IGF::OT::IGFYale UniversityHHSN275201400007IHHSN27500001

可预测临床结果的筛选模型对于药物开发计划至关重要。在酒精和药物滥用领域有优秀的动物和人类实验室范例。美国国家酒精滥用和酒精中毒研究所 (NIAAA) 开发了临床前动物模型计划（HHSN275201400004C 和 HHSN275201400005C），以使用各种动物模型筛选有前景的化合物，并建立了 NIAAA 临床研究小组 (NCIG) 计划来进行概念验证 (POC) 临床试验。 NIAAA 的治疗药物开发渠道中缺乏的是人体实验室计划，该计划将用于在进行更昂贵的 POC 临床试验之前筛选潜在的药物。总体目标是开发一个综合计划，其中将在该计划的所有三个组成部分中测试一种前瞻性治疗化合物：临床前动物模型、人体实验室测试和 POC 临床试验。 最初，有希望的化合物将在临床前动物模型计划中进行检查。那些在临床前试验中证明有效的化合物（假设满足安全性和耐受性终点）将被推进到人类实验室筛选计划（HLAB）。如果候选化合物在酒精依赖性综合征的一项或多项人体实验室检测中显示出有希望的结果，那么该预期化合物将被考虑在 NCIG POC 临床试验中进行评估。建立用于测试药物的人体实验室计划是实现高效且可预测的药物开发计划以及改进治疗酒精使用障碍 (AUD) 的药物的一个有价值且必需的组成部分。

Screening models that are predictive of clinical outcome are essential to a medications development program. There are excellent animal and human laboratory paradigms in the alcohol and substance abuse fields. A preclinical animal model program (HHSN275201400004C and HHSN275201400005C) at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) was developed to screen promising compounds using various animal models and the NIAAA Clinical Investigators Group (NCIG) program was established to conduct proof-of- concept (POC) clinical trials. Lacking in NIAAA’s therapeutic drug development pipeline is a human laboratory program which will serve to screen potential medications prior to conducting the more expensive POC clinical trials. The overarching goal is to develop an integrated program wherein a prospective therapeutic compound would be tested across all three components of the program: pre-clinical animal models, human laboratory testing, and POC clinical trial. Initially, promising compounds would be examined in the preclinical animal model program. Those compounds which demonstrate efficacy in the preclinical assays (assuming safety and tolerability endpoints are met) would be advanced to the human laboratory screening program (HLAB). If the candidate compound demonstrates promising results in one or more of human laboratory assays underlying aspects of the alcohol ependence syndrome, then the prospective compound would be considered for evaluation in the NCIG POC clinical trials. Establishment of a human laboratory program for testing medications is a valuable, needed component in achieving an efficient and predictable medication development program and for the advancement of medications to treat Alcohol Use Disorders (AUDs).