100,000 Genomes Project: the debate continues

Mark Kroese

8 February 2013

Caroline Wright has posted an important commentary on the Government's 100,000 genome project proposal on the Genomes Unzipped website. We support her assessment about the present capability of using WGS in the clinic. But there is an opportunity to develop diagnostic sequencing capacity for the NHS which includes WGS for those appropriate clinical cases. We need to start somewhere. So perhaps the key is to take Government at its word that the Project is primarily about 'patient benefit', but also in parallel about building an information database from this diagnostic sequencing activity. We believe that, through research, this will provide greater clinical benefit for NHS patients in the future.

Delivering more diagnoses and realising patient benefit clearly requires that we have detailed data on phenotype as well as genotype. Caroline's experience with the DDD project will mean that she understands the importance of getting good clinical data for other rare conditions such as inherited cardiovascular conditions, inherited cancer syndromes and the like, and for investigation of the somatic genome in common cancers and of selected aspects of infectious diseases. The project will also need to demonstrate that it is feasible to collect and analyse samples for WGS sequencing and storage in diagnostic facilities. This involves not only working out the technical aspects to achieve adequate quality within a clinical service, high quality bioinformatics and interpretation and a programme of research and public engagement to check (and hopefully achieve) public acceptability. Along the way there will be a range of ethical and regulatory matters that the service will have to deal with. It is also expected that this increased diagnostic sequencing activity for NHS patients will generate significant demands on current NHS molecular genetics services which are already under strain to provide NHS service needs. This will happen even if the new sequencing capacity is not provided by current NHS providers.

The development of new diagnostics using this expanded diagnostic sequencing capacity should include for example appropriate quality assurance for diagnostic services, defining the target population, the purpose of testing, the place of testing in the clinical care pathway, assessment of clinical utility and clear reporting methods. The key to the success of these new diagnostics in the clinic will remain whether the clinician and the patient are provided with useful information within the context of the routine consultation. If there is an intent to develop new diagnostics for the NHS ‘to realise patient benefit’ and also to sell these services to other countries then it would be a missed opportunity not to establish the data needs at an early stage of evaluation programmes such as the NICE Diagnostics and Medical Technologies Programmes.

This is the beginning of a long road for the NHS. We should be thankful that the Government has made this commitment and optimistic that we can work together to use genomic medicine for the benefit of our population. As usual, the devil will be in the detail. Given that detailed plans are not yet established there is a fantastic opportunity for those with expert knowledge, whether from research, clinical or wider regulatory or social aspects to contribute and help shape the programme. One way or another, we should try and make sure we have a chance to do so.