Progress, challenges and global approaches to rare diseases.

Rare diseases occur globally at every stage of life. Patients, families and caregivers have many unmet medical and social needs leading to extraordinary psychosocial and economic burdens. Efforts to improve diagnostic capabilities and to develop therapies for an estimated 7000 rare diseases have met with considerable success. In the United States, a rare disease or condition is one affecting fewer than 200,000 people. In the European Union (EU), a rare disease is any disease affecting fewer than 5 people in 10,000 (less than 1 in 2000 people). However, there are no effective treatments for 90 per cent of rare diseases. There is a need to expand awareness, advocacy and outreach to everyone including those with low incomes, poor literacy, minority ethnic status and living in underserved and marginalised populations in urban and rural areas as well as in developing nations throughout the world. The acceptance of patients as research partners complements the increased research emphasis and major regulatory initiatives leading to expedited review and approval programmes for products for serious or life-threatening conditions. The pipeline of new therapies provides hope to untreated patients. Advances in medical bioinformatics, artificial intelligence and machine learning with access to big data continue to identify novel therapeutics for screening and evaluation. Advanced analytics can identify the patterns of disease occurrence, predict disease progression, identify patient response to treatments, establish optimal care guidelines and generate research hypotheses with the narrowly identified research patient populations.

Survey investigating the knowledge and awareness of payers and patient advocacy groups about the health technology assessment process in Lebanon.

The survey aims to assess the knowledge and awareness of Reimbursement Bodies (RBs) and Patient Advocacy Groups (PAGs) in Lebanon and the possible involvement of patients in the health technology assessment (HTA) process in the absence of a well-established HTA structure and to identify the actions to be taken at this level. Structured questionnaires were administered to eleven key participants from both RBs and PAGs. The survey utilized two different questionnaires, each composed of two open-ended questions and ten close-ended questions. RBs recognized the need for clinical and technical guidelines to optimize the HTA process, whereas PAGs stated that they are familiar with the current assessment and reimbursement process. A lack of interaction between the payers and the PAGs was reported mainly due to the absence of laws that involve patients in the assessment process. All the payers and three out of five of PAGs encouraged the involvement of PAGs in the assessment process. They reported that patients require support, education, and training to be efficiently involved. A short-term plan for involving patients in the assessment process can be implemented in light of RBs' and PAGs' openness for such involvement. In the long run, the collaboration between both parties needs to be more formalized and structured. Education and training programs are to be suggested for other PAGs. The institutionalization of an HTA body that unifies all the fragmented RBs, including a patient's representation to optimize the reimbursement process and to engage patients, is recommended.

An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG).

Desmoid-type fibromatosis is a rare and locally aggressive monoclonal, fibroblastic proliferation characterized by a variable and often unpredictable clinical course. Currently, there is no established or evidence-based treatment approach available for this disease. Therefore, in 2015 the European Desmoid Working Group published a position paper giving recommendations on the treatment of this intriguing disease. Here, we present an update of this consensus approach based on professionals' AND patients' expertise following a round table meeting bringing together sarcoma experts from the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group with patients and patient advocates from Sarcoma PAtients EuroNet. In this paper, we focus on new findings regarding the prognostic value of mutational analysis in desmoid-type fibromatosis patients and new systemic treatment options.

Rare Diseases: Joining Mainstream Research and Treatment Based on Reliable Epidemiological Data.

