Defining Clinically Relevant Phenotypes of PPI Non-Responders

定义 PPI 无反应者的临床相关表型

• 批准号: 8637997
• 负责人: LAURIE A KEEFER
• 金额: $ 33.6万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8637997
• 关键词: Accounting; Acids; Adult; Adverse effects; Affect; Affective; Agreement; Anxiety; Automobile Driving; Awareness; Behavior; Clinic; Clinical; Clinical Trials; Cognitive; Data; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Equation; Esophageal; Event; Failure; Future; Gastroesophageal reflux disease; Generations; Goals; Gold; Healthcare; Heterogeneity; Hypersensitivity; Intervention; Lead; Logistic Regressions; Medical; Methods; Modeling; Monitor; Operant Conditioning; Operative Surgical Procedures; Outcome; Pathologic; Patients; Pharmaceutical Preparations; Phenotype; Population; Population Heterogeneity; Probability; Protocols documentation; Proton Pump Inhibitors; Questionnaires; Reflux; Refractory; Risk; Symptoms; Techniques; Testing; Visceral; base; clinical phenotype; clinically relevant; improved; inhibitor/antagonist; innovation; novel; population health; preference; response; treatment strategy

DESCRIPTION (provided by applicant): Thirty to 50 percent of patients diagnosed with gastroesophageal reflux disease (GERD) are not satisfied with symptom control derived from proton pump inhibitors (PPI). This group of patients; PPI non-responders (PPI- NR), pursue further diagnostic procedures and interventions with low yield. This approach is problematic because symptoms are not related to pathologic reflux in at least 50% of PPI-NRs referred for ambulatory reflux testing and therefore it does not lead to improved outcomes or even inform us as to why a patient did not respond to PPI. The development of novel therapies for this group is limited by lack of agreement on the definition of a PPI responder and the lack of a model that accounts for the heterogeneity of continued symptom generation. Our goal is to validate a PPI-NR model that accounts for factors above and beyond pathologic reflux, reducing the need for low-yield ambulatory reflux monitoring and informing the development of novel treatments. Study 1 will provide an equation in which pre-test clinical and questionnaire data sufficiently enables probability estimation for each of 4 reflux phenotypes, derived from ambulatory reflux monitoring. Study 2 will yield a similar equation which will predict one's ability to withdraw PPI therapy when indicated.

描述（由申请人提供）：30%至50%的诊断为胃食管反流病（GERD）的患者对质子泵抑制剂（PPI）的症状控制不满意。这组患者; PPI无应答者（PPI-NR），追求进一步的诊断程序和干预措施，产量较低。这种方法是有问题的，因为在至少50%的接受动态反流测试的PPI-NR中，症状与病理性反流无关，因此它不能改善结局，甚至不能告诉我们为什么患者对PPI没有反应。由于对PPI应答者的定义缺乏一致意见，并且缺乏解释持续症状产生异质性的模型，因此限制了针对这一人群的新型治疗方法的开发。我们的目标是验证PPI-NR模型，该模型可解释病理性反流以上和以外的因素，减少对低产量动态反流监测的需求，并为新型治疗的开发提供信息。研究1将提供一个方程，其中试验前临床和问卷数据足以估计来自动态反流监测的4种反流表型中每一种的概率。研究2将产生一个类似的方程，该方程将预测一个人在有指征时撤回PPI治疗的能力。