Health-related quality of life in people with predementia Alzheimer’s disease, mild cognitive impairment or dementia measured with preference-based instruments: a systematic literature review

02 Dec 2020

Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer’s disease scale: development and results from a mapping study

26 Oct 2020

Alignment of European Regulatory and Health Technology Assessments: A Review of Licensed Products for AD

07 May 2019

Aims: To facilitate regulatory learning, we evaluated similarities and differences in evidence requirements between regulatory and health technology assessment (HTA) bodies of Alzheimer's disease (AD) approved products.

Methods: The European marketing authorisation application dossiers and European public assessment reports (EPARs) of the licensed AD drugs were screened to identify the phase III randomised controlled trials (RCTs) and outcomes used. We also screened the assessment reports of the National Institute of Health and Care Excellence (NICE, England) and the National Health Care Institute (ZiN, the Netherlands) to identify the studies and outcomes used in HTA assessments.

Results: The application dossiers of donepezil, galantamine, rivastigmine, and memantine contained 16 phase III RCTs in total. These trials were also included in HTA assessments except that NICE excluded studies that were not published (n = 2) or trials that included patients with other types of dementia (n = 3). In the regulatory assessments the focus was on cognitive and global outcomes, and to some extent on function. In the HTA assessments of clinical effectiveness other domains were also covered including: function, behaviour and mood, and, occasionally, quality of life. In the economic analyses of NICE the domains cognition, function, and quality of life were included.

Conclusion: There was a large overlap in inclusion of trials in regulatory and HTA assessments, although the focus on specific outcomes slightly differed. Understanding the methods and perceptions of both authorities can stimulate regulatory and HTA cross-talk and further alignment, and therefore more rapid patient access to new treatments.

Epidemiology of dementia: prevalence and incidence estimates using validated electronic health records from primary care

04 Mar 2019

Purpose: Updated estimates of incidence and prevalence of dementia are crucial to ensure adequate public health policy. However, most of the epidemiological studies in the population in Spain were conducted before 2010. This study assessed the validity of dementia diagnoses recorded in electronic health records contained in a large primary-care database to determine if they could be used for research purposes. Then, to update the epidemiology of dementia in Catalonia (Spain), we estimated crude and standardized prevalence and incidence rates of dementia in Catalonia in 2016. Methods: The System for the Development of Research in Primary Care (SIDIAP) database contains anonymized information for >80% of the Catalan population. Validity of dementia codes in SIDIAP was assessed in patients at least 40 years old by asking general practitioners for additional evidence to support the diagnosis. Crude and standardized incidence and prevalence (95% CI) in people aged ≥65 years were estimated assuming a Poisson distribution. Results: The positive predictive value of dementia diagnoses recorded in SIDIAP was estimated as 91.0% (95% CI 87.5%–94.5%). Age- and sex-standardized incidence and prevalence of dementia were 8.6/1,000 person-years (95% CI 8.0–9.3) and 5.1% (95% CI 4.5%–5.7%), respectively. Conclusion: SIDIAP contains valid dementia records. We observed incidence and prevalence estimations similar to recent face-to-face studies conducted in Spain and higher than studies using electronic health data from other European populations. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. clep-186590-epidemiology-of-dementia-prevalence-and-incidence-estimates-030119 Ponjoan A, Garre-Olmo J, Blanch J, Fages E, Alves-Cabratosa L, Martí-Lluch R, et al. Epidemiology of dementia: prevalence and incidence estimates using validated electronic health records from primary care. Clinical Epidemiology. 2019 Mar;Volume 11:217–28.

Ethical and social implications of using predictive modeling for Alzheimer’s disease prevention: a systematic literature review protocol

03 Mar 2019

The therapeutic paradigm in Alzheimer’s disease (AD) has shifted towards secondary prevention, defined as an intervention aiming to prevent or delay disease onset in pre-symptomatic individuals at risk of developing dementia due to AD. The key feature of AD prevention is the need to treat years or even decades before the onset of cognitive, behavioural or functional decline. Prediction of AD risk and evaluation of long-term treatment outcomes in this setting requires predictive modelling and is associated with ethical concerns and social implications. The objective of this review is to identify and elucidate them, as presented in the literature. A systematic literature review was conducted in Medline, Embase, PsycInfo and Scopus, and was complemented with a grey literature search. All searches were conducted between March and July 2018. Two reviewers independently assessed each study for inclusion and disagreements were adjudicated by a third reviewer. Data are now being extracted using an extraction sheet developed within the group of reviewers, based on an initial sample of three manuscripts, but allowing for inclusion of newly identified data items (ethical arguments). Data will be analysed qualitatively using a thematic analysis technique. Potential biases in selection and interpretation of extracted data are mitigated by the fact that reviewers come from a range of different scientific backgrounds and represent different types of stakeholders in this ethical discussion (academia, industry, patient advocacy groups). The study does not require ethical approval. The findings of the review will be disseminated in a peer-reviewed journal and presented at conferences. They will also be reported through the Innovative Medicine Initiative project: Real World Outcomes Across the AD Spectrum for Better Care: Multi-modal Data Access Platform (IMI: ROADMAP). This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. Angehrn Z, Nordon C, Turner A, et al. Ethical and social implications of using predictive modeling for Alzheimer’s disease prevention: a systematic literature review protocol BMJ Open 2019;9:e026468. doi: 10.1136/bmjopen-2018-026468

What outcomes are important to patients with mild cognitive impairment or Alzheimer’s disease, their caregivers, and health-care professionals? A systematic review

