A New Approach to Simplifying and Harmonizing Cancer Clinical Trials—Standardizing Eligibility Criteria | Lung Cancer | JN Learning | AMA Ed Hub [Skip to Content]
Outline
Claim CME
PDF
Oncology

A New Approach to Simplifying and Harmonizing Cancer Clinical Trials—Standardizing Eligibility Criteria

To identify the key insights or developments described in this article
1 Credit CME
JAMA Oncology
August 4, 2022
Special Communication
David E. Gerber, MD1;
Harpreet Singh, MD2;
Erin Larkins, MD2;
Andrea Ferris, BS3;
Patrick M. Forde, MD4;
Wendy Selig, MS5;
Upal Basu Roy, PhD, MPH3
Author Affiliations
  • 1Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas
  • 2USFood and Drug Administration, Silver Spring, Maryland
  • 3LUNGevity Foundation, Chicago, Illinois
  • 4Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland
  • 5WSCollaborative LLC, McLean, Virginia
Read article on JAMA Network

MOC/CME Information

editorial comment icon
Editorial
Comment
 related articles icon
Related
Articles
 author interview icon
Interviews
 multimedia icon
Multimedia
Read Article Claim CME
Abstract

Importance  Clinical trial sponsors rely on eligibility criteria to control the characteristics of patients in their studies, promote the safety of participants, and optimize the interpretation of results. However, in recent years, complex and often overly restrictive inclusion and exclusion criteria have created substantial barriers to patient access to novel therapies, hindered trial recruitment and completion, and limited generalizability of trial results. A LUNGevity Foundation working group developed a framework for lung cancer clinical trial eligibility criteria. The goals of this framework are to (1) simplify eligibility criteria, (2) facilitate stakeholders’ (patients, clinicians, and sponsors) search for appropriate trials, and (3) harmonize trial populations to support intertrial comparisons of treatment effects.

Observations  Clinicians and representatives from the pharmaceutical industry, the National Cancer Institute, the US Food and Drug Administration (FDA), the European Medicines Agency, and the LUNGevity Foundation undertook a process to identify and prioritize key items for inclusion in trial eligibility criteria. The group generated a prioritized library of terms to guide investigators and sponsors in the design of first-line, advanced non–small cell lung cancer clinical trials intended to support marketing application. These recommendations address disease stage and histologic features, enrollment biomarkers, performance status, organ function, brain metastases, and comorbidities. This effort forms the basis for a forthcoming FDA draft guidance for industry.

Conclusions and Relevance  As an initial step, the recommended cross-trial standardization of eligibility criteria may harmonize trial populations. Going forward, by connecting diverse stakeholders and providing formal opportunity for public input, the emerging FDA draft guidance may also provide an opportunity to revise and simplify long-standing approaches to trial eligibility. This work serves as a prototype for similar efforts now underway for other cancers.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

See More About

Lung Cancer Oncology Research, Methods, Statistics
Article Information

Accepted for Publication: December 13, 2021.

Published Online: August 4, 2022. doi:10.1001/jamaoncol.2022.1664

Corresponding Author: David E. Gerber, MD, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Mail Code 8852, Dallas, TX 75390-8852 (david.gerber@utsouthwestern.edu).

Author Contributions: Dr Gerber had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Gerber, Singh, Ferris, Forde, Selig, Basu Roy.

Acquisition, analysis, or interpretation of data: Gerber, Larkins, Ferris, Forde, Basu Roy.

Drafting of the manuscript: Gerber, Forde, Selig, Basu Roy.

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

Administrative, technical, or material support: Gerber, Ferris, Selig, Basu Roy.

Supervision: Gerber, Ferris, Forde, Selig.

Conflict of Interest Disclosures: Dr Gerber reported nonfinancial support from Sagimet Biosciences; grants from Karyopharm and AstraZeneca; personal fees from Janssen, Sanofi, Regeneron, and Catalyst; and stock ownership in Gilead Sciences outside the submitted work. Dr Forde reported personal fees from Amgen, AstraZeneca, Janssen, Bristol Myers Squibb, Kyowa, Daiichi Sankyo, Genentech, iTeos, and Sanofi, as well as grants from Corvus outside the submitted work. Ms Selig reported personal fees from the LUNGevity Foundation during the conduct of the study as well as personal fees from Pfizer, Daiichi Sankyo, TriSalus Life Sciences, and Cytokinetics outside the submitted work. Dr Basu Roy reported grants from Boehringer Ingelheim, Takeda, Genentech, Janssen, Amgen, Bristol Myers Squibb, Merck, Blueprint Medicine, G1 Therapeutics, Jazz Pharmaceuticals, Eli Lilly, and AstraZeneca, as well as personal fees from AstraZeneca and serving as a noncompensated board member for ROS1ders outside the submitted work. No other disclosures were reported.

