Pediatrics, clinical trials

With increased success in pediatric clinical trials, the overall survival rate for pediatric cancers has increased significantly over the last 35 years. For certain disease states, the overall survival rate for specific pediatric malignancies is now up to 80%. Unfortunately, the consequences of success are that approximately two-thirds of childhood cancer survivors have at least one chronic or late-occurring complication of treatment. Long-term follow-up of survivors treated decades ago also has revealed very late sequelae.24... 

The spectrum of adverse reactions reported in 120 immunocompromised pediatric clinical trial participants with serious CMV infections receiving IV ganciclovir were similar to those reported in adults. Granulocytopenia (17%) and thrombocytopenia (10%) were most commonly reported. 

Children A similar adverse event profile was seen during the pediatric clinical trial as in adult patients. The evaluation of the antiviral activity of nelfinavir in pediatric patients is ongoing. 

Vitiello B, Davies M, Arnold LE, McDougle CJ, Aman M, McCracken JT, Scahill L, Tierney E, Posey DJ, Swiezy NB, Koenig K. Assessment of the integrity of study blindness in a pediatric clinical trial of risperidone. J Clin Psychopharmacol 2005 25 565-9. 

All these regulatory innovations have improved labeling for clinicians using drugs for children, and have increased the frequency of pediatric clinical trials manyfold. By January 1, 2006, some 720 pediatric clinical trials had been specifically requested by FDA in connexion with new product approvals, and of these 35% have been for efficacy and safety, 29% for pharmacokinetics and safety, 15% solely for safety, 9% for PK-PD assessments and 12% for various others. These trials were reckoned to be in children with 117 different diseases, distributed among 15 specific therapeutic areas. 

A. Ferster, C. Vermylen, G. Cornu, et al. Hydroxyurea for treatment of severe sickle cell anemia a pediatric clinical trial. Blood 88, 1960 (1996). 

One of the major problems in running pediatric clinical trials is the availability of pediatric patients, who tend to be scattered, because they are numerically less likely to have diseases (other than asthma and the usual childhood illnesses). This affects the logistics of screening and subsequent clinic visits. 

Barfield R C, Church C (2005). Informed consent in pediatric clinical trials. Curr Opin Pediatr 17 20-24. 

Schreiner MS. Pediatric clinical trials Redressing the imbalance. Nat Rev Drug Discov 2003 2 949-961. 

DeVincenzo et al. 2008). Phase n clinical trials in naturally infected RSV patients were initiated in April 2008. ALN-RSVOl is expected to advance into the pediatric patient population by the second half of 2008. 

Allogeneic hematopoietic stem cell transplantation (HSCT) has been used in the treatment of pediatric AML in first complete remission. In most clinical trials, the availability of HLA-matched sibling donors determined whether patients underwent HSCT as postremission treatment. To facilitate this process, it is important to obtain HLA typing on all younger patients with AML and siblings shortly after diagnosis. Patients who do not have an HLA-matched sibling will proceed to postremission therapy. 

Rifaximin, a nonabsorbable derivative of rifamycin, has shown promising bactericidal action against both aerobes and anaerobes, such as bacterioides, lactobacilli and clostridia [33, 34], The development of resistance to this antibiotic can occur, but resistant strains rapidly disappear from the intestine thus allowing cyclic administration of rifaximin. Controlled clinical trials showed efficacy of rifaximin in adult and pediatric patients with infectious diarrhea [36,37], hepatic encephalopathy [38], post-surgical complications [39] and colonic diverticulosis [40], Only recently was the efficacy of rifaximin in the treatment of SIBO demonstrated [41-43]. 

Helms, P. 2002. Real world pragmatic clinical trials what are they and what do they tell us Pediatric Allergy... 

Relatively few drugs marketed in the United States (approximately 20%) have pediatric dosing information available. Clinical trials had rarely been done specifically on pediatric patients. Traditionally, dosing regimens for children have been derived empirically by extrapolating on the basis of body weight or surface area. This approach assumes that the pediatric patient is a young adult, which simply may... 

The FDAMA bill essentially codified and expanded several regulatory actions initiated by the FDA during the 1990s. Among the incentives offered by the bill, companies will be offered an additional six months of patent protection for performing pediatric studies (clinical trials) on already approved products. In fact, the FDA was mandated by FDAMA to develop a list of over 500 drugs for which additional information would produce benefits for pediatric patients. The FDA is supposed to provide a written request for pediatric studies to the manufacturers (Hart, 1999). 

Choice of Control Group and Related Issues in Clinical Trials Clinical Investigation of Medicinal Products in the Pediatric Population... 

Isocyanide-based MCR was also applied for the total synthesis studies of natural products containing piperazine substructure. For example, trabectedin (also known as ecteinascidin 743 or ET-743) is undergoing clinical trials for the treatment of breast, prostate, and pediatric sarcomas. Ecteinascidin 743 (2) is an extremely potent antitumor agent isolated from a marine tunicate, Ecteinascidia turbinate [12]. Eukuyama et al. developed the total synthesis of ecteinascidin 743 from a Ugi reaction [13]. The reaction of p-methoxyphenyl isocyanide 3 gave Ugi product 7, which was cyclized to DKP intermediate 8 (Scheme 1). 

Arnold, L.E., Aman, M.G., Martin, A., Collier-Crespin, A., Vitiello, B., Tierney, E. Asarnow, R., Bell-Bradshaw, F., Freeman, B.J., Gates-Ulanet, P., Klin, A., McCracken, J.T., McDougle, C.J., McGough, J.J., Posey, D.J., Scahill, L., Swiezy, N.B., Ritz, L., and Volkmar, F. (2000). Assessment in multisite randomized clinical trials of patients with autistic disorder the Autism RUPP Network. Research Units on Pediatric Psychopharmacology./Autism Dev Disord 30 99-111. 

Franklin, M.E., Kozak, M.J., Cashman, L.A., Coles, M.E., Rhein-gold, A.A., and Foa, E.B. (1998) Cognitive-behavioral treatment of pediatric obsessive-compulsive disorder an open clinical trial. / Am Acad Child Adolesc Psychiatry 37 412—419. 

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