Angehrn Zuzanna, Sostar Jelena, Nordon Clementine, Turner Andrew, Gove Dianne, Karcher Helene, Keenan Alexander, Mittelstadt Brent, de Reydet-de Vulpillieres Frederic
Certara, Lörrach, Germany.
INSERM U1178, CESP, Paris, France.
J Alzheimers Dis. 2020;76(3):923-940. doi: 10.3233/JAD-191159.
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.
The objective of this study was to review the ethical concerns and social implications generated by this new approach.
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.
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.
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.
阿尔茨海默病（AD）的治疗模式正在从症状管理转向预防目标。二级预防需要识别没有临床症状但未来有患AD痴呆症“风险”的个体，因此需要使用预测模型。
本研究的目的是回顾这种新方法所产生的伦理问题和社会影响。
我们在Medline、Embase、PsycInfo和Scopus中进行了系统的文献综述，并在2018年3月至7月期间通过灰色文献检索对其进行补充。然后我们使用主题分析技术对数据进行定性分析。
我们确定了与八项伦理原则相对应的31个伦理问题和社会关注：（i）尊重自主性，（ii）有益性，（iii）不伤害，（iv）平等、正义和多样性，（v）身份和耻辱，（vi）隐私，（vii）问责制、透明度和专业性，以及（viii）避免不确定性。许多文献将疾病修饰治疗的发现视为证明AD风险评估合理的必要和充分条件，而忽视了在公平获取治疗、确定这种方法的长期治疗结果和社会后果（如医学化）方面未来的挑战。与预测模型特别相关的伦理/社会问题，如足够的预测能力和可靠性、基础设施要求、数据隐私、AD中个性化医疗的潜力以及基于风险分层限制未来AD治疗的获取，几乎没有涉及。
伦理讨论需要推进，以反映最近的科学发展，并指导现在和未来的临床实践，以便为大规模AD二级预防实施必要的保障措施。
