Overcoming Barriers to Large Global Studies: Cardiovascular Outcomes and Vaccine Trial Leaders on Research Methods That Made a Difference

Patient recruitment, retention, multi-site communication, supply chain, and many other complexities can present clinical trial challenges for any study. But when performing research on a large global scale with thousands of patients, many of those issues are further compounded across multiple languages and time zones. This is true for trials that cross numerous therapeutic areas – from cardiovascular outcomes studies to vaccine trials.

To understand these unique challenges, we enlisted the help of three operations experts to describe what they have experienced firsthand and which advancements have the best potential to transform the way we conduct worldwide trials.

Margaret-Anne Moos
Director, Project Delivery
CVOT experience in Type II Diabetes, Gout & Obesity

“When you’re running a study with 5,000, 10,000 or more patients, the key is understanding and planning for the intangibles: excellent, experienced people and real synergy between them. I always implement meticulously detailed project plans, especially during startup of a cardiovascular outcomes trial (CVOT). This includes critical communication flows to ensure transparency and responsiveness across the project team, the client, sites, academic research organizations (AROs), and vendors. Project synergy must be a deliberate focus before a trial kicks off.

I always implement meticulously detailed project plans, especially during startup of a cardiovascular outcomes trial (CVOT). This includes critical communication flows to ensure transparency and responsiveness across the project team, the client, sites, academic research organizations (AROs), and vendors. Project synergy must be a deliberate focus before a trial kicks off.

In sizeable clinical research studies, risk mitigation around enrollment is critical. Yes, achieving first subject first visit is essential and is a milestone that I celebrate with my teams. But then I will say, ‘We also need to know what’s happening with the other thousand patients.’ We’re always planning to hit the next recruitment goal.

Beyond recruitment, of course, is retention. And for CVOT studies, it can be a five plus year commitment for patients. Risk mitigation around retention is another critical success factor. One of the toughest challenges we face is making sure that drive and enthusiasm are still there to keep the study going, even more so when we know there will be variability in how patients feel throughout a trial’s lifecycle.

Several years ago, we implemented the role of retention manager to help ensure the success of a large obesity study with 8,800 patients. From day one, this person kept an eye on the ball, delivering a reality check or a pullback along the way. It helped us spot patient trends, which otherwise would be hard for teams to act on quickly. In terms of quality, the most promising outcomes flow from global research that retains all patients until the final event as defined per protocol has been acheived. Paying significant attention to patient retention helps PPD increase the integrity and reliability of our study conclusions.”

Richard Cutcher
Senior Director, Project Delivery
CVOT experience in Type II Diabetes and Coronary Artery Disease

“Survival data is one of the most challenging components of a cardiovascular outcomes study to plan for. There’s no deaths register or a central repository for reliable information we can use in many countries. That means we’re usually devising our institutional methods at each site to find out if a patient is still alive. It’s a conversation that can’t wait until the conclusion of the study. From the time you’re launching a new project, you must have a strategy in place, and to be successful, our team must reassess it throughout the program.

We often partner with contract tracing companies and strategically build a framework to capture essential information. Confirming that data’s accuracy and ensuring it won’t fall through the cracks five or six years later when a study is closing is a must. Everyone on the team must be future fluent and understand the study objective beyond basic trial execution.

Effective relationship management with our global vendors has never been more important because many vendors hold study  endpoint data, including survival information and imaging data. I’ve worked on studies involving 10-20 vendors and know that a thorough vendor management plan with thoughtful risk mitigation factors must be in place for any large global clinical trial. PPD has a proven track record of setting expectations up front to meet our clients’ needs. Recently, successful vendor relationship management confirmed the accuracy and delivered 92% of survival data for a large global study.”

Jason Berg
Executive Director, Project Management
Deep Experience in Vaccine Research and Development

“COVID-19 has accelerated many patient-centric innovations across the industry. As sites and patients are becoming much more comfortable with mobile health remote options during this time, we’ve been able to scale plans for remote data capture, analysis and sharing to improve trial design for large global studies. New technology has shown a serious potential to transform some of the industry’s more costly clinical trial processes. PPD is at the forefront of this innovation.

“ … we’ve been able to scale plans for remote data capture, analysis and sharing to improve trial design for large global studies. New technology has shown a serious potential to transform some of the industry’s more costly clinical trial processes. PPD is at the forefront of this innovation.”

The pandemic has presented key challenges for studies, each of which can pose further regulatory obstacles that require careful consideration. In the midst of this, global regulatory bodies have quickly and consistently responded to issue guidance to minimize the impact of the pandemic on clinical research, propelling the adoption of decentralized trials. For example, the launch of the FDA’s Digital Health Center of Excellence (DHCoE) demonstrates the benefits of these solutions and the agency’s commitment to advancing digital health innovation and re-imagining digital health care.

At PPD, we embrace one shared vision and strategy to build custom-fit decentralized trial solutions. As a trusted partner, we proactively shape, lead, and optimize the design and deployment of decentralized trial technology. As complex as the world of digital and decentralized clinical trials may seem to those first exploring options, it’s critical to see the big picture from the beginning and work together to achieve the right study outcomes.

This means we don’t make robotic, siloed decisions – collaboration is key. In every initiative, we’re driving agile, data-driven decision-making to ensure consistency and the highest quality standards for our clients. At the same time, we utilize this flexibility to better meet patient and site needs.”