A biomarker refers to a biological parameter that is an objective medical signal (versus medical symptom) which can be measured accurately and reproducibly.1,2 Biomarkers are widely accepted and used as an essential part of today’s healthcare environment. There are several types of biomarkers including physiological (eg, blood pressure), molecular (eg, liver enzymes, blood glucose), histological and radiographical (eg, angiography). The use of biomarkers as a diagnostic to determine treatment and guide clinical decision making is common in oncology and rare disease with growing utility in psychiatry, asthma, heart disease, Alzheimer’s disease, and other immunologic conditions.3,4 Biomarker testing is gaining complexity as the recognition of actionable biomarkers expands and as new technologies are developed.

Biomarker testing is the use of a laboratory method to measure a biomarker found in blood, other bodily fluids, or tissue. Commonly used biomarker tests include fluorescence in situ hybridization (FISH) test is used for detecting and locating a specific DNA sequence on a chromosome, immunohistochemistry (IHC) uses antibodies to check for certain antigens (markers) in a sample of tissue, liquid biopsy looks for cancer cells from a tumor or for pieces of DNA from tumor cells that are circulating in the blood, next-generation sequencing (NGS) is a high-throughput method that determines a portion of the nucleotide sequence of a person’s genome, Sanger sequencing is a low-throughput method and uses polymerase chain reaction (PCR) amplification of genetic regions of interest, whole exome sequencing is used to determine the nucleotide sequence of the protein-coding (exonic) regions of a person’s genome, and whole genome sequencing that determines almost all of a person’s complete DNA sequence (nearly 3 billion nucleotides).5 The testing method selected depends on several factors including source sample (tissue, fluid, blood) and invasiveness, disease, rarity of biomarker, test reliability and availability, cost, and payer coverage policies.

With several testing options available and expanding biomarkers almost daily, biomarker testing challenges exist across stakeholders. For providers, knowing which test to use, when, and how to interpret and apply the results can be overwhelming with the expanding markers and testing options. Add the complexity of trying to interpret which testing options are covered by different healthcare plans and it’s no wonder the testing landscape is so complicated to navigate. For patients, access to the most appropriate test can be impacted by whether a patient has healthcare coverage as the cost of many of these tests is significant, if the patient has healthcare coverage, payer coverage policy requirements may impact access to the desired diagnostic, provider awareness of available testing options, and reliability, validity, and relevancy of the test.6 Payers face some similar and yet different challenges in the diagnostic space.  Like providers, keeping up with the expansion of precision medicine and which biomarkers are actionable occupies significant time. Unlike providers, payers maintain skepticism about the utility of large panel genome testing as many of the assessed biomarkers are not yet actionable with specific targeted therapies to address that particular biomarker. Therefore, payers struggle to justify coverage across the board for larger panel testing.7 This represents a bit of the dichotomy within payers. Payers use biomarkers as criterion of many drug policy coverage requirements and yet may not cover the most efficient test or panel as part of their testing policies. Cost and utility are the main drivers of testing policy coverage requirements. Newer technologies such as liquid biopsy may be able to shift the testing paradigm. This option is less invasive, timelier, and less costly than other existing options.

The American Cancer Society Cancer Action Network and LUNGevity Foundation have developed policy recommendations for payers and providers. The recommendations call for payers to provide coverage for FDA-cleared or approved companion and complimentary diagnostics as well as all National Comprehensive Cancer Network (NCCN) guideline indicated biomarker tests. Providers and institutions are called upon to be equipped with the necessary tools, resources, sufficient and efficient collection, storage, and handling of testing tissue and the proper test selection.8 Manufacturers can support payers by seeking FDA approval for companion and complimentary diagnostics and including the testing portion in the overall value proposition for the targeted therapy.  Manufacturers can support providers and patients through awareness and education on the available testing methods, any FDA cleared or approved tests, any partnerships with labs that can support patient testing, as well the availability of affordability resources for patients. Biomarker testing is going to continue to be key in our pursuit of precision medicine and needs to be simplified for stakeholders across the board.

References:

  1. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463-466. doi:10.1097/COH.0b013e32833ed177
  2. Gromova M, Vaggelas A, Dallmann G, Seimetz D. Biomarkers: opportunities and challenges for drug development in the current regulatory landscape. Biomark Insights. 2020;15:1177271920974652. doi:10.1177/1177271920974652
  3. García-Gutiérrez MS, Navarrete F, Sala F, Gasparyan A, Austrich-Olivares A, Manzanares J. Biomarkers in psychiatry: concept, definition, types and relevance to the clinical reality. Frontiers in Psychiatry. May 15, 2020. Accessed August 2, 2021. https://www.frontiersin.org/articles/10.3389/fpsyt.2020.00432/full
  4. Chen X-H, Huang S, Kerr D. Biomarkers in clinical medicine. In: Integration of Biomarkers Into Epidemiology Study Designs. Accessed August 2, 2021. https://publications.iarc.fr/uploads/media/publication_inline/0001/02/33f111bfadb61211e9775dbf48c843c92f4220f9.pdf
  5. Biomarker testing. Oncology Nursing Society. Accessed August 2, 2021. https://www.ons.org/genomics-taxonomy/biomarker-testing
  6. Improving access to biomarker testing: advancing precision medicine in cancer care. American Cancer Society Action Network. September 2020. Accessed August 2, 2021. https://www.fightcancer.org/sites/default/files/Improving%20Access%20to%20Biomarker%20Testing_FINAL.pdf
  7. Payer coverage policies of tumor biomarker testing. American Cancer Society Action Network. September 2020. Accessed August 2, 2021. https://www.fightcancer.org/sites/default/files/ACS%20CAN%20and%20LUNGevity_Payer%20Coverage%20Policies%20of%20Tumor%20Biomarker%20Testing.pdf
  8. Blank C. Group urges increased precision medicine coverage in cancer care. Drug Topics. October 5, 2020. Accessed August 5, 2021. https://www.drugtopics.com/view/group-urges-increased-precision-medicine-coverage-in-cancer-care