Representation of Women and Minorities in Clinical Trials for New Molecular Entities and Original Therapeutic Biologics Approved by FDA CDER from 2013 to 2015

The global pandemic outbreak, SARS-COV-2, which causes COVID-19, has coerced numerous pharmaceutical companies to sprint for the vaccine and therapeutic biologics development. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing with the B cells from the convalescent patients in less than one-month post-infection. While the global public health emergency calls for medications urgently, it saves lives to expedite the clinical trials of biologics as much as possible, hence the biologics development strategies are unprecedentedly challenged. Since the advent of therapeutic biologics, transfection, and selection strategy has been continuously improving for developing more robust cell lines with greater productivity and efficiency. Next-generation sequencing (NGS) has also been implemented into cell bank testing for acceleration. These recent advances enable us to rethink and reshape the chemistry, manufacturing and controls (CMC) strategy against the pandemic outbreaks, to start supplying cGMP materials for the life-saving clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics against pandemics, including using cGMP-compliant pool materials for Phase I clinical trials, selecting the final clone with similar product quality as Phase I materials for late-stage development and commercial production and matching product quality among different manufacturing stages.

Download Full-text

Equity in clinical trials for HIV-associated cryptococcal meningitis: A systematic review of global representation and inclusion of patients and researchers

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009376 ◽

2021 ◽

Vol 15 (5) ◽

pp. e0009376

Author(s):

David S. Lawrence ◽

Tshepo Leeme ◽

Mosepele Mosepele ◽

Thomas S. Harrison ◽

Janet Seeley ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Cryptococcal Meningitis ◽

Science Data ◽

Middle Income ◽

Representation Of Women ◽

Middle Income Countries ◽

Female Authors ◽

Chi Squared ◽

Global Representation

Background It is essential that clinical trial participants are representative of the population under investigation. Using HIV-associated cryptococcal meningitis (CM) as a case study, we conducted a systematic review of clinical trials to determine how inclusive and representative they were both in terms of the affected population and the involvement of local investigators. Methods We searched Medline, EMBASE, Cochrane, Africa-Wide, CINAHL Plus, and Web of Science. Data were extracted for 5 domains: study location and design, screening, participants, researchers, and funders. Data were summarised and compared over 3 time periods: pre-antiretroviral therapy (ART) (pre-2000), early ART (2000 to 2009), and established ART (post-2010) using chi-squared and chi-squared for trend. Comparisons were made with global disease burden estimates and a composite reference derived from observational studies. Results Thirty-nine trials published between 1990 and 2019 were included. Earlier studies were predominantly conducted in high-income countries (HICs) and recent studies in low- and middle-income countries (LMICs). Most recent studies occurred in high CM incidence countries, but some highly affected countries have not hosted trials. The sex and ART status of participants matched those of the general CM population. Patients with reduced consciousness and those suffering a CM relapse were underrepresented. Authorship had poor representation of women (29% of all authors), particularly as first and final authors. Compared to trials conducted in HICs, trials conducted in LMICs were more likely to include female authors (32% versus 20% p = 0.014) but less likely to have authors resident in (75% versus 100%, p < 0.001) or nationals (61% versus 93%, p < 0.001) of the trial location. Conclusions There has been a marked shift in CM trials over the course of the HIV epidemic. Trials are primarily performed in locations and populations that reflect the burden of disease, but severe and relapse cases are underrepresented. Most CM trials now take place in LMICs, but the research is primarily funded and led by individuals and institutions from HICs.

Download Full-text

Representation of Women in Stroke Clinical Trials: A Review of 281 Trials Involving Over 500,000 Participants

SSRN Electronic Journal ◽

10.2139/ssrn.3777234 ◽

2021 ◽

Author(s):

Cheryl Carcel ◽

Sanne AE Peters ◽

Else Charlotte Sandset ◽

Grace Balicki ◽

Cheryl Bushnell ◽

...

Keyword(s):

Clinical Trials ◽

Representation Of Women

Download Full-text

Representation of Women in Randomized Clinical Trials of Cardiovascular Disease Prevention

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.110.868307 ◽

2010 ◽

Vol 3 (2) ◽

pp. 135-142 ◽

Cited By ~ 228

Author(s):

Chiara Melloni ◽

Jeffrey S. Berger ◽

Tracy Y. Wang ◽

Funda Gunes ◽

Amanda Stebbins ◽

...

