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Review
. 2021 May 1;27(9):2416-2423.
doi: 10.1158/1078-0432.CCR-20-3853. Epub 2021 Feb 9.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Laboratory Reference Ranges and Testing Intervals Work Group

Alexander I Spira  1 , Mark D Stewart  2 , Suzanne Jones  3 , Elaine Chang  4 , Anitra Fielding  5 , Nicole Richie  6 , Laura S Wood  7 , Michael A Thompson  8 , Lee Jones  9 , Abhilasha Nair  4 , Brandon A Mahal  10 , David E Gerber  11
Affiliations
Review

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the ASCO-Friends of Cancer Research Laboratory Reference Ranges and Testing Intervals Work Group

Alexander I Spira et al. Clin Cancer Res. .

Abstract

Purpose: In clinical research, eligibility criteria promote patient safety and optimize the evidence generated from clinical trials. However, overly stringent eligibility criteria, including laboratory requirements, may limit enrollment, resulting in delayed trial completion and potentially limiting applicability of trial results to a general practice population.

Experimental design: Starting in 2018, a working group consisting of experts in direct patient care, the FDA, industry, and patient advocacy developed recommendations to guide the optimal use of laboratory reference ranges and testing intervals in clinical trial eligibility criteria and study procedures. The working group evaluated current eligibility criteria across different clinical trial phases and performed a literature review to evaluate the impact of and justification for laboratory test eligibility requirements and testing intervals in clinical trials. Recommendations were developed on the basis of the goals of promoting safety and optimizing the evidence generated, while also expanding eligibility and applicability, and minimizing excess burden of trial participation.

Results: In general, we found little variation over time and trial phase in laboratory test requirements, suggesting that these eligibility criteria are not refined according to ongoing clinical experience. We propose recommendations to optimize the use of laboratory tests when considering eligibility criteria.

Conclusions: Tailoring the use of laboratory test requirements and testing intervals may increase the number and diversity of patients in clinical trials and provide clinical data that more closely represent the general practice populations.See related commentary by Giantonio, p. 2369.

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Conflict of interest statement

Conflict of Interest Disclosure

The authors declare no potential conflicts of interest other than those listed below for individual authors:

A. Fielding reports employment with AstraZeneca and stock ownership. N. Richie reports employment with Genentech, a member of the Roche group. M.A. Thompson reports personal fees from Adaptive (advisory board, registry), UpToDate (royalties), and AIM Specialty Health (advisory board) outside the submitted work; other from CRAB CTC (institutional), Amgen (institutional), Hoosier Research Network (institutional), Janssen (institutional), Lilly (institutional), LynxBio (institutional), Strata Oncology (institutional), Takeda (institutional), TG Therapeutics (institutional); personal fees and other from BMS (Celgene; advisory board, registry; institutional), Takeda (Celgene; advisory board, registry; institutional), GSK (institutional; advisory board December 12, 2017).

Figures

Figure 1.
Figure 1.. Frequency of laboratory value requirements according to therapy type for 107 oncology clinical trial protocols for solid tumors.
Protocol-specified accepted laboratory test values and number of protocols with each requirement for (A) absolute neutrophil count (ANC), (B) platelet count, (C) hemoglobin, (D) serum creatinine, (E) creatinine clearance or glomerular filtration rate (GFR), (F) total bilirubin, and (G) AST and ALT.
Figure 2.
Figure 2.. Frequency of laboratory value requirements according to therapy type for 16 oncology clinical trial protocols for hematologic malignancies.
Protocol-specified accepted laboratory test values and number of protocols with each requirement for (A) absolute neutrophil count (ANC), (B) platelet count, (C) hemoglobin, (D) serum creatinine, (E) creatinine clearance or glomerular filtration rate (GFR), (F) total bilirubin, and (G) AST and ALT. NC, no criteria specified.
See this image and copyright information in PMC

Comment in

References

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