scholarly journals Ocular adverse events in PD-1 and PD-L1 inhibitors

2021 ◽  
Vol 9 (7) ◽  
pp. e002119
Author(s):  
LeAnne Young ◽  
Shanda Finnigan ◽  
Howard Streicher ◽  
Helen X Chen ◽  
James Murray ◽  
...  
Keyword(s):  
Adverse Event ◽  
Adverse Effects ◽  
Adverse Events ◽  
Anticancer Agents ◽  
Adverse Event Reporting ◽  
Lower Grade ◽  
Serious Adverse Events ◽  
Serious Adverse Event ◽  
Programmed Death ◽  
Depth Analysis

BackgroundProgrammed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors can cause unique immune-related adverse effects due to non-specific immunological activation. However, less is known about adverse effects of these drugs in the eye.MethodsTwo adverse event databases were retrospectively reviewed. The two databases consisted of a routine adverse event database and a serious adverse event database of expeditiously submitted reports. Patients with any malignancy who had ocular adverse events while on PD-1/PD-L1 inhibitor treatment were included. Patients received nivolumab, pembrolizumab, atezolizumab or durvalumab alone or in combination with other anticancer agents per each trial’s protocol. Databases were queried up to May 19, 2020.ResultsIn the routine adverse event database, 272 adverse events from 213 patients were reported and in the serious adverse event reporting database, 59 ocular adverse events from 47 patients were reported. A lower estimate of the prevalance from the routine adverse event database showed 259/7727 patients on study treatment arms reporting ocular adverse events (3.3% prevalence). Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0–16, serious adverse events database: median 11 weeks, IQR 6–21). The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1–2) and grade 2 (moderate) (IQR 2–3) for the routine database and the serious adverse events database, respectively. In-depth analysis of the serious adverse event reports revealed varying degrees of clinical workup, with 30/47 patients (64%) receiving ophthalmological evaluation and 16/47 (34%) of patients having to delay or discontinue treatment. However, 16/47 (34%) patients experienced resolution and 14/47 (30%) patients experienced at least some improvement.ConclusionsThis is one of the largest analyses of ocular adverse events in patients treated with PD-1/PD-L1 inhibitors in the USA. We found ocular adverse events are rare complications of PD-1/PD-L1 inhibitor therapy, can be severe enough to cause treatment discontinuation/delay, and may not always be appropriately evaluated by eye specialists. Standardized plans for ophthalmology evaluation and management of ocular toxicities are needed in studies of patients treated with PD-1/PD-L1 inhibitors.

scholarly journals What should we report? Lessons learnt from the development and implementation of serious adverse event reporting procedures in non-pharmacological trials in palliative care

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lesley Dunleavy ◽  
Danni Collingridge Moore ◽  
Ida Korfage ◽  
Sheila Payne ◽  
Catherine Walshe ◽  
...  
Keyword(s):  
Palliative Care ◽  
Adverse Event ◽  
Adverse Events ◽  
Adverse Event Reporting ◽  
Trial Registration ◽  
Serious Adverse Events ◽  
Event Reporting ◽  
Serious Adverse Event ◽  
Registration Number ◽  
Reporting Procedures

Abstract Background/aims Serious adverse event reporting guidelines have largely been developed for pharmaceutical trials. There is evidence that serious adverse events, such as psychological distress, can also occur in non-pharmaceutical trials. Managing serious adverse event reporting and monitoring in palliative care non-pharmaceutical trials can be particularly challenging. This is because patients living with advanced malignant or non-malignant disease have a high risk of hospitalisation and/or death as a result of progression of their disease rather than due to the trial intervention or procedures. This paper presents a number of recommendations for managing serious adverse event reporting that are drawn from two palliative care non-pharmacological trials. Methods The recommendations were iteratively developed across a number of exemplar trials. This included examining national and international safety reporting guidance, reviewing serious adverse event reporting procedures from other pharmacological and non-pharmacological trials, a review of the literature and collaboration between the ACTION study team and Data Safety Monitoring Committee. These two groups included expertise in oncology, palliative care, statistics and medical ethics and this collaboration led to the development of serious adverse event reporting procedures. Results The recommendations included; allowing adequate time at the study planning stage to develop serious adverse event reporting procedures, especially in multi-national studies or research naïve settings; reviewing the level of trial oversight required; defining what a serious adverse event is in your trial based on your study population; development and implementation of standard operating procedures and training; refining the reporting procedures during the trial if necessary and publishing serious adverse events in findings papers. Conclusions There is a need for researchers to share their experiences of managing this challenging aspect of trial conduct. This will ensure that the processes for managing serious adverse event reporting are continually refined and improved so optimising patient safety. Trial registration ACTION trial registration number: ISRCTN63110516 (date of registration 03/10/2014). Namaste trial registration number: ISRCTN14948133 (date of registration 04/10/2017).

