Development of a panel of U.S. adult tobacco users to inform tobacco regulatory science.

The National Panel of Tobacco Consumer Studies (TCS Panel) is a probability-based panel of about 4,000 U.S. adult cigarette, cigar, and smokeless tobacco users developed by the U.S. Food and Drug Administration's Center for Tobacco Products to conduct observational and experimental studies to inform tobacco regulatory activities. This paper describes the methods and characteristics of the current panel. The TCS Panel employed a stratified 4-stage sample design and in-person screening of U.S. sampled households. Selected eligible adults participated in an enrollment interview and completed a baseline survey assessing tobacco use behaviors to enroll in the Panel; 3,893 individuals were enrolled from September 2016-August 2017. Replenishment occurred from July 2019-December 2019 with 2,260 new members, for a current panel of 3,929 members. Demographic and tobacco use characteristics of the current panel were analyzed in 2020. Most demographic characteristics of the TCS Panel are similar to those of U.S. tobacco users in the 2018 National Health Interview Survey, suggesting a lack of systematic bias in the Panel. Small, but statistically significant, differences were observed in the proportion of 18- to 25-year-olds; high school diploma and bachelor's degree/higher; never married and married (p < 0.05 for all). The TCS Panel appears to be representative of U.S. cigarette, cigar, and smokeless tobacco users; such panels can be a feasible method for conducting tobacco regulatory science research. The TCS Panel has been used to field studies examining purchasing behaviors, receipt and use of free samples/coupons, and the impact of a hypothetical tobacco product standard.

Recombinant human IgG1 based Fc multimers, with limited FcR binding capacity, can effectively inhibit complement-mediated disease.

There is a lack of effective targeted therapies for the treatment of complement dependent diseases. We developed two recombinant Fc multimers, G207 and G211, with limited ability to interact with low/moderate affinity FcγRs, but with high avidity for C1q. These drugs effectively inhibited complement dependent cytotoxicity (CDC) in vitro, and prevented the deposition of C1q, C3b and MAC, on the surface of Ab-opsonized cells. Importantly, these inhibitory effects were both C1q dependent and independent. In order to determine the biologic relevance of our findings, we evaluated the clinical efficacy of these drugs in three different animal models, acute RBC hemolysis, anti-Thy-1 nephritis and passive Heymann's nephropathy (PHN), in which disease pathophysiology relies preferentially on complement activation. While G207 was protective in the anti-Thy-1 nephritis and PHN models, G211 was protective in all of the models tested and could effectively treat PHN. In the anti-Thy-1 nephritis model, G211 prevented the characteristic histologic changes associated with the disease and limited glomerular deposition of C3. Collectively, these data suggest that "complement preferential" Fc multimers offer a novel approach to the treatment of complement mediated diseases.