Despite growing acceptance of patient registries and natural history studies to provide useful information, the rare disease community suffers from the absence of reliable epidemiological data on the prevalence and incidence of most rare diseases in national and global populations. Likewise, the patients and health care providers lack adequate information on the pathophysiology of rare diseases and expected outcomes of these disorders. The rare diseases community includes all of the stakeholders involved in the research and development and dissemination of products and information for the diagnosis, prevention or treatment of rare diseases or conditions. To replace many of the perceptions with realities, several global efforts have been implemented to sustain and increase the reported progress with the thousands of rare diseases. The first efforts is to develop a global research infrastructure of qualified investigators to stimulate and coordinate research efforts by seeking ways to provide access to clinical trials at multi-national research sites with common protocols and multi-disciplinary research teams. Next, is the continued identification and expansion of worldwide partnerships and collaborations of Patient Advocacy Groups (PAGs), research investigators, the biopharmaceutical and medical devices industries, and the government research and regulatory agencies for a specific rare disease or group of related diseases. Gaining access to information about rare diseases, patient advocacy groups, ongoing and planned research studies and products in research protocols continue to improve the lives of patients and their families. Many basic, clinical and translational research investigators, public and private sector funding organizations, patient advocacy groups, foundations, and the pharmaceutical, biotechnology, and medical devices industries are committed to translating research discoveries that will be useful in the treatment and care of patients with rare diseases over their lifespan. Evidence from well-constructed epidemiological studies will provide the evidence that point to the value of additional clinical studies to increase the understanding of rare diseases.

Facilitating Clinical Studies in Rare Diseases.

In recent years, there have been many scientific advances and new collaborations for rare diseases research and, ultimately, the health of patients living with rare diseases. However, for too many rare diseases, there still is no effective treatment, and our understanding of the incidence, prevalence, and underlying etiology is incomplete. To facilitate the studies needed to answer the many open questions there is a great need for the active involvement of all stakeholders, most importantly of patient groups. Also, the creation of streamlined infrastructure for performing multi-site clinical studies is critical, as is the engagement of multi-disciplinary teams with shared focus on a group of diseases. Another essential component of such efforts is to collect standardized data so that downstream meta-analyses and data sharing can be facilitated. To ensure high-quality protocols and datasets, a central data management and coordinating center is important. Since there are more than 6000 rare diseases, instead of focusing on single rare disease, it is more impactful to create platforms and methods that can support a group of rare diseases.

[Ophthalmological research in Germany: evaluation by an international expert panel]. / Ophthalmologische Forschung in Deutschland: Evaluation durch ein internationales Expertengremium.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society ( DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

Ophthalmological research in Germany: suggestions by an international expert panel.

PURPOSE: To evaluate the research performance in ophthalmology in Germany based on the findings of the recent research map of the German Ophthalmological Society (DOG) and to suggest strategies for future improvements on a national level both to DOG as well as to politics. The focus is on preclinical and translational clinical research. METHODS: International expert panel evaluation and discussion organized by the Task Force Research of the German Ophthalmological Society (DOG). RESULTS: The international view on the German ophthalmological research landscape was generally positive. The value for money relationship was judged as very good. As Germany is facing an aging society and vision impairment will create an ever-increasing socioeconomic burden, the reviewers suggested several lines of future activities: an increased activity of securing intellectual property, more lay audience lobbying, intensified collaboration and critical mass building between "lighthouses" of ophthalmic research in Germany, as well as the establishment of a German national eye institute equivalent. CONCLUSION: The ophthalmological research performance in Germany was rated to be very good by an international expert panel. Nonetheless significant improvements were requested in the fields of translation (clinical trials, IP), synergy between specialized institutions and governmental funding for a German center for eye research.

Perspectives of European Patient Advocacy Groups on Volunteer Registries and Vaccine Trials: VACCELERATE Survey Study.

BACKGROUND: The VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. OBJECTIVE: The aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. METHODS: In an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants' perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. RESULTS: In total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were "positive" toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being "very positive." Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. CONCLUSIONS: Factors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients' willingness to participate in clinical studies.

Patient-Reported Symptoms in the Global Multiple System Atrophy Registry.

