Activities related to dementia measures undertaken by Health and Global Policy Institute

The Research Project on the Construction and Use of a Model for an International Public-Private Partnership (PPP) in Dementia Research

Research Summary
This research was conducted with support from Japan Agency for Medical Research and Development (AMED) through the joint participation of HGPI Chairman Kiyoshi Kurokawa as research and development representative and co-researchers HGPI Vice-Chairman Hiroaki Yoshida and Yoshiki Niimi, Assistant Professor of Fujita Health University, School of Medicine.
This research program aims to propose the best possible method for establishing an International Public-Private Partnership (PPP) that will promote dementia research in an effective and efficient manner and incorporate their methods into a concrete framework in Japan. It also aims to spread Japan’s knowledge so that international initiatives can be included in frameworks created abroad when they are proposed to related government agencies and international organizations.

Research on projects and organizations related to dementia that make use of the PPP model in Japan and abroad

We conducted a survey of research projects and organizations related to dementia that make use of the PPP model. The survey also included representative organizations that are making progress in research on the formation of PPPs.

■Dementia research programs around the world－Large-scale, multi-institutional joint studies and partnerships

Abbreviation	WW-ADNI	DIAN	A4 study
Official Name	World Wide Alzheimer's Disease Neuroimaging Initiative	Dominantly Inherited Alzheimer Network	Anti-Amyloid Treatment in Asymptomatic Alzheimer’s study
Year of Establishment	2003	2008	2014
Management	Alzheimer's Association	Washington University School of Medicine	Alzheimer's Therapeutic Research Institute
Collaborated organizations	25 companies, 150 academic organizations, Foundation for the National Institutes of Health The National Institute on Aging	The National Institute on Aging	The National Institute on Ageing, Eli Lilly and Company, Philanthropic institutions
Aims	To help define the rate of progression of mild cognitive impairment and Alzheimer’s disease To develop improved methods for identifying the appropriate patient populations to participate in clinical trials. To standardize the methods used for conducting imaging scans and gathering and testing fluid samples	To find solutions to treat or To find solutions to treat or prevent Dominantly Inherited Alzheimer’s Disease (A rare form of Alzheimer’s), and potentially, all forms of Alzheimer’sprevent Dominantly Inherited Alzheimer’s Disease (A rare form of Alzheimer’s), and potentially, all forms of Alzheimer’s	To test whether a new investigational treatment, called solanezumab, an anti-amyloid antibody, can slow memory loss caused by Alzheimer’s disease

■Dementia research programs around the world－Large-scale study-funding organizations

Abbreviation	IMI	EPAD	DPUK	GAP	AMP	IADRP	GAAIN
Official Name	Innovative Medicines Initiative	European Prevention of Alzheimer Dementia Consortium	The MRC Dementias Platform UK	Global Alzheimer's Platform	Accelerating Medicine Partnership	International Alzheimer's and Related Dementias Research Portfolio	The Global Alzheimer’s Association Interactive Network
Year of Establishment	2008	2015	2014	2013	2014	2010	2010
Management	European Union、European Federation for Pharmaceutical Industries and Associations(EFPIA)	Dr. Serge Van der Geyten	Medical Research Council	The GAP Foundation	Foundation for the National Institutes of Health（FNIH）	NIH, National Institute on Aging and the Alzheimer’s Association	USC Laboratory of Neuro Imaging, USC Mark and Mary Stevens Neuroimaging and Informatics institute, Keck School of Medicine of USC
Collaborated organizations	Janssen Pharmaceutical, Eisai Pharma, Bayer Pharma, etc	35 organisations including Eurpean Union, EFPIA companies and Universities, and research organisations	The National Institute on Aging (NIA), the National Institute of Bioimaging and Bioengineering (NIBIB), Araclon Biotech, Cambridge Cognition, MedImmune, the global biologics research & development arm of AstraZeneca, GlaxoSmithKline, Invicro, Ixico, Janssen Pharmaceuticals, in collaboration with Johnson & Johnson Innovation, SomaLogic.	Janssen, Eli Lilly and Company, Roche, Lundbeck	Food and Drug dministration(FDA), National Institutes of Health (NIH), AbbVie, Biogen, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lily and Company, Merck, Pfizer, Sanofi, Takeda Pharmaceutical Company, Alzheimer‘s Association, Alzheimer’s Drug Discovery, American Diabetes Association, etc.	40 organizations from 10 countries including, Administration on Ageing, CDC, Alzheimer’s Association, BrightFocus Foundation, Canadian Institute of Health Research, Alzheimer’s Research UK	24 organizations including, Alzheimer’s Association, DIAN, Aibl, ADNI, I-ADNI, CAMD
Aims	To develop next generation vaccine, medicine, treatments	To improve the understanding of the early stages of Alzheimer’s disease and deliver new preventative treatments	To help define the rate of progression of mild cognitive impairment and Alzheimer’s disease To develop improved methods for identifying the appropriate patient populations to participate in clinical trials. To standardize the methods used for conducting imaging scans and gathering and testing fluid samples	To speed up the delivery of innovative therapies to those afflicted with Alzheimer’s by reducing the time and cost of Alzheimer’s disease (AD) clinical trials.	To transform the current model for developing new diagnostics and treatments by jointly identifying and validating promising biological targets for therapeutics	Enable public and private funders of Alzheimer’s research to coordinate research planning, leverage resources, avoid duplication of funding efforts and identify new opportunities in promising areas of growth.	Promotes big data sharing among a federated, global network of data partners who are studying Alzheimer’s disease and other dementias. To address the need to coordinate and leverage existing resources to advance research into the root causes of the disease, improve diagnostics and discover novel therapeutics, and find better ways to deliver care.

