TREAT-NMD Conference PDF Free Download

TREAT-NMD Conference 2013 Utility of patient registries for clinical care and post-marketing surveillance Jan Verschuuren Leiden University Medical Centre Newcastle 30 October 1 November 2013

Improving treatment for Neuromuscular Disease Patient Clinical Disease Gene Protein Improve Treatment Researchers Physicians

Improving treatment for Neuromuscular Disease Patient Clinical Disease Standards of Care -Cardiac -Respiratory -Rehabilitation -Drugs Gene Protein Improve treatment Researchers Physicians

Improving treatment for Neuromuscular Disease Patient Clinical Disease Standards of Care -Cardiac -Respiratory -Rehabilitation -Drugs New Drugs Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

Improving treatment for Neuromuscular Disease Patient Clinical Disease Standards of Care -Cardiac -Respiratory -Rehabilitation -Drugs New Drugs Registries: 1.Trial Feasibility 2.Trial Recruitment Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

Improving treatment for Neuromuscular Disease Patient Clinical Disease Standards New Drugs of Care Registries: -Cardiac Registries: -Respiratory 1.Trial Feasibility -Rehabilitation 3. (Natural) History 2.Trial Recruitment Standards -Drugs of Care Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

Improving treatment for Neuromuscular Disease Registries: 4. Post-marketing Patient Clinical Disease Standards New Drugs of Care Registries: -Cardiac Registries: -Respiratory 1.Trial Feasibility -Rehabilitation 3. (Natural) History 2.Trial Recruitment Standards -Drugs of Care Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

TREAT-NMD : limited number of items Mandatory data 1. Personal data 2. Genetic test results 3. Diagnosis (DMD/BMD) 4. Motor function (walk) 5. Steroids 6. Scoliosis surgery 7. Cardiac medication 8. Current trials Highly encouraged data 1. Sitting 2. Heart condition 3. Echocardiogram 4. (Non) invasive ventilation 4. Previous muscle biopsy 5. Other registry 6. Family history Newcastle 30 October 1 November 2013

TREAT-NMD various sources of data entry Curation! Patient selfreport Clinician / geneticist report National Registry TREAT-NMD Global Registry 11

TREAT-NMD: Flexible data entry Research Labs 3% Patient Organisations 9% Clinical Genetic units 22% Clinicians 32% Patients and Families 34% Sent on paper and entered by the registry staff 46% Other 4% Entered online by data providers 23% Sent electronically and entered by the registry staff 27% Data providers Data entry methods

Global Registries linking up the national registries TREAT-NMD approach Define a mandatory and highly encouraged dataset Focus on small number of items (that will be needed for clinical trials) Provide means to share core data through variable interface from country to country Apply best practice (charter, oversight)

2002 USA 2007 USA 2007 Europe 2008 France Registries on DMD and neuromuscular disease Scully, et al. Neurology, 2013 Name MD STAR net Duchenne Connect TREAT- NMD Patients Number Items Genetic confirmation required 815 Multiple No 67-94% 1756 (70% USA) >50 items No 47% >10,000 8+6 Yes 90-100% UMD-DMD 2898 6 (180 planned) Yes 100% Data Collection Trained personnnel Patients & Curators National registries Geneticists Remarks Complete data, but restricted region One entry, elaborate central curation Variable input, depends on local registries Clinical information lacking 2009 Japan Remudy 583 +105 DMD/BMD >17 items Yes Patient & Curators Selection of patients 2013 USA MDA 11,000 17 +55 Yes Trained professionals Newcastle 30 October 1 November 2013

2002 USA 2007 USA 2007 Europe 2008 France Registries on DMD and neuromuscular disease Scully, et al. Neurology, 2013 Name MD STAR net Duchenne Connect TREAT- NMD Patients Number Items Genetic confirmation required 815 Multiple No 67-94% 1756 (70% USA) >50 items No 47% Data Collection Trained personnnel Patients & Curators >10,000 8+6 Yes National registries UMD-DMD 2898 6 (180 planned) Remarks Complete data, but restricted region One entry, elaborate central curation Variable input, depends on local registries Yes Geneticists Clinical information lacking 2009 Japan Remudy 583 +105 DMD/BMD >17 items Yes Patient & Curators Selection of patients 2013 USA MDA 11,000 17 +55 Yes Trained professionals Newcastle 30 October 1 November 2013

Conclusion Trial feasibility Small set of items results in high number of complete datasets (TREAT-NMD, UMD-DMD) Surveillance method of data collection in restricted area results favors prevalence studies (MD STAR net) Many items from large groups of patients is challenging (MDA, Remudy, Duchenne Connect) Patient registries facilitate trial participation

National patient registries National Registries: Countries: 54 Registries: 67 DMD 54 SMA 28 Global Registry Myotonic Dystrophy 1 and 2: 12 FSHD: 9

Examples of online national disease specific patient registries FSHD DMD DM SMA

Examples of online national patient registries covering more than one condition MD and FSHD DMD and SMA

