Disease Specific Registries vs Product Registries

Transcription

1 1 Disease Specific Registries vs Product Registries Professor Hanns Lochmüller Newcastle University

2 2 What is TREAT-NMD? A network of excellence funded by the European Union (but with global collaborations) Aims to help promising new treatments for neuromuscular diseases make the transition from the lab to the patient Not a research project but an infrastructure project Creating the tools for trial-readiness in the neuromuscular field Helping researchers and expert centres collaborate better Improving patient care worldwide Sustained beyond 2011 as TREAT-NMD Alliance

3 3

4 4 Trial readiness: TREAT-NMD patient registries Globaldatabases of patients with the genetic and clinical data necessary for trial recruitment Many benefits to registered patients Feedback on standards of care and new research developments Feeling a sense of belonging to a broader community Not being left behind as clinical trials develop A link to the research community Many benefits to industry Easy access to patient community Clear concept of target market Feasibility and planning of clinical trials Recruitment of patients into clinical trials

5 5 DMD Global registries Pre 2007: United DystrophinopathyProject (UDP) Action Duchenne (PPUK) registry UK and Ireland French patient database Czech Parent project registry All independent and with different datasets TREAT-NMD approach Define a mandatory dataset and means to share core data Allow interface with patients to be variable from country to country Focus on the information that will be needed for clinical trials

6 6 DMD Registries before TREAT-NMD

7 7 DMD Registries in 2011 > 10,000 patients in 47 countries global data for multicentre trials

8 8 Patient registries for DMD The TREAT-NMD setup Patient self-report Clinician / geneticist report Curation! National registry TREAT-NMD Global Registry

9 9 TREAT-NMD patient registries Mandatory dataset and means to share core global data Single entry point for information Interface with patients can be variable from country to country Depending on local situation, involvement of clinical and patient groups, funding availability, size of disease group Focus on reliable information that will be needed for clinical trials Strict curation of mutation data and annual training of curators Mandatory annual update of data Ensure ethical and governance best practice Regulated by TREAT-NMD registry charter Oversight committee approves all registry requests

10 10 TREAT-NMD Oversight Committee The Oversight Committee (OC) is the governing structure of the TREAT-NMD global database Comprised of 42 members, one third of which represent patient organisations The OC reviews all enquiries of third parties to the global database, coming to a decision within 14 days

11 11 Patient registries: legal/ethical best practice Feedback to patients Possibility of data withdrawal Informed consent form Pseudonymised(encrypted) data Frequent updates of data The TREAT-NMD registries adhere to these principles via the TREAT-NMD registry charter

12 12 Third-party access to the global patient registries National registries Global Registry Local Ethics Board approval TREAT-NMD Oversight Committee approval Third parties (industry, academia)

13 13 Registries used by industry trials 8 DMD & 1 SMA feasibility enquiries completed from Feb 2009 to Dec 2010 (8 industry, 1 academic) 2 DMD & 1 SMA recruitment enquiriescompleted (June 2011, 2 industry, recruitment into clinical trial; 1 academic, recruitment into care study) All enquiries approved by OC in <14 days (>90% participation) All enquiry reports completed in time according to agreements (<3 weeks to 8 weeks) Revenue ear-marked for further education and training (curator and OC meetings)

14 14 Orphanet Report 2011 > 500 rare disease (RD) registries and databases in Europe were identified Unequal geographical distribution Academic registries (usually on diagnosis and/or follow-up of the course of disease) vsprivate company (industry) registries. Almost all industry sponsored registries are drug registries -often installed as a post-marketing requirement to assess the safety and/or effectiveness of orphan drugs 8 of the 16 industry registries are for lysosomal storage disorders!

15 15 Orphan drugs for Fabry disease Two enzymes authorized in the EU in 2001 Generic name agalsidase alfa agalsidase beta Brand name Replagal Fabrazyme Company TKT/Shire Genzyme Cell system Human fibroblasts CHO Dose Costs 0.2 mg/kg every two weeks ~ euro per patient per year 1.0 mg/kg every two weeks ~ euro per patient per year Two postmarketing databases were set-up completely independent of each other

