AACC strongly supports efforts within the healthcare community to personalize patient care and improve individual patient outcomes. Laboratory medicine plays a vital role in enabling the practice of precision medicine, including the identification of therapies or interventions that are best suited for each individual patient. We urge policymakers and payers to adopt policies that ensure access to and appropriate reimbursement for laboratory testing that will facilitate personalized therapeutic decisions.
The scientific and healthcare communities have made significant progress in understanding the physiological, genetic and biochemical composition of the healthy human body, including detailing the human genome. These efforts have improved our ability to precisely define the characteristics of each patient’s health and disease and have been instrumental in translating the concept of personalized, precision medicine into a reality. Healthcare professionals, with the use of laboratory tests, are now able to identify and monitor an increasing number of precisely targeted, individualized therapeutic interventions that may result in the best health outcome -- helping to ensure the right therapy for the patient. For an increasing number of patients, personalized medicine has become an integral component of quality healthcare.
Failed Treatments and Adverse Reactions
Many patients diagnosed with serious medical conditions do not receive effective treatment in a timely manner. This scenario is a byproduct of the traditional empirical or “trial and error” healthcare system, wherein clinicians must rely on probabilistic predictions resulting from clinical trial outcomes to determine a treatment plan for individual patients. In this system, physicians prescribe treatments and then wait to see if the individual patient will be among the patients who respond favorably to the prescribed treatment. Studies have shown that 43 percent of the population does not respond to commonly prescribed drugs for diabetes, 40 percent to drugs for cardiac arrhythmias, and 75 percent to therapeutics for cancer (1). In addition, studies indicate that 5.3 percent of all hospital admissions are associated with adverse drug reactions (2). Mortality from adverse drug reactions is a serious concern (3). Fortunately, the healthcare community has begun to move away from a one-size-fits-all approach to patient care by incorporating medicine that tailors therapeutic interventions to biomarker and genetic test results that identify the optimum care decisions for individual patients.
Advances in Care
Although healthcare professionals have always strived to customize treatment plans to meet patient needs, technological and scientific advances in laboratory medicine, including rapid advances in genomics, have provided tools for personalizing medical treatments (4). Clinicians are now able to diagnose and treat medical conditions earlier, even identifying the presence of risk for a disease before clinical symptoms or signs appear (1). In parallel with laboratory efforts, Congress and the Food and Drug Administration (FDA) have taken significant steps to facilitate the use and development of personalized or precision medicine. FDA has added pharmacogenomics information to the product labels of more than 385 drugs, enabling clinicians to target drug therapy to the patients who will best respond to it (5). FDA has also developed a regulatory pathway for companion diagnostics that can assist healthcare providers with prescribing individual therapeutic interventions based on the alignment of the drug with the individual’s laboratory test results that predict successful treatment outcomes (2). Congress passed the 21st Century Cures Act, in part to provide the FDA with additional tools, funding, and data to help foster innovation and advance this field (6).
Value of Laboratory Medicine
Laboratory testing is central to all facets of personalized medicine. From the most basic traditional biomarkers to those newly discovered, test results are used to maintain health, diagnose illness, predict and monitor drug response, stratify individuals for comparative effectiveness research and provide the informatics data needed for complex predictive algorithms to perform these health-related functions (7). Clinical laboratories support the delivery of companion diagnostics that guide clinicians in making decisions about drug and dose selection for an individual. Laboratory practitioners have a wealth of knowledge and expertise pertaining to the myriad of tests used to personalize medical diagnosis and treatment; this knowledge is critical to assisting clinicians with accurately interpreting the intricate panels of tests used in precision medicine.
Test Development and Application
The FDA has been engaged in promoting personalized medicine for many years, conducting stakeholder meetings, publishing reports, providing guidance, and issuing rules to advance the field. The agency has taken an active role in facilitating the availability of companion diagnostics, in which diagnostic tests and therapeutics are developed and reviewed simultaneously. FDA has approved or cleared dozens of companion diagnostic products through the premarket approval or 510(k) process and the number is expected to grow significantly over the coming years (8). FDA not only regulates the initial availability of these commercial products, but also provides oversight in the post-market environment by way of facilities inspections and medical device reporting regulations.
Laboratory testing processes are regulated by the Centers for Medicare and Medicaid Services (CMS) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). CLIA oversight applies when a laboratory uses an FDA approved/cleared commercial products; it also applies when a clinical laboratory develops innovative tests to meet medical needs in the absence of appropriate FDA approved/cleared commercial products. These laboratory-developed tests, or LDTs, are an integral component in precision/personalized medicine, as they allow the clinical team to tailor innovation to immediate clinical needs. Regulations should promote continued innovation while ensuring patient safety (9).
CMS determines whether adequate evidence exists for paying for a clinical laboratory test under the Medicare program and sets the amount to be paid for the service. Personalized medicine tests are developed to determine the efficacy of drugs or treatments within narrowly defined subpopulations with low disease prevalence; therefore, evidence for the effectiveness of these tests might not be extensive. CMS has sought to address this issue through its Coverage with Evidence Development program; although the level of evidence required under this initiative may still be unachievable in practical terms. Only when CMS and other insurers adapt their evidentiary requirements for coverage of these types of very low-volume tests will the full potential of personalized/precision medicine be realized (10).
