By Deborah Borfitz

January 31, 2022 | Anyone who has ever played the game of telephone as a child knows only too well how a message can become completely scrambled by the time it passes through a succession of people. A similar type of communication breakdown can happen when a protocol gets communicated by a study sponsor to a contract research organization (CRO), and then handed off to study managers or monitors and ultimately clinical trial sites, according to Erin O'Boyle, vice president of clinical operations at biopharma company Rezolute, Inc.

“Proactive and hands-on communication with all the parties involved is often the only surefire way to preserve the integrity of a study, where the expected enrollment may be only one or two subjects per site—some of whom are crossing borders to get there,” she says. The primacy of communication and transparency will be highlighted at O’Boyle’s presentation at the 2022 Summit for Clinical Ops Executives (SCOPE), where she will discuss outsourcing options and how Rezolute successfully executed a rare disease study in the middle of a pandemic.

Many hundreds of rare disease clinical trials are typically ongoing at any one time, as suggested by the brief sampling listed on the website of the National Organization for Rare Disorders (NORD), although “COVID-19 has significantly delayed, and in some cases, closed rare disease programs,” O’Boyle says. More than 7,000 rare diseases have been identified, and these smaller niche markets have piqued industry interest over the last decade.

Too often, needless worry goes into picking the right CROs and second-guessing those choices, when the focus—once outsourcing contracts have been signed—should instead turn to collaborating on study execution through clear communication, O’Boyle says. “You could work with a small or a major CRO, but if you don’t have strong communication between all parties, your study is going to struggle. Just because you outsource something doesn’t mean you’re not accountable for it.”

For rare disease clinical trials, the number of required vendors depends on internal capabilities, finances, and study timelines, she continues. A company’s infrastructure determines if studies include a few, or dozens, of partnerships.

For clinical trials of any stripe, sponsors need to be visible and stay connected to investigators, study coordinators, and participants and their support systems (i.e., family and advocacy groups), O’Boyle stresses. “Doing that well requires several ‘touchpoints’ so everyone involved feels heard, and it is important that they hear from the study sponsor and not just the CRO or the monitor or the outsourced vendor.”

Additionally, CROs need to encourage the sponsor’s communication with the sites and the monitoring team. CROs may put up barriers to the sponsor’s involvement for a variety of reasons, O’Boyle says, but doing so does not serve any study well. “Sponsors will usually know the study better than any outsourced vendor; therefore, sponsor involvement is a necessity.” 

Case Study

“Unlike other types of clinical trials with a larger enrollment base, rare disease trials provide little to no opportunity for sites to gain from lessons learned and have much less room for error,” says O’Boyle. That makes hands-on monitoring for study compliance and tracking retention vital.

Beyond attention to study setup and initial training, sponsors will always hold the ultimate responsibility for conduct of their protocol, including any outsourced party, O’Boyle continues. Making sure the pathways for communication are established early, and clear with all team members, are the foundations for safeguarding the study.

When every participant screened for a study is unique, predictability may be lacking and it can be hard for the clinical team to fully understand each patient’s experience—particularly in the absence of prior experience working in that rare disease space., says O’Boyle. Advocacy organizations can be instrumental in educating the sponsor’s study team, helping raise awareness, and connecting the study team to the greater community.

Sponsors might consider appointing someone who understands the underlying disease and can be a liaison and communication partner between the CROs, sites, and study participants, she says. This can help build trust among the study team as well as ensure all team members are properly trained and understand multiple study requirements.

Rezolute is developing a treatment for a rare pediatric and adult genetic disorder known as congenital hyperinsulinism and put several communication touchpoints into practice for its ongoing Phase 2b study, notes O’Boyle. These included sponsor attendance at initiation visits, direct communication with sites and monitors across the full lifecycle of the study, sponsor review of entered data in near-real-time, close attention to monitoring reports, and the addition of a patient and scientific affairs role to assist with disease education and help maintain the consistency in some of the many study-related tasks.

Sponsors need to encourage the necessary two-way communication and proper channels to do so, she says, and make sure they receive important questions, updates, and feedback from the CROs, sites, and study participants regarding the study. “Sponsors need to know what is going right, what is going wrong, and what study tasks may require additional training or clarification,” O’Boyle says. Most studies require amendments or process revisions, adding another layer of complexity to an already challenging environment—and further emphasizing the need for strong organization and effective communication.

“Because of the outsourcing and communication channels we had in place for our study, we were able to provide timely feedback and work through the challenges for our sites and study participants,” says O’Boyle. “We reviewed real-time data entry and were able to alert applicable parties to our observations.”

For example, she continues, “We found out that traveling and attending a site visit all in one day was an unreasonable expectation for a patient. We [also] learned about special requirements that participants required for their care.” In both instances, Rezolute was able to find ways to help the participants. “There is no doubt in my mind that these communication channels and extra attention helped with the overall quality of the study and retention of our participants.”

As was observed and reported back to O’Boyle’s team, these direct communications from the sponsor’s team created a “calming influence for sites” faced with participant-related challenges at many points throughout the study, she says. When mitigating challenges that arise in clinical operations for a rare disease trial, “there usually isn’t a next time to get it right.”

The sponsor is always “the source of the messaging” and therefore critical to keep in the communication loop, she reiterates, in terms of maintaining the clinical data, study integrity, and, more importantly, participant compliance and retention. 

“It can be tempting to underutilize, not hire, or not properly resource CROs,” O’Boyle says. “The key is to determine what roles need to be outsourced and then be a partner to those CROs and vice versa. At Rezolute, a company which required extensive outsourcing due to its size and financial capabilities, the team’s approach to overcoming the challenges was through communication and collaboration.”

Editor’s note: Erin O’Boyle will be presenting her session, “Outsourcing Models for Small Biotechs: Focus on Rare Disease,” on the opening day of SCOPE on Feb. 8 in Orlando, Florida.