scholarly journals Safety signals assessed by the pharmacovigilance risk assessement committee: biologics vs conventional medicines

2019 ◽  
Vol 16 (2) ◽  
pp. 202-212
Author(s):  
Margarida Estudante ◽  
Dinah Duarte
Keyword(s):  
Risk Assessement ◽  
Safety Signals

scholarly journals Inhibition of Fear by Learned Safety Signals: A Mini-Symposium Review

2012 ◽  
Vol 32 (41) ◽  
pp. 14118-14124 ◽  
Author(s):  
J. P. Christianson ◽  
A. B. P. Fernando ◽  
A. M. Kazama ◽  
T. Jovanovic ◽  
L. E. Ostroff ◽  
...  
Keyword(s):  
Symposium Review ◽  
Learned Safety ◽  
Safety Signals

scholarly journals Real-world safety and effectiveness of nivolumab for recurrent or metastatic head and neck cancer in Japan: a post-marketing surveillance

2021 ◽  
Author(s):  
Makoto Tahara ◽  
Naomi Kiyota ◽  
Ken-ichi Nibu ◽  
Ayumi Akamatsu ◽  
Tomohiro Hoshino ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Interstitial Lung Disease ◽  
Head And Neck ◽  
Neck Cancer ◽  
Real World ◽  
Special Interest ◽  
Real World Setting ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Safety Signals

Abstract Background On the basis of phase III CheckMate 141 results, nivolumab was approved for recurrent or metastatic head and neck cancer after undergoing platinum-containing chemotherapy in Japan. This post-marketing surveillance aimed to evaluate the safety and effectiveness of nivolumab for head and neck cancer in the real-world setting. Methods All patients with head and neck cancer who planned to receive nivolumab were centrally registered. This study monitored 607 patients for 6 months to assess nivolumab’s safety, especially treatment-related adverse events (TRAEs) of special interest, and effectiveness. Results TRAEs occurred in 36.1% patients, with no new safety signals. The most common TRAEs with grade ≥ 3 were interstitial lung disease (1.2%), diarrhea (0.8%), and hepatic function abnormal (0.7%). Meanwhile, thyroid dysfunction (10.2%), hepatic dysfunction (5.3%), and interstitial lung disease (4.1%) were the most common TRAE categories of special interest. Although the median time to the onset of each TRAE category of special interest was mostly 1–2 months, most of them occurred throughout the observation period; nonetheless, the majority of patients recovered or remitted. The 6-month survival rate was 55.9%. Conclusion Japanese patients with head and neck cancer treated with nivolumab in the real-world setting manifested no new safety signals. Clinical Trial Registration clinicaltrials.jp: JapicCTI-184071.

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4500-4500
Author(s):  
Brian I. Rini ◽  
Elizabeth R. Plimack ◽  
Viktor Stus ◽  
Tom Waddell ◽  
Rustem Gafanov ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Final Analysis ◽  
Similar Proportion ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Superior Efficacy ◽  
Treatment Naïve ◽  
To Receive ◽  
Safety Signals

