Optimizing the Dosing Regimen of Cetuximab and Ramucirumab Using the Model-Informed Drug Development Paradigm.

Model-informed drug development (MIDD) is a process that integrates drug exposure-based, biological, and statistical models to enhance the benefit-risk balance in drug development. The US Food and Drug Administration (FDA) MIDD Paired Meeting Pilot Program provides a platform to apply MIDD approaches to drug development and to seek regulatory feedback in a collaborative and streamlined process prior to submission for approval. Eli Lilly and Company (Lilly) participated in the Pilot Program to seek agency alignment to enhance the initial approved dosing regimens of cetuximab (Erbitux; Eli Lilly and Company, Indianapolis, IN) and ramucirumab (Cyramza; Eli Lilly and Company) without conducting additional clinical trials. Here, we describe the overall MIDD strategy at Lilly, the process with the FDA, and the impact of implementing the approach.

Pre-Implementation Assessment of the Acceptability of Using Circulating microRNAs for Follow-Up of Malignant Germ-Cell Tumors.

BACKGROUND: MicroRNAs from the miR-371~373 and miR-302/367 clusters, particularly miR-371a-3p, are promising biomarkers for blood-based diagnosis and disease monitoring of malignant germ cell tumors (GCTs) and are nearing clinical implementation. These biomarkers have superior sensitivity and specificity compared with current markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG). We explored patient acceptability of using circulating microRNAs to replace multiple serial computed tomography (CT) scans in malignant GCT follow-up. PATIENTS AND METHODS: Two workshops involved interactive presentations and focus groups. Discussions were digitally recorded and transcribed verbatim. Qualitative thematic analysis of transcripts identified the key themes. RESULTS: Prior to the workshops, potential participants expressed concern about the adoption of new blood tests due to personal experiences of the limitations of existing (AFP/HCG) markers. Twelve males (22-57 years of age; currently, 26-59 years of age) with a malignant GCT diagnosis participated; all were in follow-up. Three had experienced recurrence. Participants had cumulative exposure of between 1 and 15 CT scans. Data saturation was reached at the second workshop; five themes emerged underpinning preference for microRNA testing versus CT scans: (1) increased sensitivity and safety, (2) reduced financial costs, (3) reduced time for testing and results, (4) practicalities, and (5) reduced anxiety. However, some participants perceived an increased diagnostic capacity of CT scans versus blood testing. CONCLUSION: This first user consultation of circulating microRNA testing for future malignant GCT follow-up suggests high acceptability with potential patient and healthcare system benefits.