Rethinking clinical trials to improve patient care

Clinical trials are the foundation of evidence-based medicine. They determine what works, for whom and under what circumstances. Yet many of the methods and structures we rely on today were developed decades ago and have not kept pace with how clinical care is delivered.

Dr. Ryan Zarychanski, a hematologist, critical care physician and professor of internal medicine at the Max Rady College of Medicine, has been awarded a Tier 1 Canada Research Chair in Clinical Trials. His work focuses on modernizing how clinical trials are designed and conducted while embedding them directly into patient care to improve outcomes and efficiency.

We spoke with him about the challenges with current approaches, how his work aims to address them and what this means for patients and the health-care system.

What are the limitations of how clinical trials are currently conducted?

Clinical trials are essential. They are how we determine whether therapies are effective. Without them, we rely on incomplete information and are more vulnerable to bias in clinical decision-making.

One of the central challenges is that trials are often conducted separately from routine clinical care. They operate as parallel systems, with separate infrastructure, personnel and data collection processes. This separation introduces inefficiencies and limits our ability to generate evidence in real time as we care for patients. A key objective of my work is to better integrate clinical trials into care delivery so that health systems can learn while providing care, rather than treating research as something external to it.

At the same time, many trial designs and methods have remained relatively unchanged for decades. While traditional randomized trials have been enormously valuable, they are not always well-suited to answering contemporary clinical questions or to understanding how treatments affect individual patients. For example, traditional trials provide an average treatment effect, but patients are not averages; they vary in important ways that influence how they respond to therapy. In addition, many clinical trials rely on traditional approaches to consent and data collection that can limit accessibility for patients, increase operational complexity and cost, and may not optimally support patient autonomy or the accurate capture of real-world clinical data.

You’ve said clinical trials should be embedded in clinical care. What does that look like in practice?

In routine care, we already generate a tremendous amount of clinical data such as laboratory and imaging results, treatments and outcomes. In many cases, we then recreate parallel systems to collect similar data for research purposes. This duplication is inefficient and slows the pace of discovery.

Embedding trials into clinical care means using the infrastructure and data generated through routine care to support randomized studies. Rather than delivering variable or inconsistent care, we can provide structured, randomized care within a trial framework that allows us to learn which approaches are most effective.

An example of this is our work evaluating tranexamic acid in major non-cardiac surgery. The drug had been used inconsistently for decades without definitive evidence. By embedding a randomized trial directly into clinical care, we were able to rigorously evaluate its effectiveness at scale. The results, which will be published shortly, are expected to influence practice globally and reduce the need for blood transfusion for millions of patients.

This approach allows us to answer important clinical questions more efficiently while directly improving patient care.

You’re building adaptive platform trials to support this work. What do they allow you to do that traditional trials cannot?

Traditional trials are often designed to answer a single question, after which the infrastructure is dismantled and rebuilt for the next study. This approach can be slow and resource-intensive. We typically do not build complex health infrastructure to answer a single question or perform a single task and then discard it. Just as we do not build an airport for a single flight or an arena for a single hockey game.

Platform trials take a different approach. They establish durable infrastructure, supported by a master protocol, that allows multiple interventions to be evaluated over time within the same system. New treatments can be introduced, studied, and removed as evidence emerges, without having to rebuild the trial from the ground up.

In our work on pneumonia, a condition that remains one of the most common reasons for hospital admission, I lead a platform trial that evaluates multiple potential therapeutic strategies at once. This design allows us to study several interventions simultaneously and adapt as we learn, substantially reducing the time required to generate answers and improving the efficiency of research.

Alongside these designs, we are advancing methods such as adaptive statistical approaches, innovative consent models and streamlined data collection. These approaches aim not only to improve efficiency, but also to better understand how treatments work for individual patients or groups of patients, rather than relying solely on average effects.

Much of your work focuses on severe infection and sepsis. Where do you see opportunities to improve outcomes?

In severe infection, it is often not the pathogen itself that leads to poor outcomes, but the body’s response to it. Inflammation and activation of the coagulation system can lead to organ dysfunction and, in many cases, death.
While we have effective treatments to target the infectious organism, we have relatively few therapies that address this dysregulated host response. My research focuses on identifying and evaluating therapies that can reduce inflammation and abnormal clotting, prevent organ failure, and improve outcomes.

Many of the interventions we study are repurposed therapies that are already widely available and relatively inexpensive. This creates an opportunity to improve care not only locally, but globally.
 

How will this work benefit Manitobans?

The Canada Research Chair will support the development of infrastructure and methods to embed clinical trials into clinical care across Manitoba. This will allow us to more efficiently determine what works, what does not and where resources can be used most effectively.

Health systems operate at a scale comparable to large enterprises, yet they do not consistently embed research and evaluation into their core operations. Strengthening this connection between care delivery and evidence generation is essential, not only to improve patient outcomes, but also to ensure that resources are used effectively in the face of growing demands.

Building capacity is at the heart of this work. I established Aurora Clinical Research as an academic contract research organization to provide investigators across Manitoba with the infrastructure and expertise needed to design and lead their own trials and answer pressing clinical questions. The Canada Research Chair will catalyze the expansion of this platform allowing us to scale operations, train clinician–scientists and research teams and support a growing portfolio of trials across diverse clinical areas. As Aurora grows, it will not only strengthen Manitoba’s leadership in innovative trial design and delivery but also create opportunities for partners who share this vision to help extend our reach and impact.

Ultimately, the goal is to create a system where clinical care and clinical research are closely aligned so that every patient encounter contributes, in some way, to improving care for the next.