■Dementia research programs in Japan – Large-scale, multi-institutional joint studies, partnerships, and large-scale study-funding organizations

Abbreviation	J-ADNI	IROOP	ORANGE Registry
Official Name	Japanese-Alzheimer’s Disease Neuroimaging Initiative	Integrated Registry Of Orange Plan	Organized Registration for the Assessment of dementia on Nation-wide General consortium toward Effective treatment in Japan
Year of Establishment	2007	2016	2015
Management	University of Tokyo	National Center of Neurology and Psychiatry (NCNP), Japan Agency for Medical Research and Development	National Center for Geriatrics and Gerontology, National Center of Neurology and Psychiatry (NCNP), Tokyo dementia care research and training center, Ministry of Health, Labor and Welfare
Collaborated organizations	30 academic organizations	National Center for Geriatrics and Gerontology, Yokohama Brain and Spine Center, Osaka City University Faculty of Medicine	30 academic organizations
Aims	To conduct joint clinical studies with other facilities to develop criteria for evaluating the efficacy of AD drugs. To track healthy elderly patients, MCI patients, and early AD patients for 2 to 3 years.	To clarify symptoms that appear before the onset of dementia and to elucidate risk factors by improving lifestyles, habits, etc. To promote clinical research and clinical trials for the development of drugs expected to improve cognitive function.	To establish an appropriate care method for dementia by collecting information on people in various stages of health including: Healthy, Preclinical stage, MCI, Mild dementia, Moderate dementia, and Advanced dementia.

This research identified that the essential element of an effective PPP is clarity in organizational values, mission, and goals.
Furthermore, those interviewed commented on the strong need for Japan to be involved in international research collaborations including those using the PPP model. To achieve this, it is important to strengthen the basic foundations of clinical trial research in Japan, including the practices by which participants and workers who can collaborate internationally are recruited. It is also crucial to secure stable funding streams to make all of this possible.

Collection of case studies on dementia research and research promotion efforts led by PPPs

In a study of fields that can be expected to be promoted by a PPP excluding drug discovery, we conducted interviews and other surveys with care service providers and related services, local governments, town planning experts, robotics experts, and IoT researchers. We also conducted a survey of precedent cases of research promoted by PPPs on topics other than dementia and used them as references for modeling the construction of a dementia PPP.

