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Over the last decade, the development of new treatments for haemophilia has progressed at a very rapid pace. Despite all the promising advances in protein products, the prospect offered by gene therapy of a single potentially lifelong treatment remains attractive for people with haemophilia. Transfer to the liver of coagulation factor VIII (FVIII) or factor IX (FIX) transgenes has indeed the potential to stably restore the dysfunctional coagulation process. Recombinant adeno‐associated virus (AAV)‐derived vectors are widely employed for liver‐directed gene therapy, given their very good efficacy and safety profile, shown in several preclinical and clinical studies. However, there are some limitations associated with AAV vectors, such as their predominantly episomal nature in the nucleus of target cells and the widespread pre‐existing immunity against the parental virus in humans. By contrast, HIV‐derived lentiviral vectors (LV) integrate into the target cell chromatin and are maintained as the cells duplicate their genome, a potential advantage for establishing long‐term expression especially in paediatric patients, in which the liver undergoes substantial growth. Systemic administration of LV allowed stable multi‐year transgene expression in the liver of mice and dogs. More recently, improved phagocytosis‐shielded LV were generated, which, following intravenous administration to non‐human primates, showed selective targeting of liver and spleen and enhanced hepatocyte gene transfer, achieving up to supra‐normal activity of both human FVIII and FIX transgenes. These studies support further preclinical assessment and clinical evaluation of in vivo liver‐directed LV gene therapy for haemophilia. [ABSTRACT FROM AUTHOR]

This paper sets out good practice for clinicians involved in interpreting variant reports for patients with inherited bleeding disorders. It is aimed primarily at doctors, nurses and allied healthcare professionals who may not have had specific training in genetic testing methodology or reporting. It deals with uncertainty in classification of variant pathogenicity and the handling of incidental findings. [ABSTRACT FROM AUTHOR]

We encourage therapists to critically examine their own practice, as well as asking centre directors and therapy managers to see the value of a well-defined physiotherapy service within haemophilia. GLO:EVW/01mar21:hae14150-fig-0001.jpg PHOTO (COLOR): 1 Recommendation for reviewing provision of a local haemophilia physiotherapy service gl It remains unclear if new treatments (EHL's, non-substitutive therapies) will considerably reduce the frequency of bleeding in patients treated. Acute pain significantly impacts quality of life and is greater when present on a backdrop of ongoing persistent pain.6 An increase in age is also associated with a decrease in quality of life predominantly related to haemophilia-specific MSK complications, that is, joint disease. [Extracted from the article]

A recently published randomized controlled trial (RCT) showed that adherence to infusion diary record keeping was improved by the use of handheld computers. In this study, attitudes to record keeping were explored and patient preferences regarding the method of recording determined for the patients who participated in the trial. Qualitative study consisting of individual semi-structured interviews with 20 severely affected patients with haemophilia who participated in an RCT. Individuals were purposefully sampled based on their recent method of record keeping and whether child or adult. Analysis employed a constant comparative method to identify key themes from the data. Most individuals (19 of 20, 95%) considered record keeping to be important. They readily identified reasons to keep records: to benefit themselves, their families, clinical staff, product distributors and manufacturers. Keeping records helps them: feel a part of the health care team; have confidence they would be notified of product recalls; review their past history; improve their ability to advocate for themselves and improve communication among all parties. Record keeping, particularly when using paper diaries, can be burdensome and a challenge to maintain consistently. All 10 individuals (100%) who had used both paper diaries and handheld computers preferred the latter. Most patients understand that record keeping can be of benefit to them. Clinics can use this knowledge to inspire other patients by developing educational programmes that de-emphasize authority. In addition, given the evidence of both patients’ preference for handheld computers, and the effectiveness of this approach documented in an RCT, switching to handheld computers is likely to improve record keeping. [ABSTRACT FROM AUTHOR]

Summary. Treatment of severe haemophilia with factor concentrates is by self-infusion in the home. Adherence to record keeping on paper diaries is poor. A randomized-controlled trial compared adherence with record keeping of paper diaries with hand-held computers. Forty-one individuals with severe haemophilia, were randomized to hand-held computers (n = 22) or paper diaries (n = 19) and followed for 6 months. About 86.2% (679 of 788) of infusions by patients in the computer group were in compliance with the data submission schedule compared with only 48.3% (358 of 741) of infusions by patients using paper diaries (P < 0.0001). The time intervals between infusions and the receipt of data were shorter in the computer group (median 0.25 vs. 25 days respectively, P < 0.000 1). Reminder phone calls by the clinic were made less frequently to users of hand-held computers than to users of paper diaries (median one vs. five times, P < 0.0001). Accuracy of data was similar for both methods. Compliance with hand-held computers was superior to paper diaries. The clinic received data from hand-held computers mostly on the same day, and nurses could thereby provide clinical advice more effectively. Although hand-held computers did not result in increased accuracy, errors could be detected and corrected more rapidly. Electronic data can more easily be verified, analysed and summarized than that from paper diaries. [ABSTRACT FROM AUTHOR]

