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

摘要 背景资料： 游离睾酮（T）浓度的测量适用于雄激素紊乱的诊断， 包括男性性腺功能减退症、多毛症、多囊卵巢综合征（PCOS）和男性雄激素性脱发。 妇女;男孩的青春期障碍和变性人的性别确认激素疗法的管理， 性别多样性（TGD）。本IIB阶段提案旨在继续开发TruTTM 通过在以雌二醇（E2）、T和SHBG改变为特征的常见条件下验证算法 浓度和纳入E2与T的相互作用，以便在E2 水平在整个月经周期和TGD人群中变化很大。 方法： 本申请遵循FDA发布的“行业指南：生物分析方法验证”。的 确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。应验证分析方法的预期用途（例如，测定 在预期使用条件下，如E2和T水平改变的患者、PCOS女性、TGD患者 等）。在II期研究中，我们证明了该方法具有上级性能特征 并扩展了TruTTM算法在SHBG浓度变化的条件下的验证。在 在拟议的IIB期研究中，我们将通过结合以下动态生成TruTTM算法v2.0： E2诱导游离T水平扰动，在男性、女性和TGD人群中验证它（目标1），并部署 将算法安全地集成到电子病历（EMR）工作流程中（目标2）。 未来发展方向和商业化潜力： IIB阶段计划将使符合HIPAA标准（FDA注册）的试验性商业部署成为可能。 嵌入电子病历（EMR）的TruTTM（v2.0）算法商业化平台， 更广泛的临床应用。这些研究将改善临床护理，促进我们对 不同人群中T生物利用度的动态调节，包括未代表的性别和性别 少数群体

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.