■Challenges facing stakeholders undertaking advanced efforts in areas related to dementia and their needs

Stakeholder	Challenges and needs
People with dementia and their families	There is a lack of support other than public services. There is a lack of understanding towards people with dementia from industry. These stakeholders require a society designed to respond to people with dementia and that is comfortable for the entire aging population. These stakeholders desire for more recognition to be paid to the fact that people with dementia are capable of supporting society rather than unilaterally receiving support.
Medical and care service providers	Proven services and technologies should be adopted. These stakeholders require technologies that reduce the burden on caregivers.
Companies and academia involved in clinical trials and clinical research	These stakeholders need longer research periods, larger sample sizes, and generous funding to collect evidence and develop medicines needed for dementia treatment. These stakeholders need clinical research funding due to the fact that preclinical trial tests and medicines are exempt from health insurance. These stakeholders face difficulties recruiting participants in preclinical trials and need for recruitment to not only be conducted in clinics. These stakeholders need standardization in test procedures and diagnostic standards. These stakeholders lack the infrastructure needed to give integrated support during large-scale multi-institutional joint studies.
Companies providing technology and services that promote and improve care	Clearly presenting evidence of effects is difficult, and the cost effectiveness of doing so is low. Reputable private services with verified effectiveness need to be promoted and disseminated. Investments in private services and research plans commensurate with their societal achievements are needed. There is a lack of communication between research institutes and those in the field (such as at care facilities).
Self-governing bodies that implement progressive initiatives	It is difficult for lateral initiatives undertaken by local governments and NPOs to overcome regional boundaries. Collaboration between communities, social networks, and healthcare institutions is necessary. Data collected by the private sector must be utilized effectively.
As a whole	All stakeholders require a clear vision and mission to be shared among the various stakeholders. All stakeholders require neutral management that involves outside professionals while keeping conflicts of interest under consideration. All stakeholders face difficulty covering the security and operational maintenance costs of maintaining a registry with just annual public research grants.

■Suggestions for the PPP mechanism in Japan

Classification	Suggestions for PPP mechanism
Visions, missions, and values	Clear goals must be set. These goals and the methods for achieving them should be differentiated from other efforts to avoid difficulties when fundraising. It is necessary to be transparent and independent so that the decision-making process regarding project implementation and fund provider intent can be explained clearly.
Business model	To build a sustainable business model, it is necessary to involve fund-providing entities that can eventually fund the model. It is possible that initial investments can be made by the government and organizations like foundations. Continuously promoting the construction of evidence-based scientific programs is of the utmost importance.
Administrative structure	Strong fundraising and communications team are required. As dementia has issues related to multiple fields (such as treatment, the transition from care facilities to housing, and mobility), multi-stakeholders should be involved in planning the PPP. It will then be necessary that continuous efforts are made to create a unified sense of purpose among participants. To develop the next generation of human resources, it is necessary to involve multiple generations. It is important to decide how to enable people with dementia and their families to actively participate in decision-making.
Publicity campaigns	Collaboration between the public and private sectors is required to raise awareness and educate the general public. Publicity campaigns with messages based on scientific knowledge are important in promoting the correct understanding of dementia within society.
Collaboration with other organizations	Organizations such as private insurance companies have conducted various investigations and research initiatives. A system that enables the government to make use of their research findings would be useful. Evidence collected in each field should be shared as much as possible so that it may be utilized.
Institutional design	There is no definite answer or system for formulating PPPs and long-term care systems. PPPs should be designed to enable consideration of the culture of each country and region from the bottom up through discussions between multi-stakeholders. As for the medical and nursing fields, the private sector is easily influenced by changes in government systems. Therefore, a system that enables the private sector to collaborate with the government during the institutional design stage is necessary.

Interviews identified the need for a PPP to facilitate knowledge sharing within the research community and to assess new technology. Also, interviews highlighted the importance of having a clear shared vision and mission within the PPP and of promoting transparency and impartiality in project management.

Collaboration with the World Dementia Council (WDC)

Interviews with stakeholders revealed that they are highly interested in the role that Japan is expected to fill in the WDC and in other global policy planning endeavors. After sharing opinions with the WDC on this matter, the WDC decided to investigate the current situation of and future topics in each field it focuses on.

