Ethical Conduct Flashcards
What should the lab have in place in relation to ethical conduct?
a) There is no involvement in any activities that would diminish confidence in the laboratory competence, impartiality, judgement or operational integrity.
b) Management and personnel are free from any undue commercial, financial or other pressures and influences that may adversely affect the quality of their work.
c) Where potential conflicts in competing interests may exist, they shall be openly and appropriately declared
d) There are appropriate procedures to ensure that staff treat human samples, tissues or remains according to relevant legal requirements.
e) Confidentiality of information is maintained.
If a patient phoned the lab, can you give them a result and why?
Results should not be communicated to the patient without the opportunity for adequate genetic counselling. All results are confidential unless disclosure is authorised wherein the results may be reported to other parties with the patient’s consent or as required by law.
What does ISO stipulate about data protection?
The laboratory should ensure that all information is stored safely and that there are reasonable safeguards against loss, unauthorised access, tampering and other misuse.
What does ISO stipulate about informed consent?
ISO states that all procedures should be carried out with the informed consent of the patient. The standards also state that using patient samples for purposes other than those requested should only occur if the samples are rendered anonymous or have been pooled.
What are the different types of incidental findings?
1) actionable (whether immediately or remotely)
2) clinically relevant, but not actionable
3) of uncertain significance.
An actionable IF is one for which it is well known that a therapeutic or preventive measure exists that can significantly benefit the health of the individual in whom it was discovered. A clinically relevant, but not actionable, finding could, for example, be a carrier status for an autosomal recessive condition for which carrier screening is recommended. A variant of uncertain significance is a finding that cannot be unequivocally classified as clinically significant or benign. This could be because there is known variable expressivity or incomplete penetrance for the finding or because the finding is novel and has only very rarely or never been seen before. A VOUS may affect a gene that is relevant to the indication for testing or may be incidental in an unrelated gene. Thus, IFs and VOUS can overlap, creating additional complexity and clinical counselling and management challenges.
What considerations should be made when reporting and incidental finding?
- Is it clinically relevant
- Is the disease or risk clearly proven
- Would reporting the finding lead to a better clinical outcome (e.g. are treatments available)
- Has the patient given informed consented for this test
- Patient autonomy- Is there an option for the patient to opt-out for receiving feedback from incidental findings
- Would withholding the information open the department to litigation
- Is it ethical to withhold the information
What are the ACMG recommendations for reporting incidental findings?
- Constitutional mutations found in the genes on the minimum list (Table 1- see appendix) should be reported by the laboratory to the ordering clinician, regardless of the indication for which the clinical sequencing was ordered.
• Additional genes may be analyzed for incidental variants, as deemed appropriate by the laboratory.
• Incidental variants should be reported regardless of the age of the patient.
• Incidental variants should be reported for any clinical sequencing conducted on a constitutional (but not tumor) tissue. This includes the normal sample of a tumor-normal sequenced dyad and unaffected members of a family trio. - The Working Group recommends that laboratories seek and report only the types of variants within these genes that we have delineated (Table 1).
• For most genes, only variants that have been previously reported and are a recognized cause of the disorder or variants that are previously unreported but are of the type that is expected to cause the disorder, as defined by prior ACMG guidelines, should be reported.
• For some genes, predicted loss-of-function variants are not relevant (e.g., COL3A1 and most hypertrophic cardiomyopathy genes).
• For some genes (e.g., APOB), laboratories should only report variants for certain associated conditions. - It is the responsibility of the ordering clinician/team to provide comprehensive pre- and posttest counseling to the patient.
• Clinicians should be familiar with the basic attributes and limitations of clinical sequencing.
• Clinicians should alert patients to the possibility that clinical sequencing may generate incidental findings that could require further evaluation.
• Given the complexity of genomic information, the clinical geneticist should be consulted at the appropriate time, which may include ordering, interpreting, and communicating genomic testing. - These recommendations reflect limitations of current technology and are therefore focused on disorders that are caused by point mutations and small insertions and deletions, not those primarily caused by structural variants, repeat expansions, or copy-number variations.
- The Working Group recommends that the ACMG, together with content experts and other professional organizations, refine and update this list at least annually.
Controversy: Some societies such as The Phg foundation have expressed concern for patient autonomy with respect to these guidelines questioning whether patients are obliged to accept feedback from IF’s and suggesting that patients should be allowed to opt-out from such feedback if desired, unless there is near certainty of adverse yet potentially preventable medical outcome as failure to communicate such results would be unethical.
