Placebo control pediatric studies

Greenhill, L., Findling, R., Swanson, J., and Metadate Study Group. A double-blind, placebo-controlled, study of modified-release MPH MR in children with attention-deficit/hyperactivity disorder. Pediatrics, in Press. 

Several controlled studies of IMI involved less homogeneous samples of anxious children. Neither IMI nor alprazolam (a BZ) was superior to placebo in an 8-week study of 24 children (ages 7-18 years) with school refusal, which included subjects with anxiety and depression (Bernstein et ah, 1990). A more recent placebo-controlled study of IMI -I- CBT for 47 adolescents (ages 12-18 years) with school refusal, anxiety, and/or depression was designed to address the limitations of previous studies of TCA treatment for pediatric anxiety disorders (Bernstein et ah, 2000). Accordingly, sample size was based on proposed power analysis IMI dose and serum level were monitored to ensure adequate exposure (mean IMI dose 180 mg/day mean serum IMI180 pg/L and mean IMI -I- DMI 250 pg/L at week 3 and week 8) and CBT was manual based and closely monitored. Fifty-four percent of subjects treated with IMI -I- CBT met remission criteria (defined as > 75% school attendance at the end of the study), compared to 17% of subjects treated with placebo -I- CBT. No between-group differences were noted... 

The extent of Buspirone experience in children and adolescents is limited to open studies and case reports. There are no published double-blind placebo-controlled studies of Buspirone for pediatric anxiety disorders or any other psychiatric disorder. Results of a recently completed large (n = 350 ages 6-17 years), industry-sponsored, multisite study of Buspirone for children (15-30 mg/day) and adolescents (45-60 mg/ day) with GAD have not been published or presented at open academic conferences. Until such data are made available, the use of Buspirone for treatment of pediatric anxiety disorders remains speculative. 

Despite the history of robust BZ anxiolytic impact in adults, controlled studies, open studies, and case reports of BZs for pediatric anxiety have not been impressive. Concerns about BZ-related adverse events, such as behavioral disihnhibition, have since slowed interest in controlled studies of BZs for treatment of pediatric anxiety disorders. Three small placebo-controlled studies of BZs for pediatric anxiety disorders have been published and none demonstrated... 

Singer, H., Brown, J., Quaskey, S., Rosenberg, L.A., Mellits, E.D., and Denckla, M.B. (1995) The treatment of attention-deficit hyperactivity disorder in Tourette s syndrome a double-blind placebo-controlled study with clonidine and desipramine. Pediatrics 95 74-81. 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

Michelson D, Paries D, Wernicke J, et al Atomoxetine in the treatment of children and adolescents with attention-deficit/hyperactivity disorder a randomized, placebo-controlled, dose-response study. Pediatrics 108 E83 2001... 

Fine, R.N., E.C. Kohaut, D. Brown, and A.J. Perlman, Growth after recombinant human growth hormone treatment in children with chronic renal failure report of a multicenter randomized double-blind placebo-controlled study. Genentech Cooperative Study Group. J Pediatr, 1994.124(3) 374-82. 

The first agent proven to be effective in OCD was the TCA, clomipramine. Its efficacy in pediatric-age patients with OCD was demonstrated in two double-blind, placebo-controlled studies (146, 147). These findings were further supported by a double-blind crossover study with desipramine ( 148). This latter study provided support for serotonin uptake inhibition being the mechanism of action responsible for the efficacy of clomipramine in OCD. Despite this evidence, there are several limitations to the use of clomipramine because of its multiple mechanisms of action ... 

The effectiveness of sertraline in pediatric patients (ages 6 to 17 years) with OCD was demonstrated in a 12-week, double-blind, placebo-controlled study ( 150). Patients were initiated at a dose of either 25 mg per day (ages 6 to 12 years) or 50 mg per day (ages 13 to 17 years) and then adjusted over the next 4 weeks to a maximal dose of 200 mg per day as tolerated. The mean dose of completers was 178 mg per day. Dosing was once a day, either morning or evening. No differences in efficacy based on age or gender were observed. 

There is only one small (n = 12) double-blind, placebo-controlled study showing clonazepam to be effective in pediatric panic disorder and none in posttraumatic stress disorder (156). 

O Shea TM, Kothadia JM, Klinepeter KL, Goldstein DJ, Jackson BG, Weaver RG III, Dillard RG. Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants outcome of study participants at 1-year adjusted age. Pediatrics 1999 104(1 Part 1) 15—21. 

Bahceciler NN, Isik U, Bartan IB, Basaran MM Efficacy of sublingual immunotherapy in children with asthma and rhinitis A double blind, placebo-controlled study. Pediatr Pulmonol 2001 32 49-55. 

GiovaneA, Bardare M, Passalacqua G, Ruffoni S, Scordamaglia A, Ghezzi E, CanonicaGW A three years double blind placebo-controlled study with specific oral immunotherapy to Dermatophagoides Evidence of safety and efficacy in pediatric patients. Clin Exp Allergy 1994 24 53-59. 

Hirsch T, Sahn M, Leupold W Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D.pt.) in children. Pediatr Allergy Immunol 1997 8 21-27. Bahceciler NN, Isik U, Barlan IB, Basaran MM Efficacy of sublingual immunotherapy in children with asthma and rhinitis A double-blind, placebo-controlled study. Pediatr Pulmonol... 

Hirsch TH, Sahn M, Leupold W Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D.pt.) in children. Pediatr Allergy Immunol 1997 8 21-27. 

Since 1998, a number of further studies have been published. Nowadays we can rely on 19 double-blind placebo-controlled studies, performed with adequate methods and samples as summarized in table 1 [10, 12, 16-32], Six of these studies were performed in pediatric patients [16-21], Almost all the studies confirmed the effectiveness of SLIT with grass extracts. Mite, birch and Parietaria extracts showed apparent favorable results in terms of symptom... 

Suessmuth S, Freihorst J, Gappa M. Low-dose theophylline in childhood asthma a placebo-controlled, double-blind study. Pediatr Allergy Immunol. 2003 14 394-400. 

Wraith, J. E., Clarke, L. A., Beck, M., Kolodny, E. H., Pastores, G. M., Muenzer, J., Rapoport, D. M., Berger, K. I., Swiedler, S. J., Kakkis, E. D., Braakman, T., Chadbourne, E., Walton-Bowen, K. and Cox, G. F. (2004). Enzyme replacement therapy for mucopolysaccharidosis I A randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J. Pediatr. 144, 581-588. 

Levy J, Hayes C, Kem J, Harris J, Flores A, Hyams J, Murray R, Tolia V. Does cisapride influence cardiac rhythm Results of a United States multicenter, doubleblind, placebo-controlled pediatric study. J Pediatr Gastroenterol Nutr 2001 32(4) 458-63. 

Local medical and societal cultural factors impact on the ethics committee approvals, so that a study that is considered to be ethical in one country may be regarded as unethical in another. Examples of this may be the unacceptability of the use of placebo control in depression studies in Germany, whereas similar studies would be permitted elsewhere. Similarly, the common practice of extensive blood sampling in Belgium, especially in pediatric studies, would be regarded as excessive and hence unethical in other countries. 

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