■Suggestions and expectations for Japan from the WDC

Category	Suggestions and expectations for Japan
Finance	Japan only devotes 0.2% of its total research funding to dementia, making Japan’s investment into dementia research the smallest among G7 countries. Therefore, Japan is expected to rapidly increase investments into dementia research. Japan is also expected to actively adopt a successful, revolutionary private and public collaboration model like the Dementia Discovery Fund (DDF).
Integrated Drug Development	Continuing with the Pharmaceutical and Medical Device Agency (PMDA) as the main constituent, the Japanese government should form partnerships with regulatory authorities in each Asian country and establish itself as a leader in the region. Furthermore, the MHLW and insurers should make concrete proposals for drug prices and the extent to which insurance should cover dementia drugs. Policy direction should be decided after consulting with other countries to examine which approaches should be taken (for example, to examine drug evaluation methods).
Research, Open Science, and Data	Japan should actively strengthen its partnerships with research centers in other countries. As one method for accomplishing this, AMED suggested participation in the EU Joint Programme – Neurodegenerative Disease Research (JPND). Furthermore, it is desirable that a platform for sharing various data is established.
Care	As a super aging society, Japan should share best practices for dementia care and its experience with the world. It has been brought up that there are no examples of policies that involve society like the New Orange Plan. Japan is also receiving attention for its utilization of ICT in treatments.. The efforts of Dementia Friends in the UK are very highly praised. In order to contribute to the establishment and expansion of similar programs in other countries, it is important to promote the evaluation of similar programs in Japan.
Risk Reduction	Japan should follow risk reduction recommendations from the World Health Organization (WHO). In addition, since Japan is unique in that it has a super aging society, Japan should actively conduct research for identifying risk factors to delay the progression of dementia.

These conversations allowed for opinions on the concept of the PPP model to be exchanged and they reaffirmed the need for Japan to actively contribute to the WDC. They also stressed the importance of long-term strategic efforts for effective drug discovery and the standardization of care and evaluation methods.

Multinational comparative analysis of the current state of PPPs for dementia

A multinational comparative analysis was carried out to examine the current status of international PPPs for dementia research. It identified elements and functions required for cooperation between industry, government, and academia regarding dementia research in Japan.

The number of people with dementia
According to the estimate for the number of people with dementia in member nations of the OECD reported in the OECD’s Health at a Glance 2015, both the prevalence of dementia and its future rate of growth in Japan are high. Western Europe and the Nordic countries mostly had high levels of dementia among the OECD member states, and countries such as Chili, South Korea, and Brazil were projected to have high growth rates in the future.

Dementia-related research and development funding
Although funding for the Government Budget Appropriations or Outlays on Research and Development (GBAORD) in Japan is around the same as countries excluding the United States and the United Kingdom, the amount of funding for dementia and neurodegenerative disease-related research and development is very low.

Source: OECD Health Policy Studies Addressing Dementia

Cost of Dementia in Japan
The overall cost of dementia in Japan is 14.5 trillion yen (2014 estimation). The breakdown of costs reveals that the costs of nursing and informal care together account for a much larger proportion (87%) of total costs than medical treatment.
Regarding the dementia related cost ratio around the world, Asian countries have especially low medical costs, and Western countries often have high cost ratios for social centers.

Source: World Alzheimer Report 2015

Status Development status for national strategies and guidelines
The United States signed the National Alzheimer’s Project Act (NAPA) into law as a national project on Alzheimer’s disease, while Britain and Japan have implemented policy measures as part of their national strategies. It is necessary for Japan to consider establishing basic laws in the future like the United States. Furthermore, Japan’s guidelines on clinical trials are inadequate compared to Western countries, and therefore their improvement will be a goal for the future.

