PEDIATRIC CLINICAL TRIAL ANALYSIS
There is a need for researchers to justify the reason as to why they are conducting the trials. The need of investigation should be weighed against the prevalence of the condition to be treated, the seriousness of the disease, the availability of alternative treatments, the uniqueness of the compound, the conditions seen in pediatrics, the age groups of children, safety concerns in pediatrics and finally the need for pediatric formulations. A brief overview of a few of these is being discussed below.
Suitable pediatric formulation is still in demand by many practioners. The suitability includes palatability, appropriate strength and dose volume, favor and colors and route. Young children cannot swallow tablets, and liquids, suspensions, chewable tablets and suppositories may be needed for children of different age groups. The concentrations of licensed medications may be too high, necessitating further manipulation in the form of dilution with an excipient. The excipients in many liquid formulations may not be suitable for selected patient groups. For example, the propylene glycol content in amprenavir liquid formulation makes it unsuitable for children under the age of 4 to consume it. Severe delayed onset hypersensitivity reaction was associated with formulation of amoxicillin liquid; the reaction may have been caused by the exicipent. Hence manipulation with excipients should be focused as an important formulation aspect .
Pharmacokinetic studies are performed to support formulation developments and to determine pharmacokinetic parameters in different age groups to support dosing recommendations. They are generally conducted in children with a disease, which may lead to higher inter-individual variability than in adult health volunteers, although the data reflect clinical use better. Children are not usually subject to dose escalation studies similar to those carried out in adult populations. Data generation/collection becomes a main concern, hence the use of population pharmacokinetics and a sparse sampling approach is preferred which allow each patients to contribute as few as two to four observations at predetermined times to an overall population. Population pharmacokinetics seeks to discover which measurable pathophysiological factors cause changes in the dose-concentration relationship and to what degree, so that the appropriate dosage can be recommended. There is similar disease progression and response to dosage and the PK/PD relationship of the drug is similar between adults and children, only PK studies and Safety studies are suggested for dose determination.
For most of the drugs, efficacy studies are not carried out for children differently but just cut and copy pasted from adult data. Disodium pamidronate is licensed for use in Paget's disease and osteolytic lesions and bone pain in multiple myeloma and breast cancer in adults, but it has also been used in a variety of pediatric conditions, bone pain in Gaucher's disease, osteogenesis imperfecta, and malignant hypercalcaemia in childhood cancer. Therefore a number of efficacy studies for disodium pamidronate are required to ascertain the efficacy for the disease concerned. The differences in the pathology of the diseases may require different dosage and administration regimens.
Age-appropriate, normal laboratory values and clinical measurements should be used in adverse event reporting. Children with developing systems may respond differently to mature adults; some adverse events and drug interactions that occur in children may not be identified in adult studies. The effects of medicinal products on long-term growth and development may not be apparent, therefore long-term surveillance data may be needed to ascertain possible effects.
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