4500 Background: In the first interim analysis of the randomized, multicenter, open-label, phase 3 KEYNOTE-426 study (NCT02853331), treatment with pembro + axi significantly improved OS, PFS, and ORR vs sunitinib monotherapy in treatment-naive advanced ccRCC. Extended follow-up (median, 30.6 mo) continued to demonstrate the superior efficacy of pembro + axi vs sunitinib monotherapy in this patient population. Here, we present the results of the prespecified final analysis with 42.8-mo median follow-up. Methods: Treatment-naive patients (pts) with advanced ccRCC, KPS ≥70%, and measurable disease (RECIST v1.1) were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for up to 35 doses + axi 5 mg orally BID or sunitinib 50 mg orally QD on a 4-wk on/2-wk off schedule until progression, intolerable toxicity, or withdrawal. Randomization was stratified by IMDC risk (favorable vs intermediate vs poor) and geographic region (North America vs Western Europe vs Rest of World). Dual primary endpoints were OS and PFS. Secondary endpoints were ORR, DOR, and safety. The protocol-specified final analysis was based on a target of 404 OS events. No formal hypothesis testing was performed because all efficacy endpoints were met previously at the first interim analysis; nominal P values are reported. Results: Overall, 861 pts were randomly assigned to receive pembro + axi (n=432) or sunitinib (n=429). Median duration of follow-up, defined as time from randomization to the database cutoff date, was 42.8 mo (range, 35.6-50.6). At data cutoff, 418 pts had died: 193 (44.7%) of 432 pts in the pembro + axi arm vs 225 (52.4%) of 429 pts in the sunitinib arm. Compared with sunitinib, pembro + axi improved OS (median: 45.7 vs 40.1 mo; HR, 0.73 [95% CI, 0.60-0.88]; P<0.001) and PFS (median: 15.7 vs 11.1 mo; HR, 0.68 [95% CI, 0.58-0.80]; P<0.0001). The 42-mo OS rate was 57.5% with pembro + axi vs 48.5% with sunitinib; the 42-mo PFS rate was 25.1% with pembro + axi vs 10.6% with sunitinib. For pembro + axi vs sunitinib, ORR was 60.4% vs 39.6% ( P<0.0001); CR rate was 10.0% vs 3.5%; median DOR was 23.6 mo (range 1.4+ to 43.4+) vs 15.3 mo (range, 2.3-42.8+). Subsequent anticancer therapy was administered to 47.2% of pts in pembro + axi arm vs 65.5% of pts in sunitinib arm. Although a similar proportion of pts in each arm received VEGF/VEGFR inhibitors, only 10.2% of pts in the pembro + axi arm received subsequent treatment with a PD-1/L1 inhibitor compared to 48.7% of pts in the sunitinib arm. No new safety signals were observed. Conclusions: With a median follow-up of 42.8 mo, this is the longest follow-up of an anti-PD–1/L1 immunotherapy combined with a VEGF/VEGFR inhibitor for first-line RCC. These results show that pembro + axi continues to demonstrate superior efficacy over sunitinib with respect to OS, PFS, and ORR, with no new safety signals. Clinical trial information: NCT02853331.

scholarly journals Bias, precision and timeliness of historical (background) rate comparison methods for vaccine safety monitoring: an empirical multi-database analysis

2021 ◽  
Author(s):  
Xintong Li ◽  
Lana YH Lai ◽  
Anna Ostropolets ◽  
Faaizah Arshad ◽  
Eng Hooi Tan ◽  
...  
Keyword(s):  
Vaccine Safety ◽  
Negative Control ◽  
Historical Background ◽  
Background Rate ◽  
Type 1 Error ◽  
The Cost ◽  
Type 2 Error ◽  
Safety Signals

Using real-world data and past vaccination data, we conducted a large-scale experiment to quantify bias, precision and timeliness of different study designs to estimate historical background (expected) compared to post-vaccination (observed) rates of safety events for several vaccines. We used negative (not causally related) and positive control outcomes. The latter were synthetically generated true safety signals with incident rate ratios ranging from 1.5 to 4. Observed vs. expected analysis using within-database historical background rates is a sensitive but unspecific method for the identification of potential vaccine safety signals. Despite good discrimination, most analyses showed a tendency to overestimate risks, with 20%-100% type 1 error, but low (0% to 20%) type 2 error in the large databases included in our study. Efforts to improve the comparability of background and post-vaccine rates, including age-sex adjustment and anchoring background rates around a visit, reduced type 1 error and improved precision but residual systematic error persisted. Additionally, empirical calibration dramatically reduced type 1 to nominal but came at the cost of increasing type 2 error. Our study found that within-database background rate comparison is a sensitive but unspecific method to identify vaccine safety signals. The method is positively biased, with low (<=20%) type 2 error, and 20% to 100% of negative control outcomes were incorrectly identified as safety signals due to type 1 error. Age-sex adjustment and anchoring background rate estimates around a healthcare visit are useful strategies to reduce false positives, with little impact on type 2 error. Sufficient sensitivity was reached for the identification of safety signals by month 1-2 for vaccines with quick uptake (e.g., seasonal influenza), but much later (up to month 9) for vaccines with slower uptake (e.g., varicella-zoster or papillomavirus). Finally, we reported that empirical calibration using negative control outcomes reduces type 1 error to nominal at the cost of increasing type 2 error.

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