■Dementia-related national strategies and guidelines in Western countries and Japan

		United States	United Kingdom	Japan
Dementia related national strategies		The National Alzheimer’s Project Act (NAPA)	Living well with dementia: A National Dementia Strategy	Comprehensive Strategy to Accelerate Dementia Measures (New Orange Plan)
Guidance/ Guidelines	Name	Guidance for Industry, Alzheimer’s Disease : Developing Drugs for the Treatment of Early Stage Disease	Draft guideline on the clinical investigation of medicines for the treatment of Alzheimer’s disease and other dementias	Guideline on the clinical evaluation of medicines for the treatment of Alzheimer’s Disease (AD)
Guidance/ Guidelines	Explanation	The FDA’s current approach covers areas such as: diagnostic methods for early-stage Alzheimer’s disease patients who are participating in clinical trials; patient selection and diagnostic methods for patients for whom the disease has the possibility of progressing; directions for setting the endpoints of clinical trials; and directions for using biomarkers to measure treatment outcomes.	These guidelines aim to create new diagnostic criteria for AD, including early-stage and asymptomatic AD patients based on the results of impact assessments; select treatments based on outcomes for each stage of progress of AD; enable the effective use of biomarkers; and design trials to determine the long - term effectiveness and safety of dementia treatment drugs.	Currently being produced.

The results of this project emphasized the need for Japan to become involved in improving relevant guidance and guidelines for dementia. It also emphasized the importance of developing a registry framework for clinical trials in order to further advance global collaborations in dementia research.

Organizing meetings involving people with dementia and their families and representatives from government, academia, and the private sector

An advisory board and an expert committee that brought together people with dementia and their families and representatives from industry, government, and academia was established in order to exchange opinions regarding the promotion of research by a PPP. (*All affiliations are current at the time of writing)

Expert Committee

Advisory Board

Proposals for the establishment of an international PPP model and policy

Three key approaches that will enable Japan to demonstrate leadership in Asia as a society experiencing advanced aging have been identified. First, the PPP must provide a platform for data collection and assessment that can facilitate discussion among organizations from various sectors. Second, the PPP must also function as a high-quality dementia registry that can enable Japan’s participation in large-scale international clinical trials. Last but not least, the PPP should function as an organization that can raise awareness of dementia among the public and thereby promote understanding and acceptance.

Stakeholders for promoting PPP
The promotion of a PPP for dementia policy will require not only cooperation between stakeholders and people with dementia and their families, but also mutual cooperation among stakeholders. Furthermore, people with dementia should not be positioned to only receive unilateral support; rather, we should aim to create a world in which those with dementia can also actively contribute to tackling the challenges dementia presents to society.

The ideal dementia PPP as suggested by this research
Detailed below is a vision for the field of dementia and for society that the dementia PPP structure proposed by this research aims to create. In the future, we must present a vision and mission and create a PPP roadmap.

- In pursuit of an effective and efficient PPP
  Ideally, in the future this PPP will:
  - Develop research themes and activities based on the needs of people with dementia and their families.
  - Appropriately prioritize research funding and activities based on an understanding of the issues surrounding dementia and evaluate the effects of research constantly.
  - Enable all stakeholders to access and share data and knowledge from dementia research and related services.
  - Encourage the private sector to invest actively in dementia policy and motivate further participation in this area.
  - Actively adopt and utilize scientific and technical innovations for its work, including innovations related to ICT and robotics.

- Goals of the dementia PPP
  The PPP should aim to:
  - Solve latent social issues in Japan that are at the backdrop of dementia-related problems, including but not limited to issues related to low birthrates and an aging population; issues that women face; and issues related to people leaving employment to care for family members. Multifaceted and systematic solutions should be developed.
  - Take the initiative in creating global policy and serve as a hub for global research as a PPP based in the country with the highest proportion of elderly people in the population in the world. It should build links to the government’s Asia Health and Human Well-Being Initiative.

The functions that Japan’s PPP platform on dementia should have, and the course of action that it must take
We will establish a PPP platform on Dementia so that Japan can successfully manage the social challenges brought about by long life expectancies among Japanese people and to demonstrate leadership in Asia as a country already experiencing population aging.

This platform shall:

Offer a space for stakeholders, including people with dementia and their families, to cooperate and conduct discussions, evaluations, and inspections of dementia-related issues using objective data.

Work to raise awareness and understanding of dementia in society, and to disseminate information internationally.

Prioritize the development and objective evaluation of new technologies relating to dementia care.

Strengthen the foundation for implementing clinical trials via various initiatives to promote international cooperation, such as by developing a registry or participating in large-scale, international clinical trials.

*The contents of this page is based on the information as of March 2017 when we published our research results.