Phase IIB: Development of TruT Algorithm for Commercialization in Androgen Disorders

摘要 背景： 游离睾酮(T)浓度的测量在雄激素紊乱的诊断中是有用的， 包括男性性腺功能减退症、多毛症、多囊卵巢综合征(PCOS)和 妇女；男孩青春期障碍和变性人和变性人性别肯定激素疗法的管理 不同性别(TGD)的人。此IIB阶段提案旨在继续开发TruTTM 通过在以雌二醇(E2)、T和SHBG变化为特征的常见条件下验证该算法 将雌二醇与睾酮的浓度和相互作用结合起来，以便在服用雌二醇组的女性中进行更广泛的商业应用 在月经周期和TGD人群中，水平差异很大。 方法： 该应用遵循FDA发布的“行业指南：生物分析方法验证”。这个 决定生物分析方法可接受性的基本参数包括其技术性能 (准确度、精密度、灵敏度、选择性、稳定性和基质效应)。应确定参考范围 在适当的人体样本中。分析方法应针对预期用途进行验证(例如，确定 在预期使用条件下，如E2和T水平改变的人、患有多囊卵巢综合征的妇女、TGD患者 等)。在通过第二阶段的研究中，我们证明了该方法具有优越的性能特征 并扩展了TruTTM算法在以SHBG浓度变化为特征的条件下的有效性。在……里面 拟议的IIB阶段研究，我们将通过整合以下动态来生成TruTTM算法的v2.0 E2诱导游离T水平的扰动，在男性、女性和TGD人群中验证(目标1)并部署 与HIPAA兼容，将算法安全地集成到电子病历(EMR)工作流程中(目标2)。 未来方向和商业化潜力： IIB阶段计划将使符合HIPAA(FDA注册)的试验性商业部署成为可能 将嵌入电子病历(EMR)的TruTTM(v2.0)算法商业化的平台 更广泛的临床采用。这些研究将改善临床护理，并促进我们对 T生物利用度在不同人群中的动态调节，包括无代表性的性别和性别 少数族裔。

ABSTRACT Background: Measurement of free testosterone (T) concentrations is indicated in the diagnosis of androgen disorders, including hypogonadism in men; hirsutism, polycystic ovary syndrome (PCOS), and androgenic alopecia in women; pubertal disorders in boys and management of gender affirming hormone therapies for transgender and gender diverse (TGD) persons. This Phase IIB proposal aims to continue the development of the TruTTM algorithm by validating it in common conditions characterized by altered estradiol (E2), T, and SHBG concentrations and incorporating interaction of E2 with T for wider commercial adoption in women in whom E2 levels vary greatly across the menstrual cycle and in TGD population. Approach: This application follows the FDA’s published “Guidance for Industry: Bioanalytical Method Validation”. The essential parameters to determine the acceptability of a bioanalytical method include its technical performance (accuracy, precision, sensitivity, selectivity, stability, and matrix effects). Reference ranges should be determined in appropriate human samples. The analytical method should be validated for intended use (e.g., determination in conditions of intended use, such as persons with altered E2 and T levels, women with PCOS, TGD persons etc.). In studies through the Phase II, we demonstrated that the method has superior performance characteristics and extended the validation of TruTTM algorithm in conditions characterized by altered SHBG concentrations. In the proposed Phase IIB studies, we will generate the v2.0 of TruTTM algorithm by incorporating the dynamics of the E2 induced perturbation in free T levels, validate it in men, women and TGD populations (Aim 1) and deploy HIPAA compliant, secure integration of the algorithm into electronic medical records (EMR) workflow (Aim 2). Future Directions and Commercialization potential: The phase IIB program will enable the pilot commercial deployment of a HIPAA compliant (FDA registered) platform for commercializing the TruTTM (v2.0) algorithm embedded into electronic medical record (EMR) for wider clinical adoption. These studies will improve clinical care and advance our fundamental understanding of dynamic regulation of T bioavailability in diverse populations including unrepresented sexual and gender minorities.