For novel therapeutics, the path to marketing authorization is narrow and treacherous. Among promising drug candidates, fewer than 15% make it all the way from early-phase clinical trials to regulatory approval. This success rate has changed little over the past few decades, even though the costs associated with drug development have skyrocketed.
A study’s success depends on laying the right scientific groundwork as well as differentiating the product. To achieve these things, sponsors need to pay careful attention to three fundamental pillars—scientific integrity, operational feasibility and scalability. Applying a systems thinking approach can create improvements in all of these areas.
Systems thinking involves adopting a holistic perspective and keeping all the factors that influence human health in mind when conducting studies. Systems thinkers study the relationships between the components in interdependent systems. These feedback loops and complex synergies drive outcomes.
Attending to scientific integrity drives success in research
When the scientific rationale for a product’s success is strong, that product is far more likely to make it through approval and into clinical use. Selecting the right target population for the trial—based on disease pathology, the product’s mechanism of action and its expected therapeutic effect on specific patient phenotypes—helps ensure that the product’s value will be exhibited as fully and accurately as possible. At the same time, it’s vital to choose appropriate endpoints. Taking patients’ and caregivers’ perspective into account can guide researchers in identifying the symptoms that are most bothersome, and the criteria that best measure of quality of life.
Optimizing eligibility criteria is also important. The criteria can’t be so stringent that enrollment becomes challenging and delays the study’s progress, since there is no real-world benefit to patients until the product reaches the market. But they can’t be so loose that they fail to differentiate the product from a placebo or comparator.
A systems thinker will also engage a broad array of stakeholders, early and often, when designing, finalizing and amending study protocols. These stakeholders include the site team, key opinion leaders (KOLs), patients and their study partners, family members and caregivers. All should share their views on the value of the therapeutic and the study, potential challenges and which disease symptoms impact people’s lives the most. Each participant brings unique knowledge—in-depth scientific insights from KOLs and SMEs in relevant fields; practical input about operational risks, pain points and what has worked well in past studies from sites; opinions about the palatability of the study design, how burdensome assessments would be and the potential benefits of the treatment from patients and their families; and insights into future advantages of the therapy and its risk/benefit ratio from payers.
“A significant percentage of marketed products are not covered by Medicare or private payers immediately after approval,” says Richard Gambie, Senior Director of Portfolio Delivery at Fortrea. “Or patients have to pay a significant amount out of pocket. This restricts access to those products. By including early input from stakeholders with expertise in determining the financial and economic benefits of treatments, you can smooth the pathway to approval and make it easier for more patients to gain access to those treatments sooner.”
Casting a wider net will make it possible to choose endpoints that measure what’s most important for the real-world success of a treatment. It will also enable researchers to design protocols that are feasible, patient-friendly and scientifically rigorous—balancing the needs of diverse groups to create value for everyone involved in the healthcare ecosystem. Involving these stakeholders early in study planning is an integral part of the study lifecycle: without it, success is less probable.
This type of engagement should not be limited to the planning phase of the study. As is the case with any partnership, the engagement’s effectiveness and success will depend on ongoing dialogue. Humans tend to try harder when they believe that what they do matters, their voices are being heard and they are being supported. Ongoing information-sharing enables them to see this. Updates on the study’s progress, successes, roadblocks faced and lessons learned at a site, regional or study-wide level should be provided to all stakeholders on a regular basis.
“We are all human. Every one of us—and our friends, family members and other loved ones—will be a patient at some point,” Gambie says. “It’s critical to keep that in mind when executing trials. The goal is to create a therapeutically effective novel product that will have a positive impact on patients’ lives, and by so doing, make the world a better place. You cannot disconnect this bigger-picture goal from the step-by-step process of designing and executing trials.”
Increasing operational success by lightening participants’ burden
Adopting a holistic perspective during study design and execution means keeping patient and caregiver experience front and center throughout the duration of the study. We must ask ourselves: How easy (or burdensome) will it be for people to take part in the clinical research journey?
It’s critical to establish the right supporting processes for each step within the study, eliminating as much discomfort and wasted time as possible. Incorporating technologies and decentralized approaches can help. It’s important to take differences between patient populations into account when selecting technologies—younger patients might prefer more advanced tools, while older people often appreciate ease of use.
Thinking about patients’ future good so that research can scale
Systems thinkers should strive to remove as many barriers to access as possible. This way, trials can proceed quickly and efficiently, while also reaching a diverse participant population. Anything that sponsors and sites can do to reduce the burden on patients and their family members will improve a trial’s chances of success.
“At the end of the day, everything we do is for the benefit of our patients,” Gambie says. “Whether we’re applying technologies, designing innovative processes or building more efficient systems, it should all come together to increase efficiency and make it easier and faster to run trials, so that more people’s lives can be improved.”
Systems thinking is ultimately about establishing and maintaining partnerships. These relationships are based on transparency and an open exchange of ideas, thoughts and experiences. In this model, stakeholders learn from and rely on each other in ways that empower then to excel in their areas of expertise and in pursuit of their common goal: to create therapies that improve the experience of being human.
Curious to learn more? Contact Fortrea to find out how Tetyana, Richard 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.