Summary. The transportation of plasma specimens to specialized haemophilia centre laboratories for anti-factor VIII inhibitor titre determination is often necessary. The routine method of transporting frozen specimens on dry ice is limited by its cost and need for special handling. The present study was undertaken to evaluate the effect of storing specimens at room temperature on the FVIII inhibitor titre determinations using the Bethesda assay. Specimens stored both in liquid phase as well as adsorbed onto filter paper discs were studied. The results of the present study demonstrate that plasma specimens stored for up to 2 weeks at room temperature, either in liquid phase or adsorbed onto filter paper, yield equivalent measures of FVIII inhibitor titres using the Bethesda assay to plasma specimens stored frozen at -70 °C. Plasma specimens dried on filter paper discs and stored at room temperature offers a reliable, more practical and less expensive alternative to frozen plasma as a means of transport to specialized referral laboratories for analysis of anti-FVIII titres. [ABSTRACT FROM AUTHOR]

Haemophilia and inherited bleeding disorders in newborns and their carrier mothers pose unique challenges. The pattern of bleeding and the causes and risk factors for bleeding are decidedly different than an older child or an adult with haemophilia/inherited bleeding disorder. This document outlines the needs for further research and education, summarizes the state of the art background information and provides guidance regarding research, education and access to care issues in this population. [ABSTRACT FROM AUTHOR]

Presents comments on medical practioner Erik von Willebrand's first paper 'Hereditar pseudohemofili' in 1926 which was written in Swedish language. Paper based on a bleeding diseases observed in people of Aland island, Finland; English translation by professor Emeritus Peter Wahlberg; Description of Wahlberg's first case of haemorrhagic disorder in the paper; Cases of Willebrand's medical research.

Record keeping among individuals who manage haemophilia at home is an essential tool of communication between patient and Haemophilia Treatment Center ( HTC). Complete records help HTCs monitor patients, their use of factor and ensure treatment is optimal. HTCs provide patients with a number of methods to track infusion practices. The study objectives were to: [1] determine the current methods of record keeping; [2] identify previous methods of record keeping; [3] understand the strengths and weaknesses associated with each method; and [4] gather suggestions for improvement. Survey methods were used to address the research objectives. Of the 83 patients in the Hamilton-Niagara region who received the survey distributed through the local HTC, 51 returned surveys were included into the analysis. Descriptive statistics were used. Results indicate individuals with haemophilia record infusion practices using: paper diaries, excel spreadsheets, hand-held PDAs and/or the online EZ-Log Web Client. The most popular method of record keeping was EZ-Log (45.1%) followed by paper diaries (35.2%). Advantages to using paper methods include the visual tracking of information and retaining hardcopies. The disadvantage was the inconvenience of physically submitting the records monthly. Advantages to using the online EZ-Log Web Client included ease of use and improved accuracy. The primary disadvantage was technical errors that were difficult to troubleshoot. Record keeping practices among individuals with haemophilia seem to vary according to personal preference and convenience. Respondents suggested that saving infusion history, incorporating barcode scanners or a copy and paste function could improve electronic methods. [ABSTRACT FROM AUTHOR]

Reports on the English translation of Erik von Willebrand's Swedish medical paper by professor Peter E. Wahlberg. Preservation of archaistic mode of writing.

ABSTRACT Introduction Aim Methods Results Conclusion Evidence‐based clinical practice guidelines drive optimal patient care and facilitate access to high‐quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non‐randomized and well‐designed observational studies and real‐world data, is challenging. The methodology used for assessing available evidence should consider this critical fact. In formulating guidelines, it is essential to include treatment goals and patient preference.This paper comprehensively critiques, against this background, the recommendations of the ISTH clinical practice guidelines for the treatment of haemophilia.Each recommendation was critically reviewed against available evidence as well as existing guidelines and commented upon for its scientific validity, impact on clinical practice and access to care globally. The validity of the way in which the GRADE methodology was applied to existing evidence was also assessed.The critique provided shows that these recommendations have major limitations: they did not state treatment goals and contradict existing guidelines; opportunities for providing access to innovation were missed when the therapeutic benefits of the products approved in the last decades were not included. A major reason for this is the inappropriate adoption of the GRADE methodology without adaptations and without considering treatment goals and patient‐relevant outcomes.These recommendations may mislead healthcare professionals, payers and governments and therefore cannot serve the patient community well. They setback the advances made in haemophilia care because they overlook important available evidence and do not guide clinical practice to contemporary standards. [ABSTRACT FROM AUTHOR]

