A systematic review of the reporting of Data Monitoring Committees' roles, interim analysis and early termination in pediatric clinical trials

<p>Abstract</p> <p>Background</p> <p>Decisions about interim analysis and early stopping of clinical trials, as based on recommendations of Data Monitoring Committees (DMCs), have far reaching consequences for the scientific validity and clinical impact of a trial. Our aim was to evaluate the frequency and quality of the reporting on DMC composition and roles, interim analysis and early termination in pediatric trials.</p> <p>Methods</p> <p>We conducted a systematic review of randomized controlled clinical trials published from 2005 to 2007 in a sample of four general and four pediatric journals. We used full-text databases to identify trials which reported on DMCs, interim analysis or early termination, and included children or adolescents. Information was extracted on general trial characteristics, risk of bias, and a set of parameters regarding DMC composition and roles, interim analysis and early termination.</p> <p>Results</p> <p>110 of the 648 pediatric trials in this sample (17%) reported on DMC or interim analysis or early stopping, and were included; 68 from general and 42 from pediatric journals. The presence of DMCs was reported in 89 of the 110 included trials (81%); 62 papers, including 46 of the 89 that reported on DMCs (52%), also presented information about interim analysis. No paper adequately reported all DMC parameters, and nine (15%) reported all interim analysis details. Of 32 trials which terminated early, 22 (69%) did not report predefined stopping guidelines and 15 (47%) did not provide information on statistical monitoring methods.</p> <p>Conclusions</p> <p>Reporting on DMC composition and roles, on interim analysis results and on early termination of pediatric trials is incomplete and heterogeneous. We propose a minimal set of reporting parameters that will allow the reader to assess the validity of trial results.</p

Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus

Healthy kidneys maintain fluid and electrolyte homoeostasis by adjusting urine volume and composition according to physiological needs. The final urine composition is determined in the last tubular segment: the collecting duct. Water permeability in the collecting duct is regulated by arginine vasopressin (AVP). Secretion of AVP from the neurohypophysis is regulated by a complex signalling network that involves osmosensors, barosensors and volume sensors. AVP facilitates aquaporin (AQP)-mediated water reabsorption via activation of the vasopressin V2 receptor (AVPR2) in the collecting duct, thus enabling concentration of urine. In nephrogenic diabetes insipidus (NDI), inability of the kidneys to respond to AVP results in functional AQP deficiency. Consequently, affected patients have constant diuresis, resulting in large volumes of dilute urine. Primary forms of NDI result from mutations in the genes that encode the key proteins AVPR2 and AQP2, whereas secondary forms are associated with biochemical abnormalities, obstructive uropathy or the use of certain medications, particularly lithium. Treatment of the disease is informed by identification of the underlying cause. Here we review the clinical aspects and diagnosis of NDI, the various aetiologies, current treatment options and potential future developments