With Operation Trialblazer set to expedite early-stage research in the US, experts anticipate that the fast-tracked investigational new drug (IND) stage could be a significant catalyst for innovation. However, they caution that incentives provided by competing regions may influence sponsor decisions on where to conduct Phase I trials.
Operation Trialblazer seeks to accelerate the development of lifesaving treatments and ensure that patients have access to the most innovative therapies in the world. Each of the agencies nested under the US Department of Health and Human Services (HHS) will contribute to the operation.
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This guidance aims to shorten the timelines for Phase I trials, with the US Food and Drug Administration (FDA) also seeking to clarify regulatory expectations for sponsors that could reduce early trial timelines by six to 12 months.
Countries such as China and Australia have become key regions for early-stage research, and experts question whether Operation Trialblazer goes far enough to entice sponsors to bring research back to the US.
Expedited IND – the advantage
Expedited IND review is the leading benefit of Trialblazer, says Dr Richard Graham, co-founder and chairman of the board of TruTechnologies. He is supportive of the guidance on human dose prediction, which he highlights as helpful in the planning phases.
Robert Zambon, VP of ConcertAI, agrees that the expedited IND will impact early-stage research directly, but also believes it will assist sponsors who are several years down the line from an IND and moving into the later phases. Speaking on the GlobalData Healthcare podcast, Zambon said that this is one of the key areas in which Trialblazer will incite sponsors back to the US.
“Being able to take that back to the foundational elements of what goes into your IND, what goes into your overall design, what’s going to drive decisions that are made down the line when you’re moving into a Phase II. Looking at the metrics that are important, should accelerate those initial timelines, but the cascade-down effects are some of the most exciting things that will happen,” Zambon explains.
Zambon notes that while reducing the timeline, the quality of INDs must remain high to give sponsors the confidence that the system is both trustworthy and effective.
“Providing that type of regulatory guidance into the system to potentially reduce or eliminate some of the timelines on IND meetings and the feedback loops accelerates that entire process and will give sponsors the confidence that is needed to make decisions quicker and earlier,” Zambon says.
Data, interoperability, and modernisation
Key areas that Operation Trialblazer, and other initiatives announced by the FDA, touch upon the importance of high-quality data, interoperability and modernisation of research, such as the integration of artificial intelligence (AI).
This guidance, in collaboration with others, such as the real-world data (RWD) initiatives, provide standardisation, something which has been lacking as technology outpaced regulation.
Operation Trialblazer places strong emphasis on data infrastructure and interoperability across electronic health record (EHR) systems and HER-to‑EDC data transfer. The push to standardisation of these tools will therefore accelerate trial start-up times, improve feasibility and site selection and expand site access.
This in turn creates “cascade down effects” that impact the entire development pathway, Zambon believes.
“There isn’t a uniform way to approach clinical trials, and having multiple different tools that are available is great. But standardisation of how those tools work with each other can accelerate decision-making, it can accelerate timelines and startup timelines, and it opens the aperture on what kind of sites can participate in those studies overall,” Zambon says.
As the speed of AI and data innovation accelerates, Zambon believes that establishing standardised approaches for adopting these technologies will be critical. Greater alignment across stakeholders will enable companies to better integrate systems, optimise workflows, and strengthen collaboration. He adds that this will ensure that the US remains at the “forefront” of early‑stage research and ensures that the region can compete with others.
Retaining its gold standard, however, is vital, but this is not something which experts raised concerns about. “Losing that high quality review to go faster is not where anybody really wants to go,” Zambon says.
Reform at larger scale needed
While appreciating certain elements, Graham is overall quite critical of Trialblazer, adding that more needs to be done to truly impact the US clinical trial sector.
Graham’s core criticism is that Trialblazer does not address the execution phase, when sites and CROs collect, handle, and report data. Based on his experience in large pharma, Graham said he has seen significant errors such as sample switching.
He does, however, believe it targets both planning and analysis, but he says that this only resolves issues for one stakeholder at a time rather than system-wide. As a result, he believes the operation should take more of a multi-stakeholder approach, rather than being geared directly for sponsors.
“It is trying to solve one group’s problem. It’s not solving the whole infrastructure problem,” Graham explains.
Another point of note, raised by Matt Walz, CEO of TrialBee, a patient recruitment platform, is that the US’ structure means that clinical research and clinical care remain quite separated.
Walz argues that this separation creates awareness gaps for both patients and physicians, financial friction between sponsors and copays, as well as trust issues, something which has seen a significant increase in recent years in the US.
Without addressing these issues, Walz does not believe that this initiative goes far enough in addressing patient enrolment barriers. He therefore calls upon policy to improve that link, which in turn would assist in addressing the first two of these challenges that the clinical trial sector faces.
“There’s an incentive for our physicians to look at what their patients have and think about what experimental medications are out there, in addition to standard of care, that could potentially help them. If there’s an opportunity to provide those incentives, that’s something that government and policy can uniquely help with,” Walz explains.
While addressing the first two barriers would stem in closer collaboration, the trust barrier will continue to be a challenge that the sector faces. Walz therefore calls for broader, government-sponsored campaigns to help re-establish trust and bring research into the communities, something he believes Trialblazer is not addressing.
Australia and China still attractive
While Trialblazer does set out to expedite IND applications, this will not solve the issue of sponsors looking to other countries, including Australia, for early-stage research, Graham adds.
“My understanding of Operation Trialblazer is that the FDA is going to do things to help expedite IND review, so you remove some of the regulatory friction. This is good, but you are competing with Australia that has built infrastructure that does not require an IND review. You’re therefore comparing making it faster to not needing at all,” Graham says.
In addition to the absence of an IND, the Australian government offers substantial R&D tax credits of up to 43.5%, which is particularly attractive to small, budget-constrained companies.
As a result, Graham is sceptical of the impact Trialblazer will have in bringing these early-stage studies back to the US, as he says these two key attractions have not been addressed by the US.
On top of that, the US is also battling a rise in clinical trials and drug discovery in China.
Analysis by GlobalData company Deallus, highlights that a Phase I in China takes an average of seven months, compared to 17 months in the US. GlobalData is the parent company of Clinical Trials Arena.
Zambon believes that the main lever for the operation is regulatory ambiguity, not relaxing standards. While it does show the US attempting to challenge countries like China, the agency knows it must retain its gold standard rating for safety, efficacy and overall regulatory rigour.
He therefore believes Operation Trialblazer’s role is to speed up processes including guidance, feedback and transparency while preserving quality, rather than cut safety corners or lower the bar for evidence.
Graham is thankful, however, that the US government is making steps to improve the early-stage research space in the US, as it will assist many who have faced challenges in the past, but believes that it alone will not be enough to bring Phase I research back to the US.
“I am thankful and appreciative that groups, including HHS, are trying to make things better. I understand very well the political pressures here, especially with most Phase I studies now going to Australia and a lot of later-stage studies being conducted in China,” Graham says.
While there are many positives to the operation, it may still fall short. It is clear, however, based on a collection of recent moves from the HHS and FDA, that the US is trying to position itself again as the gold-standard region for early-stage research – if these initiatives will help to achieve that, only time will tell.
