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There are many barriers keeping patients out of clinical trials, even if they want to join the clinical trial. There are multiple steps along the way and each step is a hurdle for patients. A patient must first have physical access to the trial (structural barrier). For example, I found the perfect clinical trial, however, it was 3,000 miles away, which was not easily accessible. Patients also have to fit the clinical characteristics needed to be on the clinical trial (clinical barriers). Patients have no control over these two barriers. A study found that structural and clinical barriers keep many patients from joining clinical trials (Unger, 2019). These barriers keep patients from even getting to the point where they can make a decision about whether to join the clinical trial or not. They never even get this opportunity.
One clinical barrier is that patients must meet specific conditions before they can join the clinical trial. These conditions are characteristics each patient must have before they can join a trial. These conditions are called eligibility criteria (see information box Eligibility Criteria). There are two types of eligibility criteria.
- Inclusion Criteria. Conditions patients must have before joining a clinical trial. For example, one condition may be the disease type and stage, like stage III lung cancer.
- Exclusion Criteria. Conditions patients cannot have in order to join a clinical trial. For example, one condition may be the patient cannot be pregnant.
There are several reasons why patients must meet specific conditions to join a clinical trial. One reason is to make sure patients in the clinical trial are like each other in factors like age, type of cancer, and general health. This means the results of the trial are not due to chance. Another important reason is patient safety. Patients who are more likely to have severe or life-threatening side effects should not join the clinical trial. Some clinical trials only allow patients who are likely to benefit to join the trial. This is common in clinical trials looking at targeted treatments that only work in certain patients. However, not all eligibility criteria are needed. This means there are patients who cannot join a clinical trial, but who may benefit from the new treatment. Criteria for inclusion and exclusion differ from trial to trial.
Broadening eligibility criteria will allow more patients to qualify for clinical trials. Allowing more types of patients to join a clinical trial will make the results more relevant to all patients, who will eventually get the treatment. It will also increase early access to new treatments for patients who may benefit. Patients look for clinical trials as a treatment option. It is frustrating for patients when they cannot qualify for a trial.
The American Society of Clinical Oncology (ASCO), Friends of Cancer Research (FOCR), and Food and Drug Administration (FDA) joined forces in 2016. They formed working groups to look at specific conditions used to qualify patients for clinical trials. The working groups had stakeholders from various groups involved in clinical trial development including patients. Each working group examined a specific eligibility criterion. They developed guidelines about how to broaden conditions used to include or exclude patients in trials. The first set of guidelines addresses brain metastasis, HIV infection, minimum age, organ dysfunction, and prior or concurrent malignancies (Kim, 2017). In 2021, they developed a second set of guidelines addressing performance status, prior therapies, laboratory tests, washout periods, and concomitant medications (Kim, 2021). See Figure 1 (Criteria Definitions) for a list of all the conditions examined by the working groups and their definitions. See Figure 2 (Examples of New Guidance) for some of the recommendations (see Kim 2017 and Kim 21 for full recommendations). In general, eligibility for a trial should be based on science and/or patient safety.
A study looked at whether broadening eligibility allowed more patients to join a clinical trial (Harvey, 2021). They found that broadening three criteria allowed more patients to join a trial. The number of patients who could join the trial doubled using broader criteria. These broader criteria also changed the type of patients who could join the trial. The patients were more representative of those who have the type of cancer. For example, more women and older patients may be able to join a lung cancer trial. This study showed that more patients and patients that are more diverse might be able to join trials using broader eligibility criteria.
Patients want the new guidelines on broadening eligibility criteria to be used as soon as possible. The combination of both sets of guidelines can make trials accessible to more patients. All people involved in developing clinical trials need to be aware of these guidelines. Patients want to have the choice to join a clinical trial, but first, they need to qualify. Having that choice taken away based on outdated eligibility criteria is a barrier to potential life-saving treatments for patients.
Edited by MaryAnn Bowyer
Unger JM, Vaidya R, Hershman DL, Minasian LM, Fleury ME. Systematic Review and Meta-Analysis of the Magnitude of Structural, Clinical, and Physician and Patient Barriers to Cancer Clinical Trial Participation. J Natl Cancer Inst. 2019 Mar 1;111(3):245-255. doi: 10.1093/jnci/djy221. PMID: 30856272; PMCID: PMC6410951.
Kim ES, Bruinooge SS, Roberts S, Ison G, Lin NU, Gore L, Uldrick TS, Lichtman SM, Roach N, Beaver JA, Sridhara R, Hesketh PJ, Denicoff AM, Garrett-Mayer E, Rubin E, Multani P, Prowell TM, Schenkel C, Kozak M, Allen J, Sigal E, Schilsky RL. 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 Nov 20;35(33):3737-3744. doi: 10.1200/JCO.2017.73.7916. Epub 2017 Oct 2. PMID: 28968170; PMCID: PMC5692724.
Kim ES, Uldrick TS, Schenkel C, Bruinooge SS, Harvey RD, Magnuson A, Spira A, Wade JL, Stewart MD, Vega DM, Beaver JA, Denicoff AM, Ison G, Ivy SP, George S, Perez RP, Spears PA, Tap WD, Schilsky RL. Continuing to Broaden Eligibility Criteria to Make Clinical Trials More Representative and Inclusive: ASCO-Friends of Cancer Research Joint Research Statement. Clin Cancer Res. 2021 Feb 9. doi: 10.1158/1078-0432.CCR-20-3852. Epub ahead of print. PMID: 33563632.
Harvey RD, Bruinooge SS, Chen L, Garrett-Mayer E, Rhodes W, Stepanski E, Uldrick TS, Ison G, Khozin S, Rubinstein WS, Schenkel C, Miller RS, Komatsoulis GA, Schilsky RL, Kim ES. Impact of Broadening Trial Eligibility Criteria for Patients with Advanced Non-Small Cell Lung Cancer: Real-World Analysis of Select ASCO-Friends Recommendations. Clin Cancer Res. 2021 Feb 9. doi: 10.1158/1078-0432.CCR-20-3857. Epub ahead of print. PMID: 33563634.