18 Jan 2019

Clinical trials involving patients with Alzheimer's disease (AD) continue to try to identify disease-modifying treatments. Although trials are designed to meet regulatory and registration requirements, many do not measure outcomes of the disease most relevant to key stakeholders. A systematic review sought research that elicited information from people with AD, their caregivers, and health-care professionals on which outcomes of the disease were important. Studies published in any language between 2008 and 2017 were included. Participants in 34 studies described 32 outcomes of AD. These included clinical (memory, mental health), practical (ability to undertake activities of daily living, access to health information), and personal (desire for patient autonomy, maintenance of identity) outcomes of the disease. Evidence elicited directly from the people most affected by AD reveals a range of disease outcomes that are relevant to them but are not commonly captured in clinical trials of new treatments. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). Tochel C, Smith M, Baldwin H, Gustavsson A, Ly A, Bexelius C, et al. What outcomes are important to patients with mild cognitive impairment or Alzheimer’s disease, their caregivers, and health-care professionals? A systematic review. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. Available from: https://doi.org/10.1016/j.dadm.2018.12.003

Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project

15 Dec 2018

ROADMAP is a public-private advisory partnership to evaluate the usability of multiple data sources, including real-world evidence, in the decision-making process for new treatments in Alzheimer’s disease, and to advance key concepts in disease and pharmacoeconomic modeling. ROADMAP identified key disease and patient outcomes for stakeholders to make informed funding and treatment decisions, provided advice on data integration methods and standards, and developed conceptual cost-effectiveness and disease models designed in part to assess whether early treatment provides long-term benefit. This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC 4.0). Gallacher J, de Reydet de Vulpillieres F, Amzal B, Angehrn Z, Bexelius C, Bintener C, et al. Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project. Feng L, editor. Journal of Alzheimer’s Disease. 2018 Dec 15;1–7. https://doi.org/10.3233/JAD-180370

Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer’s Disease

28 Nov 2018

Although there are a growing number of well-reported, late-stage clinical trial failures in Alzheimer’s disease, the introduction of a disease-modifying therapy within the next 5 years may be anticipated. These treatments are likely to target Alzheimer’s disease in the earlier disease stages, unlike drugs that are currently available that treat symptoms of moderate-to-severe dementia. Therefore, there is a need to establish a consensus on regulatory and health technology assessment requirements for Alzheimer’s disease, as a new drug will need to undergo regulatory and health technology assessments before it becomes available to patients. This article reports the discussions and activities of the regulatory and health technology assessment expert advisory group of the 2-year ROADMAP (real-world outcomes across the Alzheimer’s disease spectrum: a multimodal data access platform) project. The expert advisory group discussions identified a lack of consensus on validated outcomes in the earliest Alzheimer’s disease stages, the need for filling gaps between outcomes used across clinical trials and real-world settings, and the role that real-world evidence might have in characterising the impact of a possible disease-modifying therapy on caregivers, resource use and long-term outcomes. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/). Bouvy JC, Jonsson P, O’Rourke D, Chadha AS, Hedberg N, Makady A, et al. Regulatory and Health Technology Assessment Considerations for Disease-Modifying Drugs in Alzheimer’s Disease. CNS Drugs [Internet]. 2018 Nov 22 [cited 2018 Nov 28]; Available from: http://link.springer.com/10.1007/s40263-018-0581-x

Systematic literature review of methodologies and data sources of existing economic models across the full spectrum of Alzheimer’s disease and dementia from apparently healthy through disease progression to end of life care: a systematic review protocol

08 Jun 2018

Dementia is one of the greatest health challenges the world will face in the coming decades, as it is one of the principal causes of disability and dependency among older people. Economic modelling is used widely across many health conditions to inform decisions on health and social care policy and practice. The aim of this literature review is to systematically identify, review and critically evaluate existing health economics models in dementia. We included the full spectrum of dementia, including Alzheimer’s disease (AD), from preclinical stages through to severe dementia and end of life. This review forms part of the Real world Outcomes across the Alzheimer’s Disease spectrum for better care: multimodal data Access Platform (ROADMAP) project.

Resource utilisation and costs in predementia and dementia: a systematic review protocol

23 Jan 2018

Dementia is the fastest growing major cause of disability globally with a mounting social and financial impact for patients and their families but also to health and social care systems. This review aims to systematically synthesise evidence on the utilisation of resources and costs incurred by patients and their caregivers and by health and social care services across the full spectrum of dementia, from its preceding preclinical stage to end of life. The main drivers of resources used and costs will also be identified.

Measuring quality of life of people with predementia and dementia and their caregivers: a systematic review protocol

30 Mar 2018

Dementia is the fastest growing major cause of disability globally and may have a profound impact on the health-related quality of life (HRQoL) of both the patient with dementia and those who care for them. This review aims to systematically identify and synthesise the measurements of HRQoL for people with, and their caregivers across the full spectrum of, dementia from its preceding stage of predementia to end of life.

Big Data For Better Outcomes

12 Mar 2017

Large amounts of data from multiple sources have led to the opportunity of deriving health benefits through using sophisticated technologies. Regardless of the frequently cited revolution of data-driven health care, promises remain to be fulfilled. The IMI2 BD4BO programme recognises this in representative disease areas, providing a framework to guide research and invite stakeholders to discuss the future of health systems shaped by big data. The projects will impact he research environment through shared definitions and methods to avoid duplication of work, while transforming health care systems in terms of clinical operations, research and development, evidence-based personalised medicine and public health.