Large Scale Sequencing Projects & Data Sharing

Question 1

List some flagship large scale genome sequencing projects

Answer 1

• UK: 100,000 genomes project
• USA: 1 million genomes (All of Us programme)
• Saudi Arabia: 100,000
• EU: Personalising Medicine programme
• Scotland: 3000 genome project

Question 2

What are the aims of the 100,000 genome project in the UK?

Answer 2

• Kickstart UK genomics industry
• Identify new genes for diagnosis, drug target, precision medicine etc (Research)
• Develop ethical and transparent method of testing and consent. By developing standardised, crowdsourced panels, held in PanelApp, patients tested across the country and guaranteed the same analysis. Consent for primary and secondary findings taken separately.
• Introduce genomic testing into the NHS.

Question 3

What are the challenges faced by the 100,000 genome project in the UK?

Answer 3

1. Recruitment – expected to have had common causes of their phenotype excluded. Needs good balance between trio vs solo
2. Data generation - limitations to selected assay
3. Data processing/analysis - QC/BIs
4. Data interpretation throughput and variant interpretation, VUS’s and incidental findings
5. Bottlenecks in process e.g. clinical data entry, processing, data analysis/interpretation
6. Data sharing

Question 4

Why is sharing specifically of genomic data becoming so important?

Answer 4

• Genomic data is a key component for the diagnosis and management of patients with rare disease and cancer.
• The sharing of genomic data from patients and the general population enables experts to;
  
  • Determine the genetic basis of undiagnosed diseases
  • Refine interpretation and diagnoses of rare diseases and cancer
  • Improve patients’ care via personalised medicine

Question 5

What key considerations should be addressed when sharing genomic data?

Answer 5

• Who is data being shared with? How will the data be used?
• Where is the data stored? Cloud vs local installation/virtual desktop
• Privacy
• Patient Confidentiality
• Data sharing and patient consent
• Data security and information governance, Caldicott.
• National or international sharing?

Question 6

What pressures can make laboratories reluctant to share data?

Answer 6

• Currently no guidelines relating to best practice of sharing of data - labs conserned of doing something wrong.
• Sharing data outside of national borders can be subject to strict regulation - labs do not want to be liable for breaking laws.

Question 7

How can large scale sequencing projects facilitate the sharing of genomic data?

Answer 7

• A large centralised project facilitates gathering variant data in one place vs locally stored in individual lab silos.
• The resources backing large scale programmes enable dedicated teams to tackle problems liek data sharing which smaller groups may not have.

Question 8

Which organisations and programmes are trying to address the problems of data sharing?

Answer 8

• GEL plan to implement a central national repository for the storage and sharing of data generated in the 100KGP
• Global Alliance for Genomics and Health
• Matchmaker exchange
• BRCA challenge

All of these groups aim to facilitate data sharing but there remain questions regarding who controls and owns the data?

Question 9

Who are the key groups that may benefit from the sharing of genomic data?

Answer 9

• Healthcare Professionals
• Patients and families
• General populations
• Academic Research groups

Question 10

What are the key benefits to Healthcare Professionals?

Answer 10

• Help establish genotype-phenotype correlations to better identify clinically significant variants
• Enable improved and faster diagnosis thereby saving time and resources (i.e. efficiency savings)
• Inform therapeutic decisions and enhance preventive care
• Improve clinical outcomes and aid clinical decision-making
• Thus, global sharing achieves the greatest clinical utility

Question 11

What are the challenges faced by Healthcare Professionals for sharing data?

Answer 11

• Uncertainty about the legality of data sharing
• Logistical - Lack of suitable and sustainable infrastructure for sharing data.
• Competition within the health system = disincentives to share data
• Lack of data sharing ‘standards’ or ‘guidelines’ - What data to share? Standard data ‘formats’ which are cross-compatible are required.
• Training professionals to effectively communicate the complexity of genomic testing to their patients

Question 12

What are the key benefits to Patients and families?

Answer 12

• Easier and faster diagnosis (especially of rare disease) via patient ‘matchmaking’
• Elucidation of rare disease genes and discovery of new therapies leading to improved and tailored treatment (‘personalised medicine’) – reducing adverse effects
• Predictive testing for other family members

Question 13

What are the challenges faced by Patients and families for sharing data?

Answer 13

• Implications of incidental findings, carrier status, adult onset disorders. Impact on wider family etc.
• Some data could be potentially identifiable information – especially WGS
• Patient consent – boundaries not clear for use of genomic data ?generic consent
• Risk of information being misused – requires safeguarding to assure security of data and data protection

Question 14

What are the key benefits to the general population?

Answer 14

• Identification of population specific benign variation in order to avoid clinical misinterpretation which can follow when whole populations are underrepresented in databases
• Enabling ancestry matched controls leading to better interpretation of disease causing variation
• Will facilitate the integration of genomics into mainstream medicine ‘for-all’

Question 15

What are the challenges faced by the general population for sharing data?

Answer 15

• Can raise difficult discussion around ‘race’ and ethnicity
• Stigmatisation through linking conditions to a particular population – could this lead to discrimination?

Question 16

What are the key benefits to research groups?