A recent article published in Haemophilia reports the results of a survey of treatment center practices in the United States, and specifically the use of prophylaxis as treatment regimen [ ] . This article discusses the issues that may contribute to utilization of prophylactic regimens and issues to consider when determining treatment programs for pediatric patients. [ABSTRACT FROM AUTHOR]

On-demand or prophylactic home-treatment is currently the treatment of choice for haemophilia patients. To allow physicians to monitor the amount of factor concentrates administered, the patients document each factor injection in a paper-diary. Nevertheless, because of the fact that most patients visit their physicians only two to four times a year, there could be considerable delay in detecting medication problems. The aim of this pilot study was to assess whether an electronic documentation tool could successfully replace traditional paper-diaries for haemophilia A patients and enable the physician to have a timely overview of the patient’s treatment. An electronic, hand-held documentation tool, Haemoassist™, was developed. In this study, patients using prophylaxis and on-demand therapies documented their factor consumption both electronically and on paper-diaries. Documentations were compared and descriptively evaluated. Patients also completed a survey to evaluate the feasibility and gather their opinions on the Haemoassist™ system. Ten patients from two haemophilia treatment centres in Germany submitted a total of 548 records via hand-held device during the observation period, from March 2006 to February 2007. Comparison of electronic and paper-based records showed differing responses among patients with some patients entering more electronic and some others more paper-based documentations. In the questionnaires on feasibility and usefulness of Haemoassist™, three patients preferred the electronic tool, two patients wanted to continue using paper-based diaries, and one had no preference. The study shows that an electronic documentation system is feasible for haemophilia patients and provides the physician with the opportunity to more closely monitor patients. However, not all patients seem to be qualified for using an electronic tool, and the tool has to run reliably without major errors for ensuring reliability and acceptability. In the future, Haemoassist™ might support quality assurance in haemophilia treatment and improve guidance in the home-care setting. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding the need of structured abstracts and explicit reporting of levels of evidence and author contributions published in the May 2004 issue of "Haemophilia."

Introduction: Hereditary factor X deficiency is a rare bleeding disorder, with limited treatment options. This paper describes the approach to pre‐clinical development and characterization of a high‐purity plasma‐derived factor X concentrate, to achieve orphan drug marketing authorization for the treatment of hereditary factor X deficiency. Methods: A chromatographic process was developed, to purify factor X from human plasma for fractionation. The product was characterized using in vitro, in vivo and ex vivo tests for potency, purity, thrombogenicity, immunogenicity, toxicity and stability. Results: The production process complied with good pharmaceutical manufacturing practice. It achieved 6000‐fold purification and 100‐fold concentration of the factor X protein compared to human plasma. The factor X protein was 94%–96% pure. Other residual plasma proteins were well below levels in plasma, minimizing potential interference in hemostasis after therapeutic administration. Effective virus‐reduction during manufacture, and the absence of thrombogenicity, toxicity and immunogenic potential were confirmed, addressing the main safety concerns historically associated with plasma‐derived therapeutics. The freeze‐dried product remained stable between +2°C and +30°C for at least three years. After reconstitution with water for injections, the factor X activity was maintained for at least 48 h at +18°C to +22°C. Conclusion: Targeted pre‐clinical development of the first highly‐purified concentrate to treat hereditary factor X deficiency is described. Following international guidelines for nonclinical safety testing, particular strategies were adopted for unmodified products derived from human blood plasma. This approach may also be relevant to the development of other ultra‐orphan medicinal products. [ABSTRACT FROM AUTHOR]

Better access to haemophilia treatment and care is currently changing the life of a great many patients with haemophilia or other inherited bleeding diseases in numerous developing countries. These changes are encouraging while stimulating local research initiatives and projects that deserve to be communicated through scientific publications. This paper addresses several opportunities and challenges, providing guidance to scientists, clinicians, researchers and health professionals from developing countries who are actively involved in multidisciplinary haemophilia care, while wishing to publish their reports in Haemophilia, the official, global, multidisciplinary journal of the World Federation of Haemophilia (WFH), the European Haemophilia and Allied Disorders (EAHAD) organization and the Hemostasis and Thrombosis Research Society (HTRS) of North America, focusing on inherited bleeding diseases. Several strategies and pathways designed to encourage, help and support successful publications from developing countries are herein discussed. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials in haemophilia product development are expanding rapidly however, the number of sites and expertise in the clinical trial conduct is limited. Guidance on the requirement for conducting clinical trials is required Aim: The aim of this paper is to outline generic requirements to participate in clinical trials in haemophilia Materials: This paper describes three elements which are the requirements for success conduct of haemophilia clinical trials. These are the study product, study participant, and the global regulatory and ethics framework Results and conclusion: In haemophilia clinical trials, requirements for participate in studies are many and include considerations of study product, study participant and ethical and regulatory framework. When these elements are in place, it is possible to conduct haemophilia clinical trials anywhere in the world. [ABSTRACT FROM AUTHOR]