Additional Contributions: We thank Gisele Sarosy, MD, Andrea Denicoff, RN, MS, ANP, Shakuntala Malik, MD, and Sheila Prindiville, MD, MPH, from the National Cancer Institute for their participation in the working group and feedback on the development of the template, as well as See Phan, MD, and Barbara Gitlitz, MD (Genentech), Nabil Chehab, PhD, MBA (AstraZeneca), and Troy Sarich, PhD (Janssen), for their feedback on the eligibility template. There was no compensation provided for these contributions.

References
1.
Tang  C , Sherman  SI , Price  M ,  et al.  Clinical trial characteristics and barriers to participant accrual: the MD Anderson Cancer Center experience over 30 years, a historical foundation for trial improvement.   Clin Cancer Res. 2017;23(6):1414-1421. doi:10.1158/1078-0432.CCR-16-2439PubMedGoogle ScholarCrossref
2.
Garcia  S , Bisen  A , Yan  J ,  et al.  Thoracic oncology clinical trial eligibility criteria and requirements continue to increase in number and complexity.   J Thorac Oncol. 2017;12(10):1489-1495. doi:10.1016/j.jtho.2017.07.020PubMedGoogle ScholarCrossref
3.
Kim  ES , Bruinooge  SS , Roberts  S ,  et al.  Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research joint research statement.   J Clin Oncol. 2017;35(33):3737-3744. doi:10.1200/JCO.2017.73.7916PubMedGoogle ScholarCrossref
4.
Considerations for the inclusion of adolescent patients in adult oncology clinical trials: guidance for industry. US Food and Drug Administration. March 2019. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-inclusion-adolescent-patients-adult-oncology-clinical-trials
5.
Cancer clinical trial eligibility criteria: patients with organ dysfunction or prior or concurrent malignancies: guidance for industry. US Food and Drug Administration. July 2020. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-organ-dysfunction-or-prior-or-concurrent
6.
Cancer clinical trial eligibility criteria: patients with HIV, hepatitis B virus, or hepatitis C virus infections: guidance for industry. US Food and Drug Administration. July 2020. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-patients-hiv-hepatitis-b-virus-or-hepatitis-c-virus
7.
Cancer clinical trial eligibility criteria: brain metastases: guidance for industry. US Food and Drug Administration. July 2020. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-brain-metastases
8.
Cancer clinical trial eligibility criteria: minimum age considerations for inclusion of pediatric patients: guidance for industry and IRBs. US Food and Drug Administration. July 2020. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cancer-clinical-trial-eligibility-criteria-minimum-age-considerations-inclusion-pediatric-patients
9.
Osarogiagbon  RU , Vega  DM , Fashoyin-Aje  L ,  et al.  Modernizing clinical trial eligibility criteria: recommendations of the ASCO-Friends of Cancer Research prior therapies work group.   Clin Cancer Res. 2021;27(9):2408-2415. doi:10.1158/1078-0432.CCR-20-3854PubMedGoogle ScholarCrossref
10.
Bonomi  P , Blumenthal  G , Ferris  AS ,  et al.  Making lung cancer clinical trials more inclusive: recommendations for expanding eligibility criteria.   J Thorac Oncol. 2018;13(6):748-751. doi:10.1016/j.jtho.2018.02.013PubMedGoogle ScholarCrossref
11.
Forde  PM , Bonomi  P , Shaw  A ,  et al.  Expanding access to lung cancer clinical trials by reducing the use of restrictive exclusion criteria: perspectives of a multistakeholder working group.   Clin Lung Cancer. 2020;21(4):295-307. doi:10.1016/j.cllc.2020.02.008PubMedGoogle ScholarCrossref
12.
Webinar—Clinical Laboratory Improvement Amendments (CLIA) waiver applications final guidances. US Food and Drug Administration. April 14, 2020. Accessed June 26, 2022. https://www.fda.gov/medical-devices/workshops-conferences-medical-devices/webinar-clinical-laboratory-improvement-amendments-clia-waiver-applications-final-guidances-04142020
13.
Framework for regulatory oversight of laboratory developed tests (LDTs): draft guidance. US Food and Drug Administration. October 3, 2014. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/framework-regulatory-oversight-laboratory-developed-tests-ldts
14.
US Department of Health and Human Services. Food and drugs: subchapter H: medical devices. 21 CFR §812. Accessed June 26, 2022. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H
