Large global clinical trials are a necessary step in clinical development for most pharmaceutical therapies, but these studies often encounter challenges that have a substantial impact on timeline and budget, two critical elements for sponsors. The most common issues relate to the timeline for enrollment and the impact of suboptimal patient retention. In response to the related demands of several large pharmaceutical sponsors, Baim Institute has developed a service line focused on a set of successful, best-practices for site motivation and engagement, which we term Academic Site Engagement (ASE). The concept, developed under the leadership of Chris Cannon, MD, Executive Director, Cardiometabolic Trials, overlays an academic perspective regarding the core science and clinical impact of a given study, and infuses support for sites to engage their patients in the study, with a goal of enhancing both enrollment and retention in the study. The approach is successful with all types of study sites, from busy private practices to large academic medical centers. It also provides the investigators and coordinators an academic link to the broader field of study, thus enhancing their participation in clinical research.
Over the course of recent engagements, we have demonstrated that ASE can be an effective tool in promoting successful enrollment. For instance, a large outcome study managed by a global CRO, suffered from slow site identification and selection, poor site response to invitation to participate and a high study decline rate for many participating sites.
We were approached to implement a sustained program of ASE that would enable our Faculty, clinicians and skilled site and project management personnel to engage directly with sites at both the coordinator and PI levels to improve the site identification and selection process and to help the sites to optimize their performance over the enrollment period.
Our implementation efforts began with an invitation to several of our Faculty to join the Steering Committee. Doing so enabled them to interact closely with the Sponsor, study leadership and the global CRO and carry the appropriate credibility to engage with sites on behalf of the study.
At this time, we were formally assigned as the scientific lead to provide ASE for North and South America, where we initially contributed to site selection. On a study-wide basis, we work within the existing National Lead Investigator (NLI) structure, where each country has an assigned NLI who does direct site outreach in that country We guide the NLIs on study status, identify the need for site escalation, as well as host regular regional PI webinars, both with our own Faculty and with guest Faculty (“Grand Rounds Webinars”). During these informative sessions, we discuss core scientific topics, relevant to the therapeutic area and the trial, and provide key updates on study operations.
In terms of enrollment monitoring, our operational team reviews enrollment data on an ongoing basis and directly contacts Site Coordinators at under-performing sites to initiate troubleshooting. If these efforts prove to be unsuccessful, our team will activate further escalation. In the US, this will result in either an Baim physician to the site physician (MD-to-MD) call or an onsite visit from a trial specialist, with subsequent escalation to the NLI, if these prior two options are not successful. In all other countries, the next step is immediate escalation to the NLI. Under this scenario, we will prepare the NLI with all necessary data about the site as well as updates regarding any broader country/study level challenges, all aimed to support a productive call with the site PI.
Our partners on this study have realized a positive impact, seeing a marked increase in investigator interest in participating in the study and then in their engagement and performance. This started with a higher and more favorable response rate from sites.
21 out of 32 (66%) sites that previously either declined participation or did not reply to an invitation email from the CRO responded to Baim’s contact
14 PIs interested in receiving the invitation again
5 PIs still not interested in the trial but willing to circulate study information to colleagues
Site escalation tactics also proved effective, particularly in terms of improvements post-NLI intervention. This dialogue between the NLI and site investigators often uncovers the root cause of enrollment issues which allows for development of targeted solutions for that site and in some cases, for the development of broader solutions for the region or beyond. As the graphic below illustrates, re-initiation of enrollment following an NLI call to a site after a period of no activity, demonstrates positive results.
Much of this success can be attributed to the sustained, creative, hands-on interest put forth by our Faculty and their colleagues, delivering scientific content to the sites in a collegial and productive format. For instance, during a recent webinar:
150 sites (60% of active sites) across 5 countries were represented on the call
Significant attendance from Site Investigators and Research Coordinators
20 minutes of lively Q&A was generated from the Grand Rounds presentation
We are excited to be currently deploying our ASE service on multiple trials as we feel that we can add value at all of the different levels discussed. A number of our Cardiometabolic Faculty members, including Jim Januzzi, MD, Hannah Gaggin, MD and David Charytan, MD, are also leading ASE efforts, supported by a strong physician and project management teams.
Our ASE team is able to help make the study more fluid and productive. All of this is done under the watchful eyes of our creative and innovative Faculty leaders. Moreover, working within a complex trial structure consisting of multiple stakeholders, including Sponsor, CRO, other ARO and Steering Committee demonstrates our commitment to collaboration as an important and necessary ingredient for a successful study.
For companies who either conduct the main study operations themselves, or partner with a preferred provider CRO, the addition of ASE can be a constructive method for keeping trial timelines and budgets on track. These services foster academic interest among investigators and research coordinators and, in turn, they can better engage patients. We always aim to work collaboratively with the partner organizations working on a trial, and find a way to fully integrate ASE with the other operational aspects of the study.