Background: The Global Multiple System Atrophy Registry (GLOMSAR) was established in 2013. It is an online patient-reported contact registry open and free that relies on self-reported diagnosis by the patient or caregiver. Objectives: To report the demographics of patients enrolled in GLOMSAR and the results of an ancillary online symptom questionnaire. Methods: Patients enrolled in GLOMSAR were invited to complete a custom-designed online questionnaire about disease onset and symptom prevalence. Results: At the time of writing, there were 1083 participants in GLOMSAR, of which 33% (365) completed the questionnaire. The onset and frequency of most symptoms was similar to those reported in the literature in physician-reported studies. Some were understudied or not typically associated with multiple system atrophy (MSA), including reduced female sexual sensation (55%), forgetfulness (60%), pseudobulbar affect (37%), olfactory changes (36%), and visual hallucinations (21%). Conclusions: Patient-reported studies and ancillary online questionnaires are valid, underused research tools useful to advance our knowledge on understudied MSA features and highlight the patients' voice.

The Meaningful Role of Patients, and Other Stakeholders in Clinical Practice Guideline Development.

Patient participation is an integral component in the development of clinical practice guidelines. However, patient engagement remains suboptimal, which signifies a predicament in guideline's legitimacy and transparency. Limited budgets, logistic constraints, and discordance in patients' and researchers' perception of a meaningful involvement are some barriers that hinder patient engagement. Advancing skill development across various roles within the guideline's process will enrich patient's contribution and allow them to voice their experience, knowledge, perspective, and concerns. Continuing patient education and evaluation of their engagement on both outcome and process will facilitate team cohesion, trustworthiness, and value to achieve optimal quality of care.

Best interests, benefit, will and preference: The influence of international human rights and external actors on decision-making frameworks in the United Kingdom and Ireland.

This article examines the development of the law relating to decision-making on behalf of adults that lack capacity in Scotland, Ireland and Northern Ireland. Using two points of tension evident in the recent Northern Irish legislative consultation process, namely the suitability of the 'best interests' standard and international debate regarding domestic compliance with the United Nations Convention on the Rights of Persons with Disabilities (United Nations, 2006) this contribution exposes the impact of international human rights and influence of external actors, principally advocacy groups and their individual members, on the resulting legislation. Given the recency of the Irish and Northern Irish legislation and the current law reform review in Scotland, the article concludes by highlighting points of tension that may emerge between domestic standards for decision-making and the CRPD.

Understanding low mobilization for non-communicable diseases among people living with NCDs: A qualitative study on hypertension in urban South India.

There is low civil society mobilization for NCD policies in low- and middle-income countries (LMICs) despite a growing NCD burden. While existing research explains low mobilization largely through constraints such as inadequate funding and capacity at the organizational level, we explore the issue from the perspective of people living with NCDs and ask how lay understandings of hypertension may inform potential mobilization for multisectoral policy actions by people living with hypertension. To explore this question, we develop a theoretical framework that casts mobilization as a function of people's recognition of disease importance, attribution of NCD risk factors to government policies, beliefs about who bears responsibility for NCD prevention and management, and beliefs around efficacy of multisectoral policies. We present findings from 45 semi-structured interviews with people living with hypertension in a qualitative study in Chennai, India. Our thematic analysis reveals that respondents can dedicate limited time and resources to actions around hypertension. People living with hypertension also strongly internalize responsibility for developing and managing their condition and focus primarily on achieving lifestyle changes. Instead of demanding multisectoral policy action around hypertension, respondents recommend that government actions focus on measures that enable their lifestyle changes, such as increasing awareness and health care capacities, and express doubts about the efficacy of government policies. Our findings expand existing theories around mobilization by revealing how people's own understanding of their illness, its risk factors and their underlying drivers, as well as their perception of challenges in NCD policy making can present barriers to mobilization around multisectoral policies. Theory on health social movements would benefit from a deeper integration of individual perspectives and a closer consideration of the specific challenges of living with NCDs given the local context.

A Longitudinal Content Analysis of the Use of Radical and Mainstream, Pro- and Anti-LGBT Organizations as Sources in The New York Times & The Washington Post.

