Methodological issues and controversies in clinical trials with child and adolescent patients with bipolar disorder: report of a consensus conference.
OBJECTIVE
To achieve consensus among researchers, pharmaceutical industry representatives, federal regulatory agency staff, and family advocates on a template for clinical trials of acute mania/bipolar disorder in children and adolescents.


METHODS
The American Academy of Child and Adolescent Psychiatry, in collaboration with Best Practice, convened a group of experts from the key stakeholder communities (including adult psychiatrists with expertise in bipolar disorder) and assigned them to workgroups to examine core methodological issues surrounding the design of clinical trials and, ultimately, to generate a consensus statement encompassing: (1) inclusion/exclusion criteria, (2) investigator training needs and site selection, (3) assessment and outcome measures, (4) protocol design and ethical issues unique to trials involving children/adolescents, and (5) regulatory agency perspectives on these deliberations.


RESULTS
Conference participants reached agreement on 18 broad methodological questions. Key points of consensus were to assign priority to placebo-controlled studies of acute manic episodes in children and adolescents aged 10-17 years, who may or may not be hospitalized, and who may or may not suffer from common comorbid psychiatric disorders; to require that specialist diagnostic "gatekeepers" screen youths' eligibility to participate in trials; to monitor interviewer and rater competency over the course of the trial using agreed upon standards; and to develop new tools for assessment, including scales to measure aggression/rage and cognitive function, while using the best available instruments (e.g., Young Mania Rating Scale) in the interim.


CONCLUSIONS
Methodologically rigorous, large-scale clinical trials of treatment of acute mania are urgently needed to provide information regarding the safety and efficacy, in youth, of diverse agents with potential mood-stabilizing properties.
Carlson
Gabrielle A
GA
Department of Psychiatry, Stony Brook University-Putnam Hall, Stony Brook, NY 11794-8790, USA. Gabrielle.Carlson@StonyBrook.edu
Jensen
Peter S
PS
Findling
Robert L
RL
Meyer
Roger E
RE
Calabrese
Joseph
J
DelBello
Melissa P
MP
Emslie
Graham
G
Flynn
Laurie
L
Goodwin
Frederick
F
Hellander
Martha
M
Kowatch
Robert
R
Kusumakar
Vivek
V
Laughren
Thomas
T
Leibenluft
Ellen
E
McCracken
James
J
Nottelmann
Editha
E
Pine
Daniel
D
Sachs
Gary
G
Shaffer
David
D
Simar
Renee
R
Strober
Michael
M
Weller
Elizabeth B
EB
Wozniak
Janet
J
Youngstrom
Eric A
EA
D000293:Adolescent; D000296:Adolescent Psychiatry; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy / Q000628:therapy*; D002648:Child; D002665:Child Psychiatry; D002986:Clinical Trials as Topic / Q000941:ethics / Q000379:methods*; D006801:Humans; D012107:Research Design / Q000592:standards*; D016896:Treatment Outcome