SGO guidance document for clinical trial designs in ovarian cancer: a changing paradigm.
SGO guidance document for clinical trial designs in ovarian cancer: a changing paradigm.
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DOI：
10.1016/j.ygyno.2014.08.004
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发表时间：
2014-10
影响因子：
4.7
通讯作者：
Coleman RL
中科院分区：
文献类型：
--
作者：
Herzog TJ;Alvarez RD;Secord A;Goff BA;Mannel RS;Monk BJ;Coleman RL
探索和促进卵巢癌药物开发和监管批准的多方面过程。妇科肿瘤学会（SGO）最近寻求并收到了多个利益相关者的意见，包括美国国家癌症研究所（NCI）临床治疗评估项目（CTEP）、美国食品和药物管理局（FDA）、制药行业和患者权益倡导者。本白皮书仅为SGO的工作成果和意见。本文件总结了SGO对这些会议的解释以及当前的监管环境，其中美国最近的批准很少。它为临床试验设计提供了指导，其明确目的是鼓励卵巢癌新药开发。重点包括：卵巢癌异质性（组织学亚型和分子遗传学改变）、临床试验设计要素、替代终点和复合终点以及临床药物开发的四个原则（未满足的医疗需求、发现、安全性和有效性）。根据卵巢癌的临床背景，替代终点的接受程度发生了变化。虽然总生存期（OS）仍然是最客观的临床试验终点，但现在意识到要求OS作为主要终点存在许多障碍。卵巢癌是一种异质性疾病，目前按组织学亚型划分。未来的登记策略需要解决疾病异质性问题。目前可接受的临床试验终点和替代监管策略的探索将有望激发卵巢癌患者新药开发的兴趣。
To explore and facilitate the multifaceted process of drug development and regulatory approval in ovarian cancer. The Society of Gynecologic Oncology (SGO) recently sought and received input from multiple stakeholders including the National Cancer Institute's (NCI) Clinical Therapy Evaluation Program (CTEP), the Food and Drug Administration (FDA), pharmaceutical industry, and patient advocates. This whitepaper is the work product and opinion solely of the SGO. This document summarizes the SGO's interpretation of these meetings and the current regulatory environment where there has been a paucity of recent approvals in the United States. It provides guidance in clinical trial design with the express purpose of encouraging novel drug development in ovarian cancer. Points of emphasis include: ovarian cancer heterogeneity (histologic subtypes and molecular genetic alterations), clinical trial design elements, surrogate as well as composite endpoints, and the four principles of clinical drug development (unmet medical need, discovery, safety, and efficacy). There has been an evolution in the acceptance of surrogate endpoints depending upon the clinical setting in ovarian cancer. While overall survival (OS) remains the most objective clinical trial endpoint, there is now realization that demanding OS as the primary endpoint has many obstacles. Ovarian cancer is a heterogeneous disease that is now divided by histologic subtypes. Future registration strategies will need to address disease heterogeneity. The exploration of currently acceptable clinical trial endpoints and alternative regulatory strategies will hopefully stimulate interest in novel drug development for patients with ovarian cancer.