Historically, children were considered ‘miniature adults’, meaning medications were only tested on adults before being deemed safe for children. However, children do not react the same way as adults and chronic childhood illnesses are continuing to rise. It is now thought that 1 in 5 children in the USA have a chronic illness that affects their daily function, making pediatric clinical trials essential in modern medicine.
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What are pediatric clinical trials?
Pediatric clinical trials are research studies designed specifically for children, aiming to assess and establish whether a new intervention is safe and effective for children. Many pediatric clinical trials focus on diseases and illnesses specific to children to discover new therapies and treatments for them.
Many advances in child health have resulted from successful pediatric trials. For example, childhood cancer survival rates have increased from 28% in the 1960s to around 80% today, through the use of these trials. Participation in pediatric clinical trials can help other children with the same condition by contributing to the wider scientific landscape and helping research teams find better and more effective treatments in the future.
Why are pediatric clinical trials important?
Clinical trials are very important, especially when it comes to pediatric research. Researchers need to study new treatments in children because children do not react like adults. Therefore treatments tested in only adults are not always suitable. When a treatment that has only been tested on adults is provided to children, it is known as ‘off-label use’. This means doctors must rely on the drug label (or prescribing information) to establish how to use it safely and successfully in children.
There is a significant requirement for more pediatric studies because the physiological, psychological, developmental, and pharmacological characteristics of children differ from adults. Children might metabolize medication differently, which can result in suboptimal results, unexpected outcomes, adverse drug reactions, or even toxicity.
Pediatric clinical trials aren’t just important for testing new medications. Clinical trials for medical devices are also of interest since some medical devices, such as glucose monitors for diabetic children, may need different settings and algorithms to that of adults to ensure safe and effective use for children.
Interested in the steps medical devices must take before being used by patients? Read all about the phases of clinical trials and how they ensure innovation is safe in our detailed guide.
A successful pediatric clinical trial can create an improved standard of care for children with certain conditions while supporting the development of new treatments for various childhood illnesses and diseases.
Differences between clinical trials for children and adults
There are several differences and considerations that researchers must think about when designing clinical trials for children. Because they often differ from traditional clinical trial designs with adult participants, a number of factors must be considered when designing a pediatric clinical trial.
The main considerations for pediatric clinical trial design include dealing with small sample sizes, ensuring teams have specialist pediatric knowledge, meeting regulatory requirements, and ensuring appropriate formulations are delivered.
Pediatric clinical trials have smaller sample sizes
Pediatric trials often have much smaller sample sizes than those in adult clinical trials. Research has shown that only 38% of 736 pediatric trials published from 1996 to 2002 had a sample of more than 100 participants. A key reason for smaller sample sizes is that pediatric recruitment is more difficult, largely due to the lower burden of disease and illness in children.
There has also been a generalized reluctance to involve children in clinical trials, particularly by parents and doctors over fears of harming children with exposure to uncertain treatment effects. Parents often fear the assignment of their child to a placebo arm or treatment arm which is later proven to be less effective than currently available options.
To mitigate the small sample sizes in pediatric trials, there have been major advances. Researchers have developed statistical methods and collaborated with specialist multinational groups and pediatric clinical trial networks to pool data and resources.
Specialist pediatric knowledge is required
While general medical or specific condition knowledge is essential in adult clinical trials, it is important that pediatric clinical trials also enlist the help of specialist knowledge in children’s health. Sponsors must be aware of the pediatric population’s specific needs as early as the trial design process so they can make sure the trial is designed and conducted in a way that meets these needs.
Professionals with pediatric experience, either in a healthcare or clinical trial setting, should be involved from the very beginning so they can impart wisdom that will enhance the trial’s chances of successful recruitment and results.
Regulatory requirements still need to be met, but may differ slightly
Research teams and sponsors must ensure they abide by regulatory requirements for pediatric studies which may differ from general regulations. For example, the criteria for IRB approval of research involving children is more restrictive, focusing on assessing the risks and benefits for children. Likewise, pediatric expertise is required for ethical review and ensuring the benefits, risks, and burdens of research on children are thoroughly assessed.
