Tuesday, August 17, 2010

Is it worth the effort to develop personalized cancer treatments?

Robert Langreth has published a series of articles about personalized cancer treatments in Forbes Magazine (see Part I, Part II, Part III, and/or this summary in GenomeWeb).  In a nutshell, the author's main point (in the first article) is that it's very difficult to develop new drugs, and the costs to produce drugs that only help a small proportion of patients may outweigh the benefits for that drug.

I agree with the author in that I don't think it's reasonable to expect to produce an individualized drug for every possible mutation that can cause a disease (such as cancer).  However, I think genetic studies can still help improve treatments for several reasons.

First, there are a wide variety of tools that physicians can use to help patients, and I think it is wrong to view this argument from an "all-or-nothing" point of view.  Pfizer's response in the third article also criticizes the "all-or-nothing" thinking, although they cite the need for "accumulated modest advances" while I am saying it is good to have more options.  For example, the first article mentions the need to develop better surgical methods.  I'd like to see more personalized drug treatments as well as new surgical technologies.  I imagine there will be certain circumstances where a personalized drug therapy is ideal and certian circumstances where surgery will be necessary.  If we reach the point where even 30% of patients can receive personalized drug treatments, then I think that is pretty good.

Second, genetic tools can assist with the diagnosis of existing drugs (or drugs in clinical trails that were not originally designed for individuals with a specific mutation).  For example, a drug company may come very close to bringing a drug to the market, but then realize that the drug has severe side-effects for certain individuals.  If the individuals with the severe side-effects can be identified ahead of time, then the company can prevent total loss of their research costs by targeting individuals without a particular mutation.  Furthermore, scientists can discover new functions for drug candidates (as happened with Viagra), so genetic information may be able to provide researchers with alternative uses for existing drugs (or novel drug candidates).

Finally, it's important to keep in mind that cancer is the 2nd leading cause of death (in the US).  I'm sure there is a going to be a point where a mutation in a particular gene (or related pathway) is too rare to warrant developing a personalized treatment, but drugs that can decrease mortality in even 10-20% of patients may still be able to help a large number of people.

Thursday, August 12, 2010

Benefits to a 3-tier system for DTC genetic testing

The popular genetic testing company 23andMe has two rankings for genetic associations present in the scientific literature: Established Research Reports and Preliminary Research Reports.  The relatively recent GAO report on genetic testing claimed that 23andMe provided "reports that showed conflicting predictions for the same DNA and profile, but did not explain how to interpret these different results" (and the response from 23andMe can be viewed here).  However, I think this system provides a useful basis to improve education about genomics research and genetic testing.  In fact, I think it would be even better to provide 3-tier system to describe genetic associations.

In particular, I think genetic associations can be classified as "Based upon Preliminary Evidence," "Based Upon Reproducible Evidence," or "Therapeutically Useful."  In this case, I would consider "Reproducible" associations to be equivalent to 23andMe's "Established Research Reports."  I would consider "Therapeutically Useful" associations to be those that have been proven useful in terms of significantly reducing patient mortality or morbidity.

The "Therapeutically Useful" classification is important because there could be many reasons why individuals with a particular mutation may have a increased risk of dying from cancer that is statistically significant, but information about that particular mutation may not be important for informative for making medical decisions.  For example, models for genetic predisposition may be complicated for certain diseases, and it may be necessary to incorporate currently unknown information about other mutations in order to provide an accurate estimate of risk to develop a given disease.   Also, there are cases where environmental factors may be more important than genetic factors.  And the list goes on.

In practice, I think the FDA could play a role in helping define the third category of genetic tests, and I can think of at least two ways to implement this.  First, genetic testing companies could post some sort of "FDA-approved" icon for tests that have shown to produce positive results when applied in a clinical setting.  Second, the FDA could post a listing of genetic tests that have been proven useful through clinical trails and provide a list of appropriate treatments that correspond to a given test result.

There are benefits to having access to genetic information that doesn't necessarily meet the criteria for a "Therapeutically Useful" test.  For example, there may be no "FDA-approved" diagnostic for a particular problem and an experimental prediction may be the best possible resource.  Furthermore, the FDA has indicated that it does not see a need to regulate the release of "raw genetic information," and it is acceptable to communicate information about genetic associations though other means.  For example, the FDA would never censor an article in the New York Time about a new discovery or preliminary result.  Genetic tests that are"Based upon Preliminary Evidence" or "Based Upon Reproducible Evidence" are basically indicating that "Hey, you have this mutation that has been described in the scientific literature."  If it is too confusing to provide separate predictions for each tier of genetic associations, then genetic testing companies should at least be able to provide a list of publications describing a mutation of interest (and possibly provide a brief summary of the findings).

Information from DTC genetic testing can also fundamentally increase understanding about human genetics and contribute to scientific research, as indicated by 23andMe's publication in PLoS Genetics.  In fact, 23andMe could actually help establish "Therapeutically Useful" tests if customers could upload clinical information that is directly incorporated into their models.  Likewise, companies like PatientsLikeMe could help test the therapeutic value of genetic tests if patients could upload their genetic information

In general, I think individuals should take a much time as they reasonably can to research a topic prior to making a life-altering decision.  Even if a diagnostic is 98% accurate, what if you happen to be in the minority that gets a false-positive?  Even well-established tests can have false positives.  Important information can be gained from independent tests, consulting with a physician or genetic counselor (or getting second opinions from multiple professionals), or even talking to friends who might have went though similar situations.

Although I understand that a "3-tier" system for genetic testing may be confusing for people at first,  I think this system could be a useful tool to educate the public about genetic testing and encourage individuals to take a more active role in making medical decisions.  In fact,  a recent post by John Timmer concluded with the suggestion that heavy regulation of the DTC testing industry will probably not be necessary if a sufficiently large proportion of the general public took the initiative to better educate themselves.
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