Wednesday, November 4, 2009
4. ASSESSMENT OF EFFICACY OF NEW MEDICINAL PRODUCTS FOR THE
TREATMENT OF OBESITY IN CHILDREN
It is recommended that the primary endpoint is a change in BMI Standard Deviation Score; however, change in adiposity should also be measured in BMI (%) units4. In adults a 10% weight reduction is accepted as a clinically meaningful effect. However, in the paediatric population the degree of change should be justified by the applicant.
While it is important to obtain statistically significant results, it is also important to consider clinical relevance defined via the responders’ rate. Research in this area is encouraged. In the meantime, justification should be provided for all design approaches to show clinically relevant effects.
Parameters relating to co-morbidities are secondary endpoints and can include improved glucose control, improved lipid profile, enhanced exercise tolerance, better mental health and/or quality of life, reduced use of adjunct medications etc. Choice of endpoints should be justified.
Behavioural changes are considered as secondary endpoints. Validated psychological tools must be used and justification for their use should be provided.
5. ASSESSMENT OF SAFETY OF NEW MEDICINAL PRODUCTS FOR THE
TREATMENT OF OBESITY IN CHILDREN
Safety aspects are dependent on the mechanism of action of the investigational medicinal product. Appropriate safety data should be collected during the entire drug treatment period, which will usually be at least one year, and for the duration of the follow-up period. This data should notably encompass the adverse events related to lipid profile, liver function, cardiovascular system function and rebound phenomenon. For centrally-acting anorectic agents, in particular, it is recommended that special attention and monitoring is afforded to neuropsychiatric events such as depression, sleep pattern and nightmares, assessment of self-esteem, aggression or suicidality. Self-esteem could fall under both the efficacy and safety category.
In growing children height velocity should also be monitored in addition to standard safety evaluations and pubertal development should be assessed by determining Tanner stage at baseline and endpoint. For centrally-acting anorectic agents the abuse potential should be considered and factored into trial design in an appropriate manner. This is especially important in the adolescent age group.
