RESUMO
Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.
RESUMO
AIMS: Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy. METHODS AND RESULTS: Male (n = 24) and female (n = 10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-transendocardial stem cell injection (TESI). At baseline, ejection fraction (EF) was lower (P = 0.004) and end-diastolic volume (EDV; P = 0.0002) and end-systolic volume (ESV; P = 0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-min walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (P = 0.04) and in females by 8.6 units (P = 0.04; males vs. females, P = 0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units, and serum tumour necrosis factor alpha improved similarly in both groups. CONCLUSION: Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM.
