Statistical Methods for Cancer Clinical Trials

描述（由申请人提供）：这个雄心勃勃的项目的总体目标仍然是为癌症临床试验开发创新的、变革性的统计方法，这些方法有可能加速新疗法和治疗策略的成功引入实践。生物学、基因组学、统计学和计算科学的进步为个性化癌症治疗的发展带来了巨大的希望。我们的多机构、跨学科研究团队将利用这些进步来创建新的临床试验设计和数据分析方法，解决当前统计方法的许多关键局限性，并最大限度地提高个性化癌症医学临床试验的有效性。此外，我们将促进将这些方法转化为实践，包括基于新方法开展动物和人类试验研究。该计划将通过五个相互关联的研究项目来实现这些目标，这些研究项目由来自三个机构的具有统计学、计算和临床科学互补专业知识的研究人员进行。前四个项目的重点是开发新的试验设计和分析方法，整合生物标志物，有效发现新的个性化治疗；关于创建分析生物标志物和患者报告结果的现有数据的方法，以告知和改进未来研究的设计；开发最大化药物基因组学在识别生物标志物和候选个体化治疗方面的作用的方法；并创造新的方法来发现和验证连续的，个性化的癌症治疗决策策略。第五个项目将把这些方法整合到胰腺癌的新的临床前和临床研究中。我们的综合方法包括一个充满活力和协调的过程来实施、沟通和传播结果，包括开发专业的、公共使用的软件和相关的教程；讲习班和其他外联机制；以及项目主办的专题讨论会和活动，以加快在实践中采用这些方法。提出的临床试验设计和分析创新有可能影响癌症临床试验进行方式的范式转变，以发现和验证个性化医疗。这种全面的、多机构的努力将导致癌症临床试验实践的重大创新，从而改善癌症患者的健康状况。

DESCRIPTION (provided by applicant): The overarching goal of this ambitious program project continues to be to develop innovative, transformative statistical methods for cancer clinical trials that have the potential to hasten successful introduction of new therapies and treatment strategies into practice. Advances in the biologic, genomic, statistical, and computational sciences hold great promise for the development of personalized cancer treatments. Our multi-institutional, interdisciplinary team of investigators will leverage these advances to create new clinical trial designs and data analysis approaches that resolve many of the key limitations of current statistical methods and that maximize the effectiveness of clinical trials for personalized cancer medicine. In addition, we will foster translation of these methods into practice, including carrying out pilot animal and human studies based on the new methodology. The program will achieve these objectives through five, interrelated research projects carried out by investigators with complementary expertise in the statistical, computational, and clinical sciences from three institutions. The first four projects focus on developing new trial designs and analysis methods that integrate biomarkers for efficient discovery of new, personalized treatments; on creating methods for analysis of existing data on biomarkers and patient reported outcomes to inform and improve the design of future studies; developing methods for maximizing the power of pharmacogenomics for identifying biomarkers and candidate individualized therapies; and creating new methods for discovering and validating sequential, personalized decision-making strategies for cancer treatment. The fifth project will integrate the methods into novel preclinical and clinical studies of pancreatic cancer. Our comprehensive approach involves an energetic and coordinated process for implementation, communication, and dissemination of results, including development of professional, public-use software and associated tutorials; workshops and other outreach mechanisms; and program-sponsored symposia and events, to accelerate the adoption of the methods in practice. The proposed clinical trial design and analysis innovations have the potential to effect a paradigm shift in the way cancer clinical trials are conducted for discovery and validation of personalized medicine. This comprehensive, multi-institutional effort will lead to significant innovations in cancer clinical trial practice that will result in improved health of cancer patients.