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Principles for the translation of ‘omics’-based tests from discovery to health care submission

ID: 
4
This submission reflects the views of
Organisation Name: 
Centre for Values, Ethics and the Law in Medicine
Please identify the best term to describe the Organisation: 
Educational institution – tertiary
Personal Details
Questions
Q1. Is the draft document presented and written in a manner that is appropriate for the target audience (ie medical researchers, health professionals, health administrators and policy makers with responsibility for oversight of research or clinical care)?: 

 

The draft document is not presented in a manner appropriate for the target audience, for the following reasons:

  1. the document offers little by way of context or introduction and a lot of knowledge is assumed. While many accessing this document will be cognisant of the language employed, not all will;
  2. the document conflates research, clinical practice and population health and does not attempt to define these domains, nor how they overlap with or depart from each other;
  3. the division of principles into ethical, operational and domain-specific principles is not explained;
  4. the ethical principles (which we take a particular interest in, given that our disciplinary area is bioethics) are poorly described and inadequately defended. They are justified by reference to a declaration that pertains only to medical professionals undertaking research – much narrower than the scope of this document. The principles themselves are very general and are not specific to omics. They are also only minimally integrated in the remainder of the document. Given that the ethics literature on omics is now significant, it is a shame that it does not seem to have been drawn on in developing these principles. The ethical principles as defined also have technical problems. The principle of ‘beneficence’, for example, does not actually define nor reflect what beneficence is.;
  5. there is no mention of how genomic technologies should be accessed, for example through clinical or research pathways. There is no mention of governance of, nor access to, omics. If these guidelines are considered to apply to a population health context (as Case study 3 appears to suggest), then this should be addressed;
  6. there seems to be little integration between the various kinds of principles that are introduced;
  7. the document contains no clauses or statements to stipulate when a revision will be required; or whether the document will have a ‘sunset clause’. In an area as fast-moving as omics, we’d suggest this is imperative.

 

Q2. The draft document includes governing principles that apply across all domains and specific principles that apply to each of the four domains. Is this structure useful?: 

 

The idea of this structure is useful but the execution in this draft document is not satisfactory. We have articulated our key reasons for this in our answer to Q1 above, but for this structure to be useful the principles need to be explained with greater context and with further consideration as to the particular application in question (e.g. research). The governing principles also need to be returned to in a meaningful way throughout the document. For example, on Page 9 there are references to some further ethical issues, but these are not discussed in any detail nor are they related back to the ethics governing principles.

In its current form, the document contains some narrative comment and some principles; but these should be linked together more effectively than they are currently.

Q3. The draft document includes five case studies. Are the case studies appropriate and do they sufficiently cover the range of situations that might be encountered in practice?: 

 

It is laudable to include case studies. However these do risk becoming obsolete given the fast pace of developments in the science and application of omics and a regular schedule for their review should be developed and recorded in this document.

Additionally, some of the case studies are problematic.

  • Case study 1: this case study overlooks significant issues regarding the definition of research and treatment, and perhaps rushes too fast to its judgement of non-maleficence.. These papers, published in 2004 and 2008, highlight these issues in a genetics context – and we would submit that this will only heighten with omics research: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC498040/; and http://www.ncbi.nlm.nih.gov/pubmed/18757643. We’d suggest further discussion and revision of the commentary on this case. We do accept, however that research results should not dictate patient treatment unless they are validated.
  • Case study 2: this case is interesting but highlights a deficiency in the document in that there is not enough mention of consent to omics investigations. This is a specific problem where national guidance would be useful.
  • Case study 3: We’d suggest that incidental findings relating to genetic findings that are “not yet made” should not be reported, or at least held ‘in trust’ until more effective interpretation is available/desired by all parties. This case study should also cross-reference current HGAC/AHEC work on incidental findings.
  • Case study 4: This case study is problematic as it appears to condone newborn population screening for Rett syndrome, which is not indicated. We’d suggest limiting this case study to the clinical question at hand and removing the population screening aspects; to then introduce a separate case study more appropriate to population screening using omics technology – and then comprehensively addressing the ethical issues that will arise. We also note that the commentary to this case notes that “it remains to be established whether NGS technologies could be applied to DNA extracted from dried blood spots.” While we are not experts in this field, we are aware of several papers in the literature that make the opposite claim, for example: http://www.ncbi.nlm.nih.gov/pubmed/23830478; and http://www.ncbi.nlm.nih.gov/pubmed/24959449.  
Q4. Would you be able to use the document as the basis for drafting specific principles, policy or actions in your local context?: 

