Faculty Bibliography

PURPOSE/OBJECTIVE:) to justify risk communication. METHODS:, we synthesize and interpret within an Austin Bradford Hill criteria framework a comprehensive, cross-disciplinary set of published information and de novo analysis, including toxicology, epidemiology, clinical pharmacology, and clinical and quantitative pharmacovigilance analysis of spontaneous reports. RESULTS:, to the extent that it is reasonably possible that APAP may sometimes be at least a contributory cause of FCCDA. CONCLUSION/CONCLUSIONS:It is reasonably possible that APAP may sometimes be at least a contributory cause of FCCDA, and this should therefore be communicated to stakeholders. TRIAL REGISTRATION/BACKGROUND:CLINICALTRIALS. GOV REGISTRATION/UNASSIGNED:NOT APPLICABLE.

Artificial intelligence (AI), a highly interdisciplinary science, is an increasing presence in pharmacovigilance (PV). A better understanding of the scope of artificial intelligence in pharmacovigilance (AIPV) may be advantageous to more sharply defining, for example, which terms, methods, tasks, and data sets are suitably subsumed under the application of AIPV. Accordingly, this article explores relevant points to consider regarding defining the scope of AIPV and offers a potential working definition of the scope of AIPV.

PURPOSE/OBJECTIVE:The COVID-19 pandemic has been widely reported to present stress to medical systems globally and to disrupt the lives of patients and health care practitioners (HCPs). Given that spontaneous reporting heavily relies on both HCPs and patients, an understandable question is whether the stress of the pandemic has diminished spontaneous reporting. Herein, the hypothesis that the COVID-19 pandemic has negatively affected the spontaneous reporting of adverse drug events was assessed. METHODS:Spontaneous-report counts from 119 weeks (January 1, 2018, to April 12, 2020) were identified using Pfizer's safety database and were analyzed. Autoregressive integrated moving-average models were fitted to aggregated and disaggregated time series (TSs). Model residuals were charted on individual-value and moving-range charts and exponentially weighted moving-average charts for the identification of statistically unexpected changes associated with the pandemic. FINDINGS/RESULTS:Overall, the reporting of serious adverse events showed no unexpected decline. Total global reporting declined, driven by HCP reporting (of both serious and nonserious events), starting after week 8 of 2020 and exceeding model expectations by week 15 of 2020, suggesting the pandemic as an assignable cause. However, reporting remained within longer-term historical ranges. The TS from Japan was the only national TS that showed a significant decline, and an unusual periodicity related to national holidays. A few countries, notably Taiwan, showed unexpected statistical increases in reporting associated with the pandemic, commencing as early as week 3 of 2020. In the literature, the reporting of adverse drug events was stable. Ancillary findings included prevalent year-end/beginning reporting minima, with more reports from HCPs than from consumers. IMPLICATIONS/CONCLUSIONS:Using data from a large-scale and diverse safety database from a pharmaceutical company, a significant global decline in total reporting was detected, driven by HCPs, not consumers, and reports of nonserious events, consistent with the pandemic as an assignable cause, but the reporting remained within long-term ranges, suggesting relative durability. Importantly, the analyses found no unexpected decline in overall reporting of serious events. Future avenues of research include the use of data from large-scale, publicly available spontaneous reporting systems for assessing the generalizability of the present findings and whether they correlate with impaired signal detection, as well as a follow-up analysis of whether the effects on spontaneous reporting abate after the pandemic.

OBJECTIVES/OBJECTIVE:Tofacitinib is a Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ulcerative colitis, and has been investigated in psoriasis (PsO). Routine pharmacovigilance of an ongoing, open-label, blinded-endpoint, tofacitinib RA trial (Study A3921133; NCT02092467) in patients aged ≥50 years and with ≥1 cardiovascular risk factor identified a higher frequency of pulmonary embolism (PE) and all-cause mortality for patients receiving tofacitinib 10 mg twice daily versus those receiving tumour necrosis factor inhibitors and resulted in identification of a safety signal for tofacitinib. Here, we report the incidence of deep vein thrombosis (DVT), PE, venous thromboembolism (VTE; DVT or PE) and arterial thromboembolism (ATE) from the tofacitinib RA (excluding Study A3921133), PsA and PsO development programmes and observational studies. Data from an ad hoc safety analysis of Study A3921133 are reported separately within. METHODS:This post-hoc analysis used data from separate tofacitinib RA, PsO and PsA programmes. Incidence rates (IRs; patients with events per 100 patient-years' exposure) were calculated for DVT, PE, VTE and ATE, including for populations stratified by defined baseline cardiovascular or VTE risk factors. Observational data from the US Corrona registries (including cardiovascular risk factor stratification), IBM MarketScan research database and the US FDA Adverse Event Reporting System (FAERS) database were analysed. RESULTS:average tofacitinib 5 mg and 10 mg twice daily treated patients for RA, respectively, were: DVT (0.17 (0.09-0.27) and 0.15 (0.09-0.22)); PE (0.12 (0.06-0.22) and 0.13 (0.08-0.21)); ATE (0.32 (0.22-0.46) and 0.38 (0.28-0.49)). Among PsO patients, IRs were: DVT (0.06 (0.00-0.36) and 0.06 (0.02-0.15)); PE (0.13 (0.02-0.47) and 0.09 (0.04-0.19)); ATE (0.52 (0.22-1.02) and 0.22 (0.13-0.35)). Among PsA patients, IRs were: DVT (0.00 (0.00-0.28) and 0.13 (0.00-0.70)); PE (0.08 (0.00-0.43) and 0.00 (0.00-0.46)); ATE (0.31 (0.08-0.79) and 0.38 (0.08-1.11)). IRs were similar between tofacitinib doses and generally higher in patients with baseline cardiovascular or VTE risk factors. IRs from the overall Corrona populations and in Corrona RA patients (including tofacitinib-naïve/biologic disease-modifying antirheumatic drug-treated and tofacitinib-treated) with baseline cardiovascular risk factors were similar to IRs observed among the corresponding patients in the tofacitinib development programme. No signals of disproportionate reporting of DVT, PE or ATE with tofacitinib were identified in the FAERS database. CONCLUSIONS:DVT, PE and ATE IRs in the tofacitinib RA, PsO and PsA programmes were similar across tofacitinib doses, and generally consistent with observational data and published IRs of other treatments. As expected, IRs of thromboembolic events were elevated in patients with versus without baseline cardiovascular or VTE risk factors, and were broadly consistent with those observed in the Study A3921133 ad hoc safety analysis data, although the IR (95% CI) for PE was greater in patients treated with tofacitinib 10 mg twice daily in Study A3921133 (0.54 (0.32-0.87)), versus patients with baseline cardiovascular risk factors treated with tofacitinib 10 mg twice daily in the RA programme (0.24 (0.13-0.41)).