Genetic Databases International Collaboration and Secondary Uses Pr Bartha Maria Knoppers Canada Research Chair in Law and Medicine Genetics and Society Project University of Montreal

Integrating data across studies will require developing approaches for facilitating pooled analyses and synthesis. We are seeing the beginning of such a global movement across international boundaries with the establishment of P3G… Muin Khoury, “The case for a global human genome epidemiology initiative”, (2004) Nature Genetics 36,

Wordwide, there are over 120 population- based biobanks with >10,000 participants

Large population-based studies around the world Principal Outcomes% of studies General focus55 % Cardiovascular diseases20 % Cancer15 % Other (diabetes, dementia, etc.)10 %

Benefits of Cohort Studies Obtain a better estimate of the population attributable risk for genetic and environmental risk factors by accounting for their joint interactions Strengthen the associations between environmental factors and diseases by examining these in genetically susceptible individuals Determine which specific compounds in a complex mixture of chemicals (from pollution, diet, etc.) cause disease. Use the information to design new preventative and therapeutic strategies Offer tailored preventive advice that is based on the knowledge of the genetic profile of an individual.

Even the largest cohort studies (such as UK biobank with 500,000 subjects lack power to study complex diseases for genetic and environmental interactions …) Davey Smith et al. Lancet 2005; 366: 1484–98 … Statistical Power is often achieved only at years

5.5 Need for resolution and guidance « Few issue clusters are identified by researchers as so urgently needing resolution as those surrounding confidentiality and anonymisation. They are not unique to data sharing activities, but they are central to them. » Lowrance W. W. (2006), Access to collections of data and materials for health research, Medical Research Council and Wellcome Trust, 36 p.

Knoppers BM, Saginur M. The Babel of genetic data terminology. Nat Biotechnol. 2005; 23(8):925-7

[T]he terminology used to ensure confidentiality mechanisms for samples and data in genetic research has become so “babelesque” as to ultimately impede the sharing of research data. The cumulative effect of the efforts of various international organizations, including the World Medical Association, the Consortium on Pharmacogenetics, the Council for International Organizations of Medical Sciences (CIOMS), the Council of Europe and the European Society of Human Genetics have resulted in confusing, redundant and contradictory terminology. Knoppers BM, Saginur M. The Babel of genetic data terminology. Nat Biotechnol 2005;23(8):925-7

Solution? « Identifiable data can be used for medical research without consent, provided that such use is necessary and is proportionate with respect to privacy and public interest benefits ». The Academy of Medical Sciences, Personal data for public good: using health information in medical research, January 2006, p.4

Public Population Project in Genomics A consortium dedicated to fostering international collaboration between researchers and projects in the field of population genomics

Major goals of P3G boost sample sizes to several million subjects allow powerful gene-environment studies of most common diseases within 10 years instead of years. address needs for replication allow comparisons of genetic effects in different environments sharing the large costs across nations enhance the exchange of information

Genomics and Biochemical Investigations Knowledge Curation and Information Technology Ethics, Governance and Public Engagement Epidemiology and Biostatistics P3G Working groups

P3G Observatory DESIGN OF STUDIES ETHICS AND GOVERNANCE IT AND COMPUTER SCIENCE STATISTICS CONTEMPORARY BIOBANKING INFORMATION COLLECTION/ PROCESSING KNOWLEDGE TRANSFER Consensus definition of terms in the field of biobanking Reference Tools for Power Calculation Reference procedures for sample collection, management and storage Guiding Principles, Legislation, and Background Papers on Population Genomics Genotyping data analysis Public Databases Tag SNP Selection Programs Genotypes Analysis Software Reference tools for statistical analysis Reference tools for preparation of publications

P3G Observatory currently tracks 89 biobanks: Protocols, Status, Ethics, Governance Data freely available:

Characteristics of the generic data set Comprehensive enough to ensure the realization of valid research Small enough to encourage buy-in. NOT a prescriptive list of all the variables to be collected by a biobank 100 data items (essential and extended) and 100 optional items % of the data items covered in a specific biobank

Aliquot: A portion of a sample of biological material that has been divided into separated parts. Anonymization:The irreversible removal of personal identifiers from data or samples, such that no specific individual can be identified. Audit: A documented review of procedures in order to evaluate adherence to written standards operating practices (SOPs) or laws and regulations (adapted from ISBER Best Practices, 2005). Biobank/biorepository: An organized collection of human biological material and associated information stored for one or more research purposes Etc. Examples

P3G Charter of Fundamental Principles PROMOTION OF THE COMMON GOOD - P3G will optimise the benefits of collaborative, publicly-funded research for the benefit of all. RESPONSIBILITY - Protection of the interests of all affected stakeholders including families, groups, populations, researchers and research sponsors is the highest priority. Every effort will be made to respond to the concerns of stakeholders in a timely and appropriate manner. MUTUAL RESPECT - The development and sustainability of P3G is based on responsibility, collaboration, co-operation, trust and mutual respect for others, which includes recognition of cultural diversity and the scientific specificity of the projects involved ACCOUNTABILITY - All standards, processes and procedures will be transparent and clear, developed on the basis of consensus, and aim to create best practice in the networking of population genomics resources. PROPORTIONALITY - All research materials (such as data and sample) must be protected to the highest standards of privacy and propriety, while at the same time allowing and promoting the free exchange of ideas, data sharing and openness for the benefit of all.

CARTaGENE project

Samples and Data Access Policy Objectives of the project General Principles Samples and Data Access Committee Samples and Data Access Limits on the Use of CARTaGENE Privacy Concerns Access to Information for Participants Material Transfer Agreement

HUGO Ethics Committee Recognizing The potential global good arising from genetic research; The scientific and clinical uses of genomic databases; The potential for conflicts between the free flow of information that is crucial to research advances and the legitimate rights to return from research expenditure; The potential risk of misusing genetic data; The need to rapidly place primary genomic sequences in the public domain. Statement on Human Genomic Databases, 2002

Recommendations Human genomic databases are global public goods. Knowledge useful to human health belongs to humanity. Human genomic databases are a public resource. All humans should share in and have access to the benefits of databases […] HUGO Ethics Committee (continued) Statement on Human Genomic Databases, 2002