Older adults bear most of the cancer burden yet remain systematically underrepresented in cancer clinical trials (CTs), largely because clinicians decide not to invite them. The QualiSAGE mixed-methods study (Hagège et al., Age and Ageing 2024) traced the whole participation pathway in five Paris-area cancer centres and found that non-invitation — not patient refusal — was structured by clinicians' perceptions of patients' social support and functional capacity, with socially isolated patients most likely to be passed over. The study left open the causal-mechanism question, and subsequent evidence syntheses confirmed that the linked intervention-effectiveness question is also unresolved in the 2026 literature: (1) the causal mechanisms by which clinician perceptions of social support and functional capacity translate into non-invitation decisions, for which further investigation of the patient–physician and participant–investigator relationship is needed; and (2) which targeted interventions (clinician bias training, routine geriatric co-assessment, dedicated recruitment staff, transport or home-help provisions, redesigned trial logistics) are effective, scalable and cost-effective in increasing invitation and uptake among older, socially isolated or socioeconomically deprived patients. A January 2026 scoping review identified only seven intervention studies (two randomised) with designs too heterogeneous to support recommendations, and no published study has directly observed the invitation interaction, so the open core is confirmed.

Background

Cancer clinical trials (CTs) — prospective studies testing treatments in patients — are the evidentiary basis for oncology, yet older adults, who constitute the majority of new cancer diagnoses, have long been underrepresented in them. Consequences include 'informed guesswork' when prescribing to older patients and trial results that do not generalise to them. Research dating back to Ford et al.'s 2008 systematic review grouped the causes into patient-level, provider-level, study-design-level and health-system-level barriers. A decisive insight of subsequent work is that the dominant loss occurs at the invitation step: treating physicians act as gatekeepers who decide whether an eligible older patient is ever asked to participate, so no patient-level motivation can matter until the invitation happens. Sedrak et al.'s 2021 systematic review (CA: A Cancer Journal for Clinicians) consolidated the barrier evidence but found minimal intervention research — only one study aimed at improving recruitment of older adults. The largest single RCT, CALGB 360001 (Kimmick et al., 2005), tested a geriatric educational intervention for clinicians at cooperative-group institutions and found no improvement in accrual of patients aged 65+ over standard information, suggesting that education alone does not overcome the barrier. The QualiSAGE study (Hagège et al., 2024; five cancer centres in the greater Paris area, 2017–2020, mixed quantitative and qualitative methods) sharpened the picture by following the entire pathway from CT availability to invitation to agreement. Of 265 eligible older solid-tumour patients, 84.2% were invited to at least one CT; non-invitation was independently associated with poor performance status (a 0–5 scale of functional impairment, ECOG-PS), receiving radiotherapy, primary education only, being single/divorced/widowed, having no children, and having home support — i.e., clinicians' judgements about a patient's social network and care needs, not just age or disease. Qualitative interviews with oncologists and clinical research staff confirmed that 'living conditions as well as general health' entered the invitation decision, and the authors concluded that efforts should target the physician–patient relationship, the medical profession and hospital funding rather than the patient alone. Geriatric assessment (a multidisciplinary evaluation of an older patient's function, comorbidity, cognition and social situation, sometimes abbreviated GA or CGA) is frequently proposed as a co-assessment tool to make these judgements explicit and equitable; a companion qualitative study of geriatrician–oncologist collaboration (Hagège et al., 2021) examined how such cooperation around inclusion decisions works in practice. What remains missing, as the study's own discussion states and later syntheses confirm, is (i) a causally specified account of how clinician perceptions become non-invitation decisions, and (ii) demonstrated effective, scalable, cost-effective remedies.

Problem Statement

The source study (Hagège et al. 2024) established that the decisive barrier to older adults' participation in cancer clinical trials (CTs) is clinician-side non-invitation, driven by perceptions of patients' social support and functional capacity, and it posed a linked set of unresolved questions that later literature has not closed. The problem is to convert this documented barrier map into validated remedies and a validated causal account, under one overarching objective — achieving fair, effective inclusion of older adults in cancer CTs by acting on the clinician-side invitation process rather than on the patient alone. Concretely: (1) Causal mechanisms — specify the mechanisms by which clinicians' perceptions of social support and functional capacity translate into non-invitation decisions, through further investigation of the patient–physician and participant–investigator relationship, including how these perceptions interact with patient sociodemographic characteristics (social isolation, education, family structure) and with ageist assumptions; (2) Targeted interventions — determine which interventions that act on this pathway (for example clinician training to reduce bias, routine geriatric co-assessment, dedicated staff to support trial participation, transport or home-help provisions, or redesigned trial logistics) are effective, scalable and cost-effective in increasing invitation and subsequent uptake among older patients, particularly those who are socioeconomically deprived or socially isolated; (3) Generalisability and institutional context — establish whether these mechanisms and remedies hold across other healthcare systems, more diverse trial portfolios (e.g., radiotherapy- or surgery-focused CTs) and populations, deepen the qualitative evidence on refusing patients' motives, and test the hypothesised institutional and policy determinants (e.g., effects of hospital funding models on clinicians' invitation behaviour). Components (1) and (2) are the primary open core — both were confirmed unresolved by the January 2026 scoping review of this exact literature — and are the components required for a complete answer; component (3) is optional context that contributes to the same objective by bounding where the remedies apply but is not required for completeness. A complete answer would allow a qualified expert in geriatric oncology and trial methodology to judge, from the submitted evidence, that the invitation mechanism is causally specified and that at least one targeted remedy demonstrably increases invitation and uptake of older adults with known effect size, scalability and cost. Given this evidence base, component (2) is resolved where direct randomised evidence is unavailable by a mechanism-grounded candidate remedy argued against the existing heterogeneous studies and specified with an explicit evaluation design, projected effect size and cost model.

