Ethical and Social Implications of Using Predictive Modeling for Alzheimer’s Disease Prevention: A Systematic Literature Review

Article type: Research Article

Authors: Angehrn, Zuzanna^{a; *} | Sostar, Jelena^a | Nordon, Clementine^b | Turner, Andrew^c | Gove, Dianne^d | Karcher, Helene^a | Keenan, Alexander^e | Mittelstadt, Brent^f | de Reydet-de Vulpillieres, Frederic^g

Affiliations: [a] Certara, Lörrach, Germany | [b] INSERM U1178, CESP, Paris, France | [c] NIHR ARC West, University of Bristol, UK | [d] Alzheimer Europe, Luxembourg | [e] Janssen Pharmaceutical NV, USA | [f] Oxford Internet Institute, University of Oxford, Oxford, UK | [g] Novartis Pharma AG, Basel, Switzerland

Correspondence: [*] Correspondence to: Zuzanna Angehrn, Certara, Chesterplatz 1, 79539 Lörrach, Germany. Tel.: +49 0 7621 98687 30; Fax: +49 0 7621 98687 39; E-mail: [email protected].

Abstract: Background:The therapeutic paradigm in Alzheimer’s disease (AD) is shifting from symptoms management toward prevention goals. Secondary prevention requires the identification of individuals without clinical symptoms, yet “at-risk” of developing AD dementia in the future, and thus, the use of predictive modeling. Objective:The objective of this study was to review the ethical concerns and social implications generated by this new approach. Methods:We conducted a systematic literature review in Medline, Embase, PsycInfo, and Scopus, and complemented it with a gray literature search between March and July 2018. Then we analyzed data qualitatively using a thematic analysis technique. Results:We identified thirty-one ethical issues and social concerns corresponding to eight ethical principles: (i) respect for autonomy, (ii) beneficence, (iii) non-maleficence, (iv) equality, justice, and diversity, (v) identity and stigma, (vi) privacy, (vii) accountability, transparency, and professionalism, and (viii) uncertainty avoidance. Much of the literature sees the discovery of disease-modifying treatment as a necessary and sufficient condition to justify AD risk assessment, overlooking future challenges in providing equitable access to it, establishing long-term treatment outcomes and social consequences of this approach, e.g., medicalization. The ethical/social issues associated specifically with predictive models, such as the adequate predictive power and reliability, infrastructural requirements, data privacy, potential for personalized medicine in AD, and limiting access to future AD treatment based on risk stratification, were covered scarcely. Conclusion:The ethical discussion needs to advance to reflect recent scientific developments and guide clinical practice now and in the future, so that necessary safeguards are implemented for large-scale AD secondary prevention.

Keywords: Biomedical ethics, dementia, early diagnosis, early intervention, prodromal symptoms, qualitative research, secondary prevention

DOI: 10.3233/JAD-191159

Journal: Journal of Alzheimer's Disease, vol. 76, no. 3, pp. 923-940, 2020