Background: The Patient Reported Outcomes, Burdens and Experiences (PROBE) study aims to develop and validate questionnaire for assessing health status in patients with haemophilia and participants without bleeding disorders. Objective: To investigate the test‐retest properties of the PROBE questionnaire. Methods: The PROBE questionnaire covers four domains and is comprised of 29 questions. People with haemophilia (PWH) and participants without bleeding disorder were invited to participate in this study. All participants were asked to complete the PROBE questionnaire three times (paper‐based survey on two consecutive days: T1 and T2 and then a web‐based version: T3). Test‐retest properties and percentage agreement were analysed. Results: A total of 63 participants were enrolled in this study with a median age of 50 (range: 17‐76) years. Of these, 30 (47.6%) were PWH. On the questions common to PWH and participants without bleeding disorder, Kappa coefficients ranged from 0.69 to 1.00, indicating substantial to almost perfect agreement (T1 vs T2). For haemophilia‐related questions (T1 vs T2), Kappa coefficients ranged from 0.5 to 1.0. Of these, 5 of 11 items were in perfect agreement (Kappa = 1.0). The web‐based questionnaire (T3) showed substantial to almost perfect agreement with the paper version (T1 test‐retest properties were comparable between PWH and individuals without a bleeding disorder). Conclusions: The results suggest that PROBE is a reliable tool to assess patient‐reported outcomes for PWH and benchmark data in participants without bleeding disorder. The web‐based questionnaire and the standard paper‐based version can be used interchangeably. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia B is a debilitating hereditary coagulation disorder characterized by prolonged or spontaneous episodes of bleeding caused by a deficiency of endogenous factor IX. In Algeria, even though many studies are being carried out to evaluate the prevalence and management of haemophilia B, there is a paucity of locally published literature that can be used to understand the most recent information on the disease's epidemiology, diagnostic techniques and treatment options. Aims: The aim of this manuscript is to raise awareness among patients and family clinicians about current practices, recent developments and unmet needs related to haemophilia B in Algeria. Methods: A comprehensive literature search was conducted through online scientific databases to review publications regarding haemophilia B in Algeria. Exclusions of the review include case studies, interregional comparisons, abstract‐only papers and studies outside the range of 2012–2022. Results: The findings discussed relate to the epidemiology of haemophilia B in Algeria, the clinical diagnostic process, disease symptoms, the benefits of molecular and genetic testing, advancements in prophylactic care, as well as unmet needs hindering the progression of optimal haemophilia B management. Conclusion: These findings are crucial to encourage the maintenance of national registries with updated epidemiological data, facilitate early and timely detection of disease symptoms, improve the provision of diagnostic facilities and enhance the overall treatment landscape for better patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. Aim: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). Methods: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in‐person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. Results: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. Conclusion: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients. [ABSTRACT FROM AUTHOR]

Introduction: In the era of electronic medical records, pen‐and‐paper‐based physician‐administered bleeding assessment tools (BAT) remain under‐utilized in the clinical setting, as they are noted to be time‐consuming. Aim: The current study reviews the use of an electronic self‐administered bleeding assessment tool (eBAT) prospectively in a paediatric haematology clinic and in comparison with a physician administered BAT (pBAT). Materials and Methods: This was reviewed and approved in the current form because the aims statement includes the method regarding comparison of 2 groups. So no additional section required. Results: A total of 94 BAT response pairs were available for analysis. The median time required for patients or parents to complete the eBAT was 8 min, with less than a third of the patients requiring over 10 min. The median bleeding scores noted in this study were 4 for both the BATs, with strong positive correlation between the eBAT and the physician administered bleeding questionnaire. The eBAT had a sensitivity of 93.8% (95% CI 82.8%–98.7%), a specificity of 34.8% (95% CI 21.4%–50.3%), a positive predictive value (PV) of 60.0% (95% CI 54.5%–65.2%) and a negative PV of 84.2% (95% CI 62.5%–94.5%) for identifying a bleeding disorder. Conclusions: Findings indicate that eBAT is a valid and time‐efficient screening tool for evaluating patients' bleeding symptoms, which can improve clinical applicability of BATs by reducing time for bleeding history review. [ABSTRACT FROM AUTHOR]

