Table B-1 below details the Genetic testing Evidence Track Tool (GETT) Checklist and Summary Table, including the subjects covered and a brief description of the data to be collected as detailed by Rousseau and colleagues (2010).
TABLE B-1 Sample of the First Page of the GETT Checklist and Summary Table
|1. Overview of the disease: epidemiology and genetics|
|1.1 Disease prevalence||Provide the prevalence estimated for the target population for age, sex, ethnic group or country.|
|1.2 Disease outcomes||Describe the outcomes for patient, family and society including life expectancy, morbidity, severity (wide clinical spectrum), onset or duration of the disease.|
|1.3 Clinical management and treatment||Clinical and social management required for this disease.|
|1.4 Costs associated with disease||What are the costs associated with this disease? Describe what is included in those expenses required by the patient, health care system, family.|
|1.5 Pattern of inheritance||What is the pattern of inheritance implicated in this disease?|
|1.6 Genetic heterogeneity||State how many genes have been implicated with this disease and provide the different mutations known for each gene.
Provide the distribution of these mutations in the target population and indicate if and how this proportion changes according to the population. Are there race-specific issues? Provide more details about the targeted mutations for the tests described below.
Specify the exact nomenclature used for genes and mutations involved in the disease and the nature of each mutation. Indicate the proportion of mutations detected by this genetic test.
|1.7 Mutation prevalence||Provide the prevalence of each mutation that will be analyzed and the population in which it has been measured.|
|1.8 Mutation penetrance||Provide the penetrance of the targeted mutations and specify if it changes according to ethnic group, age or age interval of subjects whose symptoms appear with age, life habits, environment or use of therapeutic drugs. Specify clinical end-points of penetrance data (e.g., biochemical phenotype, disease, etc.).
Does penetrance change according to the nature of the mutation?
|1.9 Neomutation rate||Provide the neomutation rate of this gene.|
|2. Diagnostic tools|
|2.1 Approaches other than molecular|
|2.1.1 Methods||Name the “gold standard” diagnostic or screening methods and their limits. Specify if the method can detect carriers.
Indicate the required sample, and the storage and/or transport conditions. Specify if each method is used separately or with other tests (algorithm). If an algorithm is used, describe it and indicate its performance if it is known.
Is the molecular analysis intended to replace or to complete existing diagnostic methods? If it does complete existing methods, how does the molecular analysis fit into an algorithm?
|2.1.2 Analytical validity||Provide the analytical validity of this test (quantitative measurements: Analytical validity accuracy, precision or reliability, sensitivity and specificity).|
|2.1.3 Clinical validity||Provide the clinical validity of this test (diagnostic specificity and sensitivity, positive and negative predictive values) according to the target population.|
|2.1.4 Infrastructures and costs||Describe the specific needs in equipment, infrastructure, personnel, transport, and storage of samples for this classical method of diagnosis. Are there cost-effectiveness and cost/utility studies for this diagnostic test? If so, describe its contents and the year of study. If not, provide an estimate of the costs and what it includes.
If there is an algorithm, provide its costs (if already estimated).
|2.2 Molecular approaches|
|2.2.1 Methods||Provide the genes and mutations sought for each molecular test. Specify if there are high quality annotated sequences, mutation databases, and professional bodies overseeing testing.
Describe the method of analyses used (tests combined in parallel or cascade) in a protocol or algorithm form.
For each test, identify the required sample, type of sample, quantity of sample needed, as well as storage and transportation conditions. What is the DNA extraction method used? For each test, describe the molecular techniques used by specifying primers, probes and/or restriction enzymes. List the size fragments or number of repeats expected. What are the limitations or pitfalls of these techniques?
Following a request for an analysis, which is the turnaround time to provide a result?
|2.2.2 Analytical validity||For each test, provide all information available on analytical performance specifying the source of this data (type of studies, population tested, reference method, number of samples of each genotype studied). Indicate the proportion of non-conclusive tests.
When they are known, specify possible sources of error.
Indicate for which types of sample the performance data are validated. Availability of well-annotated and accepted reference gene, mRNA/cDNA sequences. Provide Reference sequence number and source. Internationally accepted process for regular review of above for standardization purposes (e.g., numbering of nucleotide sequence).
|2.2.3 Clinical validity||What is the clinical performance of the test according to the target population? Specify relative to population, regional, race specific mutational spectrum.|
|2.2.4 Infrastructures and costs||Describe the specific needs in equipment, infrastructures, transport and/or storage of samples as well as personnel and training.|
|2.2.5 Interpretation||Are there any standard sentences which you will use for interpretation of the results? If so, provide them. If not, illustrate possible types of interpretation comments (positive, negative or non-conclusive test) according to the mutations tested.