Answer 16

• Get access to more data which can facilitate better reseach
• More pride that research is making an impact in the lives of patients when research data and skills are shared with clinical groups

Question 17

What are the challenges faced by research groups when sharing data?

Answer 17

• Lack of incentives to share data at the organisational level.
  
  • What risks to organisation?
  • Competetion from rival groups
  • Credibility risks if error spotted in results
  • IP issues if data shared

Question 18

What key area’s have barrier which need to be overcome before genomic data sharing can become routine day-to-day practice?

Answer 18

1. Technical barriers
2. Legal barriers
3. Political barriers
4. Motivational barriers
5. Economic barriers
6. Ethical barriers
7. Competetive barriers

Question 19

What technical barriers exist to making genomic data sharing routine?

Answer 19

• Inconsistent data collection
• Storage
• Lack of standardization of informatics
• Varying data quality
• Incompatibility (inter-operability)
• Language barriers.

Question 20

What legal barriers exist to making genomic data sharing routine?

Answer 20

• Regulatory framework and legislation needed for data privacy and security.
• Ensuring data protection,
• more explicit legal framework around data sharing,
• increased harmonization between legal requirements and health policy

Question 21

What politcal barriers exist to making genomic data sharing routine?

Answer 21

• Reducing bureaucratic hurdles
• Burying data for political reasons
• Lack of political will/commitment to promote openness and sharing
• Lack of guidelines
• Lack of trust

Question 22

What motivational barriers exist to making genomic data sharing routine?

Answer 22

• Lack of incentives to share data at the individual level
  
  • What risks to individual?
  • e.g. liability for error
• Lack of incentives to share data at the organisational level.
  
  • What risks to organisation?
  • e.g. Competetion for publication, IP

Question 23

What Economic barriers exist to making genomic data sharing routine?

Answer 23

• Lack the financial resources to invest in infrastructure required to safely share data
• Lack the skilled human resources required to safely share data due to limited training capacity or budgets to hire externally
• Difficulties in retaining staff or high staff turnover

Question 24

What ethical barriers exist to making genomic data sharing routine?

Answer 24

• Effective consenting process for data sharing
• Lack of reciprocity between those providing and those requesting data
• Lack privacy and confidentiality

Question 25

What are some of the national drivers for genomic data sharing in the UK?

Answer 25

1. (2013) A new 7th Caldicott principle established 2. PHG Data sharing report (Dec 2015) 3. National Data Guardian for Health and Care-Review: Data Security, Consent and Opt-outs (June 2016) 4. Care Quality Commission: Review of Data Security (July 2016)

Question 26

What is the 7th Caldicott principle and why was it established?

Answer 26

Principle 7 - The duty to share information can be as important as the duty to protect patient confidentiality. Professionals should; * Have the confidence to share information in the best interests of their patients * Do do within the framework of the other principles * Should be supported by the policies of their employers, regulators and professional bodies Established to overcome some of the concerns professionals had about making mistakes when sharing data.

Question 27

The PHG Data sharing report (Dec 2015) made 11 recommendations for safe and effective data sharing. What key domains did their recommendations cover?

Answer 27

* Enabling consistent and responsible data sharing * Needs a designated database for sharing data across NHS with clear governance, oversight, standards and safeguards * Data sharing within the NHS * Where: could be \>1 db so long as inter-operable * What: As a minimum all Path + LP variants * How: SOPs required and tools shared * Future-proofing: Must handle WES/WGS * Data sharing beyond the NHS * Legal framework required to share NHS data overseas * Achieving consistent and supported data sharing in the future * Mandating requirements for data sharing and monitoring compliance (EQA) * Assessment of the risks of privacy breaches occurring and the impact they may have on the patients involved

Question 28

What was the purpose of the Data Security, Consent and Opt-outs (June 2016) report?

Answer 28

Since the development of the 7th caldicott principle in 2013 there has been little positive change in the use of data across health and social care Therefore the National Data Guardian (Caldicott) was asked to work alongside the CQC to carry out an intensive review to recommend: * new data security standards * a method for testing compliance with these standards * a _new consent model_ or opt-out model for data sharing

Question 29

What was the purpose of the Care Quality Commission: Review of Data Security (July 2016) report?

Answer 29

In light of various high profile data breaches i the UK the CQC was asked to; 1. Review the effectiveness of current approaches to data security by NHS organisations 2. Make recommendations on how ensuring NHS providers protect personal data could be improved 3. Work with the data guardian (Caldicott) to understand how the principles can be assessed during CQC inspections

Question 30

Do the benefits to key stakeholders outweigh the barriers faced to get there?

Answer 30

Yes as data sharing will be vital to; 1. providing modern healthcare to the wider population 2. providing patients with an accurate diagnosis 3. empowering professions to provide a higher standard of care

Question 31

Should we be optimistic or pessimistic about overcoming the barriers for safe sharing of genomic data?

Answer 31

* Optimistic * There is a track record of success with many large scale research projects * e.g. Human Genome Project, ENCODE, International Hap Map project, 1000 genomes, ExAc * The genomics community and governments now appreciate the importance of data sharing and many well resourced organisations or working on solving this. * Success will be achieved by striking a balance between facilitating data sharing whilst securing proportionate safeguards against data breach