Pediatric clinical trials are often designed according to templates established for adults. Yet there are notable differences between adults and children across physiological, developmental, psychological, and pharmacological factors. Consequently, pediatric trials have high discontinuation rates across key research areas. Children differ from adults from a physiological, developmental, psychological, and pharmacological standpoint. As a result, they are far more complex than 鈥榮mall adults鈥� and, from a clinical perspective, there is a significant need for pediatric studies.
Children might metabolise medications at different rates, resulting in sub-optimal therapy, unexpected responses, adverse drug reactions and toxicity. Significantly, these characteristics also vary among children of different ages, developmental stages and cognitive abilities as they transition from infancy to adolescence and on to young adulthood. The tastes, preferences and abilities of pediatric patients must also be considered when specifying drug delivery. Certain children are unable to tolerate particular flavours or textures or even swallow capsules or tablets, and would need the taste of the medication to be masked and an alternative way to ingest the drug. Additionally, outcome measures in pediatric studies must be age-appropriate and developmentally sensitive, unlike adult studies which typically rely on more standardized endpoints.
In response, researchers are increasingly redesigning pediatric trials with age-appropriate methods. Clinical research organizations (CROs) have a key part to play in this, helping researchers ethically connect with – and retain – child patients.
Causes of the discontinuation of pediatric trials
Several notable trends emerged from analysis of GlobalData鈥檚 clinical trials database as of May 2025 when looking at pediatric subjects. The most active areas of pediatric research were central nervous system disorders with 211 trials, followed by infectious diseases at 168, and oncology with 152. These figures point to continued global interest in treating brain disorders, childhood infections, and cancers.
Closer analysis of the number of pediatric trials 鈥� covering those suspended, terminated, or withdrawn 鈥� revealed more about the research landscape. With the highest total of trials, the central nervous system also had the greatest number of discontinuations. However, there are other research areas with greater proportions of pediatric trial discontinuation. Two in five toxicology trials were discontinued, along with 29.1% for metabolic disorders and 27.7% for hematological conditions.
In addition, analysis revealed that more than one in five oncology and gastrointestinal pediatric trials were discontinued at rates of 22.4% and 20.6% respectively. Delving even deeper into trial discontinuation data, the greatest number occurred in Phase IV 鈥� suggesting that late-stage efficacy or safety issues can emerge even after earlier stages have been cleared.
High discontinuation rates are likely due to pediatric trials being more complex, costly, and longer to undertake than studies for adults. This is the result of children representing a vulnerable and hard-to-reach population. Pediatric clinical trials were only legislated in the US in the late 1990s and early 2000s with the Best 色界吧s for Children Act and the Pediatric Research Equity Act.
Despite these acts being in force for decades, funding for US pediatric research trials remains low, specifically in oncology. Only 4% of the billions allocated to funding cancer research is designated for pediatrics. This figure could be reduced even further as the National Institute of Health announced in February 2025 a proposal to cap the grant funding to universities at 15% from its current average reimbursement rate of 27%-28%, according to the NIH Office of Budget. Consequently, pediatric clinical researchers face the challenge of doing more with less.
Increasing child-centric clinical trials
Sample collection is one key area where more must be done with less. Monitoring the safety and efficacy of medication in a clinical trial requires regular blood sampling. However, there is a limit to how much blood can be taken from a young patient. Taking too much could lead to anemia or other complications such as hypovolemic shock. Researchers also need to ensure that patient comfort is considered and smaller-volume phlebotomy supplies and tubes are used. There are other protocols that can be put in place to put pediatric patients at ease during clinical trials. These include ensuring that all medical devices, such as blood pressure cuffs and cannulas, are size and age appropriate, and creation of a research environment that feels safe and non-threatening.
In addition, pediatric trials can integrate pain management techniques that are better suited to younger patients. Research found that pediatric patients can be taught to manage painful procedures such as bone marrow aspirations with with party blowers, resulting in higher levels of coping and lower levels of distress. Another study investigated the difference in pain perception for pediatric intravenous placement between patients receiving topical anaesthetic and no distraction, and patients being . Researchers recorded a four-fold increase in affective pain in the control group.
Ethical guidelines to protect patients must be adapted in recognition of the fact that child patients require more stringent safeguards. For pediatric trials, these guidelines center around the requirements for informed consent, which legally cannot be given by those under 18 in most countries and requires a parent or guardian. Instead, the young person must provide assent or agree to participate. From an ethical perspective, it is imperative that trial information is presented in a developmentally appropriate way.
| Country/Region | Regulatory authority | Requirement/Guideline |
|---|---|---|
| US | Food and Drug Administration | Pediatric Study Plan |
| EU | European Medicines Association | Pediatric Investigation Plan |
| China | Center for Drug Evaluation | Guideline on Clinical Trials in the Pediatric Population |
Beyond the ethical guidelines, there are regulatory requirements that apply specifically to pediatric clinical trials. In the US, sponsors wanting to submit a marketing application for a new active ingredient, indication, dosage form or regimen, and manner of administration must also submit an initial pediatric study plan (iPSP) – the outline of a proposed pediatric study. Similarly, the European Medicines Agency requires a paediatric investigation plan (PIP), a document to ensure that necessary data is gathered from clinical research studies with children.
With all these considerations, clinical trial operators need to modify their process to increase the potential for successful outcomes with child participants. To increase engagement, adherence and compliance, gamification is one technique that can work particularly well with younger patients thanks to the dopamine hits and positive feedback loops. Specially designed games that turn tasks into gameplay with key indicators and metrics logged on a leaderboard can make the repetitive tasks of a traditional trial more enjoyable.
While enjoyment is important, so too are the practicalities of physical access. Decentralized clinical trials (DCTs) can enable many trial processes to be performed remotely, making them easier for pediatric patients and their families.
A child鈥檚 ability to attend a trial in a traditional clinical setting can be negatively affected by long and expensive journeys to trial sites, as well as limited caregiver paid time off and a lack of childcare for siblings. The DCT model has the potential to remove many of these participation barriers for pediatric patients. 色界吧 by Clinical Trial Arena in 2022 found that for trials recruiting in high-income countries, 11.6% of all pediatric studies had a decentralized element compared to 8% of non-pediatric trials.
Clinical researchers may not always have the expertise to run DCT elements and redesign their trials in the most child-centric manner. However, CROs such as Caidya have extensive experience in working with pediatric patients. Offering full-service support throughout all the phases of a clinical trial, Caidya can assist with the engagement, retention, and recruitment of younger patients and their families. Working alongside clinical centers and patient advocacy groups, the company can also support optimal site selection to attain maximum reach. Furthermore, with knowledge gained from conducting similar studies, the company can ensure that the pediatric studies are compliant with regulations and observe ethical guidelines.
A concerted effort on several fronts is required to address the equity gap in clinical research that leaves infants, children and adolescents pharmacologically underserved and exacerbates health inequalities. It is critical that funding for pediatric clinical trials is increased and those that do take place have the highest chance of success.
By leveraging the proficiency of CROs with experience in pediatric trials, researchers can harness vital solutions to conduct faster, cost-efficient trials that comply with regulatory and ethical guidelines. Most importantly, these trials put the needs of children first.
To learn more about Caidya鈥檚 clinical trial solutions for pediatric studies and beyond, download the document on this page.
