Ethical implementation of the genomics revolution

Corinna Alberg

10 March 2015

The PHG Foundation recently held a dissemination event for the Realising Genomics in Clinical Practice report. This was the culmination of a two-year project that sought to inform the optimal clinical implementation of expanded next generation sequencing (NGS) gene panels, whole exome sequencing and ultimately whole genome sequencing. 

This revolution in genomic testing strategies is already underway, with many NHS genetics centres now using NGS panels and a few using whole exome sequencing. With the main phase of the UK government’s 100,000 Genomes Project starting next month, whole genome testing will soon be offered to NHS patients with rare diseases and certain cancers. 

The Realising Genomics report identifies the br oad range of ethical, legal, social and practical issues that will arise from using these technologies. It contains a series of recommendations on what needs to be put in place for the technologies to be implemented in an ethical manner, improving healthcare and minimising potential harms. 

Reactions to the Realising Genomics report

The major stakeholders involved in the delivery of genetic services across the NHS played a crucial role in the series of workshops that informed the report, and many also participated in the dissemination event. The key organisations responsible for specifying how services will be delivered across the NHS are the clinical reference groups (CRGs). The Medical Genetics CRG discussed and welcomed the report at their last meeting. Chair Professor Frances Flinter said: “There is a risk that medicine could be driven by the technology; the Realising Genomics report is of huge value because it reminds us of the importance of thinking carefully about the clinical benefits and possible risks of genome sequencing”.

Dr Angela Douglas, Chair of the British Society for Genomics in Medicine (BSGM), the organisation that represents UK human genetics professionals, said that release of the Realising Genomics report was “very timely, coinciding with the launch of national genomics initiatives and coming at the perfect time to initiate national coordinated action to address the issues it raises”, adding: “The BSGM is keen to take a leadership role in taking the report recommendations forward”.

What needs to be done

Identifying recommendations for action as highlighted by the report and endorsed by stakeholders is just the starting point: implementation requires a concerted effort from all those involved. However, the positive response to the report suggests that there is already much consensus on what needs to be done. 

There is agreement that targeted analysis, based on phenotypically driven core gene lists is the way forward. This will help to ensure that the data that is generated is of potential clinical value, and result in manageable levels of data being interpreted rather than laboratory and medical professionals being inundated with variants of unknown significance and having to spend hours deciding on what data should be fed back to patients to inform care. 

With manageable amounts of relevant data, clinicians will be better able to guide patient care while also minimising the discovery of incidental findings. These are findings that may be serious and actionable but are not pertinent to the purpose of the clinical consultation. A further advantage of targeted analysis based on gene lists is that patients across the country will receive a more consistent and equitable service, as the inclusion of genes on the gene lists will be based on careful review of the evidence. This will minimise the number of family members in different parts of the country receiving apparently inconsistent results, due to different genes being examined based on different standards of evidence.   

A second major challenge for services is to find a mechanism for sharing patients’ genomic data generated by these technologies. This issue was highlighted by all the representative organisations. Without a well-curated common database to aid interpretation of patients’ sequence data, into which sequence data is deposited by all those undertaking clinical NGS sequencing for the NHS, we will not build on successive findings to enable better diagnoses, or maximise the potential of clinically relevant information garnered from using these new technologies. 

A range of other important issues are discussed in the report, including how to make bioinformatic reports from laboratories meaningful to all relevant parties including clinicians with an expertise in genetics, clinicians without that particular expertise, and patients; how consent can be made valid against a context of uncertainty regarding what the results will ensue; and what needs to be done to facilitate public trust and confidence in the use of these technologies.   

Next steps

Some recommendations in the report provide a framework on which other initiatives such as the 100,000 Genomes Project can build. These include the development of evidence based core gene lists, streamlining mechanisms for data sharing, and enhanced consent processes. Some other recommendations are likely to be achieved in the longer term, such as developing a robust and effective database for deposition of data. This should not be limited to whole genome sequence data, but include whole exome sequence and NGS panel data. Ultimately, action is required to achieve both types of objectives in order to improve patient care and make meaningful progress towards realising genomics to enhance clinical practice.