What are the key considerations when planning and conducting pediatric clinical trials?
In order to plan and conduct pediatric clinical trials we need to address the unique ethical issues. Children require a higher standard of ethics, regulatory and developmental consideration. Since young children cannot provide consent themselves, we must rely on the parent and legal guardian for consent. Obtaining informed consent from the legal guardian versus the child depends on the age of the patient we want to enroll. For example, although a twelve-year-old cannot legally consent to participating in a trial, they can still provide assent, showing their willingness to be involved.
The key aspects to focus on are obtaining the correct informed consent, minimizing risk, adhering to pediatric-specific regulations, adjusting the dose based on pediatric pharmacokinetics – which are different than adult pharmacokinetics – and designing the study appropriately for the disease you are working in. For a genetic rare disorder, you might need to deal with a smaller population. Also, when you plan the study, you need to make sure the drug that you would like to utilize is in a child friendly formulation.
And you may need to adapt the endpoint, as each enrolled child is of a different age, which can affect the implementation of the trial. Recruitment and retention require a family-centered approach: you need the family or caregiver to understand what we are studying and how it can benefit their children or not. The safety monitoring needs to be thorough, including long-term follow up. You need to collaborate with pediatric experts. You need to plan all of this in advance. Multiple input from different sources is the key.
How is the design of pediatric clinical trials different from that of adults?
In a pediatric trial, we need to address children’s unique physiology. You need to focus on ethical needs and ensure you have consent from the parent. The safety profile needs to be solid and long-term follow up is required. Dosing in pediatric trials is different than adult trials because you need to dose based on weight or body surface area, and you need to understand pediatric-specific pharmacodynamics. For safety, most of the time you do a Phase one study in healthy adults and then go to Phase two and Phase three. The regulatory authority needs to make sure that your drug is safe before going into pediatrics. Also, the endpoints need to include growth and developmental milestones because a child is not an adult.
What approaches have proven successful in recruiting pediatric patients for trials?
To improve recruitment, you need to reduce barriers for families. You need to build trust and truly engage with advocacy groups and the physician taking care of the patient. You must create a child-friendly situation, especially in how you put the protocol together. The strategy is to involve the health care providers who can increase recruitment. You need to emphasize site selection with a strong pediatric network.
You also need to support the family through reimbursement and logistics by working with the trial’s principal investigator to schedule visits and provide incentives for travel and hotel. You need to make sure they understand how the drug can help their children and make it meaningful to them. And then you need to minimize patient discomfort through less invasive procedures. Also, nowadays, we have social media campaigns and telemedicine, which you can use for community outreach and to raise awareness about the trial.
"You need to build trust and truly engage with advocacy groups and the physician taking care of the patient."
How can CMOs effectively partner with advocacy groups?
First of all, when planning the clinical trial, you need to know if there is a disease-specific advocacy group for the area you want to study. You need to engage them very early to increase education, foster trust and integrate patient-centered insight into the trial design. The input from the patient and family advocacy groups are very important. Especially in rare diseases, these advocacy groups network with parents and children as well as physicians in the community. Their input can lead to the trial’s success.
You also need to continue to have a long-term partnership. By continuing to work with advocacy groups and the community and continuing to transition patients to long-term safety follow-up, you make your pediatric trial more patient-centric and more likely to effectively address the unique challenges of young patients.
What are some common misconceptions when it comes to conducting clinical trials with pediatric populations?
All the time, you hear the misconception that children are just small adults. A lot of CMOs who start in pediatric trials assume the trial will be risky and that it will be very hard to convince parents to get consent for their children to participate. You need to understand that children have a unique physiological need requiring a specific study protocol. If you strictly minimize harm and effectively inform parents about benefit and risk, many will be open to consenting for their children to participate.
Relying solely on adult data is not sufficient. Having some adult data does not mean you can proceed to pediatric trials right away. More data may need to be collected. Even though they can be more complicated, with proper planning pediatric trials become much more manageable. Lastly, parents are often motivated, not just by the immediate benefit to their children but also by the potential to benefit others in the longer-term as well.
"By continuing to work with advocacy groups and the community and continuing to transition patients to long-term safety follow-up, you make your pediatric trial more patient-centric and more likely to effectively address the unique challenges of young patients."
What advice would you give to a CMO getting into pediatric clinical trials?
First of all, you need to understand pediatric needs. Get to know the specific physiological and developmental needs of children. This is hugely different from adults. Engage experts, build advocacy relationships, and prioritize ethics. The IRBs pay more attention generally and also specifically to the right to participate for pediatric patients. We need to communicate very effectively to all different stakeholders. The design must be child-friendly, have long-term safety monitoring, be adaptive and focus on recruitment and retention. As your trial continues make sure to update the different stakeholders.
As someone who has run these trials for a long time, I tell people that you need to be patient and persistent. There will be challenges that may require you to change or adapt trials but if you have the patient in mind, you will achieve the best outcomes.
What valuable lessons have you gained from your experience in pediatric clinical trials?
Child-centric design is crucial. Children and adults are different, so when you design the trial, you need to have those differences in mind. You need to engage the family and patient advocacy groups early, as well as experts in the community who can encourage patients to participate. Effective communication is key. Even before you get into trial design, you need to start with ensuring patients and their families understand disease state and bring them awareness – especially for rare diseases.
Long term safety monitoring is a must. And you need a flexible trial design and recruitment period. While the company wants to recruit patients as quickly as possible to save costs, it isn’t that easy. We need to stay updated with regulations and take a multidisciplinary and collaborative approach to everything we do. Include diverse expertise from experts, primary care providers, specialists, patient advocacy groups, families, etc. The keys to succeed are thoughtful trial design, effective communication and strong partnerships with all different stakeholders.
"The keys to succeed are thoughtful trial design, effective communication and strong partnerships with all different stakeholders."
Anything else?
Patience and persistence will lead you to success.