Public opinion about LGBT rights has shifted dramatically in the last 30 years. This study, a content analysis of 659 news articles from The New York Times and The Washington Post from 1977-2013, examined the use of pro- and anti-LGBT organizations as sources to explore how coverage changed over time and to examine if there were differences in coverage of mainstream LGBT advocacy organizations versus those that are more radical in nature. Results showed that stories about the topics of marriage/families, entertainment, AIDS, politics and protests were the most likely to use LGBT advocacy organizations as sources. Use of radical organizations as sources peaked in the 1990s, when the majority of AIDS and protest stories were published. Anti-LGBT organizations were used as sources in just under 20 percent of the coded stories but stories covering some topics like marriage/families saw much higher rates of anti-LGBT organizational sourcing. Implications are discussed.

The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients.

Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan.

To what degree are orphan drugs patient-centered? A review of the current state of clinical research in rare diseases.

BACKGROUND: Over the past 30 years, the healthcare industry has increasingly turned its attention to rare diseases. Regulators have emphasized the need for clinical research in this area to be patient-centered. However, there is a lack of evidence concerning whether this need is actually met. In this paper, we aim to address this gap. METHODS: First, we describe the state of patient-centricity in clinical research in rare diseases based on a targeted literature review. Second, we discuss recommendations from scientific bodies on patient-reported outcome (PRO) measures in rare diseases. Third, we analyze data collected from EMA's and FDA's websites concerning rare disease labeling claims and data from Clinicaltrials.gov concerning the use of PRO measures in rare disease pivotal trials. Fourth, we perform an exhaustive literature review on the use of PRO measures in the pharmaceutical industry, including all phases of clinical research, observational/registry studies, and instrument development and validation. RESULTS: There is limited information on rare disease patient engagement in study design, recruitment, and retention. None of the initiatives describing methods for developing PRO measures in rare diseases provide the clear guidance clinical researchers need. Only 17.4% of orphan drug labels contain a PRO measure. Less than half of pivotal trials in orphan drugs have a PRO measure as a primary or a secondary endpoint. Although the number of publications about PRO measures in rare diseases has risen in the past fifteen years, our results indicate that substantial improvements are needed to achieve patient-centricity. CONCLUSIONS: The nature and extent of patient engagement in rare disease research is under-documented. The current paradigm for developing and using PRO measures in clinical research is failing to meet the needs of rare disease patients. Not only are PROs rarely used as high-level endpoints in clinical trials or taken into account in labeling claims, they are also under-researched overall - there are too few measures for the multitude of rare diseases. We call for a clear guidance on patient engagement and suggest a realistic approach to the adaptation of PRO strategy to the specific context of clinical research in rare diseases.

10th World Orphan Drug Congress (WODC) (November 12-14, 2019 - Barcelona, Spain).

The 10th World Orphan Drug Congress (WODC), now recognized as the largest and most established European orphan drug event, took place once again November 12-14, 2019, in Barcelona, Spain. Like in previous years, the more than 600 attendees were composed of government authorities, payers, industry and patient advocacy groups as well as biotech start-ups and investors. The 2019 congress aimed to address the strategic and commercial aspects of bringing new treatments to rare disease patients. The more than 200 speakers discussed many different rare disease aspects for clinical and product development, market access and pricing, manufacture, science and strategy, and precision medicine. A co-conference on Cell and Gene Therapy was also organized. This rare disease conference addressed many different challenges in the field with numerous discussions on how to improve cross-border communications, how to better identify patients and shorten their diagnosis time using new tools such as artificial intelligence and machine learning, as well as how to improve usage of patient data and patient empowerment.

Forming a support group for people affected by inflammatory bowel disease.

Inflammatory bowel disease (IBD) - primarily Crohn's disease and ulcerative colitis - is a debilitating lifelong condition with significant health and economic costs. From diagnosis to management, IBD can cause huge psychosocial concerns to patients and their caregivers. This study reports an experience of a Crohn's patient, leading to the formation of the first IBD patient support group in Singapore and how this group has evolved in the last 4 years in supporting other IBD patients. IBD patient advocacy and/or support groups facilitate open conversations on patients' fears, concerns, preferences and needs, and may potentially improve disease knowledge and quality of life for individuals with the condition or their families.

