Applied Clinical Trials
Sandra Pagnussat, of QPS, explores strategies to help combat the unique set of challenges that pediatric trials present.
More pediatric clinical trials are being conducted today than ever before. Since the introduction of the FDA Safety and Innovation Act (FDASIA) in 2012, more than 436 separate trials have been performed to study the affects of drugs on children. These trials are long overdue. Many drugs that are approved for use in adults-and are known to work for treating children-have never gone through trials to be approved for use in pediatrics. In fact, according to the FDA, only about 20 percent of drugs used today have been labeled for pediatric patients. This has created challenges for treating physicians and their patients. Fortunately, now that more drugs are being studied and approved for use in children, there will be more options available to treat pediatric patients.
Pediatric clinical trials present a unique set of challenges that do not exist in adult trials. Because of this, it is important for studies to be designed and conducted with the needs of the pediatric population in mind. Here are five strategies that can help make pediatric trials more successful:
Attracting enough participants to make a pediatric trial statistically relevant can be extremely challenging. Parents have reservations about subjecting their child to investigational treatments that might not produce the results they hope to achieve. Not only is it more difficult to recruit patients for pediatric vs. adult trials, but the risk of trial participants dropping out prior to a trial’s completion is higher among pediatric populations. Some patients or families will find trial participation too rigorous and ultimately choose not to continue treatments through the duration of their trial, so it is necessary to begin with a larger than needed pool of participants when conducting pediatric trials. Marketing and advertising can help generate attention for trials and fulfill the need to recruit an adequate number of participants. Of course, media buying and producing advertisements for television, radio, print or social media channels requires budget. And it costs additional money to have recruiters in place to work with families who respond to advertisements, answer their questions and enroll trial participants. Failing to allocate the right amount of money for advertising and recruiting makes it more difficult to find and secure a sufficient number of participants for trials. However, when pharmaceutical and biotech companies set aside budget for marketing trials directly to the parents and caregivers of pediatric participants, they are more likely to successfully complete a statistically relevant trial.
Timing plays a key role in the success of drug trials. Trial participants must be available for the clinical visits and treatments set forth in a trial’s parameters. With pediatric populations, there are several timing considerations that typically are not issues with adult trials that need to be considered when designing trials. One example is school schedules. Children can’t miss school excessively to participate in trials. Unlike adults who may have some flexibility in their work schedules, children can’t dictate what hours school is in session. Designing trials with this in mind is important. When trials can be conducted during times when children have breaks from school-summer, spring break, holidays-they have higher rates of success. Offering after school time slots for trial participants to receive clinical treatments may also increase a trial’s success. Additional factors such as parents’ work and siblings’ schedules can impact the availability of pediatric trial participants along with parents’ willingness to fulfill trial requirements. Whenever possible, it is important to design pediatric trials with these factors in mind.
Considering daily routines and schedules is just one part of setting realistic timelines. Keeping the overall length of pediatric trials to a minimum can prevent dropouts and boost trial completion rates. Pediatric patients-and their families-may not be able to tolerate lengthy trials. Limiting trials to a maximum of four or five months is ideal. Pediatric patients may also be less tolerant of complex procedures that take place during long treatment sessions-for example, over the course of a full day. So, rather than requiring full-day treatment sessions like those that are more common in adult trials, it is advisable to keep clinical visits for children to no more than a couple of hours.
An obvious difference between adult and pediatric trials is the need for parental permission to participate. Adults can give their own consent to be treated, but for children to participate in trials, permission must be obtained from parents or guardians. Whether a pediatric trial requires permission from one or two parents impacts the number of eligible potential participants. Many circumstances make obtaining permission from two parents (rather than one) difficult. Pharmaceutical and biotech companies will almost always have better success recruiting participants for pediatric trials if they stipulate that permission is only needed from one parent or guardian.
Pediatric trials should be as simple as possible for participants and families to complete. One way to simplify trials and make them more viable is to minimize the inpatient component. Instead of requiring frequent clinical visits from participants, pharmaceutical and biotech companies can explore opportunities to observe and capture information from pediatric trial participants outside of the clinical setting. For example, children participating in trials related to the management of ADHD have been asked to record journal entries at home. This allows for fewer clinical visits, while still capturing critical data. Beyond journals, there is potential to leverage remote monitoring devices-like blood glucose monitors or heart rate monitors-to take readings and report data during trials. Utilizing remote monitoring devices may allow pediatric trial participants (and family members) to participate with fewer in-person clinical visits.
Another pediatric-friendly protocol is to shorten the placebo period in blind trials and offer participants an extension. If parents know their child will eventually receive a treatment, even if the child initially received a placebo, they may be more likely to have their child finish a blind trial, reducing dropout rates. Therefore, blind trials should offer a guaranteed extension to allow all participants to receive treatments. Offering this helps patients feel more confident that participating in the trial is worthwhile.
Ultimately, if pediatric trials put too much strain on families, participation will dwindle. However, if parents and other caregivers are offered support throughout a trial to help minimize the disruption to family life, trials may be more successful. When conducting a pediatric trial, it is important to have coordinators who are good at communicating with not only children, but also parents. Parents who are concerned about the wellbeing of their child may ask more questions or request more thorough explanations of clinical procedures than what is typical of adult trial participants. It is important for pediatric trial coordinators to be patient, friendly with children and adults and adept at communicating with parents.
Of course, showing support for caregivers means more than communicating with them regularly. Fully supporting caregivers requires efforts to make trial participation as easy as possible during and between clinical visits. For example, parents and other caregivers will have an easier time and be more comfortable during clinical visits if they have a dedicated space to wait during treatments. Parents may have other children with them who need to be entertained or fed, or they may need to spend time catching up on work on their laptop. By providing a comfortable area for caregivers to maximize their time during clinical visits, in-office treatments become less inconvenient – a strategy that increases completion rates.
There will continue to be a demand for pediatric trials that require large numbers of parents willing to enroll their children to participate in trials. Recruiting and supporting these young volunteers and their families requires a unique approach. Children aren’t little adults – select a CRO that understands the unique requirements of pediatric trials. Designing child-friendly protocols are essential to the success of your trial.
Sandra Pagnussat, MD, serves as a full-time primary investigator for QPS