News & Activities

Methodology Monday December Roundup

31 Dec 2026

In December's #MethodologyMonday, we will look primarily at issues related to women and their underrepresentation in clinical trials. Kicking off with a systematic review and meta analysis by Daitch and colleagues of 300 randomized controlled trials (RCTs) published in 2017 across multiple major disease areas. 

They identified that the median enrollment rate of women was only 41%, with women’s inclusion markedly dropping with older participant age - indicating persistent external-validity gaps that could compromise generalizability of RCT findings for female and elderly populations.

Ref. Daitch, V., Turjeman, A., Poran, I. et al. Underrepresentation of women in randomized controlled trials: a systematic review and meta-analysis. Trials 23, 1038 (2022).

We continue the #MethodologyMonday focus on the underrepresentation of women with this paper by Tobb, Koscher and Bullock-Palmer, who analyse the inclusion of women in cardiovascular trials. They highlight not only that underrepresentation remains a persistent issue but that it is increasingly so for minority women in cardiovascular trials. They point out that the current situation leads to the extrapolation of study results from predominantly male trials to women, which have been shown to lead to more side effects and potentially worse outcomes. Dig into the paper to understand the different causes identified that contribute to this situation.

Ref. Tobb K, Kocher M, Bullock-Palmer RP. Underrepresentation of women in cardiovascular trials- it is time to shatter this glass ceiling. Am Heart J Plus. 2022 Mar 5;13:100109.

Building on the previous piece (cardiovascular trials), this #MethodologyMonday delves into a more specific topic – stroke trials. Carcel and colleagues conducted a systematic review of trials from 1990-2020 to identify the participation prevalence ratio for women in stroke RCTs. Overall, women are underrepresented, and there were no significant changes over the time period.  

Ref. Carcel C, Harris K, Peters SAE, Sandset EC, Balicki G, Bushnell CD, Howard VJ, Reeves MJ, Anderson CS, Kelly PJ, Woodward M. Representation of Women in Stroke Clinical Trials: A Review of 281 Trials Involving More Than 500,000 Participants. Neurology. 2021 Nov 2;97(18):e1768-e1774.

We move now to another subsection of the female population for the next #MethodologyMonday, pregnant women. Sewell et al summarise the scientific, ethical, and legal considerations governing research conducted during pregnancy. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.

Ref. Sewell CA, Sheehan SM, Gill MS, Henry LM, Bucci-Rechtweg C, Gyamfi-Bannerman C, Lyerly AD, McKinney LC, Hatfield KP, Baer GR, Sahin L, Nguyen CP. Scientific, ethical, and legal considerations for the inclusion of pregnant people in clinical trials. Am J Obstet Gynecol. 2022 Dec;227(6):805-811.

Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population. For this week’s #MethodologyMonday Taylor and colleagues reviewed 10 international COVID-19 registries at two timepoints. With an increase over time of the number of studies the direct exclusion of pregnant women in the trials remained at 75%. Moreover the authors highlight that the justification of this exclusion is not well done as many treatments have no or low safety concerns during pregnancy.

Ref. Taylor MM, Kobeissi L, Kim C, Amin A, Thorson AE, Bellare NB, Brizuela V, Bonet M, Kara E, Thwin SS, Kuganantham H, Ali M, Oladapo OT, Broutet N. Inclusion of pregnant women in COVID-19 treatment trials: a review and global call to action. Lancet Glob Health. 2021 Mar;9(3):e366-e371.