Keyword(s):

Cardiovascular Disease ◽

Clinical Trials ◽

Disease Prevention ◽

Randomized Clinical Trials ◽

Cardiovascular Disease Prevention ◽

Representation Of Women

Download Full-text

A31 Representation of women and minorities in published clinical trials

Controlled Clinical Trials ◽

10.1016/0197-2456(93)90097-w ◽

1993 ◽

Vol 14 (5) ◽

pp. 411

Author(s):

Barbara A. Duffy ◽

Curtis L. Meinert

Keyword(s):

Clinical Trials ◽

Representation Of Women

Download Full-text

Cerebrovascular disease in women

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286420985237 ◽

2021 ◽

Vol 14 ◽

pp. 175628642098523

Author(s):

Aditya Kumar ◽

Louise McCullough

Keyword(s):

Risk Factors ◽

Clinical Trials ◽

Cerebrovascular Disease ◽

Health Policies ◽

Management Guidelines ◽

Stroke Outcomes ◽

Men And Women ◽

Representation Of Women ◽

Traditional Risk Factors ◽

Specific Management

Cerebrovascular disease is a major cause of morbidity, mortality, and disability in women. The spectrum of disease differs between men and women, with women being particularly vulnerable to certain conditions, especially during specific periods of life such as pregnancy. There are several unique risk factors for cerebrovascular disease in women, and the influence of some traditional risk factors for stroke is stronger in women. Moreover, disparities persist in representation of women in clinical trials, acute intervention, and stroke outcomes. In this review, we aimed to explore the epidemiology, etiologies, and management of cerebrovascular disease in women, highlighting some of these differences and the growing need for sex-specific management guidelines and health policies.

Download Full-text

Abstract 148: Evaluation of Sex, Racial and Geographic Demographics and Outcomes in Clinical Trials of Spontaneous Intracerebral Hemorrhage

Stroke ◽

10.1161/str.48.suppl_1.148 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Lauren Koffman ◽

Daniel Hanley ◽

Craig Anderson ◽

David Mendelow ◽

Barbara Gregson ◽

...

Keyword(s):

Clinical Trials ◽

Intracerebral Hemorrhage ◽

Disease Process ◽

Geographic Location ◽

Pooled Analysis ◽

Spontaneous Intracerebral Hemorrhage ◽

Representation Of Women ◽

Artery Disease ◽

Poor Outcomes ◽

Ich Score

Introduction: As large clinical trials for spontaneous intracerebral hemorrhage (ICH) increasingly influence management, recruitment of diverse populations must be ensured to fully understand the disease process and benefit of interventions to the general public. There is little data on sex, race and outcomes in ICH trials. We hypothesize that women and geographic minorities are underrepresented in ICH clinical trials and that there exist population specific differences in mortality, functional outcomes and response to interventions. Methods: Pooled analysis of 5456 subjects from the following clinical trials: VISTA (985), INTERACT I (404) and II (2829), STICH II (597), MISTIE II (141) and CLEAR III (500). Patients were grouped by sex, race, and geographic location. Modified Rankin Scale [mRS] was obtained at 30 days and 3 months. Results: More men than women participated in ICH trials (61.9% vs. 38.1%); women were older and more likely to have hypertension; men had more coronary artery disease. Women presented with lower Glasgow Coma scale, higher ICH score and more intraventricular hemorrhage. Day 90 mortality was 13.9% in women and 16.6 % in men (p=0.01); 90 day poor outcome (mRS 3-5) was 57.2% in women and 51.0% in men (p<0.001). Only mortality was significantly different between sexes after adjustment for ICH score. Race representation varied in these clinical trials: 1.5% Hispanic; 6.6% black; 14% Arabic; 31% white and 43.4% Asian. Day 90 mortality and mRS 3-5 were highest in Hispanics (22.1%, 78.3%, respectively) and lowest in Asians (9.5%, 43.8%). Hispanics had higher ICH score, but blacks and Hispanics had lower day 90 mortality compared to whites in adjusted models. Asians had both lower mortality and less day 90 mRS 3-5 vs. whites while Arabics and blacks were more likely to have day 90 mRS 3-5. Study interventions were well balanced by sex and race. Conclusions: Sex and race representation in ICH clinical trials only partially equate to current understanding of epidemiology of ICH. There is a lack of trial evidence from Africa and South America and under-representation of women, Hispanics and blacks. Despite higher ICH severity, Hispanics had lower adjusted mortality risk while males had higher risk and Arabics and blacks had worse adjusted poor outcomes.

