In the 2016 aHUS Global Survey , aHUS patients and families gave their views on some aHUS Research and Registry issues.
Out of the 233 responses, 54% of patients said they were enrolled in an aHUS Registry. This was up considerably on the number enrolled in 2014. 17% said they definitely were not, and a remarkable 29% did not know if they were or not , and all but 1% are happy to continue to be in, or would wish to find out more about, Registry participation.
Registries are in important prerequisite to research for rare diseases, and aHUS is an ultra rare disease. Having sufficient participants in studies is difficult to achieve but important to make study conclusions more statistically valid. Each aHUS patient can add relatively more valuable “data” to an aHUS study, than perhaps thousands of patients with common diseases can.
aHUS registries exist in several ways. A registry may just be held by a single health institution, a hospital or clinic; or established at a national level within a country, and some countries even share data with other countries to establish international registries so that they can collaborate across borders.
For aHUS there is also a global registry. Sometimes referred to as the Alexion Registry, the aHUS Registry was set up as a clinical trial called officially:
“An Observational, Non-Interventional, Multi-Centre, Multi-National Study of Patients With atypical Hemolytic-Uremic Syndrome (aHUS Registry)“
The Registry had to be established to meet the requirements of both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for eculizumab to be licensed for use to treat aHUS. This is known as a Post Marketing Requirement (or PMR) with which Alexion has to comply, or the license for eculizumab would be withheld. PMRs are not an uncommon condition of FDA and EMA license approval.
The aHUS registry was established in 2012 and will be recruiting participants until December 2023; and with at least two years of follow-up on all patients after that. It is a longitudinal study trial over that period.
It is also a “disease based ” trial not just “drug based ” so all aHUS patients are entitled to be enrolled, irrespective of whether they have been, or are now, receiving eculizumab for treatment of their aHUS.
Enrolment of patients can only take place with their permission, and at a centre which has its self been established as an approved location where enrolment can take place. By early 2016 there are 290 centres set up in 19 countries with plans for more to participate. ( A revised Alexion policy result in drastic reduction in the sites and patients enrolled.
Once set up, approved centres are responsible for enrolling the patient, supplying basic medical information and data and updating it at regular intervals. The patient too plays a significant part by completing questionnaires about their health and feelings every six months, as it is important not only to know the personal “biological” status of a patient but also how having, and being treated for, aHUS affects a patient’s wellbeing and day-to-day life.
Although Alexion is obligated to fund the setting up and running of the aHUS Registry (it has one for PNH too) it does not decide, nor control, how the data is used, that is the responsibility of the Registry’s independent Scientific Advisory Board.
The Scientific Advisory Board, or SAB, of the aHUS Registry is composed of some of the most eminent aHUS clinical researchers in the world. Its current Chair is Dr. Christoph Licht of SickKids Hospital, Toronto; and its Vice Chair is Dr. Véronique Frémeaux-Baachi of the Hopital European George Pompidou, Paris.
They lead a team of research clinicians which oversee the collection of registry data, using accurately defined and standardise methodologies. They are also responsible for how the data is used, both for the research and investigations conducted by the SAB itself and by encouraging other investigators to use the Registry. All done with peer group reviews, thoroughly conducted by the whole SAB.
An example of a SAB investigation, which has been published in the last six months , can be seen by clicking here ; it is about the characteristics of the patients enrolled in the Registry as at 30 September 2014, when there were 516 patients from 16 Countries. There are at February 2019 852 patients enrolled and monitored ( out of 1787 registered since commencement )
Since February 2015, the aHUS alliance has been a member of the Scientific Advisory Board to provide a patient perspective* on what it does. The alliance’s role has been enhanced by the acceptance by the SAB of a patient priority based research agenda formulated at the alliance’s Third General Meeting in London in June 2015, as a key part of the aHUS Registry’s Research Programme for 2016 onwards.( This has been published in an article which can be read in the Orphanet Journal of Rare Diseases at this link)
An outcome study of renal transplant experience with, or without, a complement inhibitor is currently in progress. This was the alliance’s top priority in its agenda because aHUS dialysis patients needing a transplant are frequently excluded from scope of national policies on treatment of aHUS with Eculizumab. How best that unfortunate group of patients is treated is therefore of enormous importance in seeking funding for treatment.
Alexion does have responsibilities for the administration of the Registry database and arranging and supporting the SAB’s work. It is run as a long-term project and its current Clinical Project Leader is Donna Ames a Senior Manager at Alexion’s HQ in Connecticut, USA. The alliance asked Donna to comment on the Registry.
“The aHUS Registry was designed to capture real-world data on patients with aHUS; how they are treated, their symptoms, their overall health. By collecting this information from all over the globe, with so many patients’ data included, through analyses of these data we learn how the management of this disease may help other patients; those currently diagnosed and those who haven’t been diagnosed yet. The data also provides insight into the early diagnosis for physicians who are not experts in the field. Earlier diagnosis gives patients a much better chance of a normal life.
The patients and their physicians are extremely important and without them we would not have the depth of knowledge we have today – and we continue to learn. We appreciate all the patients who are willing to share their medical information to help others.”
Donna Ames Clinical Project Leader Alexion pharmaceuticals
(see more details about the trial by clicking here )
*Len Woodward aHUSUK/Answers for aHUS was the aHUS alliance representative on the aHUS Registry Scientific Advisory Board and was paid honoraria for doing so. Any questions about this blog can be sent to firstname.lastname@example.org