How sites manage pediatric gene therapy trials

Sponsors must design trials to meet regulatory requirements and be convenient and relevant for patients. But what about sites? Principal investigators (PIs), nurses, study coordinators, project managers, and data entry technicians at sites work on the front lines of clinical research and patient care. Gene therapy trials are complex and, when they involve pediatric patient populations with a rare disease, feasibility is paramount. Yet these trials have produced exceptional results, transforming the lives of patients and families desperate for a cure. Academic clinician Claire Booth talks about the lessons she has learned at one of Europe’s largest and most experienced gene therapy research sites.

The key to success is teamwork

We’re a group that has worked together for many years with a consistent but agile structure. The research nurses, physicians, lab and manufacturing staff, project managers, and data managers operate as a team. We meet weekly to discuss our trials, for example, which patients are coming up for visits, what samples do we need, and when we are manufacturing products We are a well-oiled machine. We have gained a lot of practical experience over the past 15 years as a team and are constantly learning, adapting, and improving. 

We’re a group that has worked together for many years with a consistent but agile structure. The research nurses, physicians, lab and manufacturing staff, project managers, and data managers operate as a team.

Claire Booth, M.B.B.S., F.R.C.P.C.H., M.Sc., Ph.D.
Mahboubian Professor in Gene Therapy and Paediatric Immunology  (UCL) and Consultant Paediatric Immunologist, Great Ormond Street Hospital (GOSH)

The biggest challenges are not necessarily clinical

Project and data management often pose greater challenges than clinical or patient-related issues. Our project managers provide tremendous regulatory support. They manage protocol amendments, sponsor monitoring visits, data audits, trial infrastructure issues like eCRFs, and sample shipping. Cell and gene therapy trial protocols often have as many as 10 or 15 amendments, requiring significant paperwork and attention to detail from project managers. 

Monitoring can be challenging for sites

Preparing for monitoring visits from sponsors and responding to the feedback we receive contributes significantly to the team's workload. Project managers, research nurses, investigators and data managers often have to set aside a lot of time for this. I don’t know how to alleviate this problem, but different solutions may work for different sites. For example, having more frequent monitoring visits could reduce the number of queries per visit, so work is more spaced out, allowing time for other projects. However, this can sometimes feel like a visit every other week. If you space out the visits by three or six months, site staff may need to spend more time sitting with monitors to review data and answer queries, which may not suit a team either. One solution that has worked—but is not always possible—is a dedicated data manager with exhaustive knowledge of the trial protocol and case report forms. That person sits with the monitors, leads them through the data, and resolves the queries in real time. 

Patient needs must be considered 

Patient-reported outcome (PRO) measures are a very topical subject across countries. Too often, PROs have been a tick-box exercise in clinical trial design and approval. Regulators and payers routinely ask trial sponsors whether they have included PROs in their trial design. However, a deeper dive is required. Do the chosen PROs capture relevant information for the patients and families? In discussions with patient advocacy groups (PAGs), I’ve heard from parents that ‘classical’ trial outcome measures may not mirror what is essential to their children’s lives. For example, if a child has a blood disorder with low platelet counts and is at risk of bleeding, the child and parent may not value the trial’s primary endpoint of a normal platelet count. They may care more whether the child can play a sport or go to school without worrying about having a major bleed. Regulators often insist on definitive evidence in the form of a number, a level that is or is not reached. That’s understandable, but it may not capture data crucial to a patient’s quality of life. Trial designs have not adequately incorporated patients’ and caregivers’ perspectives in the past, but this is changing. 

Remote patient monitoring has limits

Remote patient monitoring offered a positive revolutionary change for patients, and it can be. But we can sometimes miss important clinical data when we lose the physical connection with our patients. Face-to-face interactions are still valuable, particularly early in a study. Post-COVID, though, patients have become used to this approach and like that they can be ‘seen’ in their local center and maintain contact with the trials team. They prefer the remote approach because it reduces the burden of participation.
 
But caring for a patient is about more than blood samples or data trends. It’s about their quality of life, the quality of their family life, and general health. It’s challenging to capture a genuinely holistic approach via video or telephone. This is true for trials and general checkups. You may see a patient face-to-face for the first time in a year and say, how long have you had that lump on your neck? And the patient says what lump on my neck? And that lump could represent a significant health problem. You don’t get the detail of how a patient is doing remotely, even through completed patient diaries. 

Remote data monitoring also has limitations. Data monitors want to speak to the people doing the data entry and the PIs and nurses dealing with patients in person. If a monitor spots a recurrent problem, it’s often easier to sort that out face-to-face and get to the root cause. 

Patients deserve better communication

Patients find the lack of communication between clinical trial sites, sponsors, patients, and PAGs frustrating. They feel a lot of effort goes into the startup of trials, with a flurry of activity to boost recruitment and build excitement. And then they don’t hear updates for 6, 12, or 24 months. They might even read about developments in the newspaper before they hear anything about the results of the trial they enrolled in. So we’ve moved patient communication higher on our agenda. Patients should not find themselves in an information vacuum. 

Contributing Expert