WP7 - Integration, implications for public health and ethical, legal and social issues

Work package number 7 Start date or starting event: Month 1
Work package title Integration, implications for public health and ethical, legal and social issues
Activity Type RTD
Participant number 10 1
2
Person-months participant
41 1
2

Objectives

  1. Use results of primary research into gene disease association (WP2/3), gene-environment interaction (WP5) and individual risk prediction models (WP2) to evaluate potential for stratification of population according to individual risk of breast, ovarian and prostate cancer.

  2. Evaluate the potential to reduce incidence and mortality from these cancers by risk stratification and targeting of population based screening and prevention programmes – including cost-effectiveness analysis.

  3. To identify key organisational, ethical, legal and social issues that would arise from such targeted screening programmes and make appropriate policy recommendations.

Description of work.
The two primary components of this WP will assess

  1. the implications of emerging knowledge about the architecture of genetic susceptibility to the hormone related cancers for population health, and
  2. the implications of emerging findings for screening and prevention programmes including organisational, ethical, legal and social issues.

Task 7.1: Implications for population health (disease and death rates)
This part of the work package will cover two themes:

  1. How much can knowledge of genotype and environment together add to our ability to stratify population according to absolute risk?
  2. What is the potential to use risk stratification based on individual genetic risk to target preventative interventions on sub-populations.

The first of these will be addressed by integrating the results of the risk prediction modelling from WP2 to evaluate the implications of individual risk prediction for risk stratification in the population (objective 1).

The second will be addressed firstly by using our knowledge of population screening programmes for early disease detection (e.g. breast mammography, PSA testing for prostate cancer) to compare the effectiveness and cost effectiveness (and efficiency) of screening programmes targeted at those at greater risk with untargeted programmes (objective 2). Included within this will be an investigation of the differential application of different screening technologies, such as the use of MRI scanning for breast cancer, screening for those at higher risk.

It is anticipated that these models will be initially developed over two years. However, as the results of the other work packages, which will impact on these models, will not be available until years 3 and 4 the aim is for the models to be sufficiently flexible to allow knew knowledge to be incorporated as it becomes available.

Task 7.2: Implications for health policy (screening and prevention)
The primary purpose of the second component of this work package will be to identify the key issues and obstacles to translation into prevention and screening programmes within population health policy and to begin to propose potential solutions. These issues will be addressed through a series of workshops in which relevant stakeholders from Europe will be invited to participate. These will be supported by further public health and policy analysis undertaken directly by, or commissioned by the PHG Foundation.

A comprehensive list of relevant issues will be developed as part of the work package, but suggested questions to be addressed are:

  1. What are the relevant features of some of the different operational models for organisation of population screening programmes in different member states?
  2. What are the perceived benefits of screening as perceived by the individual/public and are these at odds with the public health perspective?
  3. How would genetic data be obtained and integrated into screening protocols?
  4. How would individual environmental/lifestyle information be collected and integrated into screening protocols?
  5. How should clinical trials be designed to test the predictive models generated in COGS?
  6. What professional education would be needed to support the new targeting paradigm? For example, how to determine and communicate risk.
  7. What are the issues for informed consent and data confidentiality?
  8. Are notions of equity and eligibility for screening programme challenged by a targeted approach based on genetic risk?
  9. How acceptable would be the use of genetic information in screening programmes to the public and to professionals. For example, would it be seen as acceptable to offer a more sensitive and more expensive screening technology only to those at higher risk? If so, how should such a strategy be communicated?
  10. Does it make a difference to the acceptability of a targeted approach whether increased risk is primarily due to lifestyle/environment or to genotype?
  11. What personal or family psychological and social consequences arise from knowledge about small/moderate increases in genetic risk and what might influence a person's desire to be tested.

Action plan
Our approach will have two complementary dimensions: the employment of a research associate to undertake risk-stratification modelling and the use of a multi-disciplinary public health Working Group to address the implications of the emerging models for screening and prevention policies, with the emphasis shifting from the first to the second during the course of the project. This WP will be jointly led by Dr Hilary Burton and Dr Paul Pharoah and will be co-ordinated by the PHG Foundation. It will commence with the employment of a Research Associate and the setting up of a small multi-disciplinary Steering Group.

The Research Associate will undertake most of the modelling work in Years 1 and 2 under the direction of Dr Paul Pharoah. The Steering Group will give supporting advice to the work on disease risk modelling and targeted prevention modelling (cost effectiveness etc) to ensure relevant aspects are included (objectives 1-3). During this time the Steering Group will also ensure that its multi-disciplinary members reach sufficient understanding of the underlying science and modelling work, begin to identify and discuss relevant implications, and research the experts from Europe who should be involved in the main Working Group.

In identifying key stakeholders the PHG Foundation will build on the close working relationships developed in Europe through its role as associated partner in the Public Health Genomics European Network (PHGEN) http://www.phgen.nrw.de. These relationships include professionals with an interest in Public Health Genomics in all European member states, applicant countries and EFTA-EFA countries as well as a large number of European and International cooperating institutes and networks including the European Society of Human Genetics and European Public Health Association. During year 1 the Steering Group will identify and invite relevant stakeholders for a wider international Working Group and organise the initial workshop. This will include experts in public health, the organisation and delivery of screening programmes, and other fields such as psychology, social science, law and ethics chosen to also provide representation across EU member states. It is hoped that this same Working Group will be involved in all three Workshops.

Workshop 1 (beginning year 2). The primary purpose of this workshop will be to inform and engage key stakeholders in the work, identify, discuss and prioritise main issues. For each of these, key questions for further analysis will be determined and, where appropriate, other experts and stakeholders identified. When the main modelling work is complete (end year 2), the Steering Group will provide a draft of a paper that includes an outline of the Population Health and ELSI issues.

Workshop 2 (beginning year 3). The primary purposes of this workshop will be the presentation and discussion of initial findings; the beginning of consideration of implications for screening and prevention policies; and agreement on any further analysis to inform recommendations Workshop 3 (beginning year 4). Discussion and agreement of final report with conclusions and recommendations.

Deliverables

D7.1 Participant list and report of first Steering Group meeting (month 3)
D7.2 Draft terms of reference and agreed participant list for main Working Group (month 9)
D7.3 International Working Group Workshop 1 (programme/participants) (month 15)
D7.4 First draft paper on risk stratification using polygenic model (month 18)
D7.5 Workshop 1 report outlining key issues in targeted prevention (month 21)
D7.6 Scientific paper on risk stratification assuming a polygenic inheritance model (month 24)
D7.7 First draft report on effectiveness/cost-effectiveness of targeted screening (month 24)
D7.8 Final report on effectiveness/ cost-effectiveness of targeted screening (month 27)
D7.9 International Working Group Workshop 2 (programme/participants) (month 30)
D7.10 Workshop 2 report (month 36)
D7.11 International Working Group Workshop 3 (programme/participants) (month 42)
D7.12 Workshop 3 report (month 45)

Additional information