scholarly journals Procedural Pain and Serious Adverse Events with Bone Marrow Aspiration and Biopsy: Real World Experience from India

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Chepsy C Philip ◽  
Inderjit Singh ◽  
Rachel Thaper ◽  
Alice David ◽  
Suvir Singh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adverse Event ◽  
Adverse Events ◽  
Pain Perception ◽  
Bone Marrow Aspiration ◽  
Procedural Pain ◽  
Routine Practice ◽  
Serious Adverse Events ◽  
Serious Adverse Event ◽  
Factors Associated

Background: Bone Marrow aspiration and Biopsy (BMAB) is perceived by patients as a painful procedure with fearsome complications. Though informed as safe and well tolerated; there is limited data about the complications and degree of pain experienced by patients undergoing BMAB.[1] Further scarce is data from the developing world where procedural fear discourages patients from pursuing treatment and diagnosis.[2] Methods Aims: To estimate the level of pain and frequency of serious adverse eventsexperienced by patients undergoing BMAB at our center. We also attempted to identify factors associated with increased pain perception. Study setting: This study was conducted at a tertiary level teaching hospital, the Christian Medical College & Hospital, Ludhiana. Ethics approval was obtained from the Institutional research committee (CMC/1495). Study period: 01 April 2015 through 30 Nov 2019 Study Design: This is a comparative cross sectional study where comparison of those with relatively more pain to those with less was done to elicit the factors associated with pain perception. Study Population: All consecutive patients who underwent a BMAB and provided informed consent which was taken pre-procedure, were included. We excluded patients who underwent the procedure under general anesthesia. Logistics of the Study: The BMAB was performed variably by Consultant Physicians, Trainee Physicians and Physician Assistants. All patients were pre-medicated with tramadol intravenous pre-procedure, and the preferred approach was from the posterior superior iliac spine (PSIS) in a left lateral decubitus under local anesthesia with lignocain. Patients were sent home or returned to their ward after upto 60 minutes of observation. A serious adverse event was considered as one requiring a prolonged observation beyond routine practice or extending to an admission to manage adverse events following and related to the BMAB. Data sources and variables Information regarding age at diagnosis, address and sex, indication to perform the BMAB, coded as malignant and non-malignant was collected from each patient. Number of prior procedures and details regarding food intake were collected as recalled by the patient. Level of pain was noted soon after the BMAB using a combined Wong-Baker grimace with numeric pain scale by the patient themselves. Statistical Analysis: Descriptive statistics were used to characterize variables. Univariate and Multivariate Logistic Regression were used to identify factors associated with higher pain severity (Score >2). Results: A total of 942 BMAB procedures were performed in this period. Baseline characteristics as tabulated below (Table1). Although the Mean + SD pain score was only 2.7 + 1.39, fourteen patients (1.48%) reported severe pain (>8). The following risk-factors were associated with increased pain on multivariate analysis: those experiencing their first BMAB procedure had very low odds of pain (OR (95 % CI): 0.23 (0.15-0.37)). However, when more than one attempt of biopsy was made, the odds of pain was much higher (OR (95 % CI): 1.62 (1.29-2.05)). Food and drink intake prior to procedure was associated only at the univariate level. Those who did not take any food prior to procedure had very high odds of pain (odds ratio (OR) 1.81 (95 % CI 1.01-3.22)). However, those who took juice had very low odds (OR (95 % CI): 0.619 (0.43-0.90)). Nine (0.95%) serious adverse events were reported. There were no deaths. The major serious adverse event was hemorrhage resulting from pseudo-aneurysm of the posterior iliac artery, which comprised 2 of the 9 serious adverse events. Other serious adverse events included persistent vomiting and severe aching pain in the ipsilateral leg. Conclusions: In our analysis BMAB is associated with a low level of procedural pain and is safe. The pain perception was not influenced by the operator. Factors associated with decreased pain perception were first procedural BMAB experience and successful completion of the procedure in the first attempt. Having at least a snack or a juice pre-procedure could reduce pain perception. Serious adverse events are rare in our experience. Disclosures No relevant conflicts of interest to declare.

