19.07.04 Assessment of tests Flashcards
Why is it important to assess performance of genetic tests
Due to increased availability of tests, important to assess performance for clinical and public health practice
What is ACCE framework
- Analytic validity
- Clinical validity
- Clinical utility
- Ethical, legal and social implications
What is analytical validity
How accurately and reliably the test measures the genotype of interest. Based on data from labs: method, validation process, sensitivity, specificity, reliability and reproducibility.
What is clinical validity
How consistently and accurately the test detects or predicts the intermediate of final outcomes of interest.
What is a clinical positive predictive value
Probability of having/ developing the disease with a positive test results. Penetrance?
What is a clinical negative predictive value
Probability of NOT having/not developing the disease with a negative test results. Locus/allelic heterogeneity.
What is clinical sensitivity
Probability of a positive result when the condition is known to be present. Will be reduced if there is locus/allelic heterogeneity.
What is clinical utility
How likely the test is to significantly improve patient outcomes
How can genetic testing improve patient outcomes
- Aids diagnosis. Avoids invasive/expensive tests. e.g.g muscle biopsy in DMD.
- Could lead to altered treatment: F508del or G551D in CF and Ivacaftor drug.
- Aids prognosis and managements. ATM mutation carriers avoid X-rays.
- Presymptomatic testing in other family members. Could lead to early disease detection (hereditary cancer predispositions)
- Genetic risk assessment: reduce the need for clinical tests in family members that have tested negative for variant.
Who developed the ACCE framework
CDC’s (Centre of disease control and prevention, in the USA) Office of Public health genomics (OPHG)
Purpose of framework
It is a process to allow policy makers to see data about DNA testing, to enable decision making. Helps to identify gaps in knowledge that will help define future research agendas.
What is UKGTN
UK Genetic testing network. An advisory organisation that provided commissioning support to NHS and Department of health. No longer active (since 2018).
Will be continued after restructuring of genetic services in NHS England.
Purpose of UKGTN
To ensure equity of access to genetic testing. Acts as a coordinated body that identifies lab services (directory of all tests offered), has a criteria for labs to be a member (accredited), evaluates new services (gene dossiers)
What is UKGTN CSAG
Clinical and Scientific advisory group. Acts in a commisionary advisory capacity to influence national policy
What does the GTEWG do?
Genetic test evaluation working group. Evaluates gene dossiers and passes successful ones on to CSAG for ratification and then to commissioners to fund tests.
What other working groups work with CSAG
- Rare disease service improvement working group
- Lab membership and audit working group
- Development working group
What are UKGTN gene dossiers
Means of evaluating genetic tests offered by labs nationally. Ensures they are scientifically valid and clinically useful
What framework is the gene dossier based on
ACCE- analytic validity, clinical validity, clinical utility, ethical/legal and social implications.
What is EGAPP
Evaluation of Genomic applications in practice and prevention
Who initiated EGAPP and when
2004 by CDC (Centre for disease control and prevention).
Purpose of EGAPP
To establish and test a systematic, evidence-based process for evaluating genetic tests. Also evaluates other technology that are transitioning from research to clinical/public health practice
What does the EGAPP working group do
Established in 2005 to support the development of a systematic process for assessing the available evidence regarding the validity and utility of newly emerging genetic tests for clinical practice. Highlights gaps in knowledge and guidance on appropriate use of tests in a specific clinical scenario
What is NIHCE
National Institute for Health and Clinical Excellence- aka NICE.
When was NICE established and why
Set up in 1999, to reduce variation in the availability and quality of NHS treatments and care. In 2013 NICE became a Non-Departmental Public Body (NDPB).
What does NICE do
Develop evidence-based guidance and quality standards in social care. Accountable to Department of Health, but independent to government. Guidance is officially for England only.
Examples of NICE guidance on genetic tests
Autism- using arrayCGH testing. Melanoma assessment and management- when is genetic testing appropriate
Examples of quality standards provided by NICE
Quality standard for Breast cancer. Indicates when a treatment/procedure is considered highly effective, cost effective and safe
Example of technology appraisal by NICE
Looks at drugs and devices, ensures equitable access across country. e.g. Trastuzumab in people with tumours expressing HER2 (human epidermal growth factor receptor 2)
What does Diagnostics and medical technologies programme do
Evaluate medical diagnostics, access to new technologies/devices on NHS
Purpose of Interventional guidance
Evaluates the safety and efficacy of procedures used for diagnosis or treatment
What is Diagnostics assessments programme (DAP)
Helps to develop guidelines to ensure NHS is able to adopt clinically and cost effective technologies rapidly and consistently.
