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Lebrikizumab (LEB) is a novel, high affinity monoclonal antibody that selectively binds to interleukin (IL)-13. Lebrikizumab has been shown to provide robust improvements in signs and symptoms in adolescent and adult patients with moderate-to-severe AD across three phase 3 clinical trials (ADvocate1, ADvocate2 and ADhere). However, little is known about the efficacy of LEB in difficult to treat regions such as the face and hands. This study aims to report efficacy of LEB in improving facial and hand dermatitis. ADvocate1 and ADvocate2 assessed LEB 250 mg every 2 weeks (LEBQ2W) vs. placebo for 16 weeks in monotherapy. ADhere compared low-to-mid potency topical corticosteroids (TCS) in addition to LEB Q2W vs. TCS and placebo for 16 weeks. In all trials, clinicians assessed for the presence or absence of facial and hand dermatitis. If present at baseline, at Week 16, clinicians assessed the change from baseline on a scale of cleared, improved, no change or worsened. Patients with improved or cleared dermatitis are described. In ADvocate1 at baseline, facial dermatitis was identified in 71.4% (202/283) of LEBQ2W patients and 80.9% (114/141) of placebo. At Week 16, 61.9% (125/202; P < 0.001) of LEBQ2W were improved or cleared vs. 31.6% (36/114) of placebo. At baseline, hand dermatitis was identified in 72.1% (204/283) of LEBQ2W patients vs. 73.0% (103/141) of placebo. At Week 16, 67.2% (137/204; P < 0.001) of LEBQ2W were improved or cleared vs. 29.1% (30/103) of placebo. In ADvocate2 at baseline, facial dermatitis was identified in 73.7% (207/281) of LEBQ2W patients and 78.8% (115/146) of placebo. At Week 16, 57.5% (119/207; P < 0.001) of LEBQ2W were improved or cleared vs. 21.7% (25/115) of placebo. At baseline, hand dermatitis was identified in 73.3% (206/281) of LEBQ2W patients and 72.6% (106/146) of placebo. At Week 16, 61.7% (127/206; P < 0.001) of LEBQ2W were improved or cleared vs. 18.9% (20/106) of placebo. In ADhere at baseline, facial dermatitis was identified in 72.4% (105/145) of LEBQ2W patients and 59.1% (39/66) of placebo. At Week 16, 68.6% (72/105; P = 0.02) of LEBQ2W were improved or cleared vs. 46.2% (18/39) of placebo. At baseline, hand dermatitis was identified in 71.0% (103/145) of LEBQ2W patients and 66.7% (44/66) of placebo. At Week 16, 72.8% (75/103; P = 0.001) of LEBQ2W were improved or cleared vs. 43.2% (19/44) of placebo. Lebrikizumab treatment is efficacious in improving and clearing hand and face dermatitis in most patients at Week 16. [ABSTRACT FROM AUTHOR]

In quality control of drug products, tolerance intervals are commonly used methods to assure a certain proportion of the products covered within a pre-specified acceptance interval. Depending on the nature of the quality attributes, the corresponding acceptance interval could be one-sided or two-sided. Thus, the tolerance intervals can also be one-sided or two-sided. To better utilize tolerance intervals for quality assurance, we reviewed the computation method and studied their statistical properties in terms of batch acceptance probability in this article. We also illustrate the application of one-sided and two-sided tolerance, as well as two one-sided tests through the examples of dose content uniformity test, delivered dose uniformity test, and dissolution test. [ABSTRACT FROM PUBLISHER]

A response by Yi Tsong and colleagues to a letter to the editor about their article "Validation Testing in Thorough QT/QTc Clinical Trials" in the 2009 issue is presented.

Objective: To explore the genetic basis for a child presented with renal failure and multi-cystic dysplastic kidney without anal atresia., Methods: Peripheral blood sample of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing., Results: The 40-day-old infant had presented with vomiting brown matter in a 7 days neonate and was transferred for kidney failure. Clinical examination has discovered renal failure, polycystic renal dysplasia, congenital hypothyroidism, bilateral thumb polydactyly, sensorineural hearing loss and preauricular dermatophyte. Genetic testing revealed that he has harbored a previously unreported c.824delT, p.L275Yfs*10 frameshift variant of SALL1 gene, which was confirmed by Sanger sequencing as de novo., Conclusion: The patient was diagnosed with Townes-Brocks syndrome due to the novel de novo variant of SALL1 gene. Townes-Brocks syndrome without anal atresia is rare. Above finding has also enriched the mutational spectrum of the SALL1 gene.

For a two-arm active control clinical trial designed to test for non-inferiority of the test treatment compared with the active control standard treatment, data of historical studies are often utilized. For example, with a cross-trial comparison approach (also called synthetic approach or lambda-margin approach), the trial is conducted to test the hypothesis that the mean difference or the ratio between the current test product and the active control is no larger than a certain portion of the mean difference or the ratio of the active control and placebo obtained in the historical data when the positive response indicates treatment effectiveness. The regulatory agency usually requires that the clinical trials of two different test treatments are independent in most regular cases. It also requires, in general, two independent trials of the same test treatment in order to provide confirmatory evidence of the efficacy of the test product. In this article, we derived the relationship between the correlation of the test statistics of two trials with the choice of lambda (the percentage to preserve), the sample sizes and variances under the normality assumption. We showed that the smaller a lambda, the higher the correlation between the two non-inferiority tests. It is further shown that when an 80 per cent or larger lambda is used, the correlation can be controlled to be less than 10 per cent if the variances of the response variables in the current trial are not much smaller than those of the historical studies.