Paediatric clinical trial recruitment is inherently challenging. There are obstacles to trial participation like school schedules, parents needing to take time off work, and finding childcare for other siblings. These challenges make decentralised clinical trials (DCTs) attractive.
There’s an increasing trend of decentralisation in paediatric studies compared with adult trials. So far this year in trials in high-income countries, 11.6% of all paediatric studies have a decentralisation element compared with just 8% in non-paediatric trials, according to Clinical Trial Arena’s exclusive data-driven analysis. Paediatric trials are ones explicitly described as such in clinical trial sources, or the participants are below the age of 18.
While there is promise in decentralisation of paediatric trials, there are also new obstacles that CROs and sponsors must face. The needs of participants under the age of 18 are different across this age spectrum and from adults, and that technology should be adapted to suit the trial participant’s language and comprehension levels. Under-18s have different degrees to their receptiveness to wearing a monitoring device in public.
Transparency is even more paramount to build trust with parents, to encourage them to allow their ward to participate in a decentralised study. Betsy Reid, senior vice president of paediatrics at Premier Research, says: In paediatrics, it is not just the child that is being enrolled, but the whole family.
Trending DCT paediatric trials
In the metabolic space overall, data shows that paediatric trials have a notable DCT rate. In trials recruiting in high-income countries, 14.4% of paediatric trials have a decentralised element compared to 7.5% in non-paediatric studies, according to GlobalData’s Clinical Trials Database. GlobalData is the parent company of Clinical Trials Arena.
Some 35% of all paediatric trials initiated since 2010 in diabetes have been using a decentralised approach, specifically involving blood glucose monitoring, compared to just 16% for non-paediatric trials. People with diabetes are ideal for decentralisation as they are used to glucose monitors, managing their own medication, and monitoring the progression of their disease, explains Anthony Poynton, Premier Research executive director of program delivery for rare disease and paediatrics.
In genetic disorders, decentralisation is also higher in paediatric (9.5%) versus non-paediatric trials (4.2%). Conditions such as Duchenne muscular dystrophy have a high burden on caregivers. Travel arrangements with a patient in a wheelchair can be a challenge, making decentralisation attractive, say Dr Isaac R. Rodriguez-Chavez, ICON senior vice president of scientific and clinical affairs, and Dr Martine Dehlinger-Kremer, vice president, paediatric scientific affairs, also at ICON.
Different paediatric ages have different DCT needs
Each age group cluster within the under-18 age range has its own challenge when implementing a DCT. For example, with wearable devices, it is important to ensure the device is well suited and comfortable for the youngest trial participant to avoid it being removed, says Dr Matthijs Kruizinga, Leiden University Medical Centre resident in paediatrics. It is hard to explain to a two-year-old why it’s important to wear a device for data collection, he adds.
Children between ages six and 12 tend to be excited about wearable monitors, as “everything digital is cool,” Kruizinga says. Meanwhile, teenagers don’t want to stand out in school by wearing a medical-grade device as it may be a magnet for bullies, he notes.
Commercial smartwatches can be used in trials recruiting teens as they are reliable to collect data but also discreet, Kruizinga notes. “Ideally, you would combine the medical-grade device and smartwatches, but then your expenses will go through the roof,” he adds.
Several sources of reported data are needed
When it comes to data reporting–such as via electronic patient reported outcomes (ePRO), electronic clinical outcome assessments (eCOA), or eDiaries–when is a child old enough to do it themselves? Children as young as five can reliably self-report their health-related quality of life (HRQOL) via age-appropriate eCOA, Rodriguez-Chavez and Dehlinger-Kremer say. Children can also report pain intensity themselves. In fact, parent-reported measures shouldn’t replace those done by the child, unless the patient is too young or unable to self-report, they add.
ePROs should have age-appropriate vocabulary and language. It should also take into consideration the participant’s perception of health concept measures, and how reliable the child is in remembering symptoms severity and improvements. Poynton explains that, while the same questionnaire can be used for all age groups, the interface and visuals should be adapted to the different age ranges. “There is obviously an element of cost to design, but it is not like designing an entirely new system for each subgroup of patients,” he adds.
Because patient-reported outcomes are subjective, varying the sources of data is recommended to bolster the integrity of the results. Additional data can come from observer-reported outcome (ObsRO) measures done by parents or caregivers, or performance outcome (PerfO) measures by a trained trial staff, Rodriguez-Chavez and Dehlinger-Kremer say. Objective endpoints, such as psychical activity and heart rate, should also be used to supplement the parent and child-reported data, Kruizinga notes.
Focus on population needs and trust
Performing a paediatric DCT requires an in-depth understanding of the paediatric research space, Rodriguez-Chavez and Dehlinger-Kremer say. When designing a paediatric study, sponsors should work with families or patient advocacy groups to understand patient needs and make it as convenient as possible. “There are certain things you won’t know unless you have a child with certain indications,” Reid adds.
"There are certain things you won't know unless you have a child with certain indications."Betsy Reid
Privacy concerns are at the forefront for parents. Being transparent and providing in-depth information are important to build trust. Still, remote data collection can be a reason to decline a study, despite efforts to explain how the process works, Kruizinga notes.
Building trust is especially paramount if recruitment is done via social media, Reid says. “It is hard for parents to take a leap from clicking ‘yes, I am interested’ on social media and actually getting randomised,” she adds. Sponsors should include information not just about the medication, but also about trial design, procedures, and everything that is going to happen in the study, she says.
Breaking through physical trial sites
There is value in investing in paediatric DCT. There is a small pool of potential paediatric trial participants to recruit from, as children are generally healthy, Rodriguez-Chavez and Dehlinger-Kremer agree. Many paediatric conditions are rare diseases, further shrinking the pool, and patients are dispersed globally, they add.
Decentralisation can be a way to attract potential participants who may typically steer away from a completely brick-and-mortar trial. Decentralisation can increase retention rates in trials, as patients and parents don’t have to visit sites as often. Because children typically don’t want to be in a hospital, using remote monitoring is an attractive proposition, Kruizinga adds.
Decentralisation of clinical trials was expedited by the Covid-19 pandemic, but there is increasing realisation that it boosts equity and diversity, particularly in studies that recruit under-18s. Poynton highlights, especially in paediatric trials, it is important to put the patient first, and if the sponsor can make participants’ experience better, it will always benefit the trial. “Without patients, there's no research.”
- Paediatric trials in diabetes have the highest rate of decentralisation uptake, likely due to patients being accustomed to monitoring their own disease status. Genetic disorder trials also see high uptake due to the demanding nature of caring for such patients.
- The design of the decentralised element should take into consideration the age of the user, how much the user understands the function of the tool, and that it should integrate smoothly with daily life.
- Sponsors and CROs need to collaborate with families when designing paediatric clinical trials. There can be parents skeptical of remote monitoring, but transparency can be a way to build trust.