Abstract Details

Title Attention to Sex as a Biological Variable in Phase III Neurological Trials Before and After the 2017 NIH Amendment: a Systematic Review in MS

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (11:45 AM-12:45 PM)

Poster/Presentation
Number 6-001

Objective

To evaluate whether analyses of SABV or gender in Phase III randomized controlled clinical trials (RCTs) for MS disease modifying treatments (DMTs) improved after 2017.

Background Despite established sex differences in risk and course for neurological diseases such as multiple sclerosis (MS), many clinical studies fail to adequately account for sex as a biological variable (SABV) or gender. In 2017, the NIH amended its SABV guidance to include all federally funded Phase III clinical trials.

Design/Methods A systematic review of all published Phase III RCTs registered on CT.gov for FDA-approved MS DMTs and published before 9/1/2022 was performed. Pharmaceutical companies provided additional information. Each study was graded according to specific criteria published by an expert review, and trials published before and after 2017 were compared.

Results 40 pivotal trials evaluating 18 pharmacological products were identified. Before and after 2017, there was no difference (p>0.10) in the: proportion of trials comparing baseline demographic or disease characteristics by sex, characteristics which might influence trial outcomes (0/31 vs 0/9); prespecified stratification of clinical outcomes by sex (10/31 vs 4/9); post-hoc stratification of clinical outcomes by sex (9/31 vs 2/9); adequate power to evaluate for significant sex-specific efficacy or safety outcomes (3/31 vs 0/9); inclusion of older populations more likely to be postmenopausal (>55 years; 5/31 vs. 3/9). Labels for products with trials published after 2017 were more likely to report on sex-specific efficacy, safety or toxicity (6/13 vs 5/5).

Conclusions The 2017 NIH amendment to consider SABV in federally funded trials resulted in a modest improvement in SABV analyses in pharmaceutically-sponsored pivotal MS clinical trials. This represents a missed opportunity, as the availability of rigorously collected data as well as guidelines for analysis would allow for the analyses necessary to maximize safety and efficacy in specific patient populations.

Authors/Disclosures
Ayushi D. Balan (UCSF) PRESENTER	Miss Balan has nothing to disclose.
Riley Bove, MD, FAAN (University of California, San Francisco)	Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Bove has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genzyme-Sanofi. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Bove has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD-Serono. Dr. Bove has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cadenza. The institution of Dr. Bove has received research support from Biogen. The institution of Dr. Bove has received research support from Eli Lilly. The institution of Dr. Bove has received research support from Novartis. The institution of Dr. Bove has received research support from Roche Genentech.
Maria Pia Sormani (University of Genoa)	Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol meyer. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunic. Maria Pia Sormani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis, Roche. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Maria Pia Sormani has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche.
Maria K. Houtchens, MD	Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Serono. Dr. Houtchens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Cravath. Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Beasley . Dr. Houtchens has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. The institution of Dr. Houtchens has received research support from Genzyme. The institution of Dr. Houtchens has received research support from Biogen. The institution of Dr. Houtchens has received research support from Genentech. The institution of Dr. Houtchens has received research support from Novartis.

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