Emma Baple and Dom McMullan 20th February 2018 MDM guidelines Emma Baple and Dom McMullan 20th February 2018

Next generation sequencing is (relatively) straightforward Variant interpretation is not…

Transformation of Genomic MDT meetings The bioinformatics pipeline was designed to retain rare variants by ……. (highlight MAF) Does this variant in this gene fit this patient’s phenotype?

MDT working group meeting 30th January 2018 Ed Blair, Dom McMullan, David Hunt, Ellen Thomas, Phil Twiss, Frances Elmslie, Julia Baptista, Ana Beleza, Thalia Antoniadi , Emma Baple, Arianna Tucci, Li Chan, Emma Clement, Ian Berry, Helen Brittain, Sandra Hing, Sarah Bowdin , Jo Mason, David Ghokale, Anthony Prudhoe, Wook Ahn, (Christine Patch, Michelle Bishop, Martina Muggenthaler, Kate Thompson, Georgina Hall)

MDT working group meeting 30th January 2018 10.40-10.50: The CRG and Genomic MDTs (Frances Elmslie) 10.50-11.00: Update on the standardised genomic report template (Sian Ellard) 11.00-11.15: Experiences of mainstreaming at Toronto Sickkids Hospital (Sarah Bowdin) 11.15-12.15: Group work to develop a draft MDT outcome form as an appendix for the standardised report (Emma Baple/Dominic McMullan) 13.30 – 14.30: Group work to develop draft guidelines for Genomic MDTs With recognition that there will be variability locally, the discussion will be around looking at the role of different types of MDTs, governance, responsibilities and expectations of attendees. 15.15-15.30: Future plans

Aims To develop a standardised MDM summary form to be incorporated as an appendix to the standardised report template To develop MDM guidelines as part of the Rare Disease Validation and Reporting guidelines

MDM summary form and guidelines plan Brief survey about current practice circulated to NHSE validation and reporting working group Provide examples of current MDM summary forms and guidelines Meeting of working group Iterative work on MDM summary form Incorporate into NHSE Rare Disease Validation and Reporting Guidelines Iterative work on MDM Guidelines

Standard report template

Standard report template

MDM guideline development MDM can involve face to face meeting, Webex, telephone, email and in the future possibly via CIP/other electronic interface Avoid multiple bystanders Clearly defined roles Different types of MDT: Decision making/Educational and training (record attendee names and roles) Smaller groups for decision making MDTs Remember MDTs are expensive MDM coordinator MDM chair

MDM guideline development Questions to be answered should be circulated in advance of the MDM Any relevant publications and collated evidence should be circulated prior to the MDM Joint clinical scientist and clinician preparation for MDM Those attending the MDM should come prepared so that informed decisions can be made

MDM guideline development Clinical scientists are responsible for collation and assessment of the scientific aspects of variant classification Clinician input generally relates to 4 areas: Does the phenotype fit the gene/variant? Are there additional family members who could provide a sample for segregation? Is there further phenotype information for the proband or family members which would provide additional evidence? Is there an expert who might know more and be willing to help? Actionable versus not actionable NHSE are investigating the legal issues around accountability for MDM outcomes

MDM guideline development MDM discussion and outcomes that influence the variant classification for variants included in the report should be documented as part of the appendix summarising the evidence for variant classification MDM summary form should be held in the laboratory linked to the report as a permanent record and for audit purposes but not circulated with the report Treatment and management may be discussed as part of the MDM, but any recommendation and decisions should be left to the referring clinician/clinical team

MDM summary form

MDM summary form

Other areas of discussion Guidelines for incidental findings to enable a consistent approach nationally Negative cases and additional analyses – indications and timeline New phenotype or family information, new published evidence for a gene/group of genes Webex security – NHSE investigating the use of N3 Webex Guidelines for which cases require more comprehensive MDT Who should attend the MDT