 

We are an academic bioethics centre and so this question does not apply directly to our practice. However we would imagine that in this very condensed form, this document would not be helpful for principles, policy or actions in many local contexts.

Further, if this is a national document, we wonder why further specific determinations should even be required in a local context?

Q5. Is the draft document comprehensive and does it cover the key issues in terms of principles? Is there further advice that should be included in the draft document?: 

 

The draft document is not comprehensive in its revised form. Several of the authors of this submission had the opportunity to read the initial draft; and one of us attended the workshop in Canberra on 20 March 2014. It is particularly disappointing to see that much of the work undertaken that day has not been incorporated.

Some additional aspects that could be considered, in addition to what we have already mentioned above, are:

  1. Importantly, in its current form, the draft document does not adequately problematise the distinction between illness, disease and predisposition and gives the clear impression that these categories are fixed and/or are defined purely in bio-scientific or genetic terms. This is at odds with the philosophy and sociology of science and medicine literature and insufficiently acknowledges how geography, culture, time and an individual’s or community’s values and preferences may be relevant to deciding whether disease exists at all and what, if anything, should be done about it.
  2. The use of ‘filters’ to shape results should be considered, as this is prevalent in the literature
  3. Domain 4 could also address the possibility of discarding a sequence – recently suggested by HUGO (referenced in http://www.ncbi.nlm.nih.gov/pubmed/25122627). That is, given that sequencing is reducing in cost so significantly, it may be more feasible from a data custodianship point of view, as well as in terms of obligations to recontact, to instead re-sequence individuals each time a clinical question is posed.
  4. Principle 3.7 talks about ‘research’ in the rationale, but the section it sits in relates to clinical practice?
  5. Regarding Principles 4.2 and 4.3, the document should recognise that it is impossible to ever completely anonymise genomic sequence information, such as prior to it being placed in the public domain. See for example: http://www.sciencemag.org/content/339/6117/321.abstract. A requirement to discuss this with those whose information may be placed in the public domain should be stipulated in this document. There is also no indication of what such open access databanks will look like, who should curate them, who will govern and manage them, and whether commercial partners should be involved.
  6. The Glossary needs further terms added: for example: genome, transcriptome, metabolome, epigenome or proteome. Not all in health policy, for example, will know what these terms mean and they are used at the very start of this document.
  7. the document makes only passing reference to culturally sensitive applications of omics
  8. the document requires more discussion around consent, including some principles indicating the paramaters of a valid consent discussion in this context. At the meeting in March, we suggested the following as a possible basis for a consent principle: “Individual or parent/guardian consent should be obtained for omics-based testing for the purpose of clinical research or practice. Consent processes should recognize the limitations of current models of informed consent and the challenges that the scale and pervasiveness of omics information will bring.”
  9. related to point 8, there is no mention of genetic counselling anywhere in the document. We submit that this is especially relevant to Principle 3.6 (multi-disciplinary team).  This is inconsistent with current clinical applications of genetic tests.
  10. the document should also include a principle that recognises the familial/shared nature of genetic/genomic information. We suggest the following as a possible basis for a family communication principle: “Omics testing, whether in research or health care, requires recognition of the shared nature of genetic information and the potential for greater relevance of genetic information in families than previously. Communication of clinically valid results in a sensitive way throughout families should be encouraged and facilitated wherever possible.”

Page reviewed: 15 April, 2015