A bit of shameless self promotion for me and colleagues at Innovative Science Solutions. This week brought us 15 seconds of “fame” through publication of a February 7, 2017 article in a widely read national legal publication known as LAW360. The article focuses on the molecular biology revolution moving slowly but steadily into litigation involving sources of diseases, such as cancers. Science will continue to move far faster than the law, but some of us are pushing lawyers and judges to try to catch up.

 

Biomarker Exposure Tests Will Revolutionize Toxic Torts

Law360, New York (February 7, 2017, 12:01 PM EST) —


Giovanni Ciavarra

Kirk Hartley

Some of the most difficult product liability cases to resolve are tough because of a lack of clarity as to the duration or amount of exposure. For example, defendants and plaintiffs sometimes take very different views of exposure in the so-called “take-home” cases where a spouse allegedly developed a cancer from a toxin in the workplace of the other spouse.

Over the next few years, some litigants will be smart enough to take advantage of the findings from new, objective tests that are arising due to the revolutionary developments in molecular biology.

Simply put, the revolution is moving towards increasingly fast, and relatively inexpensive, tools and tests usable to identify and measure objective molecular data related to mesotheliomas and other cancers.

These biomarkers are being developed because of their potential to transform disease management, including the diagnosis and prognosis of disease, and also to enhance risk stratification, therapy selection and population screening for diseases such as malignant mesothelioma (See, for example, Creaney 2015). But the tests can also provide data relevant to product liability lawyers.

What Is A Biomarker?

In 1998, the National Institutes of Health Biomarkers Definitions Working Group defined a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” (Biomarkers Definition Working Group 2001).

Broadly, a biomarker refers to any biological data point that is measured and quantified. Thus, biomarkers include everything from blood pressure to basic blood chemistry tests to more complex tests that measure myriad objective factors in biological fluids (e.g., blood) or tissues (e.g., solid tumor biopsy).

Some notable examples include circulating levels of prostate-specific antigen (PSA) for prostate cancer screening, genetic mutations (e.g. BRCA1/2 for breast and ovarian cancer risk estimates), and immunohistochemical analyses to predict response to therapy (e.g. HER2 expression for anti-Her2 therapy in breast cancer).

Clinical Trials, Biomarkers And Toxic Tort Litigation

Litigants seeking an edge understand that clinical trials are changing rapidly, and that more and more frequently, outcomes are based on measurement of biomarker data.

For example, some new forms of clinical trials are known as “basket trials” and some are “umbrella trials.” Both types are aimed at looking for genetic mutations involved in cancers, and making choices based on the observed mutations.

In addition, some leading scientific researchers are actively searching for biomarkers that can be used to demonstrate the presence or absence of a person’s exposure to substances such as cigarette smoke, benzene and asbestos, as well to aid in the diagnosis of disease.

When it comes to exposure assessment, some difficulty relates to the fact that these exposures may or may not create a unique biological response that can be effectively detected and/or measured in the form of a biomarker.

The presence or absence of a biomarker may be important for either plaintiff or defendant, and their most useful applications may be to confirm or deny past exposures, as well as to objectively quantify past exposures. In this sense, biomarkers may help generate more definitive proof that can implicate or exonerate an exposure, thereby validating or refuting arguments related to specific causation.

Five broad categories of biomarkers that are being actively investigated to refine our knowledge of asbestos-induced cancer are listed below:

  • Genetic alterations that may provide “signatures” for past exposures
  • Epigenetic alterations linked specifically to asbestos exposure
  • Micro-RNA (miRNA) expression profiles (for asbestos exposure and cancer diagnosis)
  • Protein biomarkers for early detection and/or cancer diagnosis
  • Biomarkers in exhaled breath and tests for circulating tumor cells

A discussion of each of these types of biomarkers is beyond the scope of this article, but there are many great scientific resources that explain and expand upon each of these areas. For example, a Google search using terms from any of the categories will return a variety of resources for additional reading.

Overall, biomarkers are relevant to both causation and damages. As to causation, lawyers may view biomarkers as a way bolster or weaken specific causation arguments. For damages, earlier detection of disease may prolong survival of plaintiffs, leading to more downstream costs.

To learn more about the importance of genetic biomarkers in toxic tort litigation, see this recent article by Gary Marchant or this one by Steven Gold.

An Example Arises From New Scientific Findings Related To The HMGB1 Biomarker

New developments related to the High Mobility Group Box-1 (HMGB1) protein were recently published by Michele Carbone, Harvey Pass and other leading scientists in this area.

Briefly, HMGB1 is part of the body’s inflammatory process, and when it is released from the interior of cells into the blood, it induces inflammation via activation of immune responses.

This study describes promising steps toward generating a blood test to measure HMGB1 that may provide an objective measure of levels of past asbestos exposure. Essentially, the authors found that total HMGB1 blood levels are higher in asbestos-exposed individuals and mesothelioma patients compared to healthy (unexposed) controls.

However, more interesting were data related to a specific form of this protein (referred to as hyper-acetylated HMGB1). When the authors measured this biomarker, they found that it provided an exceptionally sensitive and specific biomarker to discriminate mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls.

Therefore, these findings provide a potential new avenue to detect asbestos-exposed individuals, and among them, those who have developed MM. Overall, this biomarker may help to distinguish asbestos exposure in individuals with and without disease.

The authors mentioned that a follow-on study on this very topic will start soon, which also confirms the view that this is a new frontier and that much research remains to be done. Some will be shocked when data arrives, but the knowledgeable will be watching the trial and anticipating the arrival of the data.

Lastly, it is interesting to note that the article reported research funding support from both a plaintiff’s law firm (Belluck & Fox) and from Honeywell. Kudos to all who are investing in research.

Looking Forward

Research on biomarkers will certainly continue to move ahead at breakneck speed in 2017 and beyond. As scientists continue to unravel the science of biomarkers, much of the benefit will likely be reaped for advancing medical diagnoses and treatments.

However, savvy plaintiff and defense lawyers may find novel ways to apply the use of biomarkers to establish or refute causation in their cases. It also will be interesting to see which clients and lawyers plan ahead and invest in science, and which ones wait to be surprised.

—Giovanni Ciavarra, Innovative Science Solutions LLC, and Kirk Hartley, LSP Group LLC

Giovanni Ciavarra, Ph.D., is a scientific consultant supporting investment banks, attorneys, and pharmaceutical, biotechnology and dietary supplement firms. Kirk Hartley is the founder of LSP Group LLC, and has practiced law for over 30 years, with a focus on advising a wide range of corporations, associations and individuals (as both plaintiffs and defendants) on mass torts issues.

The opinions expressed are those of the author(s) and do not necessarily reflect the views of the firm, its clients, or Portfolio Media Inc., or any of its or their respective affiliates. This article is for general information purposes and is not intended to be and should not be taken as legal advice.