Extent of Exclusions for Chronic Conditions in Breast Cancer Trials

Abstract

Experts have expressed concerns that patients with chronic conditions are being excessively excluded from cancer randomized clinical trials (RCTs), limiting generalizability. Accordingly, we queried clinicaltrials.gov to determine the extent to which patients with chronic conditions were excluded from phase III cancer trials, using National Cancer Institute-sponsored breast cancer RCTs as a test case. Two physicians independently coded for the presence of 19 prevalent chronic conditions within eligibility criteria. They also coded for exclusions based on performance status and vague criteria that could have broadly excluded patients with chronic conditions. The search identified 58 RCTs, initiated from 1993 to 2012. Overall, 88% of trials had at least one exclusion for a chronic condition, performance status, or vague criterion. The three most commonly excluded conditions were chronic kidney disease, heart failure, and ischemic heart disease. Our study demonstrated that patients with prevalent chronic conditions were commonly excluded from National Cancer Institute-sponsored RCTs.

Ribociclib plus letrozole in subgroups of special clinical interest with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: Subgroup analysis of the phase IIIb CompLEEment-1 trial

“…Many patients with some types of distant metastases, poor PS, or prior treatment, have poor prognosis without effective treatment and are often excluded from clinical trials [8][9][10][11][12][13][16][17][18][19], resulting in a paucity of evidence regarding optimal treatment regimens [1].…”

“…The frequent exclusion from clinical trials of several of these subgroups means that data relating to optimal treatment regimens are lacking. Clinical trials are commonly limited to patients with good PS and often exclude those who have CNS metastases or who have received prior chemotherapy [16][17][18][19]. For example, patients with an Eastern Cooperative Oncology Group (ECOG) PS > 1 were excluded in most of the recent phase III clinical trials of CDK4/6 inhibitors in HR+, HER2-ABC including the PALOMA-3 (palbociclib), MONARCH-3 (abemaciclib), MONALEESA-7 and MONALEESA-3 (ribociclib) trials [20][21][22][23].…”

Multimorbidity: Implications and directions for health psychology and behavioral medicine.

“…Systematic reviews report underrepresentation of multiple chronic conditions in RCTs published in high-impact medical journals (Jadad, To, Emara, & Jones, 2011). For example, RCTs relevant to cancer have historically excluded patients with other medical conditions (e.g., Beaver, Ison, & Pazdur, 2017; see also Kronish et al, 2018), and excluded older adults, who tend to have more concurrent conditions. The number of clinical trials with explicit age exclusions has decreased, an encouraging sign (Lee, Alexander, Hammill, Pasquali, & Peterson, 2001), and trial enrollment of older patients has increased in recent decades, but it is still below levels at which older patients are affected (Van Spall, Toren, Kiss, & Fowler, 2007).…”

Comparing comorbidity scales: Attending physician score versus the Cumulative Illness Rating Scale for Geriatrics

“…There is a significant knowledge gap on how comorbidities, cancer, and cancer therapies interact and how outcomes of various cancer therapies for various types and stages of cancer are affected [51]. Patients with comorbid conditions are often excluded from participation in randomised controlled trials (RCTs) [57], and, when included, comorbidity is often not systematically assessed or is assessed by summary measures that provide little information on the impact of individual comorbidities [54]. Consequently, treatment guidelines are often vague, and decisions are left to the individual physician's judgment.…”