The Childhood Adenotonsillectomy Trial (CHAT): rationale, design, and challenges of a randomized controlled trial evaluating a standard surgical procedure in a pediatric population.

Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions.

[1]  J. Kelly,et al.  Outcome of Adenotonsillectomy for Obstructive Sleep Apnea in Obese and Normal-Weight Children , 2007, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[2]  B. E. F. Isher,et al.  Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. , 2002 .

[3]  A. Hoes,et al.  Adenotonsillectomy or watchful waiting in patients with mild to moderate symptoms of throat infections or adenotonsillar hypertrophy: a randomized comparison of costs and effects. , 2007, Archives of otolaryngology--head & neck surgery.

[4]  L. Moyé,et al.  The Cardiac Arrhythmia Suppression Trial: background, interim results and implications. , 1990, The American journal of cardiology.

[5]  S. Redline,et al.  Racial differences in sleep-disordered breathing in African-Americans and Caucasians. , 1997, American journal of respiratory and critical care medicine.

[6]  L. Kheirandish-Gozal,et al.  Corticosteroids suppress in vitro tonsillar proliferation in children with obstructive sleep apnoea , 2009, European Respiratory Journal.

[7]  Kenneth F Schulz,et al.  Allocation concealment in randomised trials: defending against deciphering , 2002, The Lancet.

[8]  Debra E Weese-Mayer,et al.  Sleep-disordered breathing symptoms are associated with poorer cognitive function in 5-year-old children. , 2004, The Journal of pediatrics.

[9]  E. Kozminsky,et al.  Adenotonsillectomy improves neurocognitive function in children with obstructive sleep apnea syndrome. , 2003, Sleep.

[10]  R. Chervin,et al.  DSM-IV diagnoses and obstructive sleep apnea in children before and 1 year after adenotonsillectomy. , 2007, Journal of the American Academy of Child and Adolescent Psychiatry.

[11]  D. Gozal,et al.  Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy. , 2006, The Journal of pediatrics.

[12]  J. Stradling,et al.  Sleep disordered breathing: Effects of adenotonsillectomy on behaviour and psychological functioning , 2005, European Journal of Pediatrics.

[13]  D. Gozal,et al.  Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits , 2002, Journal of sleep research.

[14]  A. Hoes,et al.  Large international differences in (adeno)tonsillectomy rates. , 2004, Clinical otolaryngology and allied sciences.

[15]  D. Gozal,et al.  Cognition, sleep and respiration in at-risk children treated for obstructive sleep apnoea , 2005, European Respiratory Journal.

[16]  J. Stradling,et al.  Effect of adenotonsillectomy on nocturnal hypoxaemia, sleep disturbance, and symptoms in snoring children , 1990, The Lancet.

[17]  R. Chervin,et al.  Sleep-Disordered Breathing, Behavior, and Cognition in Children Before and After Adenotonsillectomy , 2006, Pediatrics.

[18]  John O. Willis,et al.  NEPSY: A Developmental Neuropsychological Assessment , 2008 .

[19]  S. Redline,et al.  Variation of C-Reactive Protein Levels in Adolescents: Association With Sleep-Disordered Breathing and Sleep Duration , 2005, Circulation.

[20]  R. Chervin,et al.  Neuropsychological and behavioral functioning in children with and without obstructive sleep apnea referred for tonsillectomy , 2008, Journal of the International Neuropsychological Society.

[21]  C. Anderson,et al.  Ethical issues in the conduct of clinical trials in obstructive sleep apnea. , 2011, Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine.

[22]  Charles Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[23]  D. Beebe,et al.  The neuropsychological effects of obstructive sleep apnea: a meta-analysis of norm-referenced and case-controlled data. , 2003, Sleep.

[24]  K. A. Cullen,et al.  Ambulatory surgery in the United States, 2006. , 2009, National health statistics reports.

[25]  J. Kelly,et al.  Adenotonsillectomy for Obstructive Sleep Apnea in Obese Children , 2004, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[26]  J. Walsh,et al.  Prevalence and ethnicity of sleep-disordered breathing and obesity in children , 2007, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[27]  R. Shaddy,et al.  Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations , 2010, Pediatrics.

[28]  A. Wright,et al.  Obstructive sleep apnoea in children undergoing routine tonsillectomy and adenoidectomy. , 1990, Clinical otolaryngology and allied sciences.

[29]  R. Chervin,et al.  Cognitive Executive Dysfunction in Children with Mild Sleep-Disordered Breathing , 2004, Biological research for nursing.

[30]  S. Redline,et al.  Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity. , 2003, The Journal of pediatrics.

[31]  K. Gourgoulianis,et al.  Obesity and persisting sleep apnea after adenotonsillectomy in Greek children. , 2008, Chest.

[32]  L. Brooks,et al.  Adenotonsillectomy for treatment of obstructive sleep apnea in children. , 1995, Archives of otolaryngology--head & neck surgery.

[33]  D. Gozal.  Sleep-disordered breathing and school performance in children. , 1998, Pediatrics.

[34]  T. Linder,et al.  Parent satisfaction 1 year after adenotonsillectomy of their children. , 2000, International journal of pediatric otorhinolaryngology.