The effective engagement of patients in research on rare diseases is currently an area of increasing interest [8, 20]. This has come about as a result of governments giving greater priority and incentives for rare disease research, including through orphan drug legislation, [21, 22] and promotion by policy makers [20, 23]. This has occurred in parallel with a recent shift from a passive role for patients in research towards a desire to play a more involved role in the research process, as demonstrated by the survey outcomes. The lack of awareness of registry participation amongst respondents to the aHUS Alliance survey may be an area in which patient involvement in research can easily be improved. Patients may be unaware of the opportunity to enrol in a research registry if it is not offered by their physician. The fact that the Registry SAB initiated the collaboration by inviting a patient representative to join the team demonstrates that cooperation is bidirectional and reflects the recent change towards a new model of participation in research.
Amongst the research priorities identified, two diagnosis issues feature prominently. First, understanding the barriers to more rapid diagnosis and, second, how quickly diagnosis needs to be made to avoid irreversible organ damage. Understandably, a key concern of patients was around outcomes following kidney transplantation. This procedure was contraindicated in patients diagnosed with aHUS prior to the availability of eculizumab, and transplantation can also induce de novo aHUS. In some countries, aHUS patients on dialysis may be refused access to prophylactic eculizumab to prevent post-transplant recurrence of the disease and therefore this is a key issue for patient organisations around the world. However, data on this topic have been published in the medical literature, suggesting that the information available to patients with aHUS is poor. In this regard, patient organisations need to improve the dissemination of relevant information to patients and the participation of the aHUS Alliance in the Global Registry is an opportunity for patient organisations to inform and answer patient questions in a consistent and understandable way.
An ability to self-monitor aHUS symptoms also featured strongly, reflecting a desire of patients to feel in control of their condition. The issue of the time of year of aHUS onset has its roots in a casual discussion in the aHUS social media, but may be worthy of further study. Although not selected as a priority area of research, several members of the aHUS Alliance have an interest in this subject and a proposal to investigate this has been submitted to the SAB for consideration. Further, some of the questions raised demonstrate a potential lack of understanding of the disease and represent an opportunity for development of educational materials to address patient knowledge gaps.
Interestingly, no questions were raised regarding potential adverse effects of eculizumab, such as the risk of meningococcal infection, despite the primary purpose of the Registry being to determine the long-term safety of eculizumab treatment. This could be due a number of reasons, including physicians and patients considering the risk negligible, or the provision of patient information cards on treatment initiation and advice from patient organisations is sufficient explanation.
Following presentation of the report by the aHUS Alliance’s SAB representative, the research topics were given serious consideration for action. It was considered that a response to the aHUS Alliance’s list, including identification of knowledge gaps, would be a prerequisite to complete prioritisation. The subsequent work plan for the aHUS Registry in 2016 featured a number of topics proposed by the Alliance as priority activities. The aHUS Alliance had therefore not only been consulted but their response was considered and incorporated, creating a clear process of engagement for working with an international research network. This innovative way of generating research ideas has also been a learning process for the SAB members. For both parties to get the most from the collaboration, it is important to ensure the development of a long-term partnership.
A paradigm shift for patient participation in disease-related research decision-making?
Patients with rare diseases have limited access to useful information to guide treatment decisions; providing patients with the opportunity to ask research questions may help to ensure that research efforts in rare diseases address relevant clinical questions and patient-centred health outcomes [20]. The active participation of patients and their representatives in research, whether a registry or clinical trial, can potentially lead to improvements in enrolment, data collection and quality, the credibility of results and their direct applicability to patients [24]. The inclusion of a patient representative on the Global aHUS Registry SAB will also improve the dissemination of outcomes to patients, thus increasing the transparency of the research process.
In order to promote changing the role of the patient in a registry from passive (patient is a data point) to active (patient is a researcher), [24] the participation of patients in the Global aHUS Registry is now actively supported by a patient representative working alongside the SAB. The patient advocate will assist in developing strategies to encourage voluntary patient participation in the Registry, will convey information from patients about their experience with the Registry, and will help the SAB share the results of the Registry with other patients.
A formal structure for partnerships between patient groups and clinical researchers
The Dialogue Model [25] has been identified as a construct for the continuing development of the partnership in the context of the Registry. The Model has six stages (exploration, consultation, prioritisation, integration, programming and implementation), of which the emerging partnership has reached the start of the third stage. Not completing the early stages fully and satisfactorily can be predictive of a failure to sustain progress to successful implementation.
Completion of a robust systematic evidence assessment review of the knowledge gap needs to be reviewed by the SAB as well as the Alliance, to arrive at an agreed list of specific patient research priorities, which then must be integrated with the Registry’s other research agendas from clinicians and industry. With an integrated list of research topics finalised, it will then be possible to move to a sequential programming of topics for direct study by the SAB, or indirectly, through encouragement of external investigators to use the Registry data for other priority topics.