• Top
• Introduction
• Diabetes
• Sepsis
• Conclusion

Introduction

As children often suffer from the same diseases as adults, a majority of substances, although tested primarily in adults, are expected to be efficient in the pediatric population. In order to extend drug development for this age group, a first step in drug development is to determine the needs of children with a certain disease. However, pre-clinical and clinical drug development in pediatric patients is a challenge, due to the fact that this age group is, in itself, heterogeneous with regard to physiology, pathomechanism, needs and pharmacokinetics depending on age.

Diabetes

Diabetes mellitus type 1 is an autoimmune disease and, unlike other pathologies, has its peak onset during childhood and adolescence, but infants and toddlers can also be affected. As in adults, efficient therapy is primarily aimed to optimize euglycemic control without acute side effects in order to minimize long-term sequelae. Intensified insulin therapy has become a standard in diabetic care for all ages. However, when rapid acting insulin analogues became available to treat insulin dependent diabetes in adults aimed to increase treatment flexibility, children with diabetes were thought to profit from those substances as well. In particular, adolescents are usually more compliant if they are offered more treatment flexibility, and on the other hand small children, who sometimes refuse to eat after injection of regular insulin being at risk of hypoglycemia, may profit from the use of rapid acting insulin analogues even applied after a meal. Clinical trials performed in different age groups comparing regular insulin or rapid-acting insulin analogue in combination with long-acting insulin suggest that rapid-acting insulin analogues result in a similar control of glucose metabolism as regular insulin while increasing the individual treatment flexibility.

Sepsis

In contrast to diabetes type 1, having its peak-onset during childhood, severe sepsis occurs during the entire life span. Although the incidence of severe sepsis is higher in adults compared to children, mortality ranks 9^th in children from 1 – 4 years of age. Despite the fact that the need of treatment optimization in severe sepsis has been accepted in children based

on the data collected from adults, the design of clinical trials may raise a variety of problems. Children differ significantly from adults with regard to physiology, vital sign parameters defining systemic inflammation, co-morbidities, cardiovascular organ failure and the outcome of severe sepsis. In addition the spectrum of underlying infections, such as B-streptococci infection in neonates or sepsis due to Neisseria meningitidis infection in older children, and consequently the course of the disease can be very different among the various pediatric age groups. Therefore, the primary endpoints of a clinical trial on sepsis treatment may be different between children and adults. While sepsis mortality reduction in adults may account for a primary endpoint, mortality in children is significantly lower and, consequently the number of patients necessary for statistical power would be unachievable high. In contrast, for this specific age group improvement of organ dysfunction, such as shortening of artificial ventilation and consequently reducing possible negative effects on pulmonary parenchyma, may rather be the base to test for efficacy of sepsis treatment.

Conclusion

Clinical trials in children have to be carefully designed with regard to specific physiology and pathophysiology of a disease and the specific needs of each age group within childhood.

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