Diseases aren’t just disorders in physiological systems, and it’s not possible to cure them simply by discovering molecules with therapeutic effects on cellular targets. Instead, as research from the National Institutes of Health (NIH) reminds us, diseases affect individuals who live in communities, and an enormous array of social, economic, psychological and environmental factors determine their prevalence, transmission and outcomes.

Applying a systems thinking approach to clinical trial design addresses this holistic perspective. In systems thinking, we consider all the factors that influence health — and the dynamics and interactions between them — when planning and executing studies. By nature, systems are complex entities. When we understand the relationships between the parts and the whole, and the feedback loops connecting them, we can see how their synergies create outcomes.

Systems thinking requires adopting a human-centered focus. All the stakeholders in the clinical trial ecosystem are people, and their experiences and perspectives must shape our definition of success. The goal is to create a study that will be more efficient, easier to participate in, more sustainable and of greater value for everyone involved.

Bringing a more diverse group of stakeholders to the table

This human-centric approach should condition every aspect of the trial’s design and execution. This begins with involving a broader group of stakeholders in the trial design, including those with expertise in areas beyond the mechanisms of the disease or the development of the molecule.

“Traditionally, clinical trial design was a linear process,” said Melissa Harris, head of global patient recruitment and engagement at Fortrea. “A small group of people with backgrounds in the disease indication would design the study in ways that were familiar, mirroring what had been done before. When more stakeholders are involved in the trial’s design from its earliest stages, more diverse perspectives can shape the protocol, the application of digital health technologies and decisions about end points — among other things. You end up with more flexible protocols, more innovative approaches to data collection and less burden for participants.”

It’s particularly important to consider this human-centric perspective when deciding how to incorporate digital health technologies into protocols. In today’s world, it’s possible to collect far more data, more quickly and easily, off-site, than was once feasible during site visits. But that doesn’t mean all that data is valuable — either for regulators or to improve patient outcomes over the long term.

The average 12-month-long clinical trial with 2,000 participants will now generate more than 3 million data points. But only a small fraction of this data will ever be analyzed, let alone reported on. Systems thinking encourages stakeholders to consider the question of “which data to capture?” holistically. Is all the data truly needed? How will it be analyzed? What mechanisms will be used to collect it? And does its collection benefit all the stakeholders involved in the trial?

Keeping participants’ reasons for taking part in the trial front and center

Looking at the ecosystem holistically also means asking questions about what motivates people to be part of it. When we understand patients’ reasons for participating in trials, we can design them so their involvement will be more meaningful and rewarding.

“Many patients take part in studies for altruistic reasons,” Harris said. “They want to do something that will be of benefit to humankind, or they want to help people who are suffering from a particular disease. This means that sustainable ethical issues, such as protecting the health, livelihood and well-being of future generations, are extremely important to them. So considering sustainability during trial design is key.”

Keeping the ethics of sustainability in mind when designing clinical trials helps ensure that people can feel good about taking part in them. And as the world, rightly, becomes increasingly concerned about the health of the planet, incorporating wearables and digital health monitoring not only adds convenience for participants but can also reduce their travel-related carbon emissions. But this decrease must be balanced against the increased environmental costs associated with provisioning battery-operated devices for single-study use. A best-of-both-worlds approach might, for instance, incorporate a bring-your-own-device (BYOD) policy or allow for device reprovisioning in future studies. Designing studies with a systemic approach means balancing these considerations — that is, taking all aspects into account to determine the best clinical study design and execution strategy.

Leading with compassion and empathy

When stakeholders begin clinical trial design not by asking what kinds of data they’ll get but instead by adopting the systems thinking approach, they’ll be looking at the entire process through a human-centric lens. This mindset encourages the creation of more flexible protocols. Keeping participants’ experiences front and center means creating different options for different people — not everyone wants on-site visits, not everyone wants remote data collection and not everyone will be happy with the same mix of the two. Flexible trial designs can be adjusted as participants’ needs and preferences change.

Not only can this enable researchers to recruit a more diverse participant population, but it can also dramatically improve retention rates, making it that much easier — and less expensive — to gather high-quality data. Gathering outcome data that reflects patients’ lived experience — not just clinical end points — is crucial, too.

“If every single patient who finishes a study has good feelings about what they just went through, they’ll be more likely to enroll in future studies”, Harris said. “And their friends and family members will be more likely to participate in research, too. When patients feel they’re being valued, there will be greater trust in biopharmaceutical research as a whole. In the end, that’s a big win for science.”

Curious to learn more? Contact Fortrea to find out how Clare, Melissa and the team at Fortrea are using systems thinking—practically applied—to design and execute clinical trials that better address patient, site and sponsor needs.