If applicable, provide reference values for quantitative measures (e.g., the number of repetitions).
What kind of explanations will be provided with respect to genotype-phenotype correlations? Are there any locus specific databases of mutations with genotype/phenotype correlation data?
What information is needed for interpreting results (physical examination, biochemical tests, family history) and which should be provided by the prescribing physician?
Which type of information exchange has to be set up between the clinical laboratories and the consulting physician concerning explanation of the results?
|2.2.6 Consensus or best practice guidelines||Is there any consensus relating to the use of this molecular test and its interpretation?|
|3. Quality improvement program|
|3.1 Internal||What are the controls (positive or negative, normal or abnormal) and what are their origin (samples banking, cell lines)? Specify internal controls related to the analysis carried out and their limits.
Are internal quality control procedures applied to the laboratory as a whole or specific to the test? Provide the rates of errors reported. Provide the type of standards (e.g., molecular weight markers) included in the analysis.
|3.2 External||Identify the external quality control programs for this test and specify the type of programs to which you participate.
What does this program cover (e.g., analytical aspects of the test or interpretation and reporting)?
If no external QC program exists, which type of control do you make (e.g., blind tests, exchanges of various samples between laboratories).
|4. Clinical utility||For each of the strategies and target population considered, provide the documented benefits and risks, their frequency and severity.|
|4.1 Objectives||For each targeted aim, specify anticipated benefits, potential risks as well as benefits and risks documented by providing the references. Specify if these benefits and risks are related to positive, negative or non-conclusive results of the test.
Are there directives or proposals published on the indications (e.g., prognostic, predictive, susceptibility) for the discussed analysis? If so, provide references.
Internationally accepted body overseeing the area.
|5. Screening or diagnostic strategies||Describe suggested strategies for diagnosis or screening (e.g., diagnosis or familial screening, neonatal screening), the selected population, as well as eligibility criteria (e.g., diagnostic indications), and the place and recruitment scheme used for this population.
Indicate the practical use of the test in the context of a diagnostic or decisional algorithm if relevant.
|6. Impacts on the health care system|
|6.1 Foreseeable needs for testing||Provide an estimate of the need for this (these) molecular test(s) according to the disease/mutation prevalence in a population. Justify the sources used to calculate the number of tests.
What are the recommendations of professional organizations which could influence the number of requests for this test?
|6.2 Costs||Provide the cost implementation of this method, such as training of the medical and paramedical staff and the creation of new laboratories. Are there cost/effectiveness and cost/utility studies?|
|6.3 Test accessibility||What are the accessibility limits for this test?
Is information concerning this molecular test accessible to health care professionals and the public (community genetics approach)?
|6.4 Availability and accessibility of professional services, health care and follow-up, expertise and training||What are the resources needed to insure the medico-social uptake of concerned individuals and families?
Are professional services, related to health care and follow-up of the target population, available and easily accessible?
Following the introduction of the molecular test, what are the changes needed with respect to the nature of services and resources required? Is it necessary to envisage more training and to whom should training be offered?
Are there centers of expertise?
Are there support organizations for patients and their families?
|7. Psychological and social aspects of the analysis||According to the literature (if relevant), what are the potential psychological and social impacts of this test on the individual or his family?|
|8. Ethical and legal aspects of the analysis||What are the ethical and legal aspects specifically related to this test?
What ethical, legal and social stakes related to genetic tests as a whole are of a particular importance for this test?
|9. Synthesis||List missing data.
Comments on whom the test has not been validated in and the implications in testing such individuals.
|10. Research priorities||Priorities for evaluative research should be identified and classified.
Research questions and their relative importance should be identified.
|11. References||List of references used.|
NOTES: This page contains in column A the subjects covered, a brief definition of the data to collect (column B). QC = quality control.
SOURCE: Rousseau et al., 2010. De Gruyter Clinical Chemistry and Laboratory Medicine, Walter De Gruyter GmbH Berlin Boston, 2010. Copyright and all rights reserved. Material from this publication has been used with the permission of Walter De Gruyter GmbH.