Laboratory Management Session FRCPath Preparation Course 22/10/09

1. A clinician has asked you to set up a new high throughput test in your laboratory. What genetic, population and technical factors will you consider? Describe your strategy for staff equipment and laboratory management Laboratory Management Session FRCPath Preparation Course 22/10/09

2. Setting up a new service - Considerations and Planning • Clinical perspectives • Research and Literature review • Testing methodology • Resources • - Funding and Budget • - Equipment and Staffing • 5. Implementation

3. Clinical perspectives and utility The most essential points to consider prior to any commissioning for a new service • Determining the clinical requirements of a new test • - who is the user; discussion with clinical groups about the need for the service • - is there another laboratory offering the test (CMGS or research) • - is the demand for the test local, external or both • - is the demand for the test short term or long term • - is there need for interaction with other disciplines in pathology (e.g. cyto/biochemistry) • What is the prevalence of the disorder? • - any population differences on prevalence - what is the local population • - determine the target population for testing - expected referral numbers • - determine the referral pathway and criteria (gatekeeping) • Determining the clinical utility  purpose of test and the healthcare context in which the test is going to be used - why is a genetic test necessary; ?other tests possible - what is the advantage of test on patient diagnosis, prognosis, management/treatment - what is the advantage of test on family risk assessment (predictive/presymptomatic/prenatal) - what is the positive impact of the test for NHS (any financial benefit) - consider ethical, legal and social issues (ELSi)

4. Research and literature review of the disorder • Understanding what is known up to date about the disorder • Essential review literature with information with clinical context • Gene or genes involved • Patterns of inheritance • Mutation spectrum (common, variable, hotspots, types) • Population differences • Discussion with local research groups that may be interested in the disorder • - Gain valuable information in terms of test design, provision of controls. Clinical perspectives and utility contd. • Determining the clinical validity of the test • “ the measure of how well the test predicts the presence of absence of the phenotype, clinical disease or predisposition” • - positive predictive value: the probability of getting the disease given a positive test • - negative predictive value: the probability of not getting the disease given a negative test • Need to know: • prevalence of the disease in the tested population • penetrance of disorder and genetic loci and environmental factors associated

5. Funding and budget considerations • Establish workload (based on anticipated number of referrals) - is new test going to be introduced into existing workload or additional funding is required • Establish budget - this will affect planning for test method, equipment, staff, running costs - can the costs be covered by the test The test should be carried out within competitive TAT and at a competitive cost.

6. Methodology and equipment considerations • - high throughput – should be quick and easy • aim for a cost effective assay but do not compromise on test sensitivity and specificity • mutation spectrum determines what method is best to use (targeted/direct sequencing/scanning/combination) • consider the nature of gene (size, GC content, SNPs, presence of pseudogenes) • assay design is also based on what expertise and equipment is available in the lab • establish what is the time frame for validation prior to implementation • Available equipment vs new equipment (buy or lease) • determine time on machine if using available equipment so as not to clash with other services • determine set up and running costs for reagents and consumables • for new equipment determine costs of service contacts and training; time for tendering and training • Choose a method that is easy to automate; less hands on time/transfer errors • Choose a method that can be done within the expected TAT • Use appropriate controls and carry out a blind study during the validation process- determine sensitivity/specificity/ reproducibility

7. Implementation • Documentation: validation, SOPs, training records, report templates • Monitoring of workflow; may need to change processes (e.g. batching) for better efficiency • Monitoring of TAT • Monitoring of referral criteria - gatekeeping • Quality assurance: SNP checks, maintenance of training, participation on EQA scheme • Audit and review: may improve testing, or aid in understanding of the disorder • Gene dossier submission • Advertise service in conferences/ CMGS/ EDDNAL Staffing Considerations • Dependent on: workload (numbers of referrals), referral rate and hands on time for test/reporting • Establish levels and amount of staff required (technical, scientists, senior scientists, IT and secretarial, quality officer). - built into existing staffing or expand - new staff: dependent on funding, consider costs of recruitment and training period

8. References: http://www.ukgtn.nhs.uk/gtn/Home http://www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml Evaluation of genetic tests: the experience of the UK Genetic Testing Network Dr Mark Kroese UKGTN Public Health Advisor, 2008