15.
Neeman  E , Gresham  G , Ovasapians  N ,  et al.  Comparing physician and nurse Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ratings as predictors of clinical outcomes in patients with cancer.   Oncologist. 2019;24(12):e1460-e1466. doi:10.1634/theoncologist.2018-0882PubMedGoogle ScholarCrossref
16.
Christakis  NA , Lamont  EB .  Extent and determinants of error in doctors’ prognoses in terminally ill patients: prospective cohort study.   BMJ. 2000;320(7233):469-472. doi:10.1136/bmj.320.7233.469PubMedGoogle ScholarCrossref
17.
Chow  R , Chiu  N , Bruera  E ,  et al.  Inter-rater reliability in performance status assessment among health care professionals: a systematic review.   Ann Palliat Med. 2016;5(2):83-92. doi:10.21037/apm.2016.03.02PubMedGoogle ScholarCrossref
18.
Reck  M , Rodríguez-Abreu  D , Robinson  AG ,  et al; KEYNOTE-024 Investigators.  Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer.   N Engl J Med. 2016;375(19):1823-1833. doi:10.1056/NEJMoa1606774PubMedGoogle ScholarCrossref
19.
Evaluating cancer drugs in patients with central nervous system metastases: guidance for industry. US Food and Drug Administration. July 2021. Accessed June 26, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/evaluating-cancer-drugs-patients-central-nervous-system-metastases
20.
Berghoff  AS , Venur  VA , Preusser  M , Ahluwalia  MS .  Immune checkpoint inhibitors in brain metastases: from biology to treatment.   Am Soc Clin Oncol Educ Book. 2016;35:e116-e122. doi:10.1200/EDBK_100005PubMedGoogle ScholarCrossref
21.
Classes of heart failure. American Heart Association. May 31, 2017. Accessed June 26, 2022. https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/classes-of-heart-failure
22.
Ahn  DH , Mehta  N , Yorio  JT , Xie  Y , Yan  J , Gerber  DE .  Influence of medical comorbidities on the presentation and outcomes of stage I-III non-small-cell lung cancer.   Clin Lung Cancer. 2013;14(6):644-650. doi:10.1016/j.cllc.2013.06.009PubMedGoogle ScholarCrossref
23.
Hwang  JP , Feld  JJ , Hammond  SP ,  et al.  Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update.   J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757PubMedGoogle ScholarCrossref
24.
Le  T , Yang  H , Rashdan  S ,  et al.  QTc interval-prolonging medications among patients with lung cancer: implications for clinical trial eligibility and clinical care.   Clin Lung Cancer. 2020;21(1):21-27. doi:10.1016/j.cllc.2019.07.008PubMedGoogle ScholarCrossref
25.
Rashdan  S , Yang  H , Le  T , Selby  C , Gerber  DE , Alvarez  CA .  Prevalence and significance of potential pharmacokinetic drug-drug interactions among patients with lung cancer: implications for clinical trials.   Clin Drug Investig. 2021;41(2):161-167. doi:10.1007/s40261-020-00994-4PubMedGoogle ScholarCrossref
26.
Gerber  DE , Laccetti  AL , Xuan  L , Halm  EA , Pruitt  SL .  Impact of prior cancer on eligibility for lung cancer clinical trials.   J Natl Cancer Inst. 2014;106(11):dju302. doi:10.1093/jnci/dju302PubMedGoogle ScholarCrossref
27.
Laccetti  AL , Pruitt  SL , Xuan  L , Halm  EA , Gerber  DE .  Effect of prior cancer on outcomes in advanced lung cancer: implications for clinical trial eligibility and accrual.   J Natl Cancer Inst. 2015;107(4):djv002. doi:10.1093/jnci/djv002PubMedGoogle ScholarCrossref
28.
Guidances. US Food and Drug Administration. Accessed June 26, 2022. https://www.fda.gov/industry/fda-basics-industry/guidances
29.
Hurria  A , Togawa  K , Mohile  SG ,  et al.  Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study.   J Clin Oncol. 2011;29(25):3457-3465. doi:10.1200/JCO.2011.34.7625PubMedGoogle ScholarCrossref
30.
Extermann  M , Boler  I , Reich  RR ,  et al.  Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score.   Cancer. 2012;118(13):3377-3386. doi:10.1002/cncr.26646PubMedGoogle ScholarCrossref
Want full access to the AMA Ed Hub?
Become an AMA member now
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
Become an AMA member now
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Privacy Policy|Terms of Use
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close
Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue