Page 65 - 2020_08-Haematologica-web

European Consensus for treatment of hemophilia
the novel drugs to be able to handle any side effect. The need for additional hemostatic drugs, such as bypassing agents, at the time of breakthrough bleeding and surgery may increase the risk of thrombosis, and this must be carefully evaluated. In general, patients should be man- aged by EHCCC. The future objective of these expert cen- ters should be the preparation and standardization of spe- cific healthcare packages integrating comprehensive pro- cedures for the management of hemophilia patients (with and without inhibitors) using emicizumab and other novel drugs during prophylaxis, with or without the addition of other hemostatic drugs during intercurrent bleeds or at the time of a surgery. The European Association for Hemophilia and Allied Disorders (EAHAD) and the European Hemophilia Consortium (EHC) need to update their joint European certification system, moving from the current self-documentation provided by each center to the implementation of audit visits that are going to be the basis on which the decision whether or not to issue a cer- tificate will be taken.
Recommendation 7
Postmarketing data collection for the long-term safety and effica- cy of all products should be mandatory. Every country should establish a national patient registry for hemophilia and other inherited bleeding disorders, covering all treatment modalities and patient-relevant outcomes.
From the beginning, the Kreuth Initiative for optimal use of blood products has been producing recommenda- tions for hemophilia treatment,4 but so far the issue of data collection has not been addressed. Clinical registries are important tools, particularly in the context of rare dis- eases such as hemophilia characterized by a limited num- ber of patients available for clinical trials. Registries may also help to collect long-term real-life data on the usage of products and patient-relevant treatment outcomes, thus providing valuable safety information. Registries should be set up in each European country on a national basis, and ideally should include all patients with inherited bleeding disorders.
Although recent EMA guidelines set standards for clini- cal studies,24 the design and conduct of the currently avail- able studies are characterized by several differences which prevent comparative data analysis. Registries may provide relevant complementary real-life data across a variety of products.25 Alongside the reporting obligations laid down by the pharmacovigilance legislation, registries should also collect comprehensive postmarketing safety informa- tion on all treatment modalities.
Recommendation 8
Dedicated data governance, evaluation and reporting should be implemented with adequate sustainable financial support under public control. Core data elements as recommended by the European Medicines Agency (EMA)24,26 and minimal dataset for post-registration surveillance should be implemented according to the communication from the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Subcommittee (SSC) on Factor VIII, Factor IX and Rare Coagulation Disorders.27
Although there are a number of ongoing registries in Europe, their organization and status, as well as the amount and quality of collected data, is quite variable.28 There are various models of registries, and promoters may be patient organizations, scientific societies, networks of
treatment centers or government institutions. Important questions need to be answered and solutions found for the problems related to each registry. How is the collection of data organized (preferably as user-friendly online portals)? How are data integrity and quality assured? Who owns the data? Who performs which analysis? How and by whom are results reported and eventually published? Additional challenges may also be presented by some degree of reluctance from hemophilia caregivers to share their patients' data and to make the effort needed to enter the data into a registry. To tackle these challenges, the German Transfusion Act was updated to include manda- tory adherence to the German Hemophilia Register Participation agreement. The organization of registries is a complex affair, and requires thorough planning, and sub- stantial and sustainable support. Given the importance and relevance of the data for the scientific evaluation of hemophilia treatment by regulatory agencies, and the par- ticular sensitivity of patient data, registries and their fund- ing need to be under public control. In order to enable meaningful evaluation and comparative analysis, a mini- mum set of common data elements should be included, as recently recommended by the EMA.26 Detailed guidance concerning the data set required for post-registration sur- veillance was also previously communicated by the ISTH Scientific and Standardization Committee on Factor VIII, Factor IX and Rare Coagulation Disorders.27
Recommendation 9
Collaboration at the European level should be encouraged, by strengthening and harmonizing existing registries in order to facil- itate pooling and comprehensive evaluation of data.
Greater collaboration is essential in order to have more data available for evaluation, and to enable data pooling and a comprehensive evaluation of data across all treat- ment modalities at a European level. Although the per- formance, co-operation and outputs of the registries cur- rently operative in Europe are not satisfactory,28 the way forward is not to advocate a single new, pan-European super-registry, but to strengthen and harmonize those already existing, as well as to encourage the establishment of common tools and strategies for their optimal use. This is an important and ambitious task which requires the support of all stakeholders, including patients, those responsible for their treatment, and academia, regulatory authorities and policymakers involved in health care.
Recommendation 10
Data collection should include direct reporting from patients using appropriate electronic industry-independent tools. Its use should be supported by education, user-friendly applications, and positive feedback to the patients.
The ultimate success of any kind of hemophilia registry depends on the participation and commitment of the care- givers and the willingness of patients to provide their data. In particular, the accuracy and completeness of the collect- ed data are closely related to the tools made available for reporting them to the registry. Data collection by direct reporting from patients through electronic tools is an attractive approach, provided any bias resulting from industry-developed applications is excluded, and treating physicians supervise its management and exercise quality control. Appropriate information and education about the background, instruments and goals of each registry, and provision of user-friendly applications are particularly
haematologica | 2020; 105(8)
2041