Pediatric clinical trials also require modifications to the environment, equipment, and medication to meet the needs of children. For example, modifications might include accepting smaller volumes of blood and fewer blood draws than that of an adult trial or ensuring children spend less time on-site or in an exam room due to their limited attention spans.
Appropriate medicine formulations must be devised specifically for children
If a study is testing a new medication, the appropriate formula must be developed specifically for children. Formulations must be both palatable and easy for a child to consume, which often means using liquid or chewable medications.
When there is a lack of formulations appropriate for children, the use of adult forms such as tablets and capsules can be problematic for young children who may be unable to swallow tablets. Crushing tablets or opening capsules may compromise the palatability and bioavailability of the medicine, thus affecting the trial results.
Phases of pediatric clinical trials
Pediatric clinical trials mostly follow the same phases of clinical trials as those involving adult participants, but with modifications as previously mentioned.
Phase I trials are discouraged in children because they typically test the safety and efficacy of a new intervention for the first time, which means the effects are unknown. However, in children with life-threatening conditions or severe illnesses, phase I trials are more acceptable if there is no proven treatment or when standard treatments have failed.
Phase II trials are sometimes conducted in children if appropriate and thorough safety and efficacy data has been collected previously. While phase II trials focus more on the effectiveness of an intervention, they also concentrate on safety and so generally, medicinal product testing in children is deferred until phase III, as the risk in this phase is much lower. Although this deferral is designed to protect children from exposure to unnecessary and unknown harm, it often means a delay in access to potentially useful medications.
Phase III trials, mostly conducted as randomized controlled trials, compare the intervention with either standard and currently available treatment or another effective therapy. They may also compare against a placebo if there are no established alternatives to establish unbiased treatment effects.
Phase IV post-marketing trials are not usually conducted in children but this is often dependent on the type of intervention and its use case.
How are pediatric clinical trials carried out?
Pediatric clinical trials follow a detailed plan called a protocol, much like regular clinical trials, although specific safeguards will be in place to ensure the rights and well-being of children. This protocol is carefully designed to increase the opportunity to achieve useful results and to answer specific research questions.
Depending on the condition or illness being studied, children may receive the investigational intervention alongside existing treatments they are taking. The exception to this is if the risks of stopping the established treatment are low. For example, a child who takes a particular medication to control seizures will likely continue this treatment with the new intervention.
Concerned about how safe clinical trials really are? Learn everything you need to know about participant safety, regulations, and protections in our detailed guide.
How are pediatric clinical trial outcomes measured?
Outcomes for a pediatric clinical trial will be measured similarly to other clinical trials and depending on the trial type and objectives, with some restrictions. For example, some clinical trials can use wearable technology or remote options to measure outcomes, but this is not always possible with pediatric clinical trials.
An important consideration for outcomes measurement is the fact that children may grow and mature through developmental stages. This means it may not be suitable to use the same measures when comparing children of different ages and stages. Trials that include a wide range of pediatric ages will need to adjust dosages by weight or body surface area and adjust the measurements for outcomes accordingly.
What are the benefits and risks of a pediatric clinical trial?
Pediatric clinical trials are conducted to better understand childhood illnesses and discover new treatments for them. However, as with any new or existing treatment, there are both benefits and risks to pediatric clinical trials.
Potential benefits
Clinical trials for children can provide a number of benefits, from access to new treatments to additional care. Additionally, the benefits of a clinical trial may apply to the participant and their family, as well as research teams, the wider medical community, and children with the same condition in the future.
The key benefits of a pediatric clinical trial include:
- The opportunity to try new drugs or treatments that are not yet publicly available and that may be more effective
- Access to more information about the illness or condition as new discoveries are made
- Access to additional care from specialist caregivers
- Closer monitoring or extra testing that may not be a part of a child’s regular care
- Information gathering that could benefit other children with the condition in the future
Potential risks
Like any clinical trial, risks can occur. In pediatric trials, safeguards are in place to minimize risk as much as possible, but there is always a chance of adverse effects.
The potential risks or negatives of a pediatric clinical trial include:
- Unpleasant treatments that may be uncomfortable for children
- Harmful side effects which could range from minimal to serious
- The new treatment may be ineffective against the condition
- Frequent visits to a study site, more blood tests and treatments, or hospital stays can take up a lot of time and be tiring for children
- Complex medicine dosing or procedures can be confusing for children and potentially affect their quality of life.
Why participate in a pediatric clinical trial?
By participating in a pediatric clinical trial, children can play a part in supporting medical professionals to develop medicines, treatments, and vaccines that are safe and effective for children. These studies are the cornerstone for increasing medical breakthroughs and cures, making them extremely valuable.
As most clinical trials use adults, the results are not designed to meet the unique needs of children. This makes pediatric clinical trial participation highly important as it means treatments can be found specifically for use in children. This research doesn’t just help uncover new treatments, it can also help researchers find ways to make medicine easier for children to consume.
What questions should you ask before enrolling your child in a clinical trial?
Before enrolling in a pediatric clinical trial, there are several questions for consideration that you should ask your healthcare professional and trial organizers. These include:
- What is the evidence that the investigational treatment might help my child?
- What are the potential benefits?
- What are the potential risks?
- What are the potential side effects of this medicine or treatment?
- How will you check to see if the treatment is working?
- Are there any concerns that the investigational treatment could be unsafe?
- How closely will my child be monitored if there are problems?
- Who do I contact if I’m concerned there is a problem or negative side effects?
- When will I know if my child is receiving the investigational treatment, placebo, or standard treatment?
While every effort is made to ensure participants and their families are fully informed of the trial, its requirements, and potential benefits and risks, asking these questions can help alleviate any worries you may have. It can also help to further your understanding so you can better explain the trial and its purpose to your child.
Looking to cover all your bases? Find out what other questions can help you make an informed choice about joining a clinical trial in our comprehensive guide.
How are children protected in pediatric clinical trials?
Any type of medical research can incur risks, but steps are taken to minimize this in clinical trials, especially those involving children. Before children are enrolled in a clinical trial, there are several people who must review the study details to ensure it is safe and ethical to go ahead. This includes Institutional Review boards (IRBs), who review and approve a research study before it can commence, ensuring children's rights and welfare are protected throughout.
Informed consent from the parent or guardian is also gained before a study begins to ensure children are protected. During this step, everyone involved in the research will be fully informed and aware of the trial’s process, protocols, potential benefits and risks, and how it will impact the life of the child and their family. In addition to informed consent, assent from children may also be required in appropriate cases.
What to expect with pediatric clinical trials
Like adult clinical trials, pediatric studies will all be different and follow different rules depending on the condition being studied and the objectives of the trial. There are several factors you can expect to experience at all stages of a trial with children, such as informed consent, investigational treatment administration, and monitoring.
It’s important to note that your decision, whether to have your child participate, continue in the trial, or discontinue at any point does not affect the medical care of your child.
What to expect before a pediatric clinical trial
Before the clinical trial starts, you’ll be assigned a trial coordinator, also known as a Clinical Research Coordinator (CRC). They are responsible for a number of elements in the trial, including recruitment, obtaining informed consent, ensuring the safety and well-being of your child, collecting and analyzing data, adhering to regulations, scheduling visits with your child, administering interventions, and acting as a liaison for the clinical site. You will likely be in contact with them for the duration of the trial.
Your doctor will also be a key contact during the clinical trial in addition to medical professionals assigned to your child as part of the study. They will be on hand to answer any questions you may have, while also supporting the monitoring of your child to see how they respond to the new treatment.
What to expect during a pediatric clinical trial
A child’s experience during a pediatric clinical trial can vary significantly, depending on their health status, the condition being studied, and the type of trial they are in. However, there are a few instances that you can expect to occur during the trial.
In any trial, medical professionals will keep a close eye on your child and monitor them to establish whether the treatment is working or causing side effects. Your child may also be expected to visit the trial site regularly, though the frequency of this will be decided by the research team and explained to you at the beginning of the trial.
