Optimizing Patient-Oriented Outcomes for Chronic Hepatitis C

描述(申请人提供)：随着慢性丙型肝炎治疗方案的快速发展，立即治疗或推迟到未来治疗的决定变得越来越复杂。治疗考虑必须平衡多个患者的特征、偏好和治疗效果数据，其中大部分数据充满不确定性。决策分析建模可以通过阐明治疗时机在不同患者群体中的比较优势和危害来增强传统的临床研究。在建模过程中，积极整合患者和提供者直接提出的治疗优先事项和挑战，可确保这些分析与关键利益攸关方相关，并有效传播结果。这些数据对于在受影响的患者之间交流针对丙型肝炎病毒治疗的风险和益处的量身定制的、以患者为中心的评估是非常有用的，从而改善知情的医疗决策。此外，对当前文献中数据不确定性的更清晰的理解可能会为未来丙型肝炎护理和治疗的研究设定合理的优先顺序。通过完成公共卫生硕士学位，以及在麻省总医院、西北大学和现在的芝加哥大学非常严格的研究环境中的广泛分析经验，我在生物统计学、流行病学和决策分析方法方面奠定了坚实的基础。通过K99/R00提案，我将进一步发展我在复杂疾病建模方面的专业知识，并在提供者和患者互动的背景下研究如何通过利益相关者的参与以及对数据不确定性的更好理解来更好地为医疗决策提供信息。通过目标1，我建议通过创建患者和利益相关者咨询委员会(PSAB)来发展社区伙伴关系，以便为决策分析模型的设计提供信息，确定影响丙型肝炎治疗决策的因素，审查和监测模型输出，并优化结果的传播。这将通过整个颁奖过程中的系统过程来实现，并将利用名义上的小组技术、重点调查和公开讨论。然后，我将使用从这一合作伙伴关系中获得的知识来适应和进一步开发已发表的丙型肝炎病毒自然病史和治疗(目标2)的状态转换模型，该模型可以作为一个平台来评估需要在当前和未来的治疗之间进行顺序决策的临床问题。我将使用这个模型来检验即时治疗和延期治疗对不同亚群丙型肝炎患者的比较效果(目标3)。利用先进的敏感性分析技术和信息分析的价值，我将确定未来肝炎研究的领域 C对总体临床结果有最大影响的自然病史和治疗(目标4)。拟议的分析涉及卫生与公众服务部预防、护理和治疗病毒性肝炎行动计划的具体研究重点，以推进对患有病毒性肝炎的不同人群的护理研究，并与《患者保护和平价医疗法案》第6301(B)条的使命完全一致，以加强数据驱动的、以患者为中心的结果研究。为了确保这个拟议的K99/R00项目的成功，我组建了一个经验丰富的专家导师和科学顾问团队，其中包括我的导师David Meltzer MD博士和共同导师Donald Jensen博士，他们将提供高级分析方法方面的培训，如复杂模型构建、信息价值分析和定性方法，以及丙型肝炎自然病史和治疗方面的内容专业知识。芝加哥大学是一所世界级的研究机构，医学部和医院医学部基于这项建议的力度以及我自己的潜力，承诺提供资源和支持，以便为丙型肝炎的比较有效性研究领域做出有意义的贡献。K99/R00奖将提供一个关键机制，通过高强度的高级培训、专家指导和分析平台建设，实现向独立性的快速过渡，并在以患者为中心的决策分析结果研究方面建立职业生涯。

DESCRIPTION (provided by applicant): As treatment regimens for chronic hepatitis C evolve at a rapid pace, the decision to treat immediately or defer for the promise of future therapy has become increasingly complex. Treatment considerations must balance multiple patient characteristics, preferences, and treatment efficacy data, much of which fraught with uncertainty. Decision analytic modeling can augment traditional clinical studies by elucidating the comparative benefits and harms of treatment timing in different patient populations. The active integration of treatment priorities and challenges as directly elicited from patients and providers during the modeling process can ensure the relevancy of such analyses to key stakeholders as well as the effective dissemination of results. Such data could be highly useful in communicating tailored, patient-oriented estimates of risks and benefits of HCV therapy between health care providers affected patients, thereby improving informed medical decision making. Additionally, a clearer understanding of data uncertainty in the current literature could lead to rational priority setting for future research in hepatitis C care and treatment. I have developed a strong foundation in biostatistics, epidemiology, and decision-analytic methods through the completion of a Masters of Public Health, as well as through broad analytic experience within highly rigorous research environments at the Massachusetts General Hospital, Northwestern University, and now the University of Chicago. Through this K99/R00 proposal I will further develop my expertise in complex disease modeling, and examine, within the context of provider and patient interaction, how medical decision-making can be better informed by stakeholder engagement as well as better understanding of data uncertainty. Through Aim 1 I propose to develop a community partnership through the creation of a Patient and Stakeholder Advisory Board (PSAB) in order to inform the design of a decision-analytic model, identify the factors impacting decision-making surrounding hepatitis C treatment, review and monitor model outputs and optimize the dissemination of results. This will be achieved through systematic process throughout the course of the award and will utilize nominal group techniques, focused surveys and open discussion. I will then use the knowledge gained from this partnership to adapt and further develop a published state transition model of HCV natural history and treatment (Aim 2) that may serve as a platform to evaluate clinical questions requiring sequential decision-making between current and future therapies. I will use this model to examine the comparative effectiveness of immediate versus deferred treatment for different subpopulations of patients afflicted with hepatitis C (Aim 3). Using advanced sensitivity analysis techniques and value of information analyses, I will identify areas of future research in hepatitis C natural history and treatment that would have greatest impact on overall clinical outcomes (Aim 4). The proposed analysis addresses the specific research priorities of the Department of Health and Human Services Action Plan for the Prevention, Care, & Treatment of Viral Hepatitis to advance research in care for the diverse populations living with viral hepatitis, and is fully aligned with the mission of Section 6301(b) of the Patient Protection and Affordable Care Act to strengthen data-driven, patient-centered outcomes research. To ensure the success of this proposed K99/R00 project I have assembled a highly experienced and expert team of mentors and scientific advisors, including my mentor Dr. David Meltzer MD, PhD, and co-mentor Dr. Donald Jensen, MD, who will provide training in advanced analytic methodologies such as complex model building, value of information analysis, and qualitative methods, as well as content expertise in hepatitis C natural history and treatment. The University of Chicago is a world-class research institution, and the Department of Medicine and Section of Hospital Medicine have committed resources and support based on the strength of this proposal, as well as my own potential to contribute meaningfully to the field of comparative effectiveness research in hepatitis C. The K99/R00 award will provide a critical mechanism, through high intensity advanced training, expert mentorship, and analytic platform building to achieve a rapid transition to independence and to establish a career in patient-centered decision-analytic outcomes research.