Realising Genomics in Clinical Practice - a framework for action
5 December 2014
Developments in genomic sequencing promise significant improvements in disease diagnosis and treatment, and health services are on the cusp of introducing these technologies into the clinic – suggesting that this is a critical opportunity to improve population health. The publication of the Realising Genomics in Clinical Practice report is the culmination of two years of work, aimed at understanding how the potential of targeted or genome-wide sequencing technologies can be delivered within the UK NHS in a way that maximises benefits and minimises harms. We sought to do this by identifying the broad range of ethical, legal, social (ELSI) and practical issues that are likely to arise through using these technologies: our rationale was that if these issues are addressed optimally, this will facilitate quicker and more effective implementation ultimately resulting in better healthcare.
The project was informed by five workshops, each building on the preceding ones. These workshops were attended by key stakeholders including clinicians, clinical scientists, patient group representatives, policy makers and academics. The outputs have helped to generate a framework of recommendations that we hope will guide the implementation of these technologies within the NHS, and promote the quality, safety and efficiency of NHS healthcare.
The recommendations fall into six themes which support areas of ethical practice:
1. Targeting: promoting an approach where potential benefits are maximised and harms mitigated
- The NHS should adopt targeted analysis using gene lists as a first-line approach.
- Bioinformatic search strategies should minimise the generation of incidental findings (findings unrelated to the reason for undergoing testing) and findings of uncertain significance.
- Criteria need to be developed for using whole exome or genome sequencing whether as first or second line tests.
2. Core gene lists: providing services of consistent high quality based on transparent and consistent criteria thus promoting equity and justice
- NGS gene lists incorporating a core/standardised set of genes appropriate to phenotype need to be routinely adopted.
- To provide a consistent service, standardised referral criteria, and standardised evidence criteria for inclusion of genes within gene lists need to be developed. Multidisciplinary expert groups should apply these criteria to develop gene lists for different phenotypes.
3. Consent: enabling autonomous decision making
- Genomic sequencing technologies raise novel challenges for consent. Patients need to understand that the technologies may generate unexpected findings as well as findings with uncertain significance which may have implications for themselves and for relatives. Patients should be given the opportunity to express their views as to whether such unexpected findings (including those of potential clinical benefit) should be disclosed to them.
- The consent process should also address the potential for reanalysis and recontact, and clarify how a patient might initiate recontact.
- It should also describe when and how data will be shared.
4. Building an evidence base and data-sharing: promoting beneficence
- Effective implementation requires a secure, comprehensive and accessible NHS Database to be created into which data deposition is mandated
- Data sharing outside the NHS should also be encouraged and appropriate consent routinely sought. This sharing of variant information will help to improve genomic interpretation.
5. Ensuring consistent evidence based practice: promoting clinically driven and equitable access to these technologies
- Standards need to be developed for laboratory reporting to clinicians, and to guide how clinicians report those findings to patients
- Systematic approaches need to be taken to reanalysis and recontact as new findings become available.
6. Wider infrastructure: ensuring that these ethical principles are entrenched in policy development
- These developments need to be supported by educational initiatives, development of evaluation and commissioning mechanisms and a programme of ELSI and health economics research.
The publication of the Realising Genomics report coincides with implementation of the main phase of the 100,000 Genomes Project. It is currently unclear whether the recommendations that we have proposed can be addressed at least in part by the Genomic Medicine Centres and through the research that will be undertaken by the Genomics England Clinical Interpretation Partnerships. This is a highly relevant as stakeholders and policy makers will need to prioritise their efforts and resources.
At present, independent initiatives seem to be necessary to ‘make these technologies happen’ within the NHS for a number of reasons: the Realising Genomics recommendations are concerned with clinical care rather than research, (although we recognise the importance of research in fuelling bio-medical innovation and improvements in health care); an NHS Database is needed that has provision for storage and interpretation of a range of genomic tests, including NGS diagnostic panel tests, and whole exome sequence tests, and not solely limited to whole genome data; targeting the use of these technologies more narrowly in order to maximise their clinical effectiveness, by using them in cases where there is existing clinical utility, whilst minimising the generation of variants of unknown significance and incidental findings (as we have proposed) is different to maximising the data that is available for research purposes. Our recommendations also do not support actively looking for pathogenic variants in individuals without symptoms or a family history (opportunistic screening), since without sufficient evidence for clinical utility, the potential harms are likely to outweigh the potential benefits.
Despite these differences in approach, there are significant synergies between our recommendations, and the policy developments driven by the 100,000 Genomes Project. Both initiatives highlight the importance of a sustained programme of ELSI and health economic research, especially where genomic sequencing technologies raise complex and novel challenges – such as reanalysis, recontact and the evaluation and reporting of findings – which is needed to build public trust and confidence in these technologies. Together, these initiatives will undoubtedly contribute to these technologies being used to their full potential for health gain, thus supporting the NHS to become a world leader in genomic medicine.