Some clinical trials or cancer treatments require participants to have a certain level of white blood cells called 'neutrophils' to ensure that they're healthy enough to participate in the trial, and this is measured by a standard blood test.
People with the Duffy-null phenotype have relatively lower levels of neutrophils when measured in the blood. In people without the Duffy-null phenotype, low neutrophil levels would be associated with a higher risk of infection, but this isn't the case for people with Duffy-null phenotype – they are often perfectly healthy.
Dr Stephen Hibbs, lead author and HARP Fellow, said: "Health inequity in cancer treatment and research has many causes, and some are more difficult to address than others. Neutrophil criteria for clinical trials and dose modifications are a hidden contributor to inequity that can be rectified. Now, action to amend these criteria is needed to ensure Duffy-null patients are not disadvantaged".
The study, published today in JAMA Open Network, demonstrates the need to reevaluate what is considered 'normal' across healthcare to ensure that criteria and measures are not excluding races and ethnicities.
Co-author Dr Vanessa Apea has spoken about her own experiences of receiving a misdiagnosis based on an interpretation of blood test results that did not take into account her ancestry. In an interview with Stat News, Dr Apea, Consultant Physician in Sexual Health and HIV and Honorary Senior Lecturer at Queen Mary, describes being told that having lower levels of neutrophils in her blood might indicate she had leukaemia. In fact, she was healthy; the assessment of her neutrophil levels had been made against reference figures created for white European populations which erroneously flagged her results as 'abnormal'.
The study
The researchers examined participation criteria for 289 major phase III trials of drugs for the five most prevalent cancers in the United States and UK: prostate, breast, colorectal, and lung cancer, and melanoma. They found that 76.5% of the trials excluded patients whose blood neutrophil counts were in the normal range for people with the Duffy-null phenotype. The trials with the highest exclusion rate – 86.4% – were for patients with colorectal cancer. Even trials of hormonal cancer therapies – which generally don't decrease neutrophil levels – had a significant exclusion rate.
The researchers also examined the extent to which clinical trial protocols require that drug doses be modified for patients with lower neutrophil counts. In a review of 71 clinical trials that led to the establishment of ongoing treatment guidelines, researchers found that more than half required reducing the drug dose, delaying its administration, or stopping it if a participant's neutrophil count fell below a level that was still normal for people with the Duffy null phenotype. Failing to account for Duffy-null phenotype therefore led to recommendations for many standard cancer drugs to give inappropriately less-effective doses for some individuals.
Based on their findings, the researchers recommend that clinical trials of cancer drugs allow entry to patients with lower, but normal-for-them neutrophil counts. Testing for Duffy-null phenotype should also be routine. For trials that have already been completed, follow-up studies are needed to determine if administering full doses to people with Duffy-null phenotype and lower neutrophils counts are safe and effective, researchers say.
The study was funded by the National Institutes of Health, the American Society for Clinical Oncology, and the Wellcome Trust.
