Abstract P5-14-09: How exclusion criteria adversely affects the enrolment of underserved groups in breast cancer clinical trials
Authors: Moloney Carolyn , Shiely Frances 
Published: March 2022

Abstract
BackgroundThere have been recent calls globally to improve clinical trial participation by underserved or under-represented patient groups. Underserved groups are populations unrepresented or disengaged from medical research or services despite having a disproportionately high healthcare burden. In breast cancer research, disparity in clinical trial participation of underserved groups and how this affects results and conclusions is not well researched. The purpose of this study is to assess inclusion and exclusion criteria in published phase III breast cancer clinical trials, over the last 10 years, that exclude underserved groups.MethodsMedline was searched for phase III randomised control trials evaluating interventional drugs for breast cancer in high-impact journals (Impact factor &gt;3) published between January 1st 2010 and December 31st 2020.ResultsForty clinical trials were included. These included 22 metastatic, 10 adjuvant and 8 neo-adjuvant breast cancer trials. All 40 trials (100 %) had multiple exclusions that directly, or indirectly, affected underserved groups for clinical and non-clinical reasons. All trials apart from one did not explicitly justify the applied inclusion and exclusion criteria.
Conclusions. The underserved groups directly excluded, as outlined in the results were elderly patients &gt; 65 years and adolescents, patients with cognitive impairment or psychiatric conditions, pregnant and lactating women and patients with brain metastases. As well as being directly excluded, these and other underserved groups are also indirectly excluded by the eligibility criteria to a large extent, for example, bloodborne virus exclusions may affect trial participation of lower socioeconomic populations and the LGBTQ+ community. The trials we reviewed required participants to have a high level of renal, cardiac and hepatic functioning. Certain underserved groups are more likely to have organ impairment. For example, elderly people are more likely to have renal, liver or cardiac impairment due to co-morbidities or age alone. Healthy black individuals are more likely to have a higher baseline creatinine and lower Creatinine Clearance (Cr Cl) compared to white counterparts Clinical trial eligibility criteria both directly and indirectly excludes underserved groups from breast. cancer research. It is necessary to revise future eligibility criteria to further progress considerations on the inclusion of underserved groups in breast cancer research.
Table 1.Clinical Trial Exclusions for Clinical ReasonsExclusion (N=40)CriteriaN %Upper age exclusion18 – 65 years only61518 – 70 years only512.518 – 75 years only25No upper age exclusion2767.5Lower age exclusion&gt;18 years40100Prior or concurrent malignancy exclusionStrict exclusion*820≥ 3 years since diagnosis717.5≥5 years since diagnosis2050≥10 years since diagnosis25No exclusion37.5Blood borne virus exclusion:HIV:Strict exclusion*2870Excluded if on HAART25No exclusion1025Hepatitis B/C:Strict exclusion*2152.5Allowed if treated**37.5No exclusion1640Organ function exclusion:CardiacLVEF (%):&gt;551025&gt;502050No exclusion1025RenalCreatinine (mg/dl) &gt;1.5 X ULN or Cr CL &gt;60ml/min2665Creatinine (mg/dl) &gt;2.5 X ULN or Cr Cl &gt;50ml/min717.5Cr Cl &gt;30410No exclusion/adequate function for treatment37.5HepaticAST/ALT:&gt;1.5 X ULN1537.5&gt;2.5 X ULN820&gt;3.5 X ULN717.5&gt;5 X ULN615No exclusion/adequate function for treatment410Brain or leptomeningeal metastases exclusion: (N=22)Strict exclusion*940.9Untreated or symptomatic or on steroids1359.1No exclusion00ECOG performance status exclusion:ECOG=0 or 12665ECOG=0 to 21435ECOG=0 to 300Exclusion on pregnant or lactating women:Pregnant or lactating women excluded40100
Table 2.Clinical Trial Exclusions for Non-clinical Reasons.Exclusion (N=40)CriteriaN%Language exclusion:English or other language00All languages acceptable40100Cognitive impairment exclusion:Strict exclusion820No direct exclusion3280Psychiatric history exclusion:Strict exclusion717.5Allowed if treated1640Total with exclusions2357.5No direct exclusion1742.5OtherInvestigator assessment regarding ability to comply with protocol3075Written Consent required40100
Citation Format: Carolyn Moloney, Frances Shiely. How exclusion criteria adversely affects the enrolment of underserved groups in breast cancer clinical trials [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-14-09.