Pediatric clinical trials could also require your child to regularly provide blood or urine samples for results measuring, depending on the trial type. However, researchers do try to limit the amount of blood taken and the frequency of blood sampling in children as it can be traumatic for both them and you. These requirements will be explained to you at the beginning of the trial.
What to expect after a pediatric clinical trial
After a pediatric clinical trial, most parents or guardians will be asked to complete a comprehensive exit visit. During this time, researchers will compare the baseline information from the beginning of the trial to where your child is now. They will explain to you how the treatment has affected your child, if at all, and what this means for their condition and the future of the treatment.
The exit visit also provides an opportunity for you to ask any last questions. After this, your child may be monitored at agreed intervals to further assess treatment effects.
Ethical implications in pediatric clinical trials
As chronic illnesses and conditions are less common in children than adults, there are several ethical and clinical concerns surrounding pediatric clinical trials. Many ethical questions in adult clinical trials also apply to studies for children, such as ensuring risk and harm are minimized and adequate protection of participants is ensured.
Researchers often cite a dilemma when finding a balance between the obligation to conduct clinical trials to protect children from the risk of using untested treatments and to protect them against unknown risks associated with clinical trial participation.
How are ethics addressed in clinical trials for children?
In the USA, clinical studies that are funded, conducted, or regulated by the government are subject to a common set of provisions designed to protect human participants in research, including special protections for children. Likewise, the WHO International Clinical Trials Registry Platform (ICTRP) is committed to promoting the conduct of ethical and relevant clinical trials in children by improving access to guidelines, regulations, and trial registration data.
The pediatric population is particularly vulnerable, and this must be considered by researchers when establishing the need for safe and validated treatments against the risk of research. Without this consideration, a pediatric clinical trial should not be conducted. As the primary objective of pediatric clinical trials is to protect children who participate while serving the pediatric population as a whole, any study must have sufficient scientific merit to justify any risks posed to the subjects.
Additionally, clinical trials for children should be carried out according to several key principles:
- Respect for persons – children should be treated as autonomous agents and those persons with diminished autonomy are entitled to protection
- Beneficence – researchers should maximize possible benefits and minimize possible harms
- Justice – there should be a fair distribution of the burden and benefits of research
Ethics are also addressed in pediatric trials when it comes to dosage and medication. For example, when testing drugs such as new anticancer agents, for which as few children as possible should be exposed to doses too low to be therapeutic, data from phase 1 trials with adults may be used. In this instance, the data would be used to guide the selection of a pediatric starting dose and a dose escalation scheme for early-phase testing of the drug.
Regulatory overview of pediatric clinical trials
Like regular clinical trials, regulations are an important consideration in pediatric clinical trial ethics. Researchers must ensure the trial complies with regulatory guidance, as set out by governing bodies, particularly in relation to children.
In the US, the Pediatric Research Equity Act (PREA), enacted in 2003, mandates that companies include pediatric studies in their new drug applications (NDAs) for marketing approval if the drugs are expected to be used in children. Reassuringly, Congress has long provided funding and directives to the National Institutes of Health (NIH) and other agencies to support research on a variety of children’s health problems.
Conclusion
Pediatric clinical trials serve as a cornerstone for evidence-based medicine that has been tailored specifically to the needs and unique characteristics of children. While there is still some hesitation in enrolling children in a clinical trial, there have been significant strides in trial design and regulations to minimize risk and highlight the importance of clinical trials for children.
Not only are pediatric clinical trials beneficial for the wider medical community in helping them better understand certain conditions, but participation can also support other children living with the condition both now and in the future.
FAQs
What do I need to know before I sign up my child for a clinical trial?
Before enrolling your child in a clinical trial, it’s important to gather all the facts about the trial in question. It’s a good idea to first speak with your child’s doctor or healthcare professional. They can help you establish a list of questions to ask the investigator in charge of the trial, enabling you to decide if it’s right for your child.
How do I prepare my child for a pediatric clinical trial?
No matter the age of your child or the trial requirements, it’s important that you help them understand what is happening and what is expected of them. You should let them know that they will need to visit a doctor more often, but also explain why. Although it may be inconvenient and tiring for them, helping them to understand that their participation could help other children like them, can make it seem like less of a burden.