Introduction: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each. Methods: The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019. Results: The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty‐three percent (n = 49) had no joint status involvement at the end of follow‐up (HJHS and HEAD‐US = 0). The median ABR was 0.7 (IQR 0.2 –1.0) and 54.2% presented trough levels of FVIII during follow‐up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49‐5224.40) Conclusion: Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment. [ABSTRACT FROM AUTHOR]

Introduction: The Patient Reported Outcomes, Burdens, and Experiences (PROBE) questionnaire is a patient‐reported outcome tool that assesses quality of life and disease burden in people with haemophilia (PWH). Aim: To assesses the test–retest reliability of PROBE when completed using the mobile phone application. Methods: We recruited PWH, including carriers, and individuals with no bleeding disorders who attended haemophilia‐related workshops or via social media. Participants completed PROBE three times (twice on the app: T1 and T2, and once on the web, T3). Test–retest reliability was analysed for T1 versus T2 (app to app, time period one) and T2 versus T3 (app to web, time period two). Results: We enrolled 48 participants (median age = 56 [range 27–78] years). Eighteen participants (37.5%) were PWH and seven (14.6%) were carriers. On general health domain questions, we found almost perfect agreement, except for a question on the frequency of use of pain medication in the last 12 months [Kappa coefficient (κ).72 and.37 for time period one and two, respectively] and any use of pain medications (κ.75) for time period two. For haemophilia‐related questions, we found substantial to perfect agreement, except for the questions on the number of joint bleeds in the previous 6 months for time period one (κ.49) and the number of bleeds in the previous two weeks for time period two (κ.34). Conclusions: The results demonstrate the reliability of the PROBE app. The app can be used interchangeably with the paper and web platforms for PROBE administration. [ABSTRACT FROM AUTHOR]

Introduction: Due to advances in treatments, people with haemophilia (PWH) are living longer. They are not as active as the general population due to joint damage and lack confidence to be active due to concerns about further bleeds and pain. There is a need to facilitate healthy aging through promotion of physical activity (PA) and exercise. Changing patient beliefs and increasing physical literacy and confidence to move are thought to be key to helping PWH become more active. Aim: This paper describes the development of an exercise and behaviour change intervention to improve confidence to exercise in PWH. Methods: The 4‐stage Medical Research Council framework for complex intervention development was used. Results: Stakeholders included 17 PWH and 7 physiotherapists working in haemophilia. Seven online focus group meetings were held. The final intervention is a hybrid 12‐week physiotherapist led progressive exercise programme. Classes are 45 min including Pilates, High intensity interval training and balance elements, together with discussion sessions focusing on PA recommendations, the types and benefits of different exercise styles and the effects of PA, together with the effects of aging for PWH. The COM‐B model of behaviour change was used to develop the intervention. Conclusion: Co‐design helps to produce an intervention that understands the stakeholders needs. Through this process the intervention developed to incorporate not only increasing PA but also confidence to exercise. The use of behaviour change theory identified the behaviour techniques included in the intervention and aims to increase physical literacy in this population. [ABSTRACT FROM AUTHOR]

An editorial is presented on the treatment of haemophilia. Topics mentioned include the changing landscape of haemophilia treatment with inhibitors, the new type of surgical operation in a patient with haemophilia and the international practice of the physicians in treating haemophilic patients with inhibitors.

This paper is based on the assumption that psychosocial services can add important mental and social dimensions to the traditional concepts of help and medicine. Peer support which has been established world-wide for people with haemophilia and their families is invaluable and irreplaceable. However the role of the professional psychosocial worker is underutilized in most countries, mostly because of lack of financial resources. This paper will argue that skilled workers can assist individuals and groups to reach their full potential in a variety of creative and non-threatening ways. Psychosocial workers have strict codes of conduct and requirements relating to accreditation to ensure accountability in their work. They can work in a variety of individual roles and have a wide range of individual mandates within work settings. [ABSTRACT FROM AUTHOR]

