More Diverse Enrollment Means More Attention To I/E Language
By Teri Crumb, MSN, RN, CCRC, TLC Research, LLC
More attention must be paid to protocol design, specifically inclusion/exclusion (I/E) criteria, and how it can be a barrier to the enrollment of diverse populations. In part one of this series, Want More Diverse Enrollment? Slow Down And Listen To Patients, I explored how one particular exclusion criterion created an obstacle to patient enrollment. Understanding it might be representative of a larger issue, I reviewed a broad range of I/E criteria from trials posted to clinicaltrials.gov that could also present barriers and be ripe for revision.
As guidance in this practice, I looked back to the FDA guidance, Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry.1 Below, I’ve provided samples of potentially problematic I/E criteria, as well as the issues they create and ways to address them.
“Perceived inability to adhere to the medical regimen or comply with recommendations, as determined by the site investigator”
This criterion is also described in other trials as “Poor adherence to medical treatments in the opinion of the investigator,” “The participant, in the opinion of the investigator, is unable to adhere to the requirements of the study,” and “Factors judged to limit adherence to interventions based on appointment attendance and medication treatment compliance; PI will make this determination.”
Healy et al (2022) discuss the stigmatizing language that exists in our medical documentation. The authors in the article contend, “At its best, our language can humanize, empower, and build trust, and at its worst, it can exacerbate disparities for marginalized groups.”2 Labeling a patient or family as noncompliant may adversely affect their eligibility for a clinical trial. It is important to examine the root cause for missing appointments or inconsistencies with medication administration.
“Inability or unwillingness to travel to study visits”
Clinical trials are an additional activity for any person to take on. We need to remember that people lead busy lives. For many, their job or family responsibilities must be factored in before they can commit to additional visits or tests for a clinical trial. The FDA suggests that trials should consider reducing the burden of visit schedules, increasing flexibility (visit windows), and considering virtual or home-based data collection when possible. Throughout my years of coordinating clinical trials, I found that if the clinical trial “fit” the natural schedule of the patient’s disease or condition, the more likely patients were to consider participation. Similarly, if a trial’s blood draws matched the patient’s routine lab orders, they experienced less burden. Also, I found if we coordinated aspects of the trial to fit within their schedule (before or after school/work or on weekends), we not only recruited participants but also retained them in the study. In many cases, it was not the participant's inability or unwillingness, it was the inflexibility of the clinical trial.
“Not capable of informed consent”
Most people with disabilities, including those with intellectual and developmental disabilities, can make informed decisions. It is a stereotype that all people with intellectual and developmental disabilities cannot participate in clinical research. As we experience an aging population, should we pass over all people with memory impairments and the ability to process new information? Should we exclude adults with autism? These are the exact conversations we should be having, according to the results from a new report by the National Council on Disability. The NCD report calls for greater inclusion of people with disabilities in clinical trials, saying, “The inclusion and exclusion criteria embedded in clinical trial criteria can create barriers for people with disabilities — often without scientific justification.”
Experts, such as Peterson et al (2021), explore the use of a model for supportive decision-making3. Could this be employed to support a diverse range of people having the ability to participate in clinical trials? Just as we assess any barriers to participation like transportation or flexible scheduling, we could discuss support mechanisms to the informed consent process. What this could look like in practice: a family member or trusted adult participates in the extensive discussion of the informed consent and assists with questions or information processing during the consent process as well as for the duration of the study. Within the regulations for clinical research, we must protect those who participate. We also must consider the principles of respect for people and autonomy. There is a fine balance between these.
“Alcohol or drug abuse”
Could this be a stigma? The Oxford Learner’s Dictionary defines stigma as “negative feelings that people have about particular circumstances or characteristics that somebody may have.”4 There may be very strong justification to exclude populations with histories; however, could we reevaluate this criterion and broaden it? Could people who have been free from relapse or abstinent for five years be considered? How about a person who has been abstinent for two years? The protection of human subjects is at the forefront of the regulations and the objective of I/E criteria in the protocol. However, as we look to diversify our clinical trial participants, we have to examine the criteria closely to determine if it is eliminating a portion of the population that we need.
“Non-English speaking”
Also described as, “Unable to read or speak English.”
The FDA recognizes that some criteria written into protocols have become widely accepted over time. Criteria like this may even be template language in protocol outlines provided by academic medical centers, sponsors, etc.
However, the exclusion of non-English speaking patients may preclude the inclusion of patients from racial and ethnic minorities. In doing so, a study could invariably produce data that does not adequately evaluate the potential for a difference in response to a treatment. The FDA suggests offering materials/resources in multiple languages to adequately support the enrollment.
The Call To Reexamine I/E Criteria For Improved Inclusion
To gain diversity in our clinical trials, we need to reexamine the protocol language and challenge any criteria that do not offer a scientific or clinical justification.
References:
- Center for Biologics Evaluation and Research, Center for Drug Evaluation and Research. Docket number FDA-2019-D-1264 Enhancing the Diversity of Clinical Trial Populations — Eligibility Criteria, Enrollment Practices, and Trial Designs Guidance for Industry | FDA
- Healy M, Richard A, Kidia K. How to Reduce Stigma and Bias in Clinical Communication: a Narrative Review. J Gen Intern Med. 2022 Aug;37(10):2533-2540. doi: 10.1007/s11606-022-07609-y. Epub 2022 May 6. PMID: 35524034; PMCID: PMC9360372.
- Peterson, Andrew & Karlawish, Jason & Largent, Emily. (2020). Supported Decision Making With People at the Margins of Autonomy. The American Journal of Bioethics. 21. 10.1080/15265161.2020.1863507.
- Oxford Learner’s Dictionaries; online access https://www.oxfordlearnersdictionaries.com/us/definition/american_english/stigma#:~:text=
stigma-,noun,stigma%20attached%20to%20being%20divorced.
About The Author:
Teri Crumb is a clinical research nurse. She has coordinated clinical research trials for over 25 years and has experience in multiple pediatric clinical areas. She has been a speaker at local, regional, and national research conferences. She obtained her BSN from Grand Valley State University, her MSN from Drexel University in Clinical Trials Research, and her certification through the Association of Clinical Research Professionals (ACRP). Her areas of interest are the training and education of clinical research staff. In 2022, she started her own LLC as a clinical research consultant.