Age Disparities Between Enrolled Patients on Clinical Trials and Real-World Population Persist

In a study of 300 phase 3 clinical trials, researchers have found that the gap of enrollment age and the median age of patients diagnosed with cancer is increasing.

Age disparities persist in cancer clinical trials among patients enrolled on clinical trials compared to the average age of cancer patients in a real-world setting, according to research published in JAMA Oncology.1

Looking at 302 trials that met inclusion criteria, and enrolled 262,354 participants, the median trial age of participants was 6.49 years younger than the overall patient population’s age (95% CI, −7.17 to −5.81 years; P < .001). Wider age differences were seen in industry-funded trials compared to non-industry-funded trials with a difference in median age (DMA) was −6.84 years in industry-sponsored trials compared to -4.72 years in non-industry-sponsored trials (P = .002). In 8.6% of the observed trials enrollment criteria was restricted the upper age limit of participants, as well as, restricting enrollees to those with an ECOG performance score of 0 to 1 were associated with a larger DMA. Moreover, age disparities were larger in trials that evaluated systemic therapy and treatments for lung cancer.

“While prior reports have shown some successes in addressing those imbalances, our data demonstrate that age disparities remain a persistent and worsening problem for oncology trials,” the researchers wrote discussing the results of the study. “Furthermore, industry-funded trials were associated with wider age disparities, and government initiatives generally do not extend to that setting.”

Utilizing the ClinicalTrials.gov database, researchers utilized search terms to find fully enrolled phase 3 randomized multi-arm trials addressing a therapeutic intervention for patients with cancer. Only trials addressing a single cancer type, such as breast, prostate, colorectal, or lung cancer were included. The median age of patients on the trial was then compared to the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database. The SEER median age by disease was also matched to the time of trial enrollment.

Researchers found no association between industry funding and upper age limits or ECOG performance limits in clinical trials, but the differences in the trials median age showed that the age disparity is “worsening and pervasive”. The overall restrictive nature of clinical trials leads to barriers for enrollment that don’t consider the broader patient population that would take these treatments. Trials that only looked at specific subtypes, such as patients with HER2 expressing breast cancer or non-small cell lung cancers with EGFR mutations in the tumor, also showed that younger patients were enrolled on these trials.

These trials were also more likely to be industry funded than unrestricted trials, but when researchers excluded these trials from overall results, the DMA was -5.88 years (95% CI, −6.62 to −5.13 years; P < .001) between the trials and SEER median age. Systemic therapy trials were also associated with a larger DMA in comparison to studies that looked at cytotoxic chemotherapy, −7.72 vs −5.30 years (P = .01), respectively. Targeted therapies were also more likely to be industry funded and when the analysis was restricted to just studies looking at targeted therapies, industry-sponsored studies also had a larger DMA, −7.94 vs −4.33 years, respectively (P = .01).

“Concerns regarding industry sponsorship leading to bias in results reporting have been expressed previously, but to our knowledge, no prior studies have demonstrated demographic disparities among trial participants as a function of industry funding,” the researchers explained. “A potential contributing factor could be that industry-funded trials might be more available at centers treating a greater proportion of younger patients.”

According to the NCI, the median age of cancer diagnosis is 66 years old.2 For some of the most common cancer types, the median age of diagnosis is also over 60 including, breast cancer at 62 years old, 67 years old for colorectal cancer, 71 years old for lung cancer, and 66 years old for prostate cancer. Furthermore, the risk factor for cancer overall continues to climb in higher age groups up to 1,000 per 100,000 people in age groups 60 years and older. This trend is set to expand, as by the year 2030 70% of all cancers are expected to occur in adults 65 and older.3

Looking at all 302 trials observed, researchers utilized linear regression models that showed an estimated annual change of -0.19 years in DMA of trials and median age of diagnosis (95% CI, −0.37 to −0.01 years; P = .04).1 Recently, the FDA issued guidance to make trials more inclusive for patients age and performance scores and has also looked to make data more readily accessible for both patients and clinicians through the Project Patient Voice platform. However, the researchers suggest that more is needed to understand the age disparity on display in clinical trials.

“Future efforts must focus on understanding the basis for these imbalances and addressing them; as the cancer population continues to age, such efforts are necessary to ensure both generalizability of trial results and trial access equity,” researchers concluded.

References

  1. Ludmir EB, Mainwaring W, Lin TA, et al. Factors Associated With Age Disparities Among Cancer Clinical Trial Participants. JAMA Oncol. 2019;5(12):1769-1773. doi: 10.1001/jamaoncol.2019.2055
  2. Age and Cancer Risk. National Cancer Institute. March 5, 2021. Accessed May 6, 2021. https://bit.ly/2SyHrYL
  3. White MC, Holman DM, Boehm JE, et al. Age and cancer risk: a potentially modifiable relationship. Am J Prev Med. 2014;46( suppl 1):S7-15. doi: 10.1016/j.amepre.2013.10.029