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Objective: In 2016, there were an estimated 56 870 new cases of thyroid cancer (TC) in the USA. Fine needle aspiration cytology (FNAC) is the most safe, accurate and cost-effective method for the initial investigation of thyroid nodules. FNAC is limited by the inability to diagnose malignancy in follicular-patterned lesions accurately and, as a result, 20%-30% of cases under investigation for TC are classified as cytologically indeterminate, illustrating a problem with current FNAC procedure.Raman spectroscopy has shown promising results for the detection of many cancers; however, to date there has been no report on the performance of Raman spectroscopy on thyroid cytological samples. The aim of this study was to examine whether Raman spectroscopy could be used to correctly classify cell lines representing benign thyroid cells and various subtypes of TC.Methods: A benign thyroid cell line and seven TC cell lines were prepared as Thin-Prep® cytology slides and analysed with Raman spectroscopy. Principal components analysis and linear discriminant analysis were implemented to develop effective diagnostic algorithms for classification of Raman spectra of different TC subtypes.Results: The spectral differences separating benign and TC cell lines were assigned to differences in the composition of nucleic acids, lipids, carbohydrates and protein in the benign and cancer cells. Good sensitivities (74%-85%), specificities (65%-93%) and diagnostic accuracies (71%-88%) were achieved for the identification of TC.Conclusion: These findings suggest that Raman spectroscopy has potential for preoperative TC diagnosis on FNAC samples. K E Y W O R D S cell lines, Raman spectroscopy, thyroid neoplasms, thyroid nodule 1 | INTRODUCTION In 2016, there were an estimated 56 870 new cases of thyroid cancer (TC) in the USA . 1 Women account for approximately 75% of these cases, exhibiting a substantially higher rate of incidence of the disease compared to men, but similar mortality. TC incidence has been steadily increasing in recent decades, as reported in the TC epidemiology studies. 2,3 Although improved diagnostic methods, notably ultrasound (US) examination, are the likely reason for the global increase in incidence (especially of smaller nodules), recent studies show that the incidence of aggressive forms associated with higher mortality is also increasing. 4 Of the wide array of malignancies that are characterised as TC, papillary thyroid carcinoma (PTC) is the most common, accounting for approximately 80% of cases. Other histological types include follicular thyroid carcinoma (FTC), Hürthle cell carcinoma, poorly differentiated carcinoma, medullary thyroid carcinoma (MTC), and O'Dea and Bongiovanni joint first authors. Lyng and Malkin joint senior authors.

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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.

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