Biomarkers: The Future Of Healthcare

Dr. Anna Barker at the 2017 AACR Annual Meeting

While attending the 2017 American Association for Cancer Research (AACR) Annual Meeting as an advocate mentor with the Scientist Survivor Program (SSP), I worked with my group of advocates on a project about biomarkersDr. Anna Barker, founder of the SSP and director of the National Biomarker Development Alliance, kept drilling into my head that biomarkers are only useful if they are validated and show clinical utility. She challenged me to find the list of FDA-approved biomarkers and to develop an understanding for companion diagnostics. She wanted me to understand the biomarker development process: What does it mean for a biomarker to be validated, and why have so few biomarkers been validated by the FDA?

Precision Medicine Relies On Validated Biomarkers

Precision Medicine — choosing the right drug, for the right person, at the right time, in the right amount, is becoming a reality — but personalized oncology relies on validated biomarkers. Validated biomarkers are biomarkers that are approved by the FDA with a companion diagnostic that can classify patients by response to treatment. The crux of personalized oncology lies in the clinical use of validated biomarkers. Although tens of thousands of biomarkers have been identified few have made it to the clinic. The ultimate goal of biomarker validation is to design biomarker tests that can inform clinical decision-making to improve patient outcomes. Unfortunately this process is experiencing difficulties. There is not a standardized development process, and currently the reproducibility of results has been poor. For a biomarker to be useful it needs to be specific, sensitive, reproducible, and easy to use in the clinic.

Biomarker Validation: A Challenging Process

The biomarker development (bench to bedside) and qualification and validation (FDA Approval) process is complex and currently not standardized. Biomarker development is a fast growing field with new targets, and technologies to identify them constantly evolving. Recently, the National Biomarker Development Alliance was formed with the mission to standardize the biomarker development and validation processes when necessary. There are challenges associated with all the steps of the biomarker development process.

1. Identify Potential Biomarkers

First, potential biomarkers are identified in pre-clinical exploration studies. These studies need to have defined research questions. One of the biggest challenges at this phase is in the selection of biospecimens, such as tissue from a cancerous tumor or blood/bone marrow samples that are to be used in the studies. Ideally biospecimens should be prospectively collected based on well-defined inclusion-exclusion criteria. This often is not the case. Many times whatever biospecimens a researcher has on hand are the ones that are used. These specimens may be of poor quality, leading to results that can not be reproduced in other laboratories. (1)

2. Develop A Companion Diagnostic

Once a candidate biomarker has been identified, a test needs to be developed and validated to measure it. This test is called a companion diagnostic, and must be accurate, reliable, and reproducible by others. This test must also be able to divide the population into two separate groups with different clinical outcomes. Finally it must improve patient outcomes. Companion diagnostics must be validated through the clinical trial process to prove their reliability. The testing sample size used needs to be large enough to make statistically significant calculations, and represent diverse biological backgrounds. The test needs to be sensitive and specific. There should not be too many false positives (identifying cancer when none is present) or false negatives (missing a cancer that is present). To validate predictive biomarkers (a biomarker that helps determine which patients are most likely to benefit from a specific treatment), companion diagnostic strategies need to be part of the early development plan for each compound. Most biomarkers do not progress beyond this phase because the companion diagnostic biomarker tests show that that biomarker is not specific or sensitive enough to be used in the clinic. (1)

3. Qualify The Biomarker

The next step is to have the biomarker qualified by the FDA. During the biomarker qualification process the sponsor needs to tie the identified biomarker to a specific biological process and associated clinical endpoint through evidenced-based data. The endpoint can be diagnostic, prognostic, or predictive in nature. This involves a collaborative discussion with the FDA regarding their biomarker development plan. The sponsor will then submit a qualification package to the FDA who reviews it and decides whether or not to qualify the biomarker. Once a biomarker has been qualified it can be used in other drug development efforts for the same purpose. (2)

4. Validate The Biomarker

If a biomarker is used to accurately predict the effect of therapeutic intervention (predictive biomarker), it, along with its companion diagnostic test, must be validated by the FDA. Validation must be done through robust clinical trials that evaluate specificity, sensitivity, and reproducibility, to name a few of the parameters. Statistical significance needs to be demonstrated.

Summary Of The Biomarker Validation Process

First a candidate biomarker is identified in the research lab. Next a test, called a companion diagnostic, that can identify the candidate biomarker in a person, is developed and validated. Then, the biomarker needs to be linked to a biological process that has clinical meaning — either diagnostic (can diagnose a cancer), prognostic (indicates how cancer may progress in an individual who is already diagnosed), or, predictive (can predict who will benefit from a particular treatment.) Finally, predictive biomarkers need to be validated by the FDA.

FDA-Approved Biomarkers

Currently only 7 prognostic and 6 diagnostic biomarkers have been qualified by the FDA in oncology. Additionally, less than a dozen predictive biomarkers have been validated by the FDA, although several predictive biomarkers are currently in phase II or III evaluation along with their companion diagnostics. (3) Validation of predictive biomarkers will be the path to Precision Medicine.

From Sick Care To Health Care

In conclusion, this is a very exciting area of science: Biomarkers are the key to early diagnosis, accurate prognosis, and selection of appropriate therapy. They can also be a key to reducing healthcare cost. Dr. Anna Barker states: “Biomarkers are actually the way to transition from sick care to health care.”

Now I know why Dr. Barker kept on questioning me on what I was learning about biomarkers. They are the future of healthcare.


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Cindy Chmielewski Precision Medicine Advocate

Cindy Chmielewski Precision Medicine Advocate

Cynthia Chmielewski was diagnosed with multiple myeloma, a blood cancer, in 2008. Cindy’s induction therapy stopped working after a few cycles and she proceeded with a stem cell transplant which failed to put her into remission. Depressed and scared she continued her fight using newly FDA-approved targeted therapies which eventually put her in remission. Cynthia continues treatment with a maintenance protocol.  Cynthia is using her passion for education to teach a new group of “students” – myeloma patients, their caregivers and others interested in myeloma.  She is a trained mentor, advocate and Patient Ambassador.
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