Application of FDA Adverse Event Report Data to the Surveillance of Dietary Botanical Supplements

2008 ◽  
Vol 42 (5) ◽  
pp. 653-660 ◽  
Author(s):  
Robert B Wallace ◽  
Brian M Gryzlak ◽  
M Bridget Zimmerman ◽  
Nicole L Nisly
Keyword(s):  
Adverse Event ◽  
Adverse Effects ◽  
Adverse Events ◽  
Product Information ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Adverse Event Report ◽  
St John’S Wort ◽  
St John's Wort ◽  
Botanical Supplements

Background: Concerns have been raised about the sufficiency of dietary botanical supplement (DBS) surveillance in the US. The Food and Drug Administration's Center for Food Safety and Applied Nutrition's Adverse Event Reporting System (CAERS) represents one of the few existing surveillance mechanisms, but it has not been well characterized with respect to DBS adverse effects. Objective: To characterize data on DBSs associated with adverse event reports submitted to CAERS. Methods: We requested and obtained CAERS data from 1999 to 2003 involving adverse effects associated with the 6 most frequently used DBSs: Echinacea, ginseng, garlic, Ginkgo biloba, St. John's wort, and peppermint. We summarized and characterized the adverse event reports received, focusing on the composition of the DBSs and the nature of associated adverse events. We also cross-referenced reported single-ingredient DBSs with corresponding available product information. A sample of CAERS cases associated with signal DBSs was also characterized in detail. Results: CAERS reports involving ginseng DBSs were most frequently reported during the study period, whereas reports involving St. John's wort were the least frequently reported. Most CAERS reports involved multiple-ingredient DBSs, and 3-13% of reports involved multiple DBSs. Gastrointestinal and neurologic problems were the most common clinical outcomes among single-ingredient DBS-associated adverse events. Conclusions: CAERS surveillance of DBS adverse effects is potentially as effective as other passive surveillance methods, but the number of reports is relatively small, validation is incomplete, and some inconsistencies within reports were found. Reports in CAERS may underrepresent DBS adverse events associated with DBS consumption.

scholarly journals Mifepristone Adverse Events Identified by Planned Parenthood in 2009 and 2010 Compared to Those in the FDA Adverse Event Reporting System and Those Obtained Through the Freedom of Information Act

2021 ◽  
Vol 8 ◽  
pp. 233339282110689
Author(s):  
Christina A. Cirucci ◽  
Kathi A. Aultman ◽  
Donna J. Harrison
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Freedom Of Information ◽  
Freedom Of Information Act ◽  
Planned Parenthood ◽  
Serious Adverse Events ◽  
Event Reporting

Background As part of the accelerated approval of mifepristone as an abortifacient in 2000, the Food and Drug Administration (FDA) required prescribers to report all serious adverse events (AEs) to the manufacturer who was required to report them to the FDA. This information is included in the FDA Adverse Event Reporting System (FAERS) and is available to the public online. The actual Adverse Event Reports (AERs) can be obtained through the Freedom of Information Act (FOIA). Methods We compared the number of specific AEs and total AERs for mifepristone abortions from January 1, 2009 to December 31, 2010 from 1. Planned Parenthood abortion data published by Cleland et al. 2. FAERS online dashboard, and 3. AERs provided through FOIA and analyzed by Aultman et al. Results Cleland identified 1530 Planned Parenthood mifepristone cases with specific AEs for 2009 and 2010. For this period, FAERS online dashboard includes a total (from all providers) of only 664, and the FDA released only 330 AERs through FOIA. Cleland identified 1158 ongoing pregnancies in 2009 and 2010. FAERs dashboard contains only 95, and only 39 were released via FOIA. Conclusions There are significant discrepancies in the total number of AERs and specific AEs for 2009 and 2010 mifepristone abortions reported in 1. Cleland's documentation of Planned Parenthood AEs, 2. FAERS dashboard, and 3. AERs provided through FOIA. These discrepancies render the FAERS inadequate to evaluate the safety of mifepristone abortions.

