A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units:A multicentre retrospective observational study

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.</p

Adverse drug events caused by three high-risk drug–drug interactions in patients admitted to intensive care units:A multicentre retrospective observational study

Aims: Knowledge about adverse drug events caused by drug–drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. Methods: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. Results: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). Conclusion: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.</p

Prescribing among elderly patients in dutch residential homes: evaluation of a pharmacists medication review

This paper aimed to examine the impact of a medication review by a clinical pharmacist on the quality of prescribing in a setting with healthcare professionals including general practitioner (GP), nurse and pharmacist

Physiological uptake of [f]fluorodeoxyglucose in the neck and upper chest region: are there predictive characteristics?

The purpose of this study was to assess (patient) characteristics that might influence the prevalence of physiological uptake of [F]fluorodeoxyglucose (FDG) in the neck and upper chest region (FDG NUC) in positron emission tomography (PET) imaging

Massive ingestion of cardiac drugs: Toxicokinetic aspects of digoxin and sotalol during hemofiltration

Case. We present the case of a 75-year-old patient admitted to the emergency department after ingesting a large amount of several cardiac drugs, among which were digoxin and sotalol. Because of renal insufficiency, cardiogenic shock, and high serum digoxin levels, the patient received continuous venovenous hemofiltration (CVVH) and digoxin-specific Fab fragments. Digoxin and the digoxin-specific Fab fragments are normally cleared by the kidneys. Methods. Serum-free and total digoxin and serum sotalol concentrations were monitored for several days. Results. Less than 10 of the estimated ingested dose of digoxin was cleared by CVVH within 5 days. Conclusion. CVVH has little influence on the clearance of Fab-bound digoxin from the body. In contrast, sotalol is efficiently cleared by CVVH

Measurement of 18F-FDG concentrations in blood samples: Comparison of direct calibration and standard solution methods

Objective: The purpose of this study was to compare the accuracy and reliability of 2 well counter methods for measuring the activity concentration of 18F-FDG in blood samples. Methods: Three to 5 blood samples from 154 patient studies were weighed and measured in a well counter. The 18F-FDG activity concentration was derived using, first, a direct calibration factor to convert measured well counter readings into activity concentration and, second, a comparison of measured counts with those of a specified standard solution. Results: The ratio between the activity concentration results of the 2 methods was 0.996 ± 0.033, indicating that the methods provided equal results. Conclusion: Because the standard solution method is more prone to human error, less reproducible, and more labor intensive, preference should be given to the direct calibration method