Thus, all children were not in an equivalent position, but the setup was considered justified because in the absence of disease burden selleckchem Belinostat data and vaccine efficacy data in the region, the trial was deemed helpful for the decision whether or not to introduce Hib vaccination in Indonesia and the whole region. When, instead of clinical efficacy, ??only?? immunogenicity (antibody production) is measured, the rules of equipoise are looser. The comparator vaccine may function more as ??compensation?? to the child in the trial’s control arm. For instance, meningococcal C conjugate vaccine in a pneumococcal vaccine trial, or rabies vaccine in a Japanese encephalitis vaccine trial does not restore equipoise but benefit the child who would not otherwise receive that vaccine.
Age de-escalation Age de-escalation means that phase I and II trials are conducted first in adults, then in older children, and finally, if relevant, in small children. Epidemiology of the disease, the risks/benefits of the vaccine for each age group, and the safety profile are all factors to be taken into account in de-escalation. However, if a new vaccine is only for infants, trials in older children may expose them to unnecessary risks without giving any benefit to these too ??old?? vaccinees. Rotavirus vaccines are good examples in this category. Sometimes adult participants can be used in the first trials, although they are of no help in the efficacy trials. Sometimes there are grounds to use child participants already in phase I trials.
This is the case if the new vaccine would likely cause problems in adults (but not in children) because of prior immunity in adults e.g., DTP vaccine. Participation of adolescents Only a few vaccines as targeted just for adolescents: examples are human papillomavirus (HPV) and herpes virus (HSV) vaccines. However, adolescents may be used in the de-escalation studies before progressing to small children. The participation of adolescents often involves complex legal, ethical issues and operational issues. Informed consent is problematic, because adolescents often have the intellectual and emotional capacity to provide consent, but do not have the legal right to consent. Also their views may not be the same as their parents?? views, and appropriate confidentiality can be difficult to maintain.
An extreme would be a situation in which the youth disagrees but the parents agree the trial, or in which a willing adolescent would be included Carfilzomib in the absence of parental consent. The participation of adolescent girls is further complicated by the potential or soon materializing pregnancy. Not only would it perhaps risk the never young mother and the fetus, but also raise complex issues regarding the consent, confidentiality and legal liability. Routine pregnancy testing of adolescent girls prior to the inclusion in a trial would also have its cultural problems.