Medicare and other insurers are adopting payment reforms that encourage health care providers to coordinate patient care across settings. Rather than reimbursing for individual services, many insurers are paying a capitated fee to participating organizations and practices. Personalized medicine can assist these healthcare entities by providing the evidence to select the most appropriate drug therapy for their patients, thereby leading to earlier interventions and improved patient outcomes. Better patient care can also result in a reduction in healthcare costs by eliminating the purchase of ineffective drugs and avoiding any complications that may arise from their inappropriate use. While payers might encounter higher up-front costs associated with patient-specific testing, they will realize ultimate savings as a result of earlier, more effective care.
The adoption of health information technology (HIT) by healthcare providers has been vital to the advancement of personalized medicine. Patient health data captured and shared through electronic health records (EHRs) has provided researchers with valuable information for evaluating health status and the effectiveness of treatment interventions in individual patients. The use of clinical decision support systems can further promote personalized medicine by incorporating a variety of tools such as clinical guidelines and patient-specific recommendations in a timely manner.
Carefully managed and maintained EHRs also capture extremely valuable medical information characterizing potentially vast numbers of patients. When EHR data are rendered ‘anonymous’ and aggregated into health data repositories along with like data from other patients with the same clinical conditions, the result is a wealth of information comprised of real-world evidence. This evidence (subject to inspection and validation for relevance and reliability) can support research into both new diagnostics and new treatments, and also can provide clinical data to support regulatory submissions for new medical devices, new IVDs and new therapeutic agents.
AACC is encouraged by the rapid advances being made in the field of personalized/precision medicine. To ensure that the full benefits of this clinical approach can be realized, AACC supports the following positions:
- Congress should continue to promote the adoption of health information technology by healthcare providers through financial incentives that encourage the use of electronic health records.
- Lawmakers should fund efforts to create and make available interoperable health data repositories that can be used for research to advance the science of personalized medicine.
- Congress should increase funding for basic and clinical research in the field of personalized medicine tests, including efforts to translate these tests from laboratories into clinical practice.
Food and Drug Administration
- FDA should expand its efforts to include information in the product labeling for relevant drugs or other pharmaceutical products that urge healthcare providers to test for certain genetic or other biomarkers prior to prescribing the drug or other pharmaceutical product.
- FDA should not adopt policies that hinder test innovation.
CMS and Private Payers
- CMS should expand use of the Coverage with Evidence Development program for promising personalized medicine tests.
- Public and private payers should develop clear and consistent evidence criteria for coverage of companion diagnostics that would account for the relatively smaller affected patient and population subsets.
Laboratory Professionals and Other Medical Stakeholders
- The experts in clinical laboratory science and medicine should continue to work with clinicians to create accurate and reliable LDTs that identify the most effective treatments for patients when an FDA-approved companion diagnostic is not available.
- Laboratory professionals should educate clinicians about the availability, advantages and limitations of personalized medicine tests and assist with the interpretation of the test results.
- Laboratory, clinical, diagnostics, and pharmaceutical professionals should partner to author and promote guidelines and standards for the development and implementation of personalized medicine algorithms and practices.
- Food and Drug Administration. “Paving the Way for Personalized Medicine: FDA’s Role in a New Era of Medical Product Development.” October 2013 http://www.fda.gov/downloads/ScienceResearch/SpecialTopics/PersonalizedMedicine/UCM372421.pdf (Accessed April 2, 2015)
- Personalized Medicine Coalition. “The Case for Personalized Medicine.” 2014 4th Edition http://www.personalizedmedicinecoalition.org/Userfiles/PMC-Corporate/file/pmc_case_for_personalized_medicine.pdf (Accessed April 2, 2015)
- Lazaro J, et al. “Incidence of Adverse Drug Reactions in Hospitalized Patients.” JAMA. April 15, 1998; 279:1200-1204 (Accessed April 2, 2015)
- Managed Care Magazine. “The History and Future of Personalized Medicine.” August 2011http://www.managedcaremag.com/content/history-and-future-personalized-medicine (Access April 2, 2015)
- Food and Drug Administration Center for Drug Evaluation and Research. (2019, September 3). Table of Pharmacogenomic Biomarkers.
- Bresnick, J. (2016, December 14). FDA Eager for Precision Medicine Under 21st Century Cures Act
- Valdes, Jr R & Linder M. “Labs are the central providers of patient-specific information that will enable personalized medicine.” ADVANCE for Administrations of the Laboratory. July 2011 http://laboratory-manager.advanceweb.com/features/articles/clinical-laboratory-driving-personalized-medicine.aspx (Accessed April 2, 2015)
- Food and Drug Administration Center for Devices and Radiological Health. (2019, August 2). List of Cleared or Approved Companion Diagnostic Devices.
- AACC Position Statement. “Oversight of Laboratory Developed Tests.” April 2017 https://www.aacc.org/health-and-science-policy/advocacy/position-statements/2017/oversight-of-laboratory-developed-tests (Accessed January 6, 2019)
- Hresko, Andrew & Haga, Susanne B. “Insurance Coverage Policies for Personalized Medicine.” Journal of Personalized Medicine. October 30, 2012, 2, 201-216 http://www.mdpi.com/2075-4426/2/4/201 (Accessed April 9, 2015)