Scaling down: Clinical research shifts its focus
Ken Getz, director of sponsored research at Tufts University addressed the state of the pharmaceutical industry during a keynote speech at ACRP earlier this month, providing insight into the current and potential future of clinical research.
According to Getz, 2018 was a record year, with a ‘tremendous’ number of approvals of small molecules and biologics, the composition of which he said reflects the industry’s current pipeline.
Demonstrating the advancement of innovations like immune therapy, cell and gene therapy, as well as nano-technologies, Getz said 73% of 2018’s approvals were under expedited review, and many were indicated for the treatment of rare diseases.
In total, 50% of all approvals in 2018 fell into the rare disease category, and a quarter of the treatments relied on biomarker technologies and genetic material, which Getz said demonstrates the industry’s move toward precision medicine.
Small companies led the way in 2018 as well, with roughly 70% of approvals coming from small companies, and 60% of those companies submitted their first application to the US Food and Drug Administration (FDA).
“As you can see, we are starting to see strong signs of a pipeline that is shifting its focus towards rare disease and precision medicines supported by smaller companies,” said Getz.
“We’re moving away from the need to scale infrastructure,” he added. “Instead we’re now moving to scale the system that is characterized by more flexible and open innovation, that relies on data and analytics to support our decision making, our operations, and management.”
Value of data
Looking back on the industry in the period from 1980 to 2000, Getz said that the focus then was on ‘great science’ and clinical trial operations were centered around key opinion leaders. During that time 70% of all industry funding was placed in the academic sector, he said, and operations were reactive with limited access to data.
“Our primary mission now has become to not only support great science but to balance it with feasibility and our ability to execute more easily,” Getz said.
“Our operating focus has now shifted, we’re sharing more data in a pretty competitive environment” he added. “We’re trying to move toward more responsive use of data, so we can make decisions closer to real-time. We’re looking at a specific activity and making changes while it is underway.”
The value of data to make anticipatory changes in clinical research was a point Getz ensured to make, stating this will enable cost and time saving, as well as “pre-approved adaptive- type activities where we’re thinking about changes and getting them approved before we have to make them.”
He also added that the age of data will enable an operating approach that will make the clinical research a more predictive environment in which high levels of risk can be anticipated with analytics to leverage the value of data.
According to Getz, if the period between 1980 and 2000 was focused on ‘greater science’ than the current period is focused on moving into an environment to promote ‘patient engaged science.’
This movement in the industry would enable patients to provide data “whenever and wherever the patient can most easily provide it.”
“Under this era, we move to a more collaborative and flexible environment where we’re leveraging the most expert parties wherever they may be. They’re applying their expertise to help us make the best decisions that relate to that patient's care,” stated Getz, calling the transition “the natural pattern of science.”
“Ultimately we’ll see the convergence of clinical care and research and every time a patient or person that touches a therapy that’s commercially available there is something that we’ll learn from their response and we’ll continually be expanding our understanding of how to treat them over time and our knowledge of population health,” he said.
According to Getz the advancement of analytics to enable greater usage of data will shift the way the industry operates today, shifting away from “the need to scale labor-intensive infrastructure and moving more to a system that we can scale, that’s more flexible that engages in analytics.”
This change directly relates to the growing cost of research and development (R&D) in the clinical research industry.
“Over the past 20-year span, we’ve seen year-over-year roughly a 5% increase in the direct annual spending to support R&D activities, approaching $160bn just to support annual R&D costs. A growing percent is being directed toward external parties,” Getz said.
In 2015, the industry spent more on outsourcing and other vendor or contracted services than on internal infrastructure and continued growth in spending on external services has increased, he explained.
“You don’t have to look very far to see primary drivers in the reliance in outsourcing. The proliferation of smaller companies that lack the capacity and expertise to support their programs as they move into later stages of R&D,” said Getz.
By 2020, he said there will be an estimated 4,100 small companies with at least one active drug in their R&D pipeline.
Yet, Getz said, that despite increased outsourcing costs, increased data, and more analytical tools, the industry is no faster in developing than it was in the mid-90s.
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“If you’re the type of person who tends to be more of an optimist than you might look at this and say this is terrific we’ve been able to manage so many more challenges. If you’re more of a cynic this is really very disparaging – and we need to find a way to drive higher levels of efficiency,” Getz said.
Failure rates and rare diseases
Getz said that failure rates are the highest they’ve ever been. With high direct costs for R&D and long drug development timelines, the cost to develop drugs has increased.
“What we’re seeing is, if we look at all the rare disease medications that have been approved today, they typically have a much smaller scope as measured by the number of sites that support them, and number of patients recruited,” he stated.“But if you look at their cycle times they’re significantly longer and our recruitment rates and screen failure rates are poorer.”
Getz added that personalized medicines, while a more difficult area to measure success, present a ‘shining a positive light’ for the future based on recent approvals and feedback from the FDA.
“So personalized medicines may help us if we continue to operate under our current paradigm,” he said, “We may be able to see such improvements in our success rates.”