Organizing Observational Studies in the Region Conducting Observational Studies in Latin America Soledad Suarez Ordoñez,MD. Registry Associate. Chiltern Latin America
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Definition The Agency for Healthcare Research and Quality defines a patient registries as an organized system that uses observational study methods to collect uniform data to evaluate specified outcomes for a population defined by a particular disease, condition, or exposure, and that serves a predetermined scientific, clinical, or policy purpose(s).
Why we create a registry? Registries are being used to fill important gaps in evidence and contribute to understanding how trial results can be applied in practice Data from registries are also used to support timely decisions by regulatory agencies about safety and about coverage (payment). The FDA has also used observational data to expand labeled indications. Registries for Robust Evidence. Nancy A. Dreyer; Sarah Garner. JAMA. 2009;302(7):790 791
Observational studies - Genzyme Gaucher Registry Initiated in 1991 Currently over 5,900 patients worldwide enrolled Fabry Registry Launched in 2001 Currently over 3,700 patients worldwide enrolled MPS I Registry Initiated in 2003 Currently over 900 patients worldwide enrolled Pompe Registry Launched in 2004 Currently over 800 patients worldwide enrolled
LSDs registries They are ongoing observational databases that track outcomes of routine clinical practice for patients with Gaucher, Fabry, MPS I & Pompe disease. Conditioned only on informed consent from patient, regardless of treatment status or type of treatment, is eligible for inclusion. Each Registry is supported logistically and financially by Genzyme Corporation. However, its governance and scientific direction is in the hands of an independent International Board
LSDs registries in Latin America 57 90 1476 patients. 17 countries. 131 801 More than 200 physicians. 5-6 coordinaros per registry 105 260
Registry enrollment Gaucher: 5,883 Fabry: 3,637 MPS I: 932 Pompe: 860 Average increase in patients enrolled 11% per year since 2001 12000 10000 Patients Enrolled 8000 6000 4000 2000 0 2001 2,667 2002 2,943 2003 3,793 2004 5,188 2005 6,675 2006 7,661 2007 8,710 2008 9,771 2009 10855 July 2010 11,312 Gaucher Fabry MPS I Pompe
Enrollment in Latin America
Registry objectives Enhance understanding of the natural course of LSD s Increase disease awareness Basis for defining impact of intervention Identify prognostic indicators Develop guidelines for monitoring patients Individual patient reports Evaluate long-term effectiveness & safety of treatment options Define causes of morbidity & mortality Defining most efficient strategies for impact of therapy Registry programmes; to answer the unanswered questions
Stakeholders Global report Physicians Medical knowledge New insights of disease Therapeutically response Support for guidelines Country report Patients Standards of care Patient survey data SF36 Guidelines Opportunity for clinical studies Registry Rare diseases Health Authorities Cost/effectiveness Health authority reports Reimbursement Burden of disease Pharmaceutical Company Research database Treatment patterns Product utilization Support for product label extensions
Registry Program - Benefits Research Largest Gaucher, Fabry, MPS I & Pompe datasets in the world The primary source for lisosomal deseases manuscripts. Data quality is high. Relationship with patients >11,000 patients enrolled by >1,000 physicians from >70 countries. Improvement in patient s adherence to treatment and close follow-up.
Registry Program - Benefits Clinical Data Example - Gaucher Registry used as possible comparator group in Eliglustat trial Approvals, PMCs Expanded label indications. Treatment reimbursement expenses are directly tied to Registry data in some countries
Regulatory and Reimbursement commitments Agency / Country EMA FDA Canada Australia Belgium Phillipines Commitment Annual Report, Safety and effectiveness and quality of data Annual Report, Safety and effectiveness and immunogenicity Annual report and long term safety of therapy Information to support evaluation for reimbursement Long term safety and effectiveness of own patients Efficacy and safety post-approval
Quality Assurance Of Data CRFs are designed by an extensive review process, including input and review by Data Management, Registry, Medical, and Regulatory Affairs, and Registry Board of Advisors. Registries, where appropriate, use FDA clinical data standards for the content of CRFs, the technical formats for the data and standards and controlled terminology. Data collected through this Registry are entered and reviewed within a secure web-based system. All reports generated from registries data undergo quality assurance review for statistical accuracy. All data management and analysis occur in a validated computing environment.
Credibility - Quality of Data Source data verification (in process to be published) Accuracy of the data entered into the MPS 1 Registry, 6 sites around the world Data verified: demographic, informed consent, co/morbidities, lab data and therapy Global error rate 4,9%, mainly data entry errors, no systematic errors (9,4% of source to database error from other registries and clinical trials). Nahm ML, Pieper CF, Cunningham MM. Quantifying data quality for clinical trials using electronic data capture. PLoS ONE. 2008;3(8):e3049.doi:10.1371/journal.pone.0003049. Accessed on line 17 June 2009.
Publications based on Registries Andersson H, Kaplan, P, Kacena K, Yee J. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics 2008;122:1182-1190. Sims K, Politei J, Banikazemi M, Lee P. Stroke in Fabry Disease Frequently Occurs Before Diagnosis and in the absence of Other Clinical Events: Natural History Data from the Fabry Registry. Stroke. 2009; 40:788-794. Arn P, Wraith J, Underhill L. Characterization of surgical procedures in patients with mucopolysaccharidosis I: findings from the MPS I Registry. J Pediatr. 2009;154:64 e3. Nicolino M, Byrne B, Wraith JE, et al. Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease. Genet Med. 2009;11(3):210-219.
Challenges in the region Lack of specific regulation. Not standard common clinical practice. Difficulties in producing registry outcomes materials. Budget. Complex logistics.
Challenges in the region. Cont. Lost of follow up of patients in common clinical practice Understanding of the registries from physicians / regulatory agencies/irbs Awareness of rare diseases Lack of Publications policies for non English publications
Some initiatives in the region Newsletters quarterly to physicians Annual LatAm registry meetings Focus data collection Medical writers
Some initiatives in the region Patient s Materials Data review follow-up & completeness of data Data entry support in in many countries Support in regulatory presentations to EC
Conclusions A great tool to complement scientific information collected during clinical trials A real world scientific approach to raise awareness of orphan diseases & treatments A cost effective approach to comply with long term regulatory commitments
Thank you! Obrigada! Gracias! Soledad.Ordonez@chiltern.com