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Table.  Baseline Trial Cohort Characteristics and Use of Potentially Exclusionary Criteriaa
Baseline Trial Cohort Characteristics and Use of Potentially Exclusionary Criteriaa
1.
Murthy  VH, Krumholz  HM, Gross  CP.  Participation in cancer clinical trials: race-, sex-, and age-based disparities.  JAMA. 2004;291(22):2720-2726. PubMedGoogle ScholarCrossref
2.
National Institutes of Health guidelines on the inclusion of women and minorities as subjects in clinical research. Fed Regist. 1994;23(11):11146-11151. https://grants.nih.gov/grants/guide/notice-files/not94-100.html. Published March 18, 1994. Accessed August 4, 2017.
3.
DeSantis  CE, Siegel  RL, Sauer  AG,  et al.  Cancer statistics for African Americans, 2016: progress and opportunities in reducing racial disparities.  CA Cancer J Clin. 2016;66(4):290-308.PubMedGoogle ScholarCrossref
4.
Levey  AS, Bosch  JP, Lewis  JB, Greene  T, Rogers  N, Roth  D; Modification of Diet in Renal Disease Study Group.  A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.  Ann Intern Med. 1999;130(6):461-470.PubMedGoogle ScholarCrossref
5.
Hsieh  MM, Everhart  JE, Byrd-Holt  DD, Tisdale  JF, Rodgers  GP.  Prevalence of neutropenia in the US population: age, sex, smoking status, and ethnic differences.  Ann Intern Med. 2007;146(7):486-492.PubMedGoogle ScholarCrossref
6.
Hsieh  MM, Tisdale  JF, Rodgers  GP, Young  NS, Trimble  EL, Little  RF.  Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?  J Clin Oncol. 2010;28(10):1633-1637.PubMedGoogle ScholarCrossref
Research Letter
March 2018

Laboratory Eligibility Criteria as Potential Barriers to Participation by Black Men in Prostate Cancer Clinical Trials

Author Affiliations
  • 1Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, Massachusetts
  • 2Harvard Radiation Oncology Program, Boston, Massachusetts
JAMA Oncol. 2018;4(3):413-414. doi:10.1001/jamaoncol.2017.4658

Black patients are underrepresented in clinical trials despite widespread efforts to increase minority participation.1,2 Eligibility criteria may disproportionately prevent black patients from participating due to racial variations in laboratory values. We studied this potential barrier by examining clinical trials in prostate cancer, a disease in which black men face higher incidence and mortality.3

Methods

A list of trials was collected on January 16, 2017, from clinicaltrials.gov using the following criteria: (1) study type, interventional studies; (2) conditions, prostate cancer; (3) interventions, drug; and (4) outcome measures, overall survival. These results were cross-checked against variations of prostate cancer, including prostatic neoplasm and prostate, to ensure that all applicable trials were captured. Institutional review board approval was obtained from the Dana-Farber Cancer Institute before undertaking this study.

Characteristics gathered from each trial included sponsor type, phase, accrual goal, start year, and toxicity. We determined the sponsor type by categorizing each trial as sponsored by industry, cooperative group, or academic investigator. Phase was categorized as phase 1 (0, I, or I/II), 2 (II or II/III), 3 (III or IV), or unknown. Trials were defined as having high toxicity if 1 of the possible treatment arms included chemotherapy, immunotherapy, surgery, brachytherapy, and/or cryoablation. All other treatments, including hormone therapy; nonimmunotherapeutic targeted agents, including biologics; external beam radiotherapy; vitamins/supplements; and nonchemotherapeutic medications, were considered low toxicity.

We investigated the use of serum creatinine (sCr) alone instead of race-adjusted measurements for renal function and the use of an absolute neutrophil count (ANC) threshold that could exclude men with benign ethnic neutropenia. Black patients have higher sCr for any given renal function, and using this measurement may falsely underestimate their renal function.4 Similarly, the 6.7% to 8.0% of black patients with benign ethnic neutropenia, a condition defined as neutropenia (ANC<1.5 × 109 cells/L) without attributable cause, may be excluded despite healthy immune systems.5

Trial characteristics were compared using the Pearson χ2 test for categorical variables and the Wilcoxon rank sum test for continuous variables. Statistical testing was 2-sided and performed using Stata/SE, version 14.2 (StataCorp) on complete data, with a significance level set at P < .05.

Results

We identified 401 interventional prostate cancer clinical trials with an overall survival end point from clinicaltrials.gov (Table). Overall, 47.9% (192) of these trials used sCr alone and/or required participants to have an ANC of 1.5 × 109 cells/L or higher. Specifically, 25.2% (101) of the trials used sCr alone to determine eligibility and 41.4% (166) of the trials required patients to have an ANC of 1.5 × 109 cells/L or higher. The use of sCr alone and/or an ANC cutoff level of 1.5 × 109 cells/L or higher to determine eligibility was more common in trials that were sponsored by academic investigators or cooperative groups vs industry (P < .001), were phase 1 or 2 vs 3 (P < .02), had lower accrual (P < .001), or had at least 1 treatment arm that was considered high toxicity (P < .001) (Table).