Summary. Communication between patients and haemophilia centres is important in the management of the disease. Traditionally this has been done by paper records which give retrospective and often incomplete data. This paper describes the development and pilot study of a novel Internet-based electronic patient treatment log. The advantages of the system include up to date information available to the haemophilia centre, less data entry, better quality records and an individualized alert system for significant events. The system was tested with ten patients at three UK haemophilia centres and found to be feasible and easy to use. In the opinion of the patients and health care professionals involved in the pilot study, the system improves quality, accuracy, accessibility and usefulness of patient generated data. Development of the system is ongoing and its use extended to other haemophilia centres. [ABSTRACT FROM AUTHOR]

In the past decades von Willebrand disease (vWD) has, in several respects, fallen into the shadow of classical haemophilia due to all problems that have faced those dealing with congenital bleeding disorders, not least regarding blood-borne diseases. The time has come to revisit and refocus on vWD, probably the most common bleeding disorder. Accordingly, a number of Nordic physicians and scientists working in this field organized a meeting on the ferry boat from Stockholm to Mariehamn, in the Åland islands, the home of the index families with this disease, as described by Erik von Willebrand in 1926. The objective of the meeting was to make a comprehensive survey of vWD as seen from the situation in the Nordic countries. In order to achieve all goals some scientists of note from countries outside the Nordic area were invited as well. This paper gives a summary of the symposium, mainly based on the separate papers published in this issue. [ABSTRACT FROM AUTHOR]

Gene therapy will be the first long‐term therapy with potential to produce a functional cure for haemophilia. As a single dose ('once‐and‐done') therapy with significant uncertainties regarding impact and duration of factor expression, flexibility and adaptability of (1) value framework, (2) health technology assessment (HTA) methodology, and (3) development of alternative payment models will be needed for adoption of this new technology and to facilitate transparent decision‐making to support its implementation. The responsibility for each of these currently lies with distinct entities, underscoring a need for enhanced collaboration between all stakeholders, as expanded engagement by key stakeholders will be critical to optimizing the assessment of value, enabling an optimised approach to HTA, and opening receptivity to new and innovative payment models. This supplement issue describes important considerations for a gene therapy 'toolkit', highlighting key considerations for each of the aforementioned tools, which will be useful for guiding decision‐making regarding gene therapy as a novel treatment modality. In this article, we outline how the tools presented in this supplement can be applied as part of a framework to address the requirements of the relevant stakeholders, including payers, manufacturers, treaters, and patients. The paper also provides an illustrative example of how to understand the features of alternative payment models depending on the organization of and payment for healthcare. [ABSTRACT FROM AUTHOR]

KEY POINTS OF CONSIDERATION: To prepare for the introduction of gene therapies in haemophilia care, healthcare frameworks for evaluation and valuation will need to evolve to address the unique requirements of current and future innovations for treating this rare disease.The papers in this supplement provide an insightful and comprehensive state‐of‐the‐art assessment of these requirements and challenges.In terms of evaluation, the definition of a patient‐defined value framework that captures multi‐dimensional, patient‐centered outcomes is an important first step for determining the full benefit of gene therapy for persons with haemophilia.In terms of valuation and rewards for innovation, health systems will need to develop alternative payment models for risk‐sharing that will allow payers and society to address uncertainties about the ultimate clinical and economic value of these innovations. And health technology assessment authorities will need to exercise greater flexibility in evidence requirements given the unique features of data collection for a potentially curative therapy for a rare disease with long‐term uncertainties about durability of impact.Collaboration among stakeholders will be essential for developing the critical evidence requirements and providing the incentives needed to achieve sustainable budgets and broad access for persons with haemophilia worldwide. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of durable and potentially curative cell and gene therapies (also known as advanced therapy medicinal products) with high price tags is challenging conventional health care payment systems. Among these are gene therapies in various phases of development for haemophilia A and B. The emergence of these therapies comes with clinical and economic uncertainties for payers, providers, patients, and manufacturers. These include uncertainties about expression of the intended physiological response, patient outcomes, and duration of treatment effect, along with potentially high upfront costs, variable additional costs, and uncertainties about uptake of the therapy among indicated patient populations. These clinical and economic uncertainties raise interest among payers, providers, and manufacturers in risk‐sharing arrangements, including alternative payment models (APMs). Summary: APMs differ from traditional fee‐for‐service payment for health care. For example, some APMs are designed to reward clinicians and provider organizations for delivering high‐quality and cost‐effective care. The APMs described here, outcomes‐based models (or value‐ or performance‐based models) and finance‐based models, are designed to mitigate or otherwise manage financial risks associated with health care payment, including instances in which patient outcomes for costly therapies are uncertain. We examine how such APMs may be applicable in the context of emerging gene therapies for haemophilia A, including considerations in determining whether any particular APM may be most suitable. KEY POINTS OF CONSIDERATION: Gene therapies for haemophilia are among the emerging durable and potentially curative cell and gene therapies with high price tags that are challenging conventional payment systems.These therapies present clinical and economic uncertainties for payers, providers, patients, and manufacturers, including regarding expression of the intended physiological response, duration of treatment effect, patient outcomes, potentially high upfront costs and variable additional costs, and uptake among potentially indicated, diverse patient subgroups.These uncertainties raise interest among payers, manufacturers, and providers in risk‐sharing arrangements, including alternative payment models (APMs) such as various outcomes‐based and finance‐based models.This paper describes a taxonomy of APMs. Then, for the particular context of gene therapy for haemophilia A, we present a set of factors to be considered when determining whether an APM risk‐sharing arrangement may be appropriate for a given gene therapy, and, if so, which APM may be most suitable.[Correction added on 21 February 2022, after first online publication: the 'Key Points of Consideration' have been added in this version.] [ABSTRACT FROM AUTHOR]

