Thursday, January 10, 2008

The Gene Genie Gone Awry?

In an article entitled "Letting the Genome out of the Bottle — Will We Get Our Wish?" in the New England Journal of Medicine, I am left questioning if Drs Khoury and Drazen read the Sherpa. Well, I read Hsien's blog, so why can't they read mine?

These are several themes that I have been raising about Genome Scans and have even spoken with several news reporters and journalists about.

From the Article:

It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was "not a clinical service to be used as the basis for making medical decisions," he is in the office for some "medical direction." What should you do?

My first answer is to call Helix Health of Connecticut or your friendly neighborhood geneticist. My second answer is what will most physicians say? My guess is, "This is just a fad. This information is useless" They may be correct and they may not be. But until this data is reviewed by someone who is in the loop about genomic discovery, I am not so sure they can say for certain.

The next part of the article really had me thinking that they have read several of my posts.

It is likely that sample-handling errors are a greater threat to the validity of results than are genotypic misclassification errors. Yet even very small error rates per SNP, magnified across the genome, can result in hundreds of misclassified variants for any individual patient. Without transparent quality-control monitoring and proficiency testing, the real-world performance of these platforms is uncertain.

This is a significant issue. In a Journal of the American Medical Association in 2006 a group mathematically estimated that there would be a significantly high rate of false positives.

This is the problem I see with whole genome analysis for medicine. Just because we can do it, doesn't make it medicine.

But more important than any of this is the educational shortcoming that most physicians have with this data. As indicated by the authors.

For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets.

The Sherpa Says:

This is why I started the Sherpa. We must stay on the Path To Personalized Medicine. Right now, Genome scans are a dangerous shortcut. Steer Clear.

To My Colleagues: If you have one of these scans from a patient, please give us a call
To My Early Adopters: Genome scans cannot be used for medicine yet, but they can be useful for other things...
To My Detractors: I am sorry if you are upset, but I will only speak my opinion.

1 comment:

Hercules said...

ah, your post is so true, as was an earlier post of yours commenting on incorrect lab results and BRCA testing. Right now, I am looking at five sets of results (in base pair form) for the same multi-SNP panel, for the same person (me!) and I have two "mis-reads" in two different SNPs, plus two "mis-reads" of the same SNP across two sets of results -- but with three complete sets of results matching correctly, all from a properly certified, highly competent CLIA lab. This is not a problem for my purposes, but if it was just a single scan / test, and I thought the "bad" SNPs were medically significant, where would that leave me?
(maybe ready to sue someone if I'm a consumer and I took drastic action based on the first set of results ...)