Pediatric protocol development is complex
Pediatric protocol development is significantly more complex than simply modifying a corresponding adult protocol for the age of the patient. There are numerous types of pediatric trials and trial designs depending on the objective of the investigation. Although these trials designs are not unique to pediatric studies, there are pediatric specific elements that need careful consideration. Some common trial types and trial designs are listed below:
- Pharmacokinetic (PK and PK/PD) studies
- Efficacy, pharmacodynamic (PD), safety studies
- Monotherapy, or add‐on (combination), or multiple doses.
- Parallel group, or Cross‐over
- Multicenter, single center
- Blinded or un-blinded trials
- Controlled or uncontrolled trials
- Consecutive phases or periods
The following approaches may also be of special interest in pediatric trials:
- Adaptive Trial Designs. A technique that allows modifications to be made the trial while it progresses based on predefined rules. This approach may help decrease the number of children that would be required to participate in a trial.
- Age‐Staggered Inclusion. In order to protect the most vulnerable participants, the trial starts in older children before including the younger groups.
Pediatric trial protocols should address the same design elements typically included in adult trial protocol (see ICH E3) and adopt equivalent quality standards. There are a number of specific needs that need to be considered and incorporated into the design of pediatric protocols. These include features such as:
- Patient assent (if feasible)
- Informed consent of one/both parents.
- Age-appropriate and therapeutically-specific endpoints
- Additional safeguards for children that address risk vs benefit (according to21 CFR 50 subpart D)
- Detailed monitoring and safety safeguards that include rescue plans if appropriate
- Justification for the inclusion of a placebo or sham procedures
Protocols should also strive to minimize the number of invasive procedures such as blood draws for routine labs and PK/PD measurements. The incorporation of sparse sampling designs and PopPK analyses to minimize the frequency and volume of blood draws is therefore highly desirable.
Careful attention should also be paid to the development and use age-appropriate formulations that are palatable and acceptable for use in different age groups. Factors such as breast feeding versus formula feeding in newborns and infants that may impact gastric emptying time, may also be relevant for certain drug administered by the oral route.
The availability patients (particularly in rare diseases) from both an enrollment and statistical analysis perspective should also be considered in the early planning phases of protocol development. Also, complex protocol designs may pose a significant barrier to enrollment especially if the protocol places unreasonable procedural demands on both patients and staff.
KinderPharm’s pediatricians, pharmacologists and clinical operations teams work together to design well thought out protocols that strive to minimize the burden on patients and sites whilst maximizing the quality of the data to support pediatric labelling.
Contact us to discuss your pediatric protocol development needs