Pediatric devices and adverse events from A to Z: understanding the benefits and risks from a US FDA perspective

74 Background: Widespread use of immunotherapeutic agents has transformed the profile of adverse events associated with systemic cancer therapy. Management of immune-related adverse events (IRAEs) is contingent upon grading severity using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE). Nivolumab and Pembrolizumab were recently approved for metastatic non-small cell lung cancer (NSCLC). United States Food and Drug Administration (US FDA)-approved package label inserts provide guidance on IRAE management and are predicated on CTCAE grade, including when to discontinue drug. Currently, clinicians in the thoracic oncology group are documenting CTCAE grade of IRAEs infrequently, and management is varied. Methods: A retrospective chart review of baseline data revealed 45 patients (8 on Pembrolizumab, 37 on Nivolumab) who initiated immunotherapy for metastatic NSCLC between March 2015 and August 2016. A team of clinicians developed a process map from diagnosis of IRAE to initiation of toxicity management. Physicians were surveyed. The team’s aim is by February 1, 2017, at least 50% of patients who develop an IRAE on immunotherapy for metastatic NSCLC have documentation of toxicity grade using the CTCAE criteria. Results: The physician survey response rate was 12 of 16 (75%). Physicians reported not using grade to guide management of IRAEs over two thirds (67%) of the time. Time to look up CTCAE criteria and knowing that grade is needed ranked as the top barriers. At baseline, 18 of 45 (40%) patients had 22 IRAEs, of which 6 IRAEs (27%) had grading documented; all graded IRAEs (100%) were managed according to guidelines in the drug-specific package insert. IRAEs included hypothyroidism, pneumonitis, hepatitis, dermatitis, adrenal insufficiency, colitis, and encephalitis. Conclusions: Education on toxicity grading and ease of accessibility to information regarding management of IRAEs are needed. Because clinicians were engaged, a survey to evaluate the current process succeeded with a high response rate. At baseline, there are significant gaps and variability in current practice. Interventions are underway to standardize documentation of grade and management of patients experiencing IRAEs.

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US FDA proposes change in reporting of serious adverse events

Reactions Weekly ◽

10.2165/00128415-199606280-00003 ◽

1996 ◽

Vol &NA; (628) ◽

pp. 2

Author(s):

&NA;

Keyword(s):

Adverse Events ◽

Serious Adverse Events ◽

Us Fda

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Review of Reported Clinical Information System Adverse Events in US Food and Drug Administration Databases

Applied Clinical Informatics ◽

10.4338/aci-2010-11-ra-0064 ◽

2011 ◽

Vol 02 (01) ◽

pp. 63-74 ◽

Cited By ~ 44

Author(s):

R.B. Myers ◽

S.L. Jones ◽

D.F. Sittig

Keyword(s):

Adverse Events ◽

Medical Devices ◽

Clinical Information System ◽

Clinical Information ◽

Clinical Information Systems ◽

Implementation Processes ◽

The Us ◽

Potential Risks ◽

Us Fda ◽

Incorrect Data

Summary Background: The US FDA has been collecting information on medical devices involved in significant adverse advents since 1984. These reports have been used by researchers to advise clinicians on potential risks and complications of using these devices. Objective: Research adverse events related to the use of Clinical Information Systems (CIS) as reported in FDA databases. Methods: Three large, national, adverse event medical device databases were examined for reports pertaining to CIS. Results: One hundred and twenty unique reports (from over 1.4 million reports) were found, representing 32 manufacturers. The manifestations of these adverse events included: missing or incorrect data, data displayed for the wrong patient, chaos during system downtime and system unavailable for use. Analysis of these reports illustrated events associated with system design, implementation, use, and support. Conclusion: The identified causes can be used by manufacturers to improve their products and by clinical facilities and providers to adjust their workflow and implementation processes appropriately. The small number of reports found indicates a need to raise awareness regarding publicly available tools for documenting problems with CIS and for additional reporting and dialog between manufacturers, organizations, and users.

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Novel Adverse Events of Bevacizumab in the US FDA Adverse Event Reporting System Database

Drug Safety ◽

10.2165/11597600-000000000-00000 ◽

2012 ◽

Vol 35 (6) ◽

pp. 507-518 ◽

Cited By ~ 25

Author(s):

Behrooz K. Shamloo ◽

Pankdeep Chhabra ◽

Andrew N. Freedman ◽

Arnold Potosky ◽

Jennifer Malin ◽

...

