Conducting Phase I studies is always complex. At this stage in clinical research, you are examining the tolerability of the drug. The efficacy of the treatment itself is considered but patient safety is paramount. Dosing is not established yet, so researchers need to dose participants slowly and observe carefully. Whenever you combine adult patients with pediatric or adolescents, the complexity of dosing is compounded.
For example, if you are doing a skin prick test for allergies on a 200-lb man, how can you compare his reaction to that of a 40-lb little girl? The differences are huge. Weight and age surely come into play, but how? Are the reactions exponential to one another or linear? Comparing lab results is impossible. It takes massive amounts of data to draw a reasonable and statistically significant answer to that query. However, when a drug is new, researchers do not have that volume of data available to them.
This was an issue we encountered in a recent Phase I study to assess subcutaneous immunotherapy in adult and pediatric subjects with peanut allergy (read about it here). The dosing schedule was very complex because we had three different age groups and dosing was based on individual patient reactions. At each dosing, the researchers had to choose whether to maintain the same dosage amount, increase it, or scale it back.
Furthermore, younger patients have additional complexities. In the aforementioned case study, the Data Safety Monitoring Board (DSMB) rigorously reviewed the research throughout the course of the study. It conducted periodic safety reviews (3 DSMB meetings with recommendations) between cohorts with increasing complexity, moving forward from adults to adolescents, and then the pediatric population. In addition, Pulmonary Function Tests or PFTs were an integral part of the study, but these tests were especially difficult to obtain from the 5-12 age group since the majority of kids could not follow the instructions to perform PFTs in the way adult participants can. Ultimately, we had to clarify PFT issues in the pediatric cohort. This extra step would have been avoided in an adult-specific study.
Consent also becomes an issue when combining adults into a protocol with adolescent and pediatric patients. While the standard varies in different countries, it may also vary by state or country. For instance, in the United States, some states allow a single parent to give consent for an underage patient while in other states, both parents are required to sign off. There may also be issues with time out of school and compliance.
In general, Pharm-Olam recommends that study protocols be divided by age groups, with pediatrics kept separate from adult populations. At the sponsor request, it is possible to combine different ages, but individual researchers and investigators need to have deep knowledge and experience in the subject area for the study to be successful.