Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research Organ Dysfunction, Prior or Concurrent Malignancy, and Comorbidities Working Group

Abstract

Purpose Patients with organ dysfunction, prior or concurrent malignancies, and comorbidities are often excluded from clinical trials. Excluding patients on the basis of these factors results in clinical trial participants who are healthier and younger than the overall population of patients with cancer. Methods ASCO and Friends of Cancer Research established a multidisciplinary working group that included experts in trial design and conduct to examine how eligibility criteria could be more inclusive. The group analyzed current eligibility criteria; conducted original data analysis; considered safety concerns, potential benefits, research, and potential hurdles of this approach through discussion; and reached consensus on recommendations regarding updated eligibility criteria that prioritize inclusiveness without compromising patient safety. Results If renal toxicity and clearance are not of direct treatment-related concern, then patients with lower creatinine clearance values of > 30 mL/min should be included in trials. Inclusion of patients with mild to moderate hepatic dysfunction may be possible when the totality of the available nonclinical and clinical data indicates that inclusion is safe. Ejection fraction values should be used with investigator assessment of a patient's risk for heart failure to determine eligibility. Patients with laboratory parameters out of normal range as a result of hematologic disease should be included in trials. Measures of patient functional status should be included in trials to better assess fit versus frail patients. Conclusion Expanding inclusion of these patients will increase the number and diversity of patients in clinical trials and result in a more appropriate population of patients.

Immune Checkpoint Inhibitors in Real‐World Treatment of Older Adults with Non–Small Cell Lung Cancer

“…There is also a need to increase enrollment of older patients onto randomized clinical trials, the gold standard of evidence‐based medicine, and ASCO has developed recommendations to improve the evidence base for older patients with cancer . ASCO and Friends of Cancer Research have also developed recommendations on eligibility criteria with the goal of increasing participation of adults with comorbidities (which are more prevalent in older adults) without compromising safety …”

Characterization of Comorbidities Limiting the Recruitment of Patients in Early Phase Clinical Trials

“…Furthermore, creatinine clearance (CrCl) has been described as a more accurate measure of renal function for adjusting drug doses in patients with chronic kidney disease . The ASCO‐FOCR task force recommends using CrCl in the eligibility criteria, and if renal toxicity is not a direct treatment‐related concern, patients with lower creatinine clearance values of >30 mL/min should be included in trials .…”

Changes in the Use of Comprehensive Geriatric Assessment in Clinical Trials for Older Patients with Cancer over Time

“…The recent publication of these guidelines in 2011 and 2013 may help further increase the use of CGA in clinical trials in the future, but it may be necessary for the European Medicines Agency and U.S. Food and Drug Administration to require CGA in trials dedicated to older populations. Other important aspects that we need to take into account in order to improve the relevance of clinical trials dedicated to older patients include the use of broader eligibility criteria in order to make clinical trials more representative of real‐life patients , the use of endpoints relevant to older patients such as quality of life , the stratification of investigational treatment according to patients fitness, and the development of novel trial designs such as extended trials or prospective cohorts .…”