Examples of National Neuromuscular Registries Australia Canada Czeck Republic Netherlands

International patient registries Global Registry Disease Name Congenital muscular dystrophies (CMD) Congenital myasthenic syndromes (CMS) Charcot Marie Tooth disease (CMT), collaboration with NIH Limb girdle muscular dystrophies (LGMD) Myotubular and centronuclear myopathy (MTM and CNM) FKRP (launched 2011), now 350 patients Dysferlinopathy (2012) H-inclusion body myopathy (HIBM/GNE myopathy) (2013)

Conclusion Trial feasibility Small set of items results in high number of complete datasets (TREAT-NMD, UMD-DMD) Surveillance method of data collection in restricted area results favors prevalence studies (MD STAR net) Many items from large groups of patients is challenging (Remudy, Duchenne Connect, MDA) Patient registries facilitate trial participation Work step-by-step. Accept variability among registries A national/regional database can be a quality instrument

Trial recruitment Industry Clinical Trial Site Patient Registry + Clinical Trial Site Patient Registry Newcastle 30 October 1 November 2013

Trial recruitment experience Industry request to TGDOC: -feasibility enquiry -assistance for recruitment through patient registries -information letter to all patients -ethical approval (of letter) by selected trial centers Newcastle 30 October 1 November 2013

Improving treatment for Neuromuscular Disease Patient Clinical Disease Standards New Drugs of Care Registries: Registries: -Cardiac -Respiratory 1.Trial Feasibility 3. -Rehabilitation (Natural) History 2.Trial Recruitment Standards -Drugs of Care Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

DMD Standards of Care Development 84 international DMD experts Reviewed existing information International consensus Importance of well-coordinated multidisciplinary care for DMD Lancet Neurology 2010 Bushby, K. et al. The Diagnosis and Management of Duchenne Muscular Dystrophy Part 1: Lancet Neurol. 2010 Jan; 9(1):77-93, Part 2: Lancet Neurol. 2010 Feb; 9(2):177-189 32

Integration and collaboration Patient registries and Care and Trial Site Registry (CTSR) https://zks-internet.ukl.uni-freiburg.de/ctsr/

Integration and collaboration Patient registries and Care and Trial Site Registry (CTSR) Study the present standards of care Evaluate changes in care following -new guidelines or -new therapies

Publication of differences between countries, regions or centers % S teroid s China G erm any Italy Japan Netherlands Turkey UK U S

Global Patient Registries Feedback to the public Newcastle 30 October 1 November 2013

Global Patient Registries. Feedback to the public Current methods to monitor DMD patient information (MD STARnet, DuchenneConnect, and TREAT-NMD) do not yet provide patients with comparative outcome data... The CF patient registry allows for reporting of standard outcomes across clinics and is associated with improved CF outcomes A similar patient registry is under development for the Muscular Dystrophy Association (MDA) clinic network. Suggested metrics for quality care include 1) molecular diagnosis, 2) ambulatory status and 3) age at loss of ambulation, 4) age requiring ventilator support, and 5) survival Newcastle 30 October 1 November 2013

Newcastle 30 October 1 November 2013

www.patientslikeme.com Newcastle 30 October 1 November 2013

Conclusion- Improving Care Combine patient registries and CTSR to evaluate present and future standards of care. introducing site visits? Stimulate improvement by publishing (on paper/website) current standards of care natural history data patient experiences

Improving treatment for Neuromuscular Disease Registries: 4. Post-marketing Patient Clinical Disease Standards New Drugs of Care Registries: Registries: -Cardiac -Respiratory 1.Trial Feasibility 3. -Rehabilitation (Natural) History 2.Trial Recruitment Standards -Drugs of Care Pharmaceutical Industry Gene Protein Improve treatment Researchers Physicians

Product specific postmarketing surveillance registries Postmarketing surveillance strategies are becoming a necessary part of an orphan drug manufacturer s responsibilities Biopharmaceutical companies spend many millions of dollars per year implementing and maintaining surveillance registries for their own products Problems arise when there is more than one registry for the same disease, e.g. Lysosomal Storage Disorders (LSDs) Lots of fragmentation without any data being shared Data is frequently incomplete Lack of transparency

Post-Marketing Surveillance Industry new drug Optimal Care Natural history study (database) Patient Registry Clinical Trial Site Newcastle 30 October 1 November 2013

Disease specific postmarketing surveillance registries Disease specific registries will allow a centralised platform to be utilised for each product Economy of scale, better reporting to regulators and the wider NMD field, better buy-in from dedicated and experienced clinicians, reliable longer-term effectiveness data Independent governing board

Conclusion Post-marketing Over 50 countries involved in global registries involving more than10,000 patients worldwide Patient registries together with CTSR can identify clinical centers for high-quality post-marketing surveillance. Clinical trials, natural history studies and multidisciplinary care often concentrate in the dedicated centers. A global database for natural history data would ease starting post-marketing surveillance for new drugs

Thank you for your attention!