Discussion

Of clinical trials in prostate cancer collected for this study, 47.9% used criteria that disproportionately excluded black patients. The reevaluation of these 2 eligibility criteria could improve minority trial enrollment. First, 41.4% of prostate cancer clinical trials excluded patients with benign ethnic neutropenia, even though evidence suggests that these patients do not have an increased risk of infection.6 Lowering the ANC cutoff level for patients with benign ethnic neutropenia would increase the number of eligible black participants, as 89% of these patients have an ANC of 1.0 × 109 cells/L or higher.5,6 Second, 25.2% of trials used sCr alone to determine eligibility, even though black patients have higher sCr levels for any given renal function. Use of race-adjusted equations would take into account these clinically insignificant racial differences.4 This study examined only prostate cancer clinical trials and 2 laboratory measures, which may limit the generalizability of the results. While adopting race-based differences in trial criteria may add slight logistical challenges when ensuring that patients meet trial eligibility, these adjustments would prevent healthy individuals from being excluded solely because of benign laboratory differences caused by their race.

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Article Information

Corresponding Author: Paul L. Nguyen, MD, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, 75 Francis St, Boston, MA 02115 (pnguyen@lroc.harvard.edu).

Accepted for Publication: October 17, 2017.

Published Online: February 8, 2018. doi:10.1001/jamaoncol.2017.4658

Author Contributions: Ms Vastola and Mr Yang contributed equally to the study. Ms Vastola and Dr Nguyen had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Vastola, Yang, McGregor, Nguyen.

Acquisition, analysis, or interpretation of data: Vastola, Yang, Muralidhar, Mahal, Lathan, Nguyen.

Drafting of the manuscript: Vastola, Yang, McGregor, Nguyen.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Vastola, Yang, Mahal.

Obtained funding: Nguyen.

Administrative, technical, or material support: Vastola, Yang.

Study supervision: Mahal, Lathan, McGregor, Nguyen.

Conflict of Interest Disclosures: Dr Lathan reports receiving personal fees Bristol-Myers Squibb and Eli Lilly and Company and has received a philanthropic grant from CVS, all outside the submitted work. Dr McGregor reports receiving personal fees from Seattle Genetics, Bayer, Astellas, Astra-Zeneca, Genetech, and Exelixis, all outside the submitted work. Dr Nguyen reports receiving personal fees from Ferring Pharmaceuticals, Medivation/Astellas, GenomeDx Biosciences, Dendreon, Nanobiotix, Augmenix, Blue Earth, and Bayer and received research support for clinical trials from Astellas Pharma and Janssen Pharmaceuticals for his affiliated institutions, all outside the submitted work. No other conflicts were reported.

Funding/Support: This study was supported by the Prostate Cancer Foundation and Wood Family Foundation.

Role of the Funder/Sponsor: The Prostate Cancer Foundation and Wood Family Foundation had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Murthy  VH, Krumholz  HM, Gross  CP.  Participation in cancer clinical trials: race-, sex-, and age-based disparities.  JAMA. 2004;291(22):2720-2726. PubMedGoogle ScholarCrossref
2.
National Institutes of Health guidelines on the inclusion of women and minorities as subjects in clinical research. Fed Regist. 1994;23(11):11146-11151. https://grants.nih.gov/grants/guide/notice-files/not94-100.html. Published March 18, 1994. Accessed August 4, 2017.
3.
DeSantis  CE, Siegel  RL, Sauer  AG,  et al.  Cancer statistics for African Americans, 2016: progress and opportunities in reducing racial disparities.  CA Cancer J Clin. 2016;66(4):290-308.PubMedGoogle ScholarCrossref
4.
Levey  AS, Bosch  JP, Lewis  JB, Greene  T, Rogers  N, Roth  D; Modification of Diet in Renal Disease Study Group.  A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.  Ann Intern Med. 1999;130(6):461-470.PubMedGoogle ScholarCrossref
5.
Hsieh  MM, Everhart  JE, Byrd-Holt  DD, Tisdale  JF, Rodgers  GP.  Prevalence of neutropenia in the US population: age, sex, smoking status, and ethnic differences.  Ann Intern Med. 2007;146(7):486-492.PubMedGoogle ScholarCrossref
6.
Hsieh  MM, Tisdale  JF, Rodgers  GP, Young  NS, Trimble  EL, Little  RF.  Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?  J Clin Oncol. 2010;28(10):1633-1637.PubMedGoogle ScholarCrossref
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