References

  1. Hagège M, Bringuier M, Martinez-Tapia C, Chouaïd C, Helissey C, Brain E, Lempdes GR, Dubot C, Bello-Roufai D, Geiss R, Kempf E, Gourden A, Elgharbi H, Garrigou S, Gregoire L, Derbez B, Canouï-Poitrine F. Disentangling the reasons why older adults do not readily participate in cancer trials: a socio-epidemiological mixed methods approach. Age and Ageing 53(2):afae007, 2024. doi:10.1093/ageing/afae007. https://doi.org/10.1093/ageing/afae007 (full text: PMC10861365)
  2. Dillon S, Galvin R, Hartigan D, Clifford R, Peters N, Robinson K, O'Connor M, O'Donnell P. Closing the gap of older adult recruitment to cancer clinical trials: a scoping review. BMC Cancer 26:788, 2026. doi:10.1186/s12885-026-16051-w. https://doi.org/10.1186/s12885-026-16051-w (full text: PMC13321688)
  3. Sedrak MS, Freedman RA, Cohen HJ, Muss HB, Jatoi A, Klepin HD, Wildes TM, Le-Rademacher JG, Kimmick GG, Tew WP, George K, Padam S, Liu J, Wong AR, Lynch A, Djulbegovic B, Mohile SG, Dale W. Older adult participation in cancer clinical trials: A systematic review of barriers and interventions. CA: A Cancer Journal for Clinicians 71:78-92, 2021. doi:10.3322/caac.21638. https://doi.org/10.3322/caac.21638
  4. Kimmick GG, Peterson BL, Kornblith AB, Mandelblatt J, Johnson JL, Wheeler J, Heinze R, Cohen HJ, Muss HB. Improving accrual of older persons to cancer treatment trials: A randomized trial comparing an educational intervention with standard information: CALGB 360001. Journal of Clinical Oncology 23(10):2201-2207, 2005. doi:10.1200/JCO.2005.01.222. https://doi.org/10.1200/JCO.2005.01.222
  5. Campbell TC, Gedeon C, Qudah B, Jasicki M, Kwekkeboom KL, Zelenski A. Improving cancer clinical trial enrollment and patient understanding using TrialTalk, a structured communication method: a pilot randomized controlled trial. Supportive Care in Cancer 34(4):359, 2026. doi:10.1007/s00520-026-10505-4. https://doi.org/10.1007/s00520-026-10505-4
  6. Hagège M, Canouï-Poitrine F, Derbez B. Including older patients in cancer trials: A qualitative study of collaboration between geriatricians and oncologists. Journal of Geriatric Oncology 12(6):945-951, 2021. doi:10.1016/j.jgo.2021.03.002. https://doi.org/10.1016/j.jgo.2021.03.002
  7. Baldini C, Mislang ARA, Cheung K-L, Pilleron S, Wildiers H, Rostoft S, Neuendorff NR, Frelaut M, Kanesvaran R, Papamichael D, O'Hanlon S, Puts M, Canouï-Poitrine F, Dal Lago L, Soo WK, O'Donovan A, Gomes F, Cooper L, Canin B, Bringuier M, Battisti NML, Biganzoli L, Brain E. The ESMO/SIOG Cancer in the Elderly Working Group pragmatic strategies for clinical trial designs and endpoints in older adults with cancer. ESMO Open 11:105940, 2026. doi:10.1016/j.esmoop.2025.105940. https://doi.org/10.1016/j.esmoop.2025.105940
  8. O'Hanlon S. Cancer and older people. A research collection and commentary on the theme. Age and Ageing 54(5):afaf113, 2025. doi:10.1093/ageing/afaf113. https://doi.org/10.1093/ageing/afaf113
  9. Ford JG, Howerton MW, Lai GY, Gary TL, Bolen S, Gibbons MC, Tilburt J, Baffi C, Tanpitukpongse TP, Wilson RF, Powe NR, Bass EB. Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review. Cancer 112(2):228-242, 2008. doi:10.1002/cncr.23157. https://doi.org/10.1002/cncr.23157
  10. Yang C, Joosten H, Chepulis L, Varallo FR, van Dijk P, Crews DC, Vart P. Bridging the age gap: improving representation of older adults in clinical trials for type 2 diabetes and chronic kidney disease. The Lancet Healthy Longevity 6:100796, 2025. doi:10.1016/j.lanhl.2025.100796. https://doi.org/10.1016/j.lanhl.2025.100796