Recruitment and retention challenges in the new era of Alzheimer’s trials - could advance research planning play a role?

Agreement: I Agree Body: Dear Editor, Given the urgent need for effective, safe, and affordable treatments for Alzheimer's disease, news that a new clinical trial might cut years off the search [1] has been met with huge interest in the UK. The AD-SMART trial (Alzheimer’s disease Systematic Multi-arm Adaptive Randomised Trial) is described as a ‘first-of-its-kind’ trial that aims to test whether existing medicines can improve symptoms in patients with Alzheimer’s [2]. Around 1,200 adults aged 55 and over with symptomatic Alzheimer’s disease (mild cognitive impairment or mild to moderate Alzheimer’s disease) will be recruited, randomised to receive one of two re-purposed medicines or a placebo, and followed up for 18 months with regular assessments of their cognitive symptoms (e.g. memory, problem solving) and ability to perform daily activities (e.g. showering, cooking). MRI scans will be conducted at the start and end of the trial to look for changes in brain structure and function. At the same time, the UK Government has announced a £33 million investment in dementia research, including the flagship BARBARA programme which is a co-ordinated platform linking the UK’s health data, research and clinical trial capabilities with the aim of making it easier for researchers to find participants and for people to take part in studies [3]. These announcements coincided with publication of the 2026 World Alzheimer Report which highlights that clinical trials have now led to the first disease modifying treatments for Alzheimer’s disease [4]. However, it also reports that recruiting, and in particular retaining, participants in Alzheimer’s trials is proving to be especially challenging. Trials typically run for 18 months or more, and recent multi-year Alzheimer’s disease studies have lost up to 54% of their participants during this time [4]. Longer follow-up periods make this issue more common, partly due to the progressive nature of Alzheimer's disease which may mean that participants who have capacity to consent at the time of enrolment then lose decisional capacity during their participation in a study. As new therapies emerge, including treatments for later stages of Alzheimer’s, the challenges surrounding informed consent are likely to become even more complex. Successfully delivery of trials will be limited unless the practical and ethical challenges are tackled [5]. Efforts to address the ethical challenges of Alzheimer’s trials to date have largely focused on enrolment decisions [6] rather than ongoing participation. As more people with later stage Alzheimer’s disease enter clinical trials, questions about future decision-making become increasingly important. Advance research planning (ARP) – a process in which people are encouraged to think about, discuss and document their future research preferences [7] - should become a routine part of dementia care and research discussions. ARP could enable people living with Alzheimer’s to express their preferences about future research participation while they retain decision-making capacity. These preferences may help guide proxy decision-makers involved in participation decisions for participants who lack capacity to consent to a trial, or who lose capacity during a trial. Research has demonstrated widespread support for ARP as well as identifying a number of regulatory and methodological considerations that may help guide the implementation of ARP in dementia research [8,9]. This includes practical guidance on the development of an advance research directive for documenting wishes about future research participation [10]. As Alzheimer's research enters a new era with innovative trials such as AD-SMART, planning ahead for research decisions should be considered an important extension of dementia care. Future Alzheimer’s trials should consider opportunities to support participants to discuss and document their preferences about participating in, and remaining in, a trial should they later lose the capacity to make such decisions. References: 1. Iacobucci G. AD-Smart: Alzheimer’s trial will test diabetes and ADHD drugs on patients. BMJ 2026; 395: e101219. 2. AD-SMART website, https://www.adsmarttrial.org/ (accessed 3 November 2026). 3. “I have real hope that Britain can come together to defeat dementia" – PM. GOV.UK, https://www.gov.uk/government/news/i-have-real-hope-that-britain-can-com... (accessed 3 November 2026). 4. Alzheimer’s Disease International. World Alzheimer Report 2026: A new era in dementia clinical trials, https://www.alzint.org/resource/world-alzheimer-report-2026/ (21 September 2026, accessed 3 November 2026). 5. Milne R, Richard E, Brayne C. Challenges associated with the development of “trial ready cohorts” for dementia prevention trials. BMJ 2025; 388: e080275. 6. Jacobson M, Deuschle C, Peneva D, et al. Evaluating evidence-based recruitment strategies for Alzheimer’s disease and related dementias clinical trial research: A literature review. The Journal of Prevention of Alzheimer’s Disease 2026; 13: 100532. 7. Ries N, Johnston B, Jeon Y-H, et al. Advance planning for research participation: Time to translate this innovation into practice. Australasian Journal on Ageing 2023; 42: 225–233. 8. Shepherd V, Hood K, Wood F. Planning ahead for research participation: survey of public and professional stakeholders’ views about the acceptability and feasibility of advance research planning. BMC Medical Ethics 2023; 24: 1–11. 9. Shepherd V, Ries N. Public and professionals’ perceptions and experiences of advance planning for research: a scoping review. Epub ahead of print 13 August 2026. DOI: 10.21203/rs.3.rs-8891061/v1. 10. Ries NM, Johnston B. Making an advance research directive: An interview study with adults aged 55 and older with interests in dementia research. Ethics & Human Research 2023; 45: 2–17. No competing Interests: Yes The following competing Interests: Electronic Publication Date: Thursday, November 5, 2026 - 15:37 AI use: No, I have not used AI Highwire Comment Subject: Workflow State: Released Full Title: Recruitment and retention challenges in the new era of Alzheimer’s trials - could advance research planning play a role? Highwire Comment Response to: Check this box if you would like your letter to appear anonymously:: Last Name: Shepherd First name and middle initial: Victoria Email: shepherdvl1@cardiff.ac.uk Address: Centre for Trials Research, Cardiff University, Heath Park, Cardiff Occupation: Professorial Research Fellow Other Authors: Nola Ries, Faculty of Law, University of Technology Sydney Affiliation: Cardiff University BMJ: Additional Article Info: Rapid response