Hereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient\'s life.
This online international Delphi survey aimed to evolve clinical-patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs).
A 14-member joint patient advocate-HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient-doctor dialogue; access to social support and social networking.
From June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%).
Both level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds.
Based on an a priori threshold for consensus of ≥75% agreement, the clinical-patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%-45% of HCPs. By comparison, PAGs recorded lower implementation levels.
Further consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.

BACKGROUND: The leukodystrophy \"Vanishing White Matter\" (VWM) is an orphan disease with neurological decline and high mortality. Currently, VWM has no approved treatments, but advances in understanding pathophysiology have led to identification of promising therapies. Several investigational medicinal products are either in or about to enter clinical trial phase. Clinical trials in VWM pose serious challenges, as VWM has an episodic disease course; disease phenotype is highly heterogeneous and predictable only for early onset; and study power is limited by the small patient numbers. To address these challenges and accelerate therapy delivery, the VWM Consortium, a group of academic clinicians with expertise in VWM, decided to develop a core protocol to function as a template for trials, to improve trial design and facilitate sharing of control data, while permitting flexibility regarding other trial details. Overall aims of the core protocol are to collect safety, tolerability, and efficacy data for treatment assessment and marketing authorization.
METHODS: To develop the core protocol, the VWM Consortium designated a committee, including clinician members of the VWM Consortium, family and patient group advocates, and experts in statistics, clinical trial design and alliancing with industries. We drafted three age-specific protocols, to stratify into more homogeneous patient groups, of ages ≥ 18 years, ≥ 6 to < 18 years and < 6 years. We chose double-blind, randomized, placebo-controlled design for patients aged ≥ 6 years; and open-label non-randomized natural-history-controlled design for patients < 6 years. The protocol describes study populations, age-specific endpoints, inclusion and exclusion criteria, study schedules, sample size determinations, and statistical considerations.
CONCLUSIONS: The core protocol provides a shared uniformity across trials, enables a pool of shared controls, and reduces the total number of patients necessary per trial, limiting the number of patients on placebo. All VWM clinical trials are suggested to adhere to the core protocol. Other trial components such as choice of primary outcome, pharmacokinetics, pharmacodynamics, and biomarkers are flexible and unconstrained by the core protocol. Each sponsor is responsible for their trial execution, while the control data are handled by a shared research organization. This core protocol benefits the efficiency of parallel and consecutive trials in VWM, and we hope accelerates time to availability of treatments for VWM.
BACKGROUND: NA. From a scientific and ethical perspective, it is strongly recommended that all interventional trials using this core protocol are registered in a clinical trial register.

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Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

BACKGROUND: Underutilization of evidence-based pain management in nursing homes (NHs) is common. Evidence toward effective approaches to improve adoption of evidence-based practices in NHs is limited. Application of theory in evaluation approaches can increase understanding of implementation challenges.
OBJECTIVE: To get a better understanding of the impact of implementation strategies by exploring the underlying mechanisms using behavioral theory.
METHODS: This mixed-methods study is embedded in an implementation-effectiveness study of a pain management guideline in four Swiss NHs. To evaluate our implementation strategies, training workshops were held, and trained pain champions were introduced. We also developed a conceptual framework. Based on Bandura\'s self-efficacy theory, we hypothesized how our implementation strategies might affect changes in care workers\' behavior. Care workers\' questionnaire surveys were conducted at baseline (n = 136), after 3 months (n = 99), and after 6 months (n = 83) to assess self-efficacy in pain management and self-reported guideline adoption. We computed linear mixed-effect models to assess changes over time in self-efficacy and logistic regressions to assess associations between self-efficacy and guideline adoption. Concurrently, we conducted focus groups with care workers (n = 8) to explore their response to the implementation strategies.
RESULTS: Overall, there was a significant increase in self-efficacy at both time points (p < .001). We found significant associations between self-efficacy and adoption of two guideline components, that is, performing a comprehensive pain assessment and using observational pain assessment tools in cognitively impaired residents. Qualitative findings showed that implementation strategies were received positively by care workers. Focus group participants reported more attentiveness to residents\' pain experience. The participants also reported increases in assessment and documentation of pain with more detail than before.
UNASSIGNED: Our findings highlighted that the training and use of pain champions increased self-efficacy and thereby induced behavior change leading to guideline adoption. Regarding persistent implementation challenges, a theory-based conceptual model contributes to the overall understanding.

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Rare diseases are a global public health concern, affecting an estimated 350 million individuals. Only 5% of approximately 7000 known rare diseases have a treatment, and only about half have a patient advocacy organization. Biopharmaceutical companies face complex challenges in developing treatments for rare diseases. Patient advocacy organizations may play a major role by positively influencing research and development, clinical trials, and regulations. Thus, collaboration among patient advocacy organizations and industry is essential to bring new therapeutics to patients.
We identified an unmet need for guidelines on day-to-day decision-making by rare disease patient advocacy organizations when working with biopharmaceutical partners. We convened an Independent Expert Panel experienced in collaborations between patient advocacy organizations and biopharmaceutical companies (April 2017) to develop consensus guidelines for these relationships. The guidelines were based on an original version by the International Fibrodysplasia Ossificans Progressiva Association (IFOPA). The Expert Panel reviewed and broadened these to be applicable to all patient advocacy organizations. Comments on the draft Guidelines were provided first by Panel participants and subsequently by six independent experts from patient advocacy organizations and industry.
The Panel comprised four experts from the rare disease community who lead patient advocacy organizations; three leaders who perform advocacy functions within biopharmaceutical companies; and two facilitators, both having leadership experience in rare diseases and industry. The finalized Guidelines consist of four main sections: Identification and Engagement With Companies, Patient Engagement and Patient Privacy, Financial Contributions, and Clinical Trial Communication and Support. The Guidelines address the daily considerations, choices, and consequences of patient advocacy organizations as they engage with biopharmaceutical companies, and offer recommendations for volunteer/paid leaders of the organizations on how to interact in a thoughtful, responsible, ethical way that engenders trust.
These Guidelines recommend best practices and standards for interactions between patient advocacy organizations and industry that will ultimately have a positive effect on the development of novel treatments. Patient advocacy organizations will be provided free access to these Guidelines to help bring clarification to day-to-day decision-making around their interactions, and for use as a living document with the potential for regular revisions and updates.