Sources of Evidence Triggering and Supporting Safety-Related Labeling Changes: A 10-Year Longitudinal Assessment of 22 New Molecular Entities Approved in 2008 by the US Food and Drug Administration.

Introduction: New safety issues concerning US FDA-approved drugs are commonly communicated through safety-related labeling changes. Therefore, to optimize and refine postmarket safety surveillance strategies, it is important to comprehensively characterize the sources of data giving rise to safety-related labeling changes.

Objectives: Our objective was to characterize the sources of data triggering and supporting the identification of new safety risks of FDA-approved drugs communicated through safety-related labeling changes.

FDA Approval Summary: Pembrolizumab, Atezolizumab, and Cemiplimab-rwlc as Single Agents for First-Line Treatment of Advanced/Metastatic PD-L1-High NSCLC.

FDA's approval of cemiplimab-rwlc on February 22, 2021, follows prior approvals of pembrolizumab and atezolizumab for similar indications as first-line treatment for patients with programmed death ligand-1 (PD-L1)-high advanced non-small cell lung cancer (NSCLC). Approvals of these anti-PD-L1 agents were supported by statistically significant and clinically meaningful improvements in overall survival (OS) in international, multicenter, active-controlled randomized trials. In KEYNOTE-024, the OS HR was 0.

The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes.

We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by the US Food and Drug Administration (FDA) between October 1, 2002, and December 31, 2014, evaluating the relationship of premarket safety population size to regulatory characteristics and postmarket safety outcomes. The median size of the safety population was 1,044, and was lower for NTBs than NMEs (median: 920 vs. 1,138, P = 0.

Postmarketing Safety-Related Regulatory Actions for New Therapeutic Biologics Approved in the United States 2002-2014: Similarities and Differences With New Molecular Entities.

We examined the relationship of regulatory and review characteristics to postmarketing safety-related regulatory actions for 61 new therapeutic biologics (NTBs) approved between October 1, 2002 and December 31, 2014. We also compared NTBs with small-molecule new molecular entities (NMEs) on these measures. Postmarketing safety-related regulatory actions were defined as a safety-related withdrawal or a safety-related update to a safety section of the label through June 30, 2018.

Untreated insomnia increases all-cause health care utilization and costs among Medicare beneficiaries.

Study Objectives: To examine the impact of untreated insomnia on health care utilization (HCU) among a nationally representative sample of Medicare beneficiaries.

Methods: Our data source was a random 5% sample of Medicare administrative data for years 2006-2013. Insomnia was operationalized as the presence of at least one claim containing an insomnia-related diagnosis in any given year based on International Classification of Disease, Version 9, Clinical Modification codes or at least one prescription fill for an insomnia-related medication in Part D prescription drug files in each year.

Functional status predicts major complications and death after endovascular repair of abdominal aortic aneurysms.

Objective: Endovascular aneurysm repair (EVAR) is considered a lower risk option for treating abdominal aortic aneurysms and is of particular utility in patients with poor functional status who may be poor candidates for open repair. However, the specific contribution of preoperative functional status to EVAR outcomes remains poorly defined. We hypothesized that impaired functional status, based simply on the ability of patients to perform activities of daily living, is associated with worse outcomes after EVAR.

Radiologic Characterization of Ischemic Cholangiopathy in Donation-After-Cardiac-Death Liver Transplants and Correlation With Clinical Outcomes.

Objective: The purpose of this study was to define the cholangiographic patterns of ischemic cholangiopathy and clinically silent nonanastomotic biliary strictures in donation-after-cardiac-death (DCD) liver grafts in a large single-institution series. We also examined the correlation of the radiologic findings with laboratory data and clinical outcomes.

Materials And Methods: Data were collected for all DCD liver transplants at one institution from December 1998 to December 2011.

Inferior long-term outcomes of liver-kidney transplantation using donation after cardiac death donors: single-center and organ procurement and transplantation network analyses.

Limited data are available for outcomes of simultaneous liver-kidney (SLK) transplantation using donation after cardiac death (DCD) donors. The outcomes of 12 DCD-SLK transplants and 54 SLK transplants using donation after brain death (DBD) donors were retrospectively compared. The baseline demographics were similar for the DCD-SLK and DBD-SLK groups except for the higher liver donor risk index for the DCD-SLK group (1.

Liver transplantation in the critically ill: donation after cardiac death compared to donation after brain death grafts.

 Patients with end stage liver disease may become critically ill prior to LT requiring admission to the intensive care unit (ICU). The high acuity patients may be thought too ill to transplant; however, often LT is the only therapeutic option. Choosing the correct liver allograft for these patients is often difficult and it is imperative that the allograft work immediately.

Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP < 50 mmHg; oxygen saturation <30%; mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida.

Proteinuria following sirolimus conversion is associated with deterioration of kidney function in liver transplant recipients.

Background: The role of sirolimus (SRL) conversion in the preservation of kidney function in liver transplant (LT) recipients with calcineurin inhibitor (CNI) nephrotoxicity is unclear.

Methods: Data on 102 LT recipients with deteriorating kidney function after CNI exposure who were later converted to SRL were retrospectively reviewed. Kidney function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR) at time of conversion and serially thereafter.

Is a mandatory intensive care unit stay needed after liver transplantation? Feasibility of fast-tracking to the surgical ward after liver transplantation.

The continuation of hemodynamic, respiratory, and metabolic support for a variable period after liver transplantation (LT) in the intensive care unit (ICU) is considered routine by many transplant programs. However, some LT recipients may be liberated from mechanical ventilation shortly after the discontinuation of anesthesia. These patients might be appropriately discharged from the postanesthesia care unit (PACU) to the surgical ward and bypass the ICU entirely.

Should donation after cardiac death liver grafts be used for retransplantation?

Introduction: Donation after cardiac death (DCD) donors provide an important source of livers that has been used to expand the donor pool. As a consequence of increased numbers of OLT, allograft failure due to early and late complications and disease recurrence are more commonly encountered. The only life saving treatment for patients with liver allograft failure is liver re-transplantation (LR).

Events in procurement as risk factors for ischemic cholangiopathy in liver transplantation using donation after cardiac death donors.

The use of donation after cardiac death (DCD) liver grafts is controversial because of the overall increased rates of graft loss and morbidity, which are mostly related to the consequences of ischemic cholangiopathy (IC). In this study, we sought to determine the factors leading to graft loss and the development of IC and to compare patient and graft survival rates for recipients of DCD liver grafts and recipients of donation after brain death (DBD) liver grafts in a large series at a single transplant center. Two hundred liver transplants with DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida.

Use of liver grafts from donation after cardiac death donors for recipients with hepatitis C virus.

Hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation in the United States. Although studies have addressed the use of expanded criteria donor organs in HCV(+) patients, to date the use of liver grafts from donation after cardiac death (DCD) donors in HCV(+) patients has been addressed by only a limited number of studies. This retrospective analysis was undertaken to study the outcomes of DCD liver grafts used in HCV(+) recipients.