Disparity of Race Reporting and Representation in Clinical Trials Leading to Cancer Drug Approvals From 2008 to 2018

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]

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Sex Representation in Clinical Trials Associated with FDA Cancer Drug Approvals Differs Between Solid and Hematologic Malignancies

The Oncologist ◽

10.1002/onco.13534 ◽

2020 ◽

Author(s):

Shehara Mendis ◽

Seerat Anand ◽

Joanna M. Karasinska ◽

Arvind Dasari ◽

Joseph M. Unger ◽

...

Keyword(s):

Clinical Trials ◽

Hematologic Malignancies ◽

Cancer Drug ◽

Drug Approvals

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Landmark Cancer Clinical Trials and Real-World Patient Populations: Examining Race and Age Reporting

Cancers ◽

10.3390/cancers13225770 ◽

2021 ◽

Vol 13 (22) ◽

pp. 5770

Author(s):

Thejus Jayakrishnan ◽

Sonikpreet Aulakh ◽

Mizba Baksh ◽

Kianna Nguyen ◽

Meghna Ailawadhi ◽

...

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Real World ◽

Age Distribution ◽

Mean Difference ◽

Cancer Drug ◽

P Value ◽

World Population ◽

Drug Approvals ◽

Age Disparity

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

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Trends in PRO reporting in clinical trials leading to GU cancer drug approvals from 2007 to 2018.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.641 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 641-641

Author(s):

Monica Tamil ◽

Houssein Safa ◽

Adele Semaan ◽

Jad Chahoud

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Standards Of Care ◽

Cancer Drug ◽

Type I ◽

Cancer Drugs ◽

Urological Cancer ◽

Quality Reporting ◽

Patient Reported ◽

Drug Approvals

641 Background: Having standardized and high quality reporting of patient reported outcomes (PRO), especially in clinical trials that establish standards of care in oncology is important for patient centered care. This study assessed the status of reporting and quality of analysis of PROs in FDA approved drugs for genitourinary malignancies. Methods: We conducted a systematic review of the FDA archives to identify urological cancer drugs approved between 2007-2018. We retrieved the clinical trials that led to these drug approvals from ClinicalTrials.gov and PubMed. We systematically screened for PROs and reviewed their analytic tools and interpretation methods reported in their published manuscripts and study protocols. A clinical trial was considered to include PROs if they were reported in either the primary or a subsequent manuscript. Results: We identified 22 clinical trials leading to FDA approval of urological cancer drugs between 2007-2018. Only 63% of trials had published PROs. PROs were reported in the primary clinical trial manuscripts for two drugs (9%), and in a secondary PRO manuscript for 12 drugs (54%). The median time between the primary and secondary papers was 12 months (IQR:7.5-26 months). Among the 14 published PRO papers, the hypothesis was broad in 79%, and not reported in 21%. PROs were never included as a primary endpoint of a study. Instead, PROs were reported as secondary endpoints in 5 (36%) and as exploratory endpoints in 7 (50%) studies, while two papers (14%) did not mention PRO reporting in their endpoints. The most common PRO instruments were EQ-5D (64%) and FACT-P (50%). In 92% of PRO papers, statistical analyses were conducted to account for missing data. Control for type I error was needed but not done in 57% of the trials. Conclusions: Delays in publication of PROs occur regularly in trials leading to drug approval in GU malignancies. Our study highlights the need to enhance standardization of the analysis and interpretation of PROs to maximize the value of this data for drug development and approval.

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Core limitations in clinical trials leading to anticancer drug approvals by the U.S. Food and Drug Administration.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2057 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2057-2057

Author(s):

Talal Hilal ◽

Miguel Gonzalez-Velez ◽

Vinay Prasad

Keyword(s):

Clinical Trial ◽

Optimal Control ◽

Overall Survival ◽

Clinical Trials ◽

Drug Administration ◽

Randomized Trials ◽

Food And Drug Administration ◽

Cancer Drug ◽

Anti Cancer ◽

Drug Approvals

2057 Background: To date, a comprehensive evaluation of core limitations in clinical trials leading to anti-cancer drug approvals by the US Food and Drug Administration (FDA) has not been undertaken.The aim of this analysis was to assess the percentage of clinical trials with core limitations, defined as lack of randomization, lack of overall survival data, inappropriate use of crossover, and use of sub-optimal control arms that led to FDA approvals from 2014 to 2019. Methods: This observational analysis included all approved anti-cancer drug indications by the FDA from July 2014 through July 2019. All indications were investigated and each clinical trial evaluated for design, enrollment period, primary endpoints, and presence of core limitations. The standard of care therapy was determined by evaluating the literature and published guidelines 1-year prior to start of clinical trial enrollment. Crossover was examined and evaluated for optimal use. We then calculated the percentage of approvals based on clinical trials with any or all core limitations. Results: A total of 187 anti-cancer approvals were evaluated. The number of anti-cancer drug approvals doubled over time with 68 in first half of study period (June 2014 to December 2016) to 119 in second half of study period (January 2017 to July 2019). Of those, 125 (67%) were based on a clinical trial with at least one core limitation. 64 (34%) approvals were based on a single-arm clinical trial. Of the remaining 123 approvals based on randomized trials, 60 (32%) had a core limitation. Of all randomized trials, 37 (30%) lacked overall survival benefit, 31 (25%) had a sub-optimal control, and 17 (14%) used crossover inappropriately. Conclusions: The majority of cancer drugs are approved based on clinical trials with core limitations. Efforts to minimize core limitations at the time of clinical trial design are essential to ensure that new anti-cancer drugs being marketed truly improve patient outcomes over current standards.

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