Shortly after the Duke trial scandal broke, the Institute of Medicine convened a committee to write a report on translational omics. Several statisticians (including one of our interviewees) either served on the committee or provided key testimony. The report came out yesterday. Nature, Nature Medicine, and Science had posts about the release. Keith Baggerly sent an email with his thoughts and he gave me permission to post it here. He starts by pointing out that the Science piece has a key new observation:
The NCI’s Lisa McShane, who spent months herself trying to validate Duke results, says the IOM committee “did a really fine job” in laying out the issues. NCI now plans to require that its cooperative groups who want to use omics tests follow a checklist similar to that in the IOM report. NCI has not yet decided whether it should add new requirements for omics tests to its peer review process for investigator-initiated grants. But “our hope is that this report will heighten everyone’s awareness,” McShane says.
Some further thoughts from Keith:
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First, the report helps clarify the regulatory landscape: if omics-based tests (which the FDA views as medical devices) will direct patient therapy, FDA approval in the form of an Investigational Device Exemption (IDE) is required. This is in keeping with increased guidance FDA has been providing over the past year and a half dealing with companion diagnostics. It seems likely that several of the problems identified with the Duke trials would have been caught by an FDA review, particularly if the agency already had cause for concern, such as a letter to the editor identifying analytical shortcomings.
Second, the report recommends the publication of the full data, code, and metadata used to construct the omics assays prior to their use to guide patient therapy. Had such data and code been available earlier, this would have greatly reduced the amount of effort required for others (including us) to check and potentially extend on the underlying results.
Third, the report emphasizes, repeatedly, that the test must be fully specified (“locked down”) before it is validated, let alone used to guide patient therapy. Quite a bit of effort is given to providing an explicit definition of locked down, in part (we suspect) because both Lisa McShane (NCI) and Robert Becker (FDA) provided testimony that incomplete specification was a problem their agencies encountered frequently. Such specification would have prevented problems such as that identified by the NCI for the Lung Metagene Score (LMS) in 2010, which led the NCI to remove the LMS evaluation as a goal of the Phase III cooperative group trial CALGB-30506.
Finally, the very existence of the report is recognition that reproducibility is an important problem for the omics-test community. This is a necessary step towards fixing the problem.