On Thursday 20 March 2014, I participated in a National Health and Medical Research Council (NHMRC) workshop on “Translation of Omics-Based Discoveries into Clinical Research and Practice”. This was the first time I have had this kind of experience and I want to give you a sense of the event, particularly the motivation behind it and the process that followed.
The motivation? Omics-based tests are well and truly upon us, but we have a way to go to know how best to use and interpret the information they provide. Part of that involves going “beyond the hype” (cf. Gartner’s Hype Cycle) and having a mature view of their strengths and limitations relative to the canon of medical diagnostics, prognostics and such like.
In some ways, omics-based tests are just like any other medical tests—issues of accuracy, precision, predictive power, interpretation, strength of evidence, etc., apply. As far as I can see, the main differences are that ‘omics-based tests
- Can yield results that have implications for family relatives
- Can yield vast numbers of high-resolution measurements in which there is ample scope for information to be revealed about things other than the specific conditions for which the test was conducted.
Against this background, the NHMRC are drafting a framework and guiding principles about the translation of omics-based findings into decisions that affect people—the meeting emphasised “patients” but many participants pointed out that omics-based tests can be, and are being explored with the general population (e.g., screening for mutations in the BRCA1 gene as a risk factor for breast cancer).
You might say “Principles? Ha! What use are a bunch of lofty ideas and aspirational goals?” (and indeed, I think that was on the minds of a few participants). My take is that if we can’t articulate sound, well-reasoned and defensible statements about how to use omics-based information wisely, then we can’t expect these tests to have a positive impact on humanity; the role of deciding how best to use these tests and the information they generate will be taken up by those motivated by ends other than health and wellbeing (e.g., profit). So I’m very glad the NHMRC is taking this issue on and facilitating the elicitation of wisdom.
Imagine a room of fifty or sixty people, ranging from clinicians and medical researchers, statisticians, ethicists, pathologists, bioinformaticians, plus a few more professions to boot—a huge breadth and depth of experience. How do you get sage advice and penetrating insights from this bunch without descending into chaos?
Well, in addition to these participants, the starting ingredients included a 28-page consultation draft of “Principles for the translation of omics-based tests”, five table groups, plus facilitators from the NHMRC and its Human Genetics Advisory Committee (HGAC).
The morning focused on the principles—each table group looked at the five draft overarching principles (harm minimisation; beneficence; collaboration and harmonisation; transparency and integrity; fair and equal access to health care) and, per table, principles specific to one of the five “domains” (Test development and validation; Clinical research; Clinical practice; Data repositories; Ethical, legal and social issues). These discussions were skilfully led, wrangled, recorded, summarised and replayed by the facilitators.
The afternoon focused on case studies in five areas (including neurology and immunology). The idea was to look at these cases through the lens of the principles discussed in the morning. I was in the immunology group and our two scenarios involved how to interpret additional genomic information associated with certain conditions. At a high level, I saw this as a process of combining different kinds (and strengths) of evidence to form an opinion about what might be happening, then making a decision about what to do in light of that and the costs and benefits of different possible actions.
And, for me, this emphasises one of the central issues with the interpretation of ‘omics data (especially genomics data): what strength of association, what weight of evidence should we attach to an omics measurement. From what I saw on the day (bear in mind I don’t work in medical genomics) I found it very difficult to assess how many observations form the basis of an assertion like “mutation X is possibly damaging”.
In addition to serving as guidelines for practice, I think the principles discussed and developed further at the meeting serve to set expectations. My hope is that, through the kind of meeting we had at the NHMRC and subsequent broader consultation, we will get a set of principles that accurately embody the strengths and limitations of omics-based analysis in a clinical setting.
So what did I do at the meeting? A lot of listening and learning… as usual, I seemed to ask a lot of questions (Nature abhors a vacuum). Some of my input was motivated strongly by the desire for clinical decisions to be based on sound statistical inference from data. To that end, I suggested that reproducibility be somehow included as a governing principle, maybe using words like:
At the heart of science is the idea that we can develop understanding based on observations, evidence and models that we can test and, ideally, generalise for broader application.
The complexity and number of steps involved in omics-based analysis, coupled with the large number of measurements and often small number of subjects makes reproducibility a governing principle for incorporating omics-tests into clinical research and practice.
After making that suggestion, I had the good fortune to hear Professor Victoria Stodden speak about reproducibility in three flavours: empirical, statistical and computational. Since omics research often pushes the envelope empirically, statistically and computationally, I feel this suggestion is on track and I look forward to seeing whether there is something along those lines in the next iteration of Principles for Translation of Omics-Based Tests into Clinical Research and Practice.
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At this stage, questions about these Principles and the process by which they are being developed are best directed to the NHMRC's Human Genetics Advisory Committee by email to email@example.com
 Wisdom being, as Charles Spurgeon put it, the knowledge of how to use knowledge