Division of Oncology, Department of Medicine, Stanford University Stanford, California, United States
Objective: Children and older adults have traditionally been underrepresented in clinical trials, which hampers the ability to understand the efficacy and safety of medical treatments across all stages of life. Recognizing this critical gap, the National Institutes of Health established the Inclusion Across the Lifespan Policy in January 2019 to expand representation of children and older adults in clinical trials. Soft tissue sarcomas (STS) are rare tumors arising in mesenchymal tissue occurring at higher proportion in children and with poorer survival outcomes in older adults. The disparate impact of STS across age groups underscores the importance of including diverse age populations in clinical trials.
Methods: We identified all phase 3 and 4 interventional studies in the United States for STS from February 29, 2000 to January 31, 2024. Trials were classified as pre-policy if they commenced enrollment before the NIH policy enacted on January 25, 2019 and post-policy if they commenced enrollment before or on January 25, 2019. Data was manually extracted via reviewing inclusion and exclusion policies of trial recruitment information and published abstracts and papers. Factors were analyzed pre-policy and post-policy via Fisher exact test.
Results: In total, 40 clinical trials were identified of which 23 were pre-policy and 17 were post-policy and consisting of approximately 12,000 patients. Most trials did include some age limitations in the pre-policy or post-policy eras (22 of 23 [95.6%] vs 2 of 17 [11.8%], p = 0.56). Most trials included either lower age limitations (15 of 23 [65.2%] vs 11 of 17 [64.7%], p = 1.0) and/or upper age limitations (8 of 23 [65.2%] vs 6 of 17 [64.7%], p = 1). Trial sponsorship was similar in the pre-policy vs post-policy periods, with a trend toward public compared to industry (9 of 23 [39.1%] vs 10 of 17 [58.8%] respectively, p = 0.34). Trials with upper age limits were mostly funded by the Children’s Oncology Group (11 of 14 [78.6%]). Overall, 14 trials had upper age limits with the median being 49 years and most being publicly funded studies (13 of 14 [92.9%]) both pre-policy and post-policy (8 of 8 [100%] vs 5 of 6 [83.3%], p = 0.43); meanwhile, 26 trials had lower age limits with the median being 18 years with most being industry funded (15 of 26 [57.7%]) both pre-policy and post-policy (9 of 15 [60%] vs 6 of 11 [54.5%], p = 1).
Conclusion: Five years after the adoption of the Inclusion Across the Lifespans Policy, challenges remain in ensuring children and older adults are adequately represented in sarcoma clinical trials. The policy has not seen a significant increase in inclusion of both vulnerable populations. Given that many trials with lower age limits were industry funded while trials with upper age limits were publicly funded, it is important to closely monitor implementation of this policy given the variety of stakeholders who can change the landscape of STS treatment for patients. Notably, industry funded trials often limit access to children, likely given the risks associated with novel medications; however, given that STS are more common in the pediatric population, there is a large gap between disease burden and drug research. Overall, there needs to be greater focus on clinical trial inclusion especially given the heterogeneity of this disease affecting patients of all ages. Comprehensive data that includes children and older adults will not only enhance our understanding of disease progression and response to treatment but also drive advancements in personalized medicine.
