). Reason for admission appeared likely related to the underlying DDI in 58 cases. Within these, 36 admissions were assessed as probably due to a DDI (0.6% of hospitalizations) and 22 as certainly (0.4% of hospitalizations). Of these, there were 24 (45%) admissions related to a long QT syndrome (LQTS), nine (16%) related to a drug overdose, and eight (14%) related to a hemorrhage. An antidepressant was involved in 22 of the 24 cases of LQTS. Seven of the eight cases of hemorrhage involved the antithrombotic agents / non-steroidal anti-inflammatory drugs combination. Elderly patients admitted to emergency departments are particularly exposed to high-risk potential DDIs. These drug combinations lead mainly to LQTS and involve certain antidepressants.

Risk of bradyarrhythmia related to ticagrelor: A systematic review and meta-analysis.

CONTEXT: Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk patients. Nevertheless, this risk was not systematically assessed nor measured. OBJECTIVES: To estimate the risk of bradyarrhythmia associated with ticagrelor. STUDY DESIGN: Systematic review and meta-analysis. DATA-SOURCE: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ISI web of Science, clinicaltrial.gov, clinicaltrialsregister.eu. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies in patients treated with ticagrelor or comparator(s). META-ANALYSIS: Risk of bias in each RCT was assessed using Cochrane tool. Relative Risks (RR) with 95 % confidence intervals (95 %CI) were calculated for each RCT, and pooled using fixed-effect or random-effects models, when appropriate. Subgroup and sensitivity analyses were performed. A potential publication bias was searched. RESULTS: Among 82 eligible studies, event data were missing for 56 studies, due to detected reporting bias (i.e. inability to confirm zero events). Fifteen RCTs were selected and the combined RR of bradyarrhythmia was 1.15 (95 %CI 1.05-1.26), and 1.29 (1.02-1.65) for severe bradyarrhythmia. The risk appeared to be dose dependent. Restricting the analysis only to RCTs performed in patients without previous bradyarrhythmia resulted in a non-increased risk. CONCLUSION: This meta-analysis confirmed the risk of bradyarrhythmia or severe bradyarrhythmia related to ticagrelor, and its use in patients without previous bradycardia was effective in preventing it. The evidence coming from this meta-analysis was low to moderate due to missing outcome in 2/3 of eligible studies. Waiting for access to these data, the use of ticagrelor in patients with risk factors of bradycardias should be avoided.