scholarly journals The need and availability of support systems for physicians involved in a serious adverse event

2018 ◽  
Vol 7 (2) ◽  
pp. 23 ◽  
Author(s):  
Esther H.M. Leferink ◽  
Aline Bos ◽  
Martijn P. Heringa ◽  
Elizabeth L.J. van Rensen ◽  
Dorien L.M. Zwart
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Healthcare Professionals ◽  
Well Being ◽  
Working Environment ◽  
Support Needs ◽  
Quality And Safety ◽  
Serious Adverse Events ◽  
Serious Adverse Event ◽  
Staff Members

Objective: Serious adverse events occur in healthcare, and do not solely have consequences for patients (first victims), but also affect physicians involved (second victims). These second victims experience diminished emotional well-being and less professional performance. An increasing number of hospitals organize support for second victims, although scientific evidence on the kind of support that is expected and needed is poor. This study therefore investigates support needs after serious adverse events from both personal (physicians) and organizational (quality and safety staff members) perspectives.Methods: We conducted semi-structured interviews in a Dutch university medical center. Physicians (N = 19) who had been directly involved in a serious adverse event participated. In addition, quality and safety staff members (N = 3) reflected on the support needs as expressed by physicians. Verbatim transcripts were three-fold coded, which led to several themes for our inductive thematic analysis.Results: Contrary to recent developments in healthcare organizations, participants did not plea for a hospital-wide support team. Acceptance of the emotional and professional impact of an adverse event by direct colleagues and supervisors is more important. Where such a cultural context is provided, physicians prefer support of a close and reliable colleague to cope with emotions and doubts, a supervisor who monitors recovery, and a healthcare organization that provides information about required procedures to learn from the events. However, this ideal was seldom found in the competitive working environment. This underlines the need for a shift from a competitive professional culture into a more supportive one.Conclusions: Ideally, direct colleagues support each other after an adverse event. This form of collegial support can only be successful if there is general acceptance of healthcare professionals’ vulnerability and their support needs within the direct working environment. To create the right circumstances to meet these support needs, both healthcare professionals and hospital organizations have to recognize and take their responsibilities.

scholarly journals Adverse event reporting in intervention research for young autistic children

Autism ◽  
2020 ◽  
pp. 136236132096533
Author(s):  
Kristen Bottema-Beutel ◽  
Shannon Crowley ◽  
Micheal Sandbank ◽  
Tiffany G Woynaroski
Keyword(s):  
Adverse Event ◽  
Adverse Effects ◽  
Adverse Events ◽  
Adverse Event Reporting ◽  
Autistic Children ◽  
Policy Makers ◽  
Event Reporting ◽  
Autism Intervention ◽  
Potential Benefits ◽  
Published Research