Chronic disorders such as haemophilia and yon Willebrand disease can rob people of a feeling of control over their lives. Added to this is often a feeling of confusion or intimidation when dealing with the healthcare system. People may begin to feel like victims of their disorders and of the healthcare system. The healthcare system defines people who are in receipt of care as patients. The word patient comes from the Latin word patiens, which means to suffer, endure, allow, permit or undergo. Even the term implies a sense of victimization. People who become partners in their care and view the receipt and delivery of healthcare as a service wherein they are the consumer and the doctor or clinician is the provider, will feel more in control and will likely have better outcomes than people who assume the more traditional role of 'patient'. [ABSTRACT FROM AUTHOR]

Introduction: Social Workers (SWs) provide valuable services on multidisciplinary teams of Haemophilia Treatment Centres (HTCs). However, their roles have not been defined and standardized. This paper identifies six major SW roles, including counselling, case management, financial/insurance, outreach/programs, administrative, and grants/research. Roles were further classified as 'actual' roles, those that SWs were actively practicing, and 'ideal' roles, those that SWs felt were most important for their clients. Aim: The goal of this study was to determine the actual and ideal roles of HTC SWs and the barriers to ideal roles. Methods: An online survey was tested with a focus group and then e‐mailed to 147 SWs who were working in the 141 HTCs across the United States. Results: Fifty‐five percent of the SWs completed the survey. Data revealed that SWs' most prominent actual role was case management in their work with three client sub‐populations: adult patients, paediatric patients and family members. However, SWs identified counselling as the ideal role that was most important for all client groups. Barriers to practicing ideal roles included lack of SW input, insufficient budgeted time and inadequate training. Salaries were found to be stagnant compared to 2010. Twenty‐five percent of SWs reported no supervision. Conclusions: Survey results gave evidence that although HTC SWs were primarily engaged in case management roles, they wanted to take on larger counselling roles. Efforts should be made to eliminate barriers to ideal SW roles so that SWs can provide additional psychosocial services for HTC patients. [ABSTRACT FROM AUTHOR]

Introduction: Turoctocog alfa is a recombinant factor VIII (FVIII) molecule, approved for treatment and prophylaxis of bleeding in patients with haemophilia A. In the guardian 1 (adolescents/adults) and guardian 3 (children) phase 3 trials, turoctocog alfa demonstrated a favourable efficacy and safety profile. Guardian 1 or 3 completers could enrol in the guardian 2 extension. Final guardian 2 results are reported here. Aim: Investigate long‐term safety and efficacy of turoctocog alfa administered for prophylaxis and treatment of bleeds. Methods: In this phase 3b open‐label trial, previously treated males of all ages with severe haemophilia A received prophylaxis regimens of turoctocog alfa or on‐demand treatment of bleeds. The primary safety endpoint was frequency of FVIII inhibitor development. Efficacy endpoints included annualized bleeding rate (ABR) during prophylaxis, haemostatic response in treatment of bleeds and number of injections required to treat bleeds. Results: Overall, 213 patients were dosed with turoctocog alfa; 207 patients received prophylaxis; 19 received on‐demand treatment. No FVIII inhibitors (≥0.6 BU) were reported. For all patients on prophylaxis, overall median ABR was 1.37 bleeds/y; success rate for treatment of bleeds was 90.2%; and 88.2% of bleeds were controlled with 1‐2 injections of turoctocog alfa. For the on‐demand regimen, overall median ABR was 30.44 bleeds/y; success rate for treatment of bleeds was 96.7%; and 94.9% of bleeds were controlled with 1‐2 injections of turoctocog alfa. Conclusion: Extended use of turoctocog alfa is safe and effective for prevention and treatment of bleeding episodes in previously treated patients with haemophilia A across all ages. [ABSTRACT FROM AUTHOR]