16 16 Orphan drugs for Fabry disease Post-marketing databases were a requirement to industry to collect data Completely separate databases -two groups of academia and industry worked completely separately on identical issues, such as the effect of treatment in children Resulted in fragmentation of data and overwhelming industry influence (a large proportion of publications was supported by one of the companies) Fragmentation has delayed our knowledge on critical issues with respect to the appropriate use of these expensive treatments The registries are astonishingly incomplete, due to the voluntary character of the registers and the lack of standardisation Prof C Hollak; EUCERD/EMA Workshop; London 2011

17 17 EPIRARE Project EPIRARE Project (funded by DG SANCO, April 2011) -to assess RD registries in Europe and lay the foundations for a common European rare disease platform The key problems affecting the utility of registries for future research are: o lack of harmonisation: high variability among RD databases, geographical coverage and type of data collected; the majority of databases are national or regional, only a minority are European or international o lack of data sharing: about half of the registries share some data with other databases but only a minority share data with biobanks or centres of expertise o lack of sustainability: a significant proportion of RD registries expire due to lack of commitment from data providers, lack of funding or study termination, and so discontinuation often leads to loss of data and loss of investment o lack of utility for research: owes to absence of quality control, standardised data elements, and genetic data

18 18 EPIRARE Project Databases and registries are important tools for RD research -remains a clear need for standardisation, coordination and further development. Open-access LSDBs and LOVDs using standardised genetic coding for a large number of RD and other genes -usually do not capture detailed or longitudinal phenotypic information and do not allow access to patients for study inclusion. More details from Domenica Taruscio!

19 19 Multiple treatments for the same orphan disease Multiple product registries for the same disease Each registry competes for the same patients limited patient population Re-inventing the wheel each time Not cost-effective No real stakeholder involvement No data sharing Company s responsibility to sustain the registry

20 20 What is the purpose of rare disease registries for which an orphan drug is developed? Assessment of patients, not drugs Appropriate use of all treatments Cost effectiveness o Comparison with no treatment o Comparison with other treatments Safety Long term complications

21 21 What are the requirementsfor rare disease registries for which an orphan drug is developed? Complete and detailed data on: Diagnosis Natural course Clinically meaningful outcome data, including QoL Safety Long term complications

22 22 What models can we use for rare disease registries for which an orphan drug is developed? Public-private partnerships Registry is set up as a disease registry before marketing authorisation received Each company with an approved novel therapeutic can have their own secure portal within a disease registry to enter postmarketing surveillance data Disease registry collects longitudinal data on patients with a certain condition that are not taking any treatments Independent steering committee to govern the registry Outcome data is shared with the regulators Submission of treatment data to the registry is mandatory

23 23 Objectives of a registry platform Sharing of key resources Cost sharing -companies who implement and maintain registries for their own products spend millions of dollars every year Collects longitudinal data for disease natural history Meet regulatory postmarketing commitments for safety and efficacy Stakeholder involvement (industry/academia/patient/patient organisation) - build advocacy Planning ahead will reduce the barriers to patients receiving potential treatments as quickly as possible

24 24 Benefits of a registry platform to industry A centrally managed registry platform -will be independent, credible and cost saving Necessary for companies to have a surveillance system that is able to manage regulatory postmarketing commitments Cost and time effective use of a shared infrastructure Allows early detection, assessment, reporting and minimisation of risks of the novel treatments Access to a network of key opinion leaders Scientific credibility of entering data into a collaborative platform Access to anonymous aggregate data from the centralised database - industry partners will be highly encouraged to share a core anonymous data set Postmarketing databases can close the evidence gap

25 25 Feasibility study 2011 (collaboration between TREAT- NMD and AVI Biopharma) Centrally managed DMD postmarketing surveillance platform Linking the TREAT-NMD Global DMD Registry to individual surveillance modules TREAT-NMD Global Registry would be utilised as: - a way of finding patients - monitoring the natural history of the condition Industry partners would pay to use the platform separate secure modules - economy of scale, more cost and time efficient Shared anonymous data set from each surveillance module

26 26 Schematic of the proposed registry platform

27 27 Conclusions Multiple product registries for the same disease - fragments the care pathway for patients - data is not shared on critical issues - knowledge on the appropriate use of the drugs is delayed - the same patient population is being targeted each time Disease specific registries - multi-stakeholder involvement - shared cost model - compares appropriate use of all novel therapeutics - emphasis on patients not just drugs - provides a way of monitoring the natural history (NH) of the disease - regulators are advocating for more disease registries vsmultiple product specific registries

28 28 For more information: