Genetic Testing Guidance Drafted with CLIAC

The Clinical Laboratory Improvement Advisory Committee (CLIAC) met on September 10-11, 2008, to provide updates on government activities, review details of a guidance document on genetic testing, discuss approaches to quality control through risk management, and examine the potential for waiver of automated hematology devices.  Auburn Health Strategies was there for the CLIAC discussion of good laboratory practices for molecular genetic testing.  The CLIAC Genetics Workgroup, led by Carol Greene, MD, outlined the scope and details for a future guidance document to be published in the Morbidity and Mortality Weekly Report (MMWR).  The full CLIAC reviewed and commented on the workgroup’s recommendations, which included the following suggestions for molecular genetic testing:

Preanalytic Phase

Laboratory is responsible for providing information to clients to facilitate selection and ordering of appropriate tests

Laboratory should determine effective ways to provide the information, including – at a minimum – websites, in-service directories or information sheets.  More proactive methods for imparting information are encouraged.

A distinction is needed between what a clinician needs for a specific patient versus information on how a test is performed.  Among the details laboratories should provide to users, include:  lists of tests performs; intended use of test; indications for its use; specifications of performance characteristics; test methodology and procedures; limitations; FDA clearance information; details on collection and handling; patient information required; availability of consultation; and statement indicating if test results impact family members.

Laboratories should have written policies and procedures for correcting problems surfacing in the preanalytic phase.

Informed Consent

Laboratory testing should be based on informed decision-making.  (CLIAC discussed the distinction between informed decision-making and informed consent).

The individual ordering the test is responsible for obtaining informed consent, if required.

Analytic Phase

Do homework before introducing a new genetic tests (e.g., review scientific literature, select appropriate test methodology).

Determine performance characteristics before introducing test to patients (e.g., accuracy, precision, sensitivity, specificity, reportable range, reference range/normal values, stability, reproducibility, lowest limit of detection).

Laboratory Director responsible for clinical validity documentation oversight.

Control procedures are needed to ensure quality of total genetic testing process.

Control procedures should be performed on each run of patient testing, and selected based on patient population, prevalence of disease, mutation/variant to be detected.

Alternative control procedures – targeted mutation detection (direct sequencing or confirmed results by a reference laboratory); sequencing (include a normal control; bidirectional sequencing and/or separately extracted nucleic acid sample if positive control is not available); test detecting multiple mutations or variants (rotate positive controls in a reasonable timeframe, if not practical to include all positive controls).

Use unidirectional workflow and no-template control to minimize cross-contamination in molecular amplification procedures that are not fully closed.

Proficiency testing should be required for all genetic tests for which an accredited proficiency testing program is available.  Use at least twice a year.  Corrective actions should be implemented for disparate results.

To help laboratories meet proficiency testing and alternative assessment needs, a list of proficiency testing programs and sources that facilitate sample exchange should be made available.  If inter-laboratory exchange or externally derived materials are not feasible, laboratories should repeat testing of blinded samples, exchange with research or international laboratories, compare inter-laboratory data comparison.

Post-analytic Phase

In addition to the requirements of the Clinical Laboratory Improvement Amendments of 1988 (CLIA), the guidance suggests the test report include: patient’s name, date of birth, indication for testing, date/time specimen collected, date/time specimen arrived, referring physician or authorized individual, test method used, performance specifications and limitations, test results in current standard nomenclature, result interpretation, literature references, recommendation for consultation (if appropriate), implications of test results for relatives (if appropriate), required statement for in-house developed tests using analyte specific reagents, statement indicating that result is based on current knowledge and technology.

Suggested clarifications to CLIA regarding normal values.

Test reports should be reviewed and signed by qualified personnel, although it may not be practical for all genetic testing reports to include signatures.

Quality control and proficiency testing records should be retained for at least 2 years.

While CLIAC felt that test reports should be retained for the “longest possible” timeframe, there was considerable discussion on how to define that time.  There was some consensus for keeping reports at least a “generation” or 25 years after the test is performed.  A push for electronic records and reports that remain accessible while technology changes was urged.

Specimens should be retained for the longest possible timeframe, as space, cost and technology allow.  At a minimum, specimens should be kept until the next proficiency testing (alternative assessment) event.


As with other laboratory tests and medical information, genetic testing information should be kept confidential and in line with federal, state laws and accreditation and professional standards.

If test results reference family members, the laboratory should establish policies and procedures to ensure the confidentiality of all patient information. If a patient’s results are needed to management the care of a family member, the laboratory should release information only to the ordering physician or the physician cooperating in the care of the patient who was tested.  Results should not be released without the authorization of the patient.


Qualifications under CLIA for a laboratory director are sufficient in the molecular genetic testing area.  However, the responsibilities of a laboratory director should be expanded to include ensuring documentation of the clinical validity of any genetic test offered, and determining specimen retention policies.

CLIAC engaged in lengthy debate over the qualifications for the technical supervisor.  It appears that current CLIA qualifications for a technical supervisor for high complexity tests may be sufficient to avoid restricting access to simple molecular genetic testing.

Technical supervisors should add to their responsibilities, if approved by the laboratory director, ensuring appropriate documentation of clinical validity information, assessing the suitability of a test for a particular use, reviewing the test results and interpretation, reviewing/signing the report, answering questions about the test report, and providing on-site time in the laboratory.

Qualifications for a clinical consultant should include at a minimum CLIA requirements plus experience or training.  Preferred clinical consultants have a MD or DO degree with two years of training or experience in genetic testing; or a PhD in a relevant specialty with board certification and two years of training or experience in genetic testing.

CLIAC notes the important role of master-degree genetic counselors, but notes that they are not qualified, under CLIA, to serve as clinical consultants.

General supervisor qualifications under CLIA remain, but should include training or experience with high complexity molecular genetic testing.

Training or experience in molecular genetic testing should be added for testing personnel.  Testing personnel without this training or experience should be placed in a trainee category.


Additional information on when to consider introducing genetic testing into a laboratory and the use of quality management systems were outlined.

It is anticipated that the complete guidance document will be published in the MMWR in early 2009.