Introduction: Jamaica has an estimated 200 persons with haemophilia (PWH), who face significant constraints in access to specialized haemophilia care, including access to clotting factor concentrates. Aim: The aim of this paper is to establish the current burden of disease in PWH in Jamaica. Methods: PWH were enrolled through the University Hospital of the West Indies, Jamaica. The impact of haemophilia was assessed using a comprehensive battery of heath outcome measures that included the following: laboratory, clinical information and validated outcome measures of joint structure and function, activity, and health‐related quality of life (HRQoL) to provide a health profile of the Jamaican haemophilia population. Results: In all, 45 PWH were registered (mean age: 29, range: 0.17‐69 years), including 13 children (<18 years of age) and 32 adults. In this sample, 41 had haemophilia A (30 severe) and 4 had haemophilia B (3 severe); 10 patients with haemophilia A were inhibitor positive. The results indicate that adults with haemophilia in Jamaica have significant joint damage: mean Haemophilia Joint Health Score (HJHS) = 42.1 (SD = 17.3); moderate activity levels − mean Haemophilia Activities List (HAL) score = 64.8 (SD = 17.8); and low HRQoL scores − mean Haemo‐QoL‐A score = 62.3 (SD = 19.4). Results for children are also reported but should be interpreted with caution due to the small sample size. Conclusions: There is a very high burden of disease in PWH in Jamaica. The health profiles reported in this paper are an essential first step in advocating for a multidisciplinary Comprehensive Care Program for assessment and care of PWH in Jamaica. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of joint recommendations by healthcare professionals (HCP) and patient organizations when a partnership between high and low‐income countries in the field of haemophilia is planned. Aim: To draft recommendations to clarify the methodology when a partnership between low‐ and high‐income countries is planned with the objective of a long‐term implication. This methodology is to be implemented for fulfilling both medical and associative aims. Methods: Based on the available literature, a first document was written, then diffused to AFATH (Alliance Franco‐Africaine pour le Traitement de l'Hémophilie) members, and after a one‐day meeting and further amendments, a second draft was approved by all members before submission for publication. Results: Based on 6 years experience, several recommendations regarding the joint and separate roles of patient association and HCP for a first mission in French‐speaking sub‐Saharan African countries have been established. The proposed methodology for establishing preliminary contacts, the first visit and the key points for diagnostic action, medical follow‐up, patient education and advocacy strategy outlines a model of partnership between patients and HCP. Conclusion: This paper written jointly by patients and physicians underlines the importance of reciprocal expert guidance and a partnership based on complementary inputs. [ABSTRACT FROM AUTHOR]

This paper presents the results of a study talking to children and young people affected with severe haemophilia A and/or haemophilia B about their knowledge and understanding of genetics and inheritance. These data were gathered in a qualitative study using semi-structured interviews with thirty boys aged four to sixteen discussing the impact of haemophilia on their lives. Responses were tape recorded, transcribed and analysed, using thematic analysis; one of the themes identified was genetic knowledge which is presented in this paper. Genetic knowledge was formed within the context of normal day-to-day lives within families affected by haemophilia, with parents and haemophilia centre staff being sources of information about individual inheritance patterns as well as providers of information about the future genetic impact of having haemophilia. [ABSTRACT FROM AUTHOR]

Introduction: The experiences of patients with mild‐to‐moderate haemophilia differ from those of patients with severe haemophilia or those without a bleeding disorder and include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, there is a significant lack of data on mild‐to‐moderate haemophilia, and many unmet needs remain to be identified and addressed in this group of patients. Methods: Challenges for these patients, including women with haemophilia, were identified during a roundtable meeting attended by a group of US‐based experts including healthcare professionals (e.g., physicians, nurses, and physical therapists) and patients who live with a bleeding disorder. Results: Identified unmet needs included a lack of proper education on the management of their disorder and prompt treatment of bleeds, absenteeism from school and work, and challenges with personal relationships. Initiatives to assist with alleviating these unmet needs were proposed and include suggestions for healthcare professionals, haemophilia treatment centres (HTCs) and national and local organizations within the bleeding disorders community. These included HTC and community engagement programmes for patients with mild‐to‐moderate haemophilia, revised transition guidelines for these patients as they approach adulthood and revised diagnostic classification of mild and moderate haemophilia. Challenges unique to women with haemophilia and ways to address these issues were also discussed. Conclusion: This paper summarizes the challenges, initiatives and suggestions that were identified by the haemophilia experts during the roundtable meeting. [ABSTRACT FROM AUTHOR]