Download Full-text

Female representation in clinical trials leading to FDA cancer drug approvals for gastrointestinal (GI) cancers between 2008 to 2018.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.809 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 809-809 ◽

Cited By ~ 1

Author(s):

Shehara Ramyalini Mendis ◽

Seerat Anand ◽

Arvind Dasari ◽

Joseph M. Unger ◽

Anirudh Gothwal ◽

...

Keyword(s):

Clinical Trials ◽

Cancer Incidence ◽

Drug Approval ◽

Cancer Drug ◽

Representation Of Women ◽

Gi Cancer ◽

Enrollment Rates ◽

Gi Cancers ◽

Drug Approvals ◽

The U.S

809 Background: Proportionate representation of women in health research is an area for improvement. This study aims to assess the representation of women in gastrointestinal (GI) cancer clinical trials leading to FDA cancer drug approvals over the past 10 years. Methods: FDA cancer drug approvals between 07/2008-06/2018 were identified and trial reports supporting approvals sourced. The ratio of female to male (F:M) enrollment was compared with F:M cancer incidence in the U.S., and U.S. cancer prevalence and mortality. Results: Although F:M enrollment for all 229 trials leading to FDA cancer drug approvals in this period was similar to overall F:M cancer incidence in the U.S. (0.89 vs 0.86; Odds Ratio for female enrollment (OR) 1.05, 95% Confidence Interval (CI) 1.03-1.06, P<0.0001), in 17 trials that led to drug approvals in GI cancers there was lower F:M trial enrollment compared to cumulative U.S. incidence at those tumor sites (0.55 vs 0.79, OR 0.71, 95% CI 0.68-0.74, P<0.0001). F:M enrollment and U.S. incidence by the main GI tumor sites where approvals occurred is shown in Table. Female enrollment rates were also lower than U.S. female cancer mortality and prevalence rates in these tumor sites (P<0.0001 for all). Female enrollment in GI trials fell between 2008-2013 and 2014-2018 (38 vs 33%, OR 0.80, 95% CI 0.74-0.87, P<0.0001). Conclusions: Although disparity in female enrollment may be improving across combined FDA cancer drug approval trials, underrepresentation of females has persisted in GI cancer trials when compared to F:M cancer incidence, prevalence and mortality in the U.S. More work is required to determine the drivers of this disparity, in order to mitigate it. [Table: see text]

Download Full-text

Disparities in patient enrollment on glioblastoma clinical trials

CNS Oncology ◽

10.2217/cns-2020-0008 ◽

2020 ◽

Vol 9 (2) ◽

pp. CNS59

Author(s):

Yang Liu ◽

Andrea Wasilewski ◽

Nimish A Mohile

Keyword(s):

United States ◽

Clinical Trials ◽

Brain Tumor ◽

Population Data ◽

The United States ◽

Tumor Registry ◽

Representation Of Women ◽

Central Brain ◽

The Usa ◽

Patient Enrollment

Aim: To determine if enrollment on glioblastoma (GBM) interventional clinical trials (ICTs) in the USA is representative of the population. Materials & methods: We queried ClinicalTrials.gov for all ICTs in GBM from 1994 to 2019. Demographics were obtained from ClinicalTrials.gov or the trial publication and compared with population data from Central Brain Tumor Registry of the United States. Results: In total, 10617 GBM patients were enrolled in 118 adult ICTs: median age was 54.0 (10.05 years younger than Central Brain Tumor Registry of the United States). Age was most discrepant in recurrent tumors, nonrandomized trials and consortium studies. Median age improved from 52.0 to 59.5 over 25 years. Women represented 37.5% of subjects. Conclusion: GBM ICTs under-represent older patients but representation of women reflects the population. ICTs need to be designed to better represent the population.

Download Full-text