Validation

With respect to quality assurance and laboratory accreditation requirements, all laboratories have to generate and validate Standard Operating Procedures (SOPs), for all the methods in use. However, although validation is required for accreditation, there is little consensus on definitions or guidelines of what is acceptable or appropriate in the field of medical genetics.
Therefore, the main objective for the diagnostic validation workgroup is to establish a structure to centralize and promote the use of SOPs and guidelines and facilitate the implementation of technologies, methods and kits into diagnostic routine activities. It will be reached by coordinating the currently fragmented activities on validation of laboratory methods, technologies and kits, by editing guidelines and by organizing specific and dedicated working groups.
We also propose to create a network of expertise to harmonize approaches and reduce redundancy in the preparation of the SOPs and their validation. The aim is to draft 'generic' method SOPs for the largest possible number of different methods and technological platforms. The network will also be involved in the training of the 'Users' of the different methods and technologies, and in teaching about validation. This will be done in Best Practice Meetings and by on site training sessions.

Objectives

• • General objective: Procedures and guidelines for the diagnostic validation of methods and technologies
  • Specific objectives:
    1. Establish and issue guidelines for the validation of molecular diagnostic tests and (commercial) kits
    2. Training in validation
    3. Diagnostic validation of available methods, with the aim of facilitating their implementation by diagnostic laboratories: DNA extraction, MLPA, Luminex-based genotyping, ...
    4. Diagnostic validation of methods after technical validation (collaboration with unit 5): HRMCA, CSCE
    5. Further evaluation of the performance/validation of commercial kits/technologies for CFTR testing

Activities and related documents

Achievements

• Validation of technologies and kits meeting, 29 September 2005, Leuven
• Guidelines for molecular karyotyping in constitutional genetic diagnosis - 20-11-2007
• Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This article identifies areas for which the technology seems matured and areas that require more investigations. Molecular karyotyping should be part of the genetic diagnostic work-up of patients with developmental disorders. For the implementation of the technique for other constitutional indications and in prenatal diagnosis, more research is appropriate. Also, the article aims to provide best practice guidelines for the application of array comparative genomic hybridisation to ensure both technical and clinical quality criteria that will optimise and standardise results and reports in diagnostic laboratories. In short, both the specificity and the sensitivity of the arrays should be evaluated in every laboratory offering the diagnostic test. Internal and external quality control programmes are urgently needed to evaluate and standardise the test results between laboratories.

Validation of technologies and kits meeting, 29 September 2005, Leuven Guidelines for molecular karyotyping in constitutional genetic diagnosis - 20-11-2007 Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. This article identifies areas for which the technology seems matured and areas that require more investigations. Molecular karyotyping should be part of the genetic diagnostic work-up of patients with developmental disorders. For the implementation of the technique for other constitutional indications and in prenatal diagnosis, more research is appropriate. Also, the article aims to provide best practice guidelines for the application of array comparative genomic hybridisation to ensure both technical and clinical quality criteria that will optimise and standardise results and reports in diagnostic laboratories. In short, both the specificity and the sensitivity of the arrays should be evaluated in every laboratory offering the diagnostic test. Internal and external quality control programmes are urgently needed to evaluate and standardise the test results between laboratories.

Contacts and Members

Contact information and members of the 'Validation' work package