Keyword(s):

Adverse Event ◽

Adverse Events ◽

Reporting System ◽

Adverse Event Reporting System ◽

Adverse Event Reporting ◽

Event Reporting ◽

System Database ◽

The Us ◽

Us Fda

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0917 Finasteride is Associated with a Higher Odds of Obstructive Sleep Apnea (OSA): Results from the US FDA Adverse Events Reporting System (FAERS)

SLEEP ◽

10.1093/sleep/zsy061.916 ◽

2018 ◽

Vol 41 (suppl_1) ◽

pp. A340-A341

Author(s):

M A Gupta ◽

B Vujcic ◽

A D Sheridan ◽

A K Gupta

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Adverse Events ◽

Reporting System ◽

Obstructive Sleep ◽

The Us ◽

Us Fda

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Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer

Cancers ◽

10.3390/cancers13061219 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1219

Author(s):

Philip S. Bernard ◽

Whitney Wooderchak-Donahue ◽

Mei Wei ◽

Steven M. Bray ◽

Kevin C. Wood ◽

...

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Adverse Events ◽

Proton Pump ◽

Gene Interactions ◽

Potential Utility ◽

Dose Selection ◽

The Us ◽

Inflammatory Drugs ◽

Us Fda

Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Drug–drug and drug–gene interactions contribute to the risk of adverse events (AEs), which could lead to non-adherence and reduced efficacy. Here we investigated several well-characterized inherited (germline) pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant clinical, pharmaceutical, and PGx diplotype data were aggregated into a single unifying informatics platform to enable an exploratory analysis of the cohort and to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for which high levels of evidence for clinical actionability with PGx was available from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium (CPIC). These data were associated with 10 pharmacogenes: DPYD, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, G6PD, MT-RNR1, SLCO1B1, and VKORC1. All patients were taking at least one of the 38 drugs and had inherited at least one actionable PGx variant that would have informed prescribing decisions if this information had been available pre-emptively. The non-cancer drugs with PGx implications that were common (prescribed to at least one-third of patients) included anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, opioids, and proton pump inhibitors. Based on these results, we conclude that pre-emptive PGx testing may benefit patients with breast cancer by informing drug and dose selection to maximize efficacy and minimize AEs.

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Relationship between plasma pazopanib concentration and incidence of adverse events in renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.7_suppl.345 ◽

2011 ◽

Vol 29 (7_suppl) ◽

pp. 345-345 ◽

Cited By ~ 8

Author(s):

Y. Lin ◽

H. A. Ball ◽

B. Suttle ◽

F. Mehmud ◽

R. G. Amado ◽

...

Keyword(s):

Adverse Events ◽

Clin Oncol ◽

Renal Cell ◽

Color Change ◽

Cell Cancer ◽

Angiogenesis Inhibitor ◽

Fold Increase ◽

Hair Color ◽

Optimization Strategy ◽

Us Fda

345 Background: Pazopanib (P), an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit, is approved by the US FDA for the treatment of advanced renal cell cancer (mRCC). Exploratory analyses of data from a Ph II mRCC study (Hutson T, J Clin Oncol. 27, 2009:1) indicated that 70% of patients (pt) receiving 800mg once daily had a week (wk) 4 plasma P trough (Cmin) >20.6μ g/mL that is associated with improved efficacy (Suttle B, J Clin Oncol. 28, 2010:S3048). In this further analysis of the dataset, we investigated the relation between plasma P concentrations at wk 4 and clinically important adverse events (AE) reported within the first 12 wks of treatment. Methods: The % of patients with hypertension (defined as ≥ 15mmHg - baseline on 3 occasions)- a recognized PD marker for this class of agents- or other AEs (CTC grades), occurring during the first 12 wks of treatment were calculated by wk4 Cmin quartiles (Q1-Q4: median and range). Results: P concentrations at 4 wks and AE data were available for 205 out of 225 pts. The incidence of hypertension was 58% in Q1, increasing with concentration to 78% at Q4. The incidence of diarrhea, hair color change, ALT increase, HFS (marked increase), and stomatitis were concentration-dependent, with ≥ 2 fold increase from Q1 to Q4. The incidence of nausea, fatigue, vomiting, dysgeusia, and rash were variable or displayed a flat relationship with Cmin. Conclusions: The incidence of some AEs, such as diarrhea, ALT, HFS (marked relation), and stomatitis increased with plasma Cmin while others did not. We suggest that concentration-dependent AEs are more likely to respond to P dose reduction and as such, provides support for development of a dose optimization strategy. [Table: see text] [Table: see text]

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