Clinical trials investigating neuromyelitis optica spectrum disorder (NMOSD) — a rare, disabling autoimmune disorder of the central nervous system — offer unique design and statistical challenges in light of the clinical ethical issues in order to effectively determine treatment outcomes as well as to minimize risk. In the double-masked, placebo-controlled N-MOmentum trial, Dr. Gary R. Cutter, professor in the department of biostatistics at the University of Alabama at Birmingham, and Dr. Kaushik Patra, science director at MedImmune biotechnology company, are among the team that designed a trial to test the effectiveness and safety of MEDI-551 (an anti-CD 19 B-cell depleting monoclonal antibody) in NMOSD patients. Lead clinical investigator is Dr. Bruce A. C. Cree, at the University of California San Francisco Medical Center; Dr. Eliezer Katz, senior medical director at MedImmune, is a co-investigator.
Study participants are randomized (3:1) to receive MEDI-551 or placebo for up to 197 days, the endpoint being time to first relapse as determined by an independent adjudication committee, which also confirms incidence of NMOSD as evaluated by the investigator. “Sample size re-estimation and futility analyses are planned interim analyses. Novel multiplicity adjustment methods are developed to control the study-wide type I error. Methods for assessing inter- and intrarater reliability are proposed,” says Dr. Cutter. “The N-MOmentum study minimizes exposure to placebo for individual patients, while accepting that in 25 percent of the patients they may experience a relapse prior to being treated. The application of several statistical methods in the N-MOmentum trial is novel in NMOSD and aims to achieve a balance between minimizing excess risk and maintaining the scientific rigor required by the FDA.”
“Statistical Considerations for an Adaptive Design for a Serious Rare Disease” was published online in December 2015 in the journal Therapeutic Innovation & Regulatory Science.
(To read the related article “Placebo-controlled Study in Neuromyelitisoptica—Ethical and Design Considerations,” published in December 2015 in the journal Multiple Sclerosis Journal: http://www.ncbi.nlm.nih.gov/pubmed/26666258)