Our team examined 150 reports on group-design, non-pharmacological interventions for young autistic children, to determine the prevalence of adverse event reporting. We found that only 11 studies mentioned adverse events; one indicated adverse events occurred, and an additional three indicated adverse effects occurred (i.e. adverse events that could be attributed to the intervention). We also coded reasons for participant withdrawal and found that of the 54 studies that reported reasons for withdrawal, 10 studies reported reasons that could be categorized as adverse events, 8 reported reasons that could be categorized as adverse effects, and an additional 12 studies reported reasons that were too vaguely described to determine adverse event status. We recommend that autism intervention researchers make concerted efforts to monitor, classify, and report adverse events so that practitioners, policy-makers, and families are better equipped to weigh potential benefits of interventions against potential harms. Lay abstract In this study, we looked at published research on interventions for young autistic children that did not involve administering medication. We were interested in determining how often studies reported on whether adverse events (i.e. physical or psychological distress to the participants) or adverse effects (i.e. adverse events that are thought to be caused by the intervention) had occurred. We found that of the 150 reports we examined, only 11 mentioned adverse events. One of these studies reported adverse events occurred, and three reported that adverse effects occurred. We also reviewed the studies to examine the reasons that were given to explain why any participants dropped out of the intervention (termed “withdrawal”), to determine if any of these reasons could be considered adverse events or adverse effects. Fifty-four studies described reasons for withdrawal, and 10 of these studies had reasons that could be categorized as an adverse event, 8 studies had reasons that could be categorized as an adverse effect, and an additional 12 studies had reasons that were too vaguely described to determine whether they were adverse events or not. We recommend that autism intervention researchers develop more systematic methods of looking for and reporting adverse events and effects, so that professionals and families can be better informed when choosing to enroll their autistic children in interventions.

scholarly journals Overlap between adverse events (AEs) and serious adverse events (SAEs): a case study of a phase III cancer clinical trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Elizabeth C. James ◽  
David Dunn ◽  
Adrian D. Cook ◽  
Andrew R. Clamp ◽  
Matthew R. Sydes
Keyword(s):  
Clinical Trial ◽  
Adverse Event ◽  
Adverse Events ◽  
Safety Data ◽  
Event Data ◽  
Serious Adverse Events ◽  
Serious Adverse Event ◽  
Adverse Event Data ◽  
Grade 3 ◽  
Mapping Exercise

Abstract Background Safety data is required to be collected in all clinical trials and can be separated into two types of data, adverse events and serious adverse events. Often, these types of safety data are collected as two discrete data sets, where adverse events that also meet the criteria for seriousness should be reported in both datasets. Safety analyses are often conducted using only the adverse event dataset, which should feature all safety events reported. We investigated whether the reporting of safety in both datasets was systematically followed and explored the impact of this on safety analyses in ICON8, an ovarian cancer clinical trial. Methods Text searches of serious adverse event data identified events that could potentially match the data reported in the adverse event dataset (looking at pre-specified AE terms only). These serious adverse events were then mapped to adverse event data according to predefined criteria: (a) event term matches, (b) date of onset and date of assessment within 30 days of each other, (c) date of assessment lies between date of onset and date of resolution and (d) events confirmed to occur in the same chemotherapy cycle. A combined dataset of all unique safety events (whether originally reported in the adverse event or serious adverse event dataset) was created and safety analyses re-performed. Results 51,019 adverse events were reported in ICON8, of which 42,410 were included in the mapping exercise. One thousand five hundred six serious adverse event elements were reported, of which 668 were included in the mapping exercise. Sixty-one percent of serious adverse event elements was matched to an already-reported adverse event. Supplementing these additional safety events and re-performing safety analyses increased the proportion of patients with at least one grade 3 or worse safety events in all arms from 42 to 47% in the control arm and 61 to 65% and 52 to 59% in the research arms. The difference in proportions of grade 3 or worse event in the research arms compared to the control arm changed by 18% (95% confidence interval [CI] 12 to 24%) and 12% (95% CI 6 to 18%), respectively. Conclusions There was low agreement in mapping serious adverse events to already reported adverse events, with nearly 40% of serious adverse events included in the mapping exercise not mapped to an already reported adverse event. Any analyses of safety data that use only adverse event datasets or do not clearly account for serious adverse event data will likely be missing important safety information. Reporting standards should make clear which datasets were used for analyses.

scholarly journals Assessment of the Potential Adverse Events Related to Ribavirin-Interferon Combination for Novel Coronavirus Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Wenya Shan ◽  
Dongsheng Hong ◽  
Jieqiang Zhu ◽  
Qingwei Zhao
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Drug Event ◽  
Reporting Odds Ratio ◽  
Serious Adverse Events ◽  
Bayesian Confidence Interval ◽  
Novel Coronavirus ◽  
Safety Signals

Purpose. We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). Methods. Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. Results. A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. Conclusion. The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.

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