Darwin's theory of evolution is a framework by which we understand the diversity of life on Earth. But there is no equation sitting there in Darwin's 'Origin of Species' that you apply and say, 'What is this species going to look like in 100 years or 1,000 years?' Biology isn't there yet with that kind of predictive precision.--Neil deGrasse Tyson
Our precise understanding of the complex biology behind cancer immuno-oncology lags the reported outcomes observed in clinical research. Case in point--the best therapies on average confirm clinical trial endpoints in approximately 20 to 30 percent of patient populations. I would argue that we are measuring the wrong thing but more about that later.
In the last 6 months to a year I have been working almost exclusively in the immuno-oncology space. Either directly with industry, on a collaborative team, or as a numeracy expert helping physician groups and/or patient advocacy groups unpack the latest findings.
After attending the World Vaccine Congress, Immunology 2017, DIA/FDA Statistics Forum, and Duke-Margolis Center for Health Policy/FDA workshop on analytical validation of assays used in qualifications of biomarkers I can tell you the headlines announcing potential cures and breakthrough approvals for checkpoint inhibitors are misleading and superficial in their conveyed messages.
Here is a simplistic representation of immunotherapy to introduce you to the basic premise in case this isn't an area of expertise.
The Cure in the Code: How 20th Century Law is Undermining 21st Century Medicine by Peter W. Huber describes the historical precedence and evolving shift of a small molecule mind-set to the rise of biomedical science and the power of a data-enabled framework. The first-pill costs are markedly more expensive than the later-pill costs--the true excipient is the "know-how". Are we ready to rethink our mindset? How do we market knowledge?
What if we approved drugs based on the biochemistry. Similar to Eureresist what if drugs were classified based on their ability to increase trafficking and penetration of tumor by T cells, T cell activation, and quantity of tumor-specific T cells for example. We can look at the graphic and see the myriad of options. What may result is the combination of HIV style cocktails that tailor treatment to the specific biochemistry of the tumor AND the patient. In the absence of clunky monotherapy or combination therapies we don't truly understand--we now have measurable endpoints beyond overall survival, progression free survival, etc.
Why is the latest data from Keytruda heralded as the success of ASCO while Opdivo, once the industry leader is losing it's footing with less than impressive two-year survival update on its Opdivo-Yervoy first-line lung cancer? I am going to point to the complexity of identifying appropriate biomarkers.
The most-effective to date has been PD-L1 expression but we shouldn't be convinced of a simplistic one biomarker gateway. An article published in 2016 by Manson and colleagues Biomarkers associated with checkpoint inhibitors highlight biomarkers with the potential to predict efficacy and toxicity.
The Biomarker Assay Collaborative Evidentiary Considerations Writing Group, Critical Path Institute (C-Path) includes scientists from the FDA, industry and academia collaborating to establish scientific and regulatory validation of biomarker assays. The process is ongoing and complex and includes a "framework" approach vs. a "checklist" to help stakeholders quantify and validate their assays effectively.
Inherent in the measurement of biomarkers, unlike the measurement of xenobiotics (drugs), is that biomarkers are endogenous entities or molecules. Therefore, biomarker assays typically measure an increase or decrease in the endogenous level of the molecule which often fluctuates because of individual variability in physiology, disease biology, pathology, comorbidities, treatment administered, and environmental factors. Given these factors, the requirements and expectations for assays used in the qualification of biomarkers must take into consideration 1) the type of molecules being measured and 2) the context in which the biomarker is being applied in drug development and in regulatory decision-making.--Public Workshop Duke Margolis Center for Health Policy, DC
The new prescription for medicine might indeed be ex uno plura--out of one, many--an evolution from epidemiology and crowd-sourced aggregated solutions to single-gene perspectives and truly tailored treatment for the unique biochemistry of an individual.
Bonny is a data enthusiast applying curated analysis and visualization to persistent tensions between health policy, economics, and clinical research in oncology.