Friday, July 22, 2011

Biomarkers: Time, more time (and bit a more money), please

The Duke University scandal and a recent JAMA article questioning the usefulness of biomarkers has sparked general “navel-gazing” in the scientific and drug development communities about the worth of biomarkers. When put into perspective with the traditional lengthy cycle of discovery and development in the biotechnology and pharmaceutical environment, one can argue that we are still in the early stages of biomarker research. There is a use for these markers, and a potentially cost-effective and treatment-effective one at that.  

There has been growing support for the concept of personalized medicine over the last five years.  Coinciding with the human genome project, personalized medicine and targeted treatments became accepted terminology in the industry. Once these terms entered the lexicon, we seemed to forget  the reality—personalized medicine hasn’t quite arrived. To paraphrase what has been said well other times, good science hasn't quite caught up with the stampede of financing, early licensing deals, and business. It will take much more time, resources and research to truly develop the personalized medicine field the way that it is broadly pictured—using biomarkers and proteins to actually select those who will benefit most from certain treatments, or to develop targeted treatments or to be able to more accurately predict treatment outcomes. 

Questions from the AMA and others regarding the usefulness of biomarkers are not new.  It seems that every time there is a data disappointment or a string of favorable articles regarding new findings, articles in prestigious journals appear disregarding the potential of biomarkers in providing better treatment. This is, in many ways, what a research community should do —provide a healthy exchange of theories and ideas. However, to discount the potential use of genetic signatures or protein markers is to disregard an area with remarkable potential.

The biotechnology industry has seen many surprises over the years. (A recent large scale government study, co-sponsored by Abbott, showing that elevating good cholesterol has no impact on one’s risk for cardiovascular events is but one example.) Questionable leadership and data issues in the Duke University project aside, there is no reason to toss promising research out the window. Biomarkers have proven effective in certain rare cancers, where the correlations are very strong.  (HER-2 /neu marker is a good example.)  There is still room for more findings to impact cancer and other diseases that present serious public health issues. The answer to the dilemma is time, patience and funding.  Pick and choose what we pursue. However, walking away from an area that has had some success seems premature at best.  Biomarkers are not an answer in themselves, at least not at this point.  In practice, they are—as in the case of PSA measures for prostate cancer—taken into account with other factors. But as data points, depending on risk correlation, they can be effective.

Doctors are not likely to use journal articles on new findings to guide the treatment of their patients.  Researchers should share their information in the public domain so that others can validate and build on the data. The community should show more patience. We have barely reached the halfway mark in the average 20 year cycle of development. This may not pan out, but we owe it to ourselves to continue in the effort. After all, it is too early to call. In the last 20 years, research and investment have helped many cancers, certain cardiovascular diseases and HIV to an extent to become chronic manageable diseases rather than life sentences. Emphasis on diagnosis has aided in the transitions. Biomarkers and their surrogates played a definite role.  These transitions did not happen overnight—and nor did the pay-off. 

Often, new technologies and concepts will have drastic ups and downs on the way to real answers.  (Anyone else recall the excitement over RNA inhibitors, accompanied by significant early funding which begat dismissal of the technology 2 to 3 years ago, which in turn recently begat some successful data? RNAi is currently on an upswing.)  We still have time to see if biomarkers can realize their full potential.  Let's wait it out.