Patient attitudes and understanding about biosimilars: an international cross-sectional survey.

OBJECTIVE: To understand the levels of awareness, usage, and knowledge of biosimilars among patients, caregivers, and the general population in the US and the European Union; perceptions of biosimilars compared to originator biologics; perceived benefits and drawbacks of clinical trials; and whether advocacy groups impact patients' willingness to try a biosimilar. METHODS: An international survey was conducted which contained up to 56 closed-ended (requiring yes/no or ranking answers) and open-ended questions, depending on the population assigned. The survey was divided into distinct sections, including medication-class awareness, usage, and knowledge about biologic and biosimilar therapies; perceptions of clinical trials; and involvement in advocacy groups. Interviews were conducted in adults categorized as: 1) diagnosed: patients with inflammatory bowel disease including Crohn's disease and ulcerative colitis, rheumatoid arthritis, psoriasis, breast cancer, lung cancer, colorectal cancer, or non-Hodgkin's lymphoma; 2) diagnosed advocacy: individuals with these diseases who participated in patient support groups; 3) caregiver: has a loved one with these conditions and is involved in medical decisions; 4) general population: aged 18-64 years, without these conditions. Statistical analyses among groups within a region (US or EU) used column proportions test with a 95% confidence interval. RESULTS: In all, 3,198 individuals responded. Awareness about biologic therapies was significantly higher in diagnosed, diagnosed advocacy, and caregiver groups (45%-78%) versus general population (27%; P<0.05). Across all groups, awareness of biosimilars was low; only 6% of the general population reported at least a general impression of biosimilars. Awareness was significantly higher in the diagnosed advocacy group (20%-30%; P<0.05). Gaps in knowledge about biosimilars included safety, efficacy, and access to these agents. Respondents had generally positive perceptions of clinical trials, although barriers to participation were identified. CONCLUSION: An immediate need exists for patient education about biosimilars and clinical trials to ensure educated and informed decisions are made about biosimilar use.

Cultural carrying capacity: Organ donation advocacy, discursive framing, and social media engagement.

Social media sites such as Facebook have become a powerful tool for public health outreach because they enable advocacy organizations to influence the rapidly increasing number of people who frequent these forums. Yet the very open-ness of social media sites creates fierce competition for public attention. The vast majority of social media messages provoke little or no reaction because of the sheer volume of information that confronts the typical social media user each day. In this article, I present a theory of the "cultural carrying capacity" of social media messaging campaigns. I argue that advocacy organizations inspire more endorsements, comments, and shares by social media users if they diversify the discursive content of their messages. Yet too much diversification creates large, disconnected audiences that lack the sense of shared purpose necessary to sustain an online movement. To evaluate this theory, I created a Facebook application that collects social media posts produced by forty-two organ donation advocacy organizations over 1.5 years, as well as supplemental information about the organization, its audience, and the broader social context in which they interact. Time series models provide strong evidence for my theory net of demographic characteristics of social media users, the resources and tactics of each organization, and broader external factors. I conclude by discussing the implications of these findings for public health, cultural sociology, and the nascent field of computational social science.

Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients' and professionals' expertise - a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative.

Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. It may affect nearly all parts of the body including extremities, trunk and abdomen. Considering the variable clinical presentations, anatomic locations and biological behaviours, an individualised treatment approach is required. No established or evidence-based approach for the treatment of this neoplasm is available as of today. Therefore, we propose a consensus treatment algorithm based on a round table meeting bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). The aim of the meeting was to develop - for the first time ever - a consensus approach based on professionals' AND patients' expertise. As a fundamental prerequisite, all patients should be discussed in a multidisciplinary setting in centres or professional networks with a specific expertise in the disease.