Improving Metformin Utilization And Diabetes Control Through Patient-Centered Outcomes Research

 描述(由申请人提供)：这是詹姆斯·弗洛里博士的K08初始申请，他是一名内分泌学家和年轻的研究员，致力于以患者为导向的2型糖尿病(T2 DM)护理的比较有效性研究。K08奖项将为他提供在三个关键职业发展领域获得技能的手段：1)临床流行病学，2)定性研究，3)临床试验设计。通过掌握这些技能，弗洛里博士将实现他成为一名独立临床研究员的长期职业目标。弗洛里博士有一位主要导师阿尔文·穆什林博士，他是一位领先的流行病学家和内科医生，拥有指导K-Grant获奖者的丰富经验。他还将与共同导师肖恩·亨尼西博士合作，他是一位领先的药物流行病学家。此外，弗洛里还有两个关键的合作者：约书亚·理查森博士，他是将定性研究应用于生物医学信息学的专家；大卫·布里隆博士，他是内分泌学家和临床研究人员，专门研究糖尿病。这项建议的临床问题是，尽管二甲双胍是治疗T2 DM的一线药物，并提供无与伦比的长期临床益处，但它没有得到充分利用。特别是，16%的患者在6个月时停止使用二甲双胍，近三分之一的患者在一年后停止使用。弗洛里博士的中心假设是，这种非持久性(即早期停药)在很大程度上是由于二甲双胍特有的以患者为中心的因素，更好的处方实践和处方者与患者之间的沟通可以增强二甲双胍的持久性。为了验证这一假设，并将其转化为务实的干预措施，弗洛里博士建议收集有关二甲双胍非持久性的流行病学和定性数据，然后在一项小型务实临床试验中设计和试点干预措施。这些活动将为在K08获奖期间在R01申请中提出的大规模务实随机试验奠定基础。目的1将验证这样的假设，即二甲双胍非持久性是常见的，并导致明显更糟糕的短期临床结果。目标2将检验这样一个假设，即非持久性患者和他们的提供者将为二甲双胍非持久性提供潜在的可修改的原因。目的3将验证这样的假设，即以患者为中心的干预措施的实际临床试验将二甲双胍重新引入先前非顽固性患者是可行的，并可能导致更多的适当使用二甲双胍来治疗T2 DM。这项拟议的研究意义重大，因为积极的结果将导致确定一种干预措施，使更多的患者受益于二甲双胍。阴性结果将提供有关二甲双胍非持久性的性质的信息，并为优化这些患者的护理的替代方法奠定基础。

 DESCRIPTION (provided by applicant): This is a K08 initial application for Dr. James Flory, an endocrinologist and young investigator pursuing patient-oriented comparative effectiveness research on the care of type 2 diabetes mellitus (T2DM). A K08 award will provide him with the means to acquire skills in three key career development areas: 1) clinical epidemiology, 2) qualitative research, and 3) clinical trial design. By acquiring these skills, Dr. Flory will fulfil his long-term career goal of becoming an independent clinical investigator. Dr. Flory has a primary mentor, Dr. Alvin Mushlin, who is a leading epidemiologist and internist with extensive experience mentoring K-grant awardees. He will also work with a co-mentor, Dr. Sean Hennessy, a leading pharmacoepidemiologist. In addition, Dr. Flory has two key collaborators: Dr. Joshua Richardson, an expert in the application of qualitative research to biomedical informatics, and Dr. David Brillon, an endocrinologist and clinical researcher specializing in diabetes. The motivating clinical problem for this proposal is the fact that although metformin is the first-line drug therapy for T2DM and confers unequalled long-term clinical benefits, it is under-utilized. In particular, 16% of patients discontinue metformin at 6 months and close to a third discontinue it at one year. Dr. Flory's central hypothesis is that much of this non-persistence (i.e., early discontinuation) is due to patient-centered factors specific to metformin and that better prescribing practices and prescriber-patient communication can enhance metformin persistence. To test this hypothesis and translate it into a pragmatic intervention, Dr. Flory proposes to collect epidemiologic and qualitative data on metformin non-persistence and then design and pilot an intervention in a small pragmatic clinical trial. These activities will la the groundwork for a large-scale pragmatic randomized trial to be proposed in an R01 application during the K08 award period. Aim 1 will test the hypothesis that metformin non-persistence is common and leads to observably worse short-term clinical outcomes. Aim 2 will test the hypothesis that non-persistent patients and their providers will offer potentially modifiable reasons for metformin non-persistence. Aim 3 will test the hypothesis that a pragmatic clinical trial of a patient-centered intervention to reintroduce metformin to previously non-persistent patients is feasible and likely to result in increased appropriate use of metformin to treat T2DM. The proposed research is significant because positive results will lead to identification of an intervention to allow more patients to benefit from metformin. Negative results would provide information on the nature of metformin non-persistence and lay groundwork for alternative approaches to optimizing care of these patients.