Generalizing data from randomized trials to predict long-term treatment outcomes in older populations

概括随机试验的数据来预测老年人群的长期治疗结果

• 批准号: 9752414
• 负责人: Mehdi Najafzadeh
• 金额: $ 45.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752414
• 关键词: Age; Anticoagulation; Case Study; Characteristics; Clinical; Complex; Confidence Intervals; Data; Disease; EFRAC; Elderly; Evaluation; Event; Follow-Up Studies; Gold; Heart failure; Hemorrhage; Heterogeneity; Incidence; Individual; Long-Term Effects; Marketing; Medicare; Methods; Modeling; Morbidity - disease rate; Older Population; Outcome; Patient risk; Patients; Population; Provider; Quality-Adjusted Life Years; Randomized; Randomized Controlled Trials; Recording of previous events; Risk Factors; Safety; Specific qualifier value; Stroke; Structure; Target Populations; Therapy trial; Time; Translating; Treatment Efficacy; Treatment outcome; Uncertainty; Update; base; beneficiary; clinical practice; follow-up; innovation; interest; models and simulation; mortality; novel strategies; older patient; outcome prediction; patient population; predict clinical outcome; predictive modeling; preservation; prospective; randomized trial; treatment arm; treatment effect; valsartan

Project Summary/Abstract Randomized controlled trials (RCTs) are considered the gold standard for assessing efficacy of treatments. However, two characteristics of typical RCTs limit their utility for patient, providers, and other decision-makers. First, RCTs often focus on narrow patient populations to increase internal validity. This limits generalizability of the RCT results to older and sicker target populations, especially when heterogeneity of treatment effect (HTE) is present. Second, many RCTs have short follow-up even though many treatments that they evaluate are intended to be used for a long time. Although RCTs provide evidence about treatment efficacy during the study follow-up, estimating the long-term impact of treatment is difficult. As patients age, their disease state can change and they can develop new and worsening conditions that modify the effect of a treatment. Therefore, the average treatment effect observed during an RCT may not accurately reflect long-term treatment outcomes. Lack of generalizability due to these limitations causes uncertainty in translating RCT findings in clinical practice, especially in the early post-marketing stages. There is an urgent need to develop methods that can make trial results more useful to patients, clinicians, and other decision-makers. We propose a novel approach to expand RCT results to broader patient populations and over longer periods in the presence of HTE. The approach uses evidence about HTE derived from individual-level RCT data and an individual-level simulation model to estimate effects applicable to the characteristics of external target populations, such as older individuals. Existing individual-level data from three landmark RCTs will be used as case studies to evaluate the feasibility and application of the proposed approach for generalizing RCT results to older patients identified in existing Medicare data: the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE- LY) trial, the Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF), and the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction (PARAGON-HF). Our hypothesis is that information about HTE in the RCTs can be leveraged to predict treatment outcomes in a larger target population and over longer time periods than studied in the RCTs.

项目总结/文摘