Making Clinical Trial Recruitment More Efficient

Larissa Silva, MD
Buenos Aires, Argentina

Rebecca Sayers, PhD
Raleigh, North Carolina, United States

Jens Dietrich, PhD
Berlin, Germany

Russell Brown, PharmD, PhD
South Yarra, Victoria, Australia

NOVEMBER 26, 2018

At PRA, we strive to be innovative, to challenge accepted ways in pursuit of the best solution to the problems faced in clinical research. This continued pursuit led us to create the Clinical Trial Liaison (CTLs) team in 2014 to fulfill a greatly unmet need in clinical research—doctoral-level site engagement and assistance personnel within clinical research organizations. Clinical Trial Liaisons are experts in best practices for site engagement and patient recruitment, working directly with the PRA study team and our sponsors to select the best sites and to make sure each site is performing to the best of its ability.

We recently caught up with a few of our global Clinical Trial Liaisons – Rebecca Sayers, Jens Dietrich, Russell Brown, and Larissa Silva – to learn more about the assistance they bring to clinical trials all over the world:

What value do Clinical Trial Liaisons bring to clinical research?

Russell: Clinical Trial Liaisons all have doctoral degrees and stay current with the latest scientific research, helping investigators and sites fully understand the mechanisms of the treatment. We build relationships with investigators and key opinion leaders, so we can help identify the right sites and establish the relationship for the study. We are best brought in from the beginning, attending the site initiation visit and facilitating a discussion around the drug mechanisms to be sure there is understanding by the site. When sites fully understand the study and the key objectives, they are more likely to recruit patients.

Larissa: CTLs bring value not only to the sites but also to the local teams, where we can serve as a “bridge” to ensure that valuable information is collected from both sides. With our scientific background we can speak the investigator’s language, which gives us an advantage in obtaining the answers we need to improve their performance. We can discuss current treatment options and competitive trials showing them we have the most updated information, and we can use this knowledge to improve their performance in recruitment. Once they understand our role, they see us as a part of their team as we are not only pushing them to include patients, but we are working with them to provide all the tools they need to succeed.

With your education and experience, you could have any number of jobs. What attracts you to the CTL position?

Larissa: I believe the CTL position brings clinical research closer to the patients, so I feel I’m changing the myth that “clinical trial participants are guinea pigs.” This is a widely misguided concept in Latin America, probably spread because of the lack of information on this subject. I always loved being a part of the development journey along with a huge group of people that have one main thing in mind…the patient’s wellbeing.

Russell: It’s a fantastic job. I get to talk about science all day! With my background in academia as a researcher and lecturer, I very much enjoy talking about the latest research with people who also have this interest. As a CTL, I can apply my understanding to the trials I am involved with, and continue to teach, albeit in a different setting than a classroom. I am always learning something new and applying that knowledge, becoming an expert in new therapeutic areas continuously.

What challenges for investigators and sponsors do CTLs solve?

Rebecca: When a CTL is first on-site, we identify all the key stakeholders at the site who are responsible for recruiting potential clinical study patients. Through discussions of the patient pathway and proactive identification of potential barriers, we come up with a feasible plan the site can implement that takes into consideration their patient population, standard of care, and community. Many of the studies PRA conducts require finding patients from relatively small patient populations that are defined by low prevalence, competing clinical studies, or highly specific eligibility criteria for disease status or treatment background/history.

Jens: We pay particularly close attention to assessing the effectiveness of each site’s strategy used to identify potentially eligible subjects, to ensure the strategy will be a success. As CTLs, we understand how the trial fits into the site’s pattern of treatment for the condition and how any competing clinical trials or upcoming drug approvals may affect the progress of recruitment. We also regularly interact with investigators and staff to go over the course of the trial to ensure that the trial remains “top of mind.”

Larissa: It’s very important that we create a respectful and trusting environment, so investigators feel comfortable with being honest about their difficulties and challenges. From confirmation of participation to activation, sites may have been working on a study for over a year, and it’s common for them to become frustrated when the enrollment period is near closing and they cannot meet their enrollment targets. We work together with the investigators to create an enrollment plan that includes pre-screening and referral networking strategies with the aim of accelerating patient inclusion.

Russell: We also help identify challenges for the sites we work with, before they become a problem for the site. We work with a number of sites for each study, so we have extensive experience with catching the trends that lead down the wrong path, before they progress.

How do CTLs differ from Clinical Research Associates (CRAs)?

Larissa: CTLs and Clinical Research Associates are different in a number of ways. The entire CTL team has a scientific background, enabling us to clearly understand the different mechanisms of action of the investigational drugs. This understanding, along with a clear picture of the patient population we need to include in each clinical trial, is what we base our discussions on with the Principal Investigators, so we can engage and motivate the investigators in studies in ways that are not part of the typical CRA role. Together, we create a realistic recruitment plan for each site considering the advantages and barriers they might have. We don’t do source data verification, like CRAs. Our work is focused on helping sites become successful at recruiting using their own capabilities and our experience.

Russell: CTLs also build long-term relationships with the sites and investigators, so they feel more comfortable giving us honest feedback on what is working and what doesn’t work. We can each go to each other with questions because we have established that trust and proven our value. We are very accessible by phone as well, meaning questions that come up can almost immediately be answered.

Can you talk about a time when you really felt the value of CTLs in advancing drug development and the future of healthcare?

Rebecca: One of the studies we are working on is in pediatric type 2 diabetes mellitus. It’s fairly common knowledge that there are many different classes of medications available for the adult population. However, for children, there are only two approved options: insulin and metformin. Although pediatricians and pediatric endocrinologists always encourage healthy diet and lifestyle to help improve hemoglobin A1c in these patients, recent studies have demonstrated that pediatric type 2 diabetes patients who had an add-on medication of a different class to their metformin had better treatment outcomes. Based on these results, we understand that investigating approved medicines such as sodium-glucose transport 2 (SGLT2) inhibitors and dipeptidyl-peptidase 4 (DPP-4) inhibitors in pediatric patients is helping to get us closer to having better options for this disease that is on the rise in adolescents and children globally. This population of patients is inherently difficult to enroll in clinical studies, so I get to work one-on-one with doctors and study coordinators who are working to bring medical care and better options to patients in their community who have limited options for their diabetes.

Why are CTLs needed for the future of successful clinical trials?

Jens: CTLs will be more needed as the science behind clinical trials becomes increasingly more sophisticated. CRAs do not have the education and background needed to explain the science behind the trial, so CTLs will be essential to ensuring all site personnel understand the treatment.

Many sites also interact mainly with their CRA and lack contact with the sponsor. Although CTLs work for a CRO, we are often perceived as a link between sponsor and CRO, because we have more of a high-level strategic approach than the day to day work of a CRA. CTLs talk on all levels with the study team: with the Principal Investigator about the current scientific developments and also with the study nurse, making sure they understand the practical aspects of the trial. Because CTLs see many sites in different countries and across therapeutic areas, we are experts in best practices.

Rebecca: Within our industry, there is a big shift to remote monitoring, which means that a site is going to see less of their CRA overall. The CTL will be there, in person, as a representative of PRA and the sponsor to have in-person time to build relationships, and make sure that Principal Investigators and their site staff want to partner with PRA on clinical studies. As patient recruitment for clinical trials becomes increasingly difficult, keeping the investigator engaged with updates on new data or additional scientific rationale will help keep that study in the physician’s mind when interacting with eligible patients.

HOW REAL WORLD EVIDENCE IS CHANGING PHARMA

THE FIGHT AGAINST ALS

OVERCOMING BARRIERS IN RARE DRUG DEVELOPMENT