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

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $463,316

## Abstract

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.

## Key facts

- **NIH application ID:** 10434650
- **Project number:** 5R01AG060163-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shirley Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $463,316
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434650

## Citation

> US National Institutes of Health, RePORTER application 10434650, Generalizing data from randomized trials to predict long-term treatment outcomes in older populations (5R01AG060163-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10434650. Licensed CC0.

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