Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Abstract

Purpose Slow-accruing clinical trials delay the translation of basic biomedical research, contribute to increasing healthcare costs, and may prohibit trials from reaching their original goals. Experimental Design We analyzed a prospectively maintained institutional database that tracks all clinical studies at the MD Anderson Cancer Center. Inclusion criteria were: activated phase I-III trials, maximum projected accrual ≥10 participants, and activation prior to March 25, 2011. The primary outcome was slow accrual, defined as <2 participants/year. Correlations of trial characteristics with slow accrual were assessed with logistic regression. Results 4,269 clinical trials meeting inclusion criteria. Trials were activated between January 5, 1981, and March 25, 2011, with a total of 145,214 participants enrolled. Median total enrollment was 16 (interquartile range [IQR]: 5-34), with an average enrollment rate of 8.7 participants/year (IQR: 3.3-17.7). There were 755 (18%) trials classified as slow accruing. On multivariable analysis, slow accrual exhibited robust associations with national cooperative group trials (odds ratio [OR] =4.16, P<0.0001 vs. industry sponsored), time from trial activation to first enrollment (OR=1.13 per month, P<0.0001), and maximum targeted accrual (OR=0.16 per Log10 increase, P<0.0001). Recursive partitioning analysis identified trials requiring more than 70 days (2.3 months)between activation and first participant enrollment as having higher odds of slow accrual (23% vs. 5%, OR=5.56, P<0.0001). Conclusions We identified factors associated with slow trial accrual. Given the lack of data on clinical trials at the institutional level, these data will help build a foundation from which targeted initiatives may be developed to improve the clinical trial enterprise.

Randomized evaluation of trial acceptability by INcentive (RETAIN): Study protocol for two embedded randomized controlled trials

“…Even when investigators enroll an adequate number of participants, they rarely do so on schedule [4, 7], or in a manner that attracts the full range of eligible participants [8, 9]. Further, participant recruitment represents one of the largest costs of conducting clinical trials, requiring an average of 13 hours and $500 per subject in cancer trials at academic medical centers [10].…”

Finding Success in Clinical Trial Recruitment: A Trial Registry Analysis

“…Due to this patient recruitment dilemma, a number of analyses have assessed the impact of individual clinical trial characteristics on patient recruitment in an effort to understand how best to structure and design new studies (9)(10)(11). Tang et al focused on oncology trials at MD Anderson Cancer Center and found that sponsor type, longer time to first enrollment, and high target accrual were associated with slow recruitment rate (12). For clarity, the official National Cancer Institute definition for trial sponsor is "a person, company, institution, group, or organization that oversees or pays for a clinical trial and collects and analyzes the data" (13).…”

Low clinical trial accrual of patients with myelodysplastic syndromes: Causes and potential solutions

“…[2][3][4][5] Even at National Cancer Institutedesignated comprehensive cancer centers with large referral populations, approximately 20% to 40% of interventional trials accrue slowly (defined as the enrollment of fewer than 2 participants per year). 3,6 Barriers to clinical trial enrollment are a topic of active investigation because these obstacles are of concern to oncologists, policy makers, advocacy groups, trial sponsors, and professional societies, as well as to the general population, who call for more rapid progress in therapy for cancer. 3,6 Barriers to clinical trial enrollment are a topic of active investigation because these obstacles are of concern to oncologists, policy makers, advocacy groups, trial sponsors, and professional societies, as well as to the general population, who call for more rapid progress in therapy for cancer.…”

“…1 As a result, approximately 20% of publicly funded prospective clinical trials fail due to a lack of accrual, and oncology has the lowest likelihood of drug approval from phase 1 among 14 major disease areas, despite public interest in access to novel agents as exemplified by "Right To Try" legislative proposals. [2][3][4][5] Even at National Cancer Institutedesignated comprehensive cancer centers with large referral populations, approximately 20% to 40% of interventional trials accrue slowly (defined as the enrollment of fewer than 2 participants per year). 3,6 Slow accrual may worsen as trials increasingly enroll small, molecularly defined patient subgroups.…”

“…3,6 Slow accrual may worsen as trials increasingly enroll small, molecularly defined patient subgroups. 3,6 Barriers to clinical trial enrollment are a topic of active investigation because these obstacles are of concern to oncologists, policy makers, advocacy groups, trial sponsors, and professional societies, as well as to the general population, who call for more rapid progress in therapy for cancer. [7][8][9][10] Specific subgroups of patients (older adults, racial and ethnic minority populations, and patients with chronic illnesses) are particularly underrepresented in clinical trials, thereby limiting the general applicability of results.…”