Pharmacovigilance: reporting requirements throughout a product's lifecycle.

Comprehensive methods for evaluating safety are needed to objectively assess the full risk profile of a medication. The confidence of the prescribing provider in the safety and effectiveness of pharmaceuticals is extremely important. Pharmacovigilance is a key component of drug safety regulatory processes and is paramount for ensuring the safety profile of medications used to treat patients. All participants in the healthcare system, including healthcare providers and consumers, should understand and meaningfully engage in the pharmacovigilance process; healthcare providers should integrate pharmacovigilance into everyday practice, inviting feedback from patients. This narrative review aims to give an overview of the main topics underlying pharmacovigilance and drug safety in pharmaceutical research phase after the authorization of a drug in the United States. The US Food and Drug Administration guidance and post-approval regulatory actions are considered from an industry perspective. Plain language summary: Regulatory processes that ensure the safety of drugs is monitored Government agencies regulate the safe use of medicinal products. By determining and enforcing pharmacovigilance, the monitoring of drugs for potential risks, they safeguard the welfare of consumers of medicines. Comprehensive, documented methods for evaluating the safety of a drug during its development and its subsequent use allow identification of any risks associated with the drug's use throughout its lifetime. The comprehensive identification of safety issues associated with a drug is improved when all parties involved in the development and use of drugs participate in the pharmacovigilance process. For example, clinicians should regularly ask their patients if they are experiencing any issues with their treatment, and patients should be encouraged to report problems they encounter with a particular medication to their healthcare provider. This narrative review provides an overview of the main topics underlying pharmacovigilance and drug safety after approval of a drug in the United States. Guidelines and actions from the US Food and Drug Administration are considered from an industry perspective.

Risk of hypertension in erenumab-treated patients with migraine: Analyses of clinical trial and postmarketing data.

OBJECTIVE: To assess the risk of hypertension in patients with migraine who received erenumab in clinical trials and in the postmarketing setting. BACKGROUND: Erenumab is a monoclonal antibody for migraine prevention that targets the calcitonin gene-related peptide (CGRP) receptor. Hypertension is a theoretical risk for inhibitors of the CGRP pathway. Although no evidence of an association between erenumab treatment and hypertension was observed during the clinical development program, adverse events (AEs) of hypertension have been identified in the postmarketing setting. METHODS: Safety data from four phase 2 and phase 3 clinical trials were used to perform a pooled analysis of hypertension AEs in patients with migraine receiving erenumab. Postmarketing AEs of hypertension were identified from the Amgen Global Safety database from May 17, 2018, through January 31, 2020. RESULTS: In the pooled analysis of clinical trials, hypertension AEs (placebo, 9/1043 [0.9%]; erenumab 70 mg, 7/893 [0.8%]; erenumab 140 mg, 1/507 [0.2%]) and percentage of patients initiating medication to treat hypertension (12/1043 [1.2%], 7/893 [0.8%], 1/507 [0.2%], respectively) were similar across treatment groups. A total of 362 AEs of hypertension were identified from the postmarketing setting, 26.2% (95/362) of which were serious, >245,000 patient-years of exposure. The exposure-adjusted incidence of hypertension was 0.144 per 100 patient-years. CONCLUSIONS: Clinical trials did not demonstrate an increased risk of hypertension with erenumab compared with placebo, and AE rates of hypertension reported with erenumab in the postmarketing setting were generally low. Additional data are needed to fully characterize the extent to which hypertension is a risk associated with erenumab.

A cost analysis of the impact of a new intravenous antihypertensive in managing perioperative blood pressure during cardiac surgery.

OBJECTIVE: To examine the impact of intravenous antihypertensive selection on hospital health resource utilization using data from the Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events (ECLIPSE) trials. METHODS: Analysis of ECLIPSE trial data comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine and unit costs based on the Premier Hospital database to assess surgery duration, time to extubation, and length of stay (LOS) with the associated cost. RESULTS: A total of 1414 patients from the ECLIPSE trials and the Premier hospital database were included for analysis. The duration of surgery and postoperative LOS were similar across groups. The time from chest closure to extubation was shorter in patients receiving clevidipine group compared with the pooled comparator group (median 7.0 vs 7.6 hours, P = 0.04). There was shorter intensive care unit (ICU) LOS in the clevidipine group versus the nitroglycerin group (median 27.2 vs 33.0 hours, P = 0.03). A trend toward reduced ICU LOS was also seen in the clevidipine compared with the pooled comparator group (median 32.3 vs 43.5 hours, P = 0.06). The costs for ICU LOS and time to extubation were lower with clevidipine than with the comparators, with median cost savings of $887 and $34, respectively, compared with the pooled comparator group, for a median cost savings of $921 per patient. CONCLUSIONS: Health resource utilization across therapeutic alternatives can be derived from an analysis of standard costs from hospital financial data to matched utilization metrics as part of a randomized controlled trial. In cardiac surgical patients, intravenous antihypertensive selection was associated with a shorter time to extubation in the ICU and a shorter ICU stay compared with pooled comparators, which in turn may decrease total costs.

Impact of perioperative blood pressure variability on health resource utilization after cardiac surgery: an analysis of the ECLIPSE trials.

OBJECTIVE: To examine the impact of blood pressure control on hospital health resource utilization using data from the ECLIPSE trials. DESIGN: Post-hoc analysis of data from 3 prospective, open-label, randomized clinical trials (ECLIPSE trials). SETTING: Sixty-one medical centers in the United States. PARTICIPANTS: Patients 18 years or older undergoing cardiac surgery. INTERVENTIONS: Clevidipine was compared with nitroglycerin, sodium nitroprusside, and nicardipine. MEASUREMENTS AND MAIN RESULTS: The ECLIPSE trials included 3 individual randomized open-label studies comparing clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine. Blood pressure control was assessed as the integral of the cumulative area under the curve (AUC) outside specified systolic blood pressure ranges, such that lower AUC represents less variability. This analysis examined surgery duration, time to extubation, as well as intensive care unit (ICU) and hospital length of stay (LOS) in patients with AUC≤10 mmHg×min/h compared to patients with AUC>10 mmHg×min/h. One thousand four hundred ten patients were included for analysis; 736 patients (52%) had an AUC≤10 mmHg×min/h, and 674 (48%) had an AUC>10 mmHg×min/h. The duration of surgery and ICU LOS were similar between groups. Time to extubation and postoperative LOS were both significantly shorter (p = 0.05 and p<0.0001, respectively) in patients with AUC≤10. Multivariate analysis demonstrates AUC≤10 was significantly and independently associated with decreased time to extubation (hazard ratio 1.132, p = 0.0261) and postoperative LOS (hazard ratio 1.221, p = 0.0006). CONCLUSIONS: Based on data derived from the ECLIPSE studies, increased perioperative BP variability is associated with delayed time to extubation and increased postoperative LOS.