Are Pragmatic Trials The Patient Recruitment Solution We've Been Looking For?

A conversation with Rob DiCicco, VP of portfolio management, TransCelerate BioPharma

The age-old problem for clinical research has been the ability to recruit patients. Many clinical research professionals have tried to crack this nut, whether with technology or partnerships or both. Let’s not forget the height of DCTs during the pandemic, which served their purpose but appear to have lost luster in the last few years. In fact, we still see similar stats regurgitated year after year: Half or more of clinical trials fail to meet recruitment requirements. All the while, sites are still feeling overwhelmed, and patients are still wanting trials that fit more seamlessly into their everyday lives. The crux is that while industry may be inclined to alleviate both, the bottom line is that the scientific data must be robust and uncompromised.

One potential solution is not something novel at all. In fact, it’s been around for decades: pragmatic trials.

In this Q&A, we hear from Rob DiCicco of TransCelerate, who reintroduces this design concept, discusses its potential benefits, and provides resources for its integration.

Clinical Leader: What are pragmatic trials, and what benefits can they bring?

Rob DiCicco: The term “pragmatic trial” has been around since the 1960s, yet there’s still no universal definition. At their core, pragmatic trials aim to bridge clinical research and routine care by embedding pragmatic components into clinical trials. For the purpose of this conversation, pragmatic trials are typically conducted when risks are well characterized — such as in late Phase 3 or with new indications for an approved drug — to either inform care or answer a regulatory question. Some experts feel that pragmatic trials are best suited for non-interventional or comparative effectiveness studies.

From TransCelerate’s perspective, our focus is on developing a scalable approach to implementing pragmatic elements, which leverage the following features:

• Broader eligibility criteria
• Simpler designs with procedures that are more routinely aligned with clinical practice
• Fit-for-purpose informed consent processes
• Visit schedules that are compatible with those more commonly used to provide routine care to patients
• Streamlining data collection to hone the focus more intensely on answering the question of interest, i.e. a limited number of endpoints and objectives

Primarily, pragmatic trials allow for a greater number of patients and investigators to participate. This improves the representativeness of the data and can help accelerate trial conduct. It also reduces the burden on healthcare staff and improves the overall experience for patients, benefiting everyone involved.

What are the current challenges to rolling out pragmatic trials — from all sides, including sponsor, CRO, site, patient, and even regulators?

From a CRO and sponsor point of view, there are many challenges. Data acquisition and data quality, when it is obtained directly from the EMR, introduce both technical challenges and data privacy challenges, as well as encumber the ability to monitor the data in a traditional fashion. There are many nonprofits, including TransCelerate, that are working on the data interoperability barrier, but to implement this at scale, policymakers must lean in to facilitate it.

Likewise, the traditional approaches to investigator qualification, training, and oversight do not always align with pragmatic trials, since these protocols are tightly linked to real-world clinical practice. Regulators have recognized this and support a different approach. The most important thing a sponsor can do to enable practitioners at the point of care to participate is to simplify. A healthcare system that is already overburdened cannot manage the types of demands of an earlier phase trial, where the purpose may be very different.

Why is now the time to embrace pragmatic trials in the U.S. and globally?

Globally, health authorities have increased their interest in data collected in real-world settings. The ability to align study designs with clinical practice paradigms helps to address this at scale. It not only answers important regulatory questions, but it also informs clinical practice. 

The ability to drive representativeness into clinical trials also benefits all stakeholders, and it has the potential to significantly accelerate recruitment. Improving recruitment into clinical trials has remained elusive for decades. Additionally, the pressure to demonstrate the value of new innovative medicines continues to grow globally. Data derived in this setting at pace again benefits all stakeholders. 

Finally, technology and data science are rapidly evolving in a way that supports both the operational and the design aspects of clinical trials, making things possible today that weren’t feasible 10 to 20 years ago. Together, these factors create a unique window to advance pragmatic trials.

What are the most important regulatory and operational considerations for embedding trials in care settings?

Operationally, it is worth repeating that simplification is the single most important thing that sponsors and CROS can do to make this possible at scale. Given where we are today, partnering with health authorities on both the design and the operational plan is not only critical to successful implementation but also essential for standing up to regulatory scrutiny during audits and inspections. Recent ICH updates to E6 and E8 emphasize quality-by-design principles, which can guide study teams through change management and help engage the right stakeholders early in planning.

What is the FDA’s STEP initiative, and how can it accelerate industry collaboration?

The FDA’s CDER Center for Clinical Trial Innovation launched the Streamlined Trials Embedded in Clinical Practice (STEP) project as a unique mechanism for sponsors to engage with the Agency when planning pragmatic or point-of-care trials. This process brings together a wide-ranging group of experts across the Agency to align on important elements of design and trial conduct. This encourages sponsors by reducing the risk of implementing a novel approach to answering a regulatory question, assuming an agreement on those elements can be reached. That said, not every study or every setting is appropriate for a pragmatic trials approach.

How can TransCelerate’s Resource Guide help sponsors implement pragmatic designs effectively?

Because TransCelerate is not the only organization focused on this problem, it can be challenging to stay current on what is evolving without visiting multiple sources, all of which address different aspects.

TransCelerate developed this Resource Guide to curate existing resources relevant to pragmatic trials. By compiling available resources, the goal is to improve the perception and awareness of embedded pragmatic clinical trials. This guide serves as a comprehensive starting point for those seeking to better understand pragmatic trials, from design and implementation to interpretation, regulatory considerations, and case study learnings.

About The Expert:

Rob DiCicco is vice president, portfolio management at TransCelerate BioPharma, a nonprofit consortium of 20 global biopharmaceutical companies. TransCelerate aims to drive innovation, simplify clinical trials and help bring new treatments to patients faster, safer and more efficiently. Rob joined TransCelerate from IBM Watson Health where he was the deputy chief health officer. At IBM, he worked closely with software teams to inform product road maps and assess the performance of e-clinical solutions.

Prior to joining IBM, Rob served in a variety of leadership positions at GlaxoSmithKline, including as vice president of clinical pharmacology sciences and study operations. In addition to his GSK responsibilities, Rob also led TransCelerate’s Common Protocol Template and Digital Data Flow workstreams and served as team lead for the Clinical Trials Transformation Initiative (CTTI)-sponsored Mobile Clinical Trials Novel Endpoints project. Rob received his Doctor of Pharmacy from the University of the Sciences in Philadelphia.