By Deborah Borfitz

February 18, 2021 | A Protocol Design Lab (PDL) launched by GlaxoSmithKline (GSK) at the end of 2019 is endeavoring to harness insights from real-world data, clinical trials, and patients themselves to create “operationally viable” protocols linked to predetermined value drivers—notably, clinical studies that are faster and less costly to conduct and include a greater diversity of patients. The earlier in the study design process the information can be leveraged, the higher the impact, says Jason Gubb, head of delivery optimization and informatics in global clinical operations at GSK.

The PDL was spearheaded by Gubb and is based on the deceivingly simple concept that data can be used to focus conversations and inform decision-making about the science (e.g., right populations and entry criteria) and operations (e.g., recruitment and delivery modeling) of clinical studies. But the required “cultural shift and change in mindset can be one of the hardest nuts to crack,” he says.

Editor’s Note: Gubb will present on the PDL methodology when he joins two of his GSK colleagues (Ryan Tomlinson and Clarissa Watts) for a fireside chat, “Challenging the Status Quo during Protocol Design and Development,” at the 2021 Summit for Clinical Ops Executives (SCOPE) being held virtually March 2-4.

The PDL takes form every time there is a “draft outline of a [study] concept,” says Gubb. It is underpinned by a “tech-enabled workflow orchestration framework” that supports the study team through the protocol development process.

Individuals on the multifunctional study team bring different perspectives and skills, but a common task during meetings is to review data to help inform their decision-making—initially to build a solid draft of the research concept and later to refine it, he says. Along with the final protocol, the group generates a study delivery plan.

The goal of the PDL is to help GSK speed the delivery of transformational therapies to the “patients, people, and public” who need them, says Gubb. Coupling big data with significant advances in technology and analytics to accelerate clinical trial delivery is the means.

One “key hope” of the PDL is that internal and external data, and patient input, can be used to challenge key assumptions of study teams, says Gubb. Modeling patient recruitment scenarios and using geospatial mapping to pinpoint suitable study participants and locations are among the tools in its arsenal to enable better, evidence-based decision-making.

Shining Some Light

One early result of the PDL is the “rapid and iterative review of potential study entry criteria,” says Gubb. Study teams can now see, based on an analysis of electronic health records, and claims data, the possible impact of certain inclusion and exclusion criteria on the ability to recruit patients.

This has prompted adjustments to age ranges, lab ranges, and medication criteria in some protocols, expanding the potential study population, he says. Possible new sites can then be approached, since the PDL can locate where those patients are, and solutions developed to optimally engage and recruit them.

A variety of analytical tools are used by the PDL to gain insights on patients and trial participation burdens, says Gubb, which get juxtaposed against the proposed schedule of study procedures and events. This has… “enabled us to challenge the rationale and need for certain procedures within our protocols.”

Most recently, the PDL has been helping GSK understand the prevalence of COVID-19 and its global spread to ensure the safety of patients in its trials as well as enable clinical trial continuity, Gubb says. Specifically, data from Johns Hopkins Coronavirus Resource Center has been used to model the pandemic’s impact on the study of experimental treatments and guide recruitment strategies in support of GSK trials.

The analytics exercise has shined a light on the PDL as well as the value of building processes and systems that are agile enough to incorporate data, says Gubb. The structure of the PDL enables it to leverage emerging data and apply quantitative methods to do simulation modeling for clinical trials.

As new digital biomarkers emerge and additional data sources become available, cutting-edge analytics and technologies can be deployed that will “exponentially increase our predictive capability,” says Gubb. Ultimately, he adds, the hope is to match patients to GSK studies based on their eligibility.

The Laundry List

As with any innovation or novel approach, says Gubb, challenging the “status quo mindset” of multidisciplinary teams is of paramount importance. To that end, anyone who makes important contributions to the design of studies—including physician investigators, clinical operations managers, biostatisticians, patient-focused teams, and technology partners—are at the table throughout the protocol development process.  

A laundry list of problems currently plagues study protocols, “not just at GSK but every pharma company,” Gubb continues. Among them are the imbalance between science and operational viability, trial complexity, overly strict entry criteria, and superfluous data collection for secondary and tertiary endpoints. “It is quite scary how much data is collected across the industry that is never actually used.”

An additional area of concern is the inability to access meaningful data from patient registries due to its formatting, he says. The competitive landscape is yet another challenge, further highlighting the need to simplify studies and make participation more attractive for both investigators and patients.

The industry continues to struggle with “listening to patients at scale” as well as providing optionality to study participants—particularly when it comes to offering digital decentralized technologies that patients like and sites want to use, says Gubb. The constantly evolving technology landscape has made it difficult to work out “what is the right fit to meet a clearly defined gap or problem statement” in a study.

Decentralized Solutions

The pandemic “catalyzed” the expansion and acceleration of decentralized strategies to maintain patient safety and enable clinical trial continuity, says Gubb. The key focus areas included direct-to-patient shipping, eConsent, home health visits (either by existing sites or new agency partnerships), telemedicine, digital data collection, wearables, remote monitoring, and the use of local labs.

At the early study planning stage, the PDL poses a series of questions to ensure study teams are aware of the “opportunities and possibilities” with decentralized strategies and to consider which approaches could play a supporting role, he says. “An important element of the decentralized strategy is to understand customer and stakeholder needs—what is important to patients, to sites, to regulators, to the sponsor”—and what technology solutions are currently available.

“Important factors to consider still are the need to characterize and understand and [extend our] work with patients,” to determine which approaches would have the desired effect, says Gubb. The intent is multifold: to give patients greater optionality in how they participate in a trial, give GSK access to more diverse populations, and launch studies with greater speed.

The challenge for industry is to “articulate the return on investment, and not just the financial return,” he says. The value of decentralized approaches in easing study activation, enhancing patient engagement, and improving participation in trials also needs to be factored into the equation.

“Our focus is shifting toward the use of behavioral economics,” says Gubb, where patients are viewed as clinical trial consumers. “We’re experimenting with how to gain deeper and comprehensive insights at scale.”

GSK is also exploring the use of segmentation analysis to create patient cohort personas linked to factors such as their demography, media preference, affluence, and education level to optimize their engagement in trials, says Gubb. As GSK strives to co-create protocols with patients, it will also be looking into novel approaches such as gamification to crowdsource patient insights and uncover barriers to study enrollment.

Editor’s Note: Jason Gubb’s presentation on the Protocol Design Lab (PDL) at the 2021 SCOPE virtual event will be on March 3. Other PDL-related sessions include “Utilizing Modelling and Quantitative Decision Making To Better Predict and Plan Enrollment” and “Quantitative Decision-Making for Enrollment Prediction” (also on March 3) as well as “Dynamic Portfolio Oversight with COVID-19 Clinical Control Tower” and “Implementing Digital Biomarkers in GSK Studies: Two Use Cases in RA and ALS” (on March 2).