Study: Clinical trial eligibility excludes more Black than white patients

IN-DEPTH REVIEW OF RESEARCH

Study background

Numerous studies have identified a disparity in cancer outcomes between Black and white people.  One reason for this may be due to differences in access to clinical trials, which offer newer therapies or combinations of therapies. Eligibility criteria are strict barriers to enrolling in these trials. Traditional criteria may not always be medically guided and may promote inequitable access to clinical trials.

Results are less generalizable when the diversity of participants in a clinical trial is low. If results are similar between racial groups, doctors can be more confident in treatments. And if results differ, understanding those racial differences in treatment safety and effectiveness allows physicians to anticipate complications and tailor treatments more appropriately. This study suggests that revising the eligibility criteria to align with recommendations by the Food and Drug Administration (FDA), ASCO and Friends of Cancer Research (Friends) in a medically sound way would improve equitable access to clinical trials.
 

Researchers of this study wanted to know

Do eligibility criteria contribute to racial disparities in accessing clinical trials? If so, would aligning eligibility criteria with recommendations by FDA impact racial disparities in accessing clinical trials?
 

Populations looked at in this study

People aged 18 years or older who were treated for pancreatic ductal adenocarcinoma at Virginia Commonwealth University’s Massey Cancer Center from January 1, 2010 to December 31, 2019, were included in this study.
 

Study design

This was a retrospective cross-sectional study, meaning that it evaluated the medical records of people who had been diagnosed with pancreatic cancer over a specified period.

Patients were evaluated to see if they met the eligibility criteria for clinical trials that were enrolling during 2010-2017, as identified through clinicaltrials.gov.  A total of 676 people (42.5 percent Black and 51.6 percent white) were evaluated for eligibility for 86 available Phase II and Phase III clinical trials. 

This study looked at traditional eligibility criteria that could be determined by history, such as laboratory test results. Researchers looked at the number of people who were eligible for clinical trials out of all who presented for treatment, comparing the percentage of Black to white people who were found eligible.  Researchers then recompared eligibility by race, using revised criteria as recommended by FDA guidelines released in 2020, ASCO and Friends guidelines. The proposed revisions to traditional eligibility criteria for pancreatic cancer clinical trials are outlined in the table below.

Study findings

This study examined the medical records of patients and found that Black people were less likely to be eligible for pancreatic cancer clinical trials compared to white people who were treated at the same institution during the same period.

• 42.4% of Black people vs. 33.2% of white people were ineligible for clinical trials based on objective eligibility criteria.

Specific eligibility criteria that contributed to the differential access included:

• Blood albumin levels (14.1% of Black people were ineligible vs. 7.9% of white people)
• Infectious history
  • HIV (3.1% of Black people were ineligible vs. 0.3% of white people)
  • Hepatitis B (1.7% of Black people were ineligible vs 0% of white people)
  • Hepatitis C (9.1% of black people were ineligible vs. 3.4% of white people)
• The researchers also looked at the following:
  • Uncontrolled diabetes mellitus (8.6% of Black people were ineligible vs 6.0% of white people)
  • Kidney function (5.7% of Black people were ineligible vs. 3.0% of white people)
  • Recent coronary stent (1.4% of Black people were ineligible vs. 0 white people)
  • Prior cancer (2.4% of Black people were ineligible vs. 2.6% of white people)
  • Prior cancer treatment (9.1% of Black people were ineligible vs. 14.0% of white people)

None of these factors met statistical significance.

When the researchers applied the revised criteria to the participants, the disparity in access was resolved. Using the revised criteria:

• 26.8% Black vs. 24.8% white people (p =0.023) were ineligible for clinical trials.

Strengths and limitations

Strengths

• Virginia Commonwealth University is in an area with a very diverse population.  Black patients make up a large proportion of the patient population.
• The authors appropriately recognized that revising eligibility criteria is one factor in addressing racial differences in clinical trial participation. 

Limitations

• This study was retrospective; it may be limited by missing or improperly recorded data.
• This study covered a decade of patient records, during which time there may have been changes in documentation, coding or health management.  As researchers studied Black and white people during this same time, both groups should be equally affected by potential changes. However, these changes may have a differential impact due to racial bias.
• This study was small and involved a single institution.
  • A larger, multi-institution study may evaluate differential access by other races and add depth to Black and white disparities to ensure comprehensive modification of eligibility criteria.
  • Because this was a small, retrospective study, the focus was necessarily narrow and cannot address all potential barriers to clinical trial eligibility. 
  • The authors specifically commented that their study does not address subjective criteria.
• Additional barriers to accessing clinical trials in a real-world setting include:
  • Documented delays in diagnosing Black patients compared to white patients. Delays in diagnosing cancer can impact trial eligibility, as overall health may deteriorate the longer cancer is unidentified and untreated. Additionally, some clinical trials are restricted to earlier stages, which would need to be identified earlier. Barriers in diagnosing cancer may be due to racial bias of medical providers, socioeconomic or geographical barriers to accessing care that differentially impacts black versus white people and younger age at onset among black people. 
    • Relatively decreased wealth accumulation due to race and younger age of cancer onset in Black people can lead to a different ability to access insurance, sustain time off from work and/or manage other responsibilities such as childcare.  This may also impact trial eligibility, as the frequency and demands of required visits can be more challenging for those with less financial or temporal resources.
    • Geographical availability of clinical trials in areas with high Black populations. Novel therapies may require specific tools or specialists, which may not be funded in areas with higher Black populations.

• The proposed strategy of loosening eligibility criteria was not evaluated for medical appropriateness across the identified trials.
   

Conclusions

Although this study was limited to pancreatic cancer, revising eligibility criteria is likely applicable to other cancer types. This study identified eligibility criteria for pancreatic cancer clinical trials as a potential cause of decreased access to clinical trials for Black people compared to white people. Decreased access means that Black people are less likely to benefit from newer therapies.  Also, studying newer therapies in a less diverse group of people means that the safety and effectiveness of these therapies may not be well understood for diverse recipients of these therapies outside the context of a clinical trial.  This, in turn, perpetuates racial disparities in cancer treatment outcomes.

The authors of the study encourage clinical trial designers and regulators to make eligibility criteria less restrictive, if medically appropriate, which can make access to clinical trials more racially equitable.  They propose specific criteria changes and show that these changes promote equitable access to clinical trials using the same patient population.

Overall, this study identifies room for improvement and the need for further evaluation of clinical trial design in improving equitable access to clinical trials. It also encourages physicians and patient advocates to push for more medically justifiable eligibility criteria that do not perpetuate disparities in clinical trial participation.

Although this study was specific to pancreatic cancer, restrictive exclusion criteria have been identified as a concern for many types of cancer. Just how applicable this research is across cancer types is unclear, although there may be criteria among many trials that are unnecessarily restrictive for the question being asked.
 

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posted 8/23/22