Mortality

June 25, 2026: New Podcast Addresses Challenges Associated With Death as an Endpoint

Posted on by Sophia Ramirez

In a new episode of the Rethinking Clinical Trials Podcast, Brad Hammill and Keith Marsolo of the Duke University School of Medicine discussed the use of death as an endpoint, a section in the Living Textbook chapter on Choosing and Specifying Endpoints and Outcomes.

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Death is “the hardest of hard endpoints,” moderator Lesley Curtis observed. It’s objective and unambiguous at the individual level but surprisingly complicated to capture in clinical trials.

“ Unless somebody died while they were at your healthcare facility, you need to learn about that death,” Hammill said. “ But how are you planning to learn about the deaths of your participants in your trial? What methods do you have in place for that?”

The more decentralized or pragmatic a trial is, the more complicated and expensive it can be to keep track of participants.

“In a perfect world you’d have extensive follow-up, participant monitoring and the like, but that’s not really feasible from a budgetary perspective. You have to rely on proxy measures, and all of those come with trade-offs,” said Marsolo.

The discussion covered several methods used to ascertain participant mortality and their associated logistical considerations.

Hammill and Marsolo were both contributors to the Living Textbook chapter. Hammill is an associate professor of population health sciences. Marsolo is an associate professor of population health sciences and chair of the NIH Collaboratory’s Electronic Health Records Core.

Grand Rounds March 20, 2026: FLUID: A Cross-Over Trial of Hospital Wide Ringer’s Lactate vs Normal Saline (Lauralyn McIntyre, MD, FRCPC, MSc; Monica Taljaard, PhD)

Posted on by Sophia Ramirez

Speakers

Lauralyn McIntyre, MD, FRCPC, MSc
Senior Scientist, Acute Care Research Program
Ottawa Hospital Research Institute
Professor, University of Ottawa

Monica Taljaard, PhD
Senior Scientist
Methodological and Implementation Research
Ottawa Hospital Research Institute
Full Professor, School of Epidemiology and Public Health
University of Ottawa

Keywords

Fluids; Crystalloid fluids; Mortality; Hospital Readmission; Health Systems; Hospitals; Ringer’s Lactate; Saline

Key Points

  • Crystalloid fluids are among the most common interventions administered to patients; they touch nearly every person admitted to the hospital. However, the evidence base to inform their use is limited. Few trials were done until this past decade, and recent trials tend to focus on the critically ill. Though those studies found very small clinical outcome differences between fluids, even a 0.5% reduction in death and hospital readmission translates to 2,500 lives and $5 million saved in Ottawa alone.
  • The study team sought to address this study question at the hospital/health system level by comparing the effects of two usual care fluids, normal saline and Ringer’s Lactate, on the death or readmission of all hospitalized patients. After a pilot trial indicated feasibility, they launched FLUID: a cluster-randomized, cross-over trial across four Ontario hospitals.
  • The FLUID trial found a 0.5% reduction in death in the patients that received Ringer’s Lactate. This is a small but clinically meaningful reduction, with major implications for mortality at the hospital and health care system level. The findings are limited by the study’s early termination due to the COVID-19 pandemic.

Discussion Themes

While there are theoretical benefits to multiple crossovers, including the mitigation of period effects, the logistical burden of restocking an entire hospital’s fluid supply more than once was insurmountable.

The study team used a composite endpoint that gave hospital readmission the same weight as death. McIntyre attributed this decision to the significance of readmission for their patient partners and to its status as an indicator of resource use and subsequent mortality risk.

Trials disrupted by crises such as a pandemic or supply chain issues may be salvaged by Bayesian sequential testing, which allows researchers to assess data continuously without alpha penalties.

FLUID exemplifies the importance of asking simple, high-impact research questions. It was also incredibly cost-effective, costing less than $400,000 (in Canadian dollars) to conduct.