Protecting Patient Safety in the Era of Precision Medicine and Advanced Diagnostics

  • OCRA believes that all diagnostic tests – regardless of whether they are developed by a laboratory in-house or by a manufacturer offsite – should be independently verified to ensure safety and clinical validity, and support regulatory reform to that end.
  • OCRA believes that patient voices should be heard at the regulatory level and encourages patient advocate representation on panels that consider the safety of new and advancing drug therapies.
  • OCRA believes that genomic tumor profiling and other applications in precision medicine have ushered in a new era of oncology care and will accelerate progress toward ensuring long-term survival for every woman diagnosed with ovarian cancer.
  • OCRA believes that in accordance with National Cancer Center Network (NCCN) guidelines, all women diagnosed with ovarian cancer should receive genetic testing and supports for policies that lift barriers to these services.
  • OCRA believes that requirements for insurance coverage of genetic counseling and testing are incomplete unless they also include provisions for the necessary and appropriate risk-reducing interventions in the event of positive results.
  • OCRA supports the Genetic Information Nondiscrimination Act (GINA) and similar policy proposals that provide protections against discrimination on the basis of genetic information.

Medical treatments have historically been designed as “one-size fits all” for the “average patient” – which is effective for some but not all. “Precision medicine” shifts away from this paradigm and uses a tailored approach to disease prevention and treatment that takes into account an individual variability in genes, environment, and lifestyle for each person. Advancements in diagnostic testing technologies have been key to the evolution of precision medicine in oncology; enabling earlier detection through screening for high-risk genetic mutations and creating a path forward for individualized treatments that are tailored to a tumor’s specific genetic alterations. These new, targeted therapies are less toxic and associated with improved patient outcomes. Roughly 21 percent of ovarian cancer patients have tumors that are driven by certain genetic mutations that could be targets for specific drugs.

Diagnostic tests are critical tools in clinical decision-making, providing a wealth of information that is used by doctors and patients to make critical decisions at every stage of care.

Currently, a diagnostic test produced by a manufacturer and sold to a laboratory must first obtain pre-market clearance or approval from the FDA to support the safety and effectiveness of the test. These tests are also subject to comprehensive quality system requirements from design through distribution, as well as post-market oversight that includes mandatory adverse event reporting and FDA’s recall authority. Labs that develop, manufacture, and use their own similar tests (laboratory developed tests or LDTs) are not, however, are under the regulatory authority of CMS, not FDA, and as such, are not subject to the same rigorous standards to certify reliability, safety, and effectiveness as FDA-cleared diagnostic tests developed offsite by a manufacturer.

LDTs have proliferated the health care ecosystem in the last two decades, and are widely used interchangeably with FDA-approved or cleared diagnostics. Often patients or even doctors are unaware of the regulatory status of the test being used to make critical treatment decisions.

Evidence showing the harmful repercussions of unregulated LDTs has amassed, and several disease areas have been adversely impacted, including the ovarian cancer community. In January 2017, FDA issued Discussion Paper on Laboratory Developed Tests that outlines an effective case for the need for regulation.

  • In 2008, OvaSure was introduced, marketed as an early detection test for ovarian cancer. The test was not independently verified to insure clinical validity. It was soon discovered that the test did not accurately predict ovarian cancer cases, leading otherwise healthy women to have their ovaries removed based on bad information.
  • More recently Abcodia released the ROCA Test and marketed it directly to consumers as an effective “early detection” test for ovarian cancer. Prior to wide release, OCRA convened a group of experts over the course of two scientific meetings which produced a white paper published in American Family Physician which concluded that the findings of the related studies did not demonstrate the necessary results needed to warrant screening the general public. Despite the challenge, Abcodia moved forward and expanded access to the test throughout the country. The company finally pulled the test only after FDA issued a safety alert to consumers.

Due to the incredible importance of diagnostic accuracy and patient safety, it is essential that LDTs are properly regulated. OCRA is working closely with Members of Congress and FDA to promote a regulatory mechanism to ensure that LDTs are independently tested to verify their clinical validity and safety.

Genetic Testing as Tool for Cancer Prevention and Risk Reduction

In addition, genetic testing and other applications in precision medicine have created new opportunities in cancer prevention and risk management through screening and early identification of inherited cancer-causing genetic mutations. Asymptomatic women carrying these genes may opt for risk-reducing interventions like prophylactic surgery and increased surveillance.

  • The most common inherited genetic mutation that can cause ovarian cancer is an inherited mutation in one of two genes called breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2). Mutations in these genes increase a woman’s risk of breast, ovarian and other cancers. In the general population, BRCA mutations are rare, but may account for up to 15-20% of all cases of ovarian cancer. It is estimated that about 44% of women who inherit a harmful BRCA1 mutation and about 17% of women who inherit a harmful BRCA2 mutation will develop ovarian cancer by the age of 80. Women of Ashkenazi Jewish descent are at higher risk of carrying BRCA1 or BRCA2 mutations than the general public; however, people of other ancestries also carry these mutations. People who have no known family history of ovarian cancer can also acquire these mutations, though those with a family history of the disease are at highest risk.
  • Another known hereditary genetic link to ovarian cancer is called Lynch Syndrome. Lynch Syndrome increases a woman’s risk for colorectal, endometrial, ovarian and other cancers. Lynch Syndrome is found in about 1 in 33 women with ovarian cancer.

Coverage and access

There is broad variation in how payers reimburse and cover genetic screening and testing services. In many cases, health insurance plans will cover genetic testing and services when recommended by a physician, but that isn’t always the case and often coverage is incomplete.

Under the Affordable Care Act’s preventive health benefit, all health insurance plans must cover BRCA testing and genetic counseling for women with a family history of breast and ovarian cancer at no out-of-pocket cost to the patient. The provision is narrow in scope and does not cover several high-risk segments of the population, nor make any specifications about coverage for risk-management services in the event of a positive genetic test. In addition, the requirement only applies to BRCA 1 and BRCA 2 mutations and does not extend to other known cancer-causing mutations.

Protections Against Genetic Discrimination

The Genetic Information Nondiscrimination Act (GINA), passed in 2008, prohibits genetic discrimination in employment and health insurance. GINA prohibits employers from using genetic information in hiring, firing and promotion decisions. Employers also are barred from requesting their employees submit to genetic testing. GINA bans health insurers from rejecting coverage or raising premiums for healthy individuals based on their genetic information. Notably, GINA’s protections do not extend to life, disability and long-term care insurance.

Several states have passed laws that bolster GINA’s protections in life, disability and long-term care insurance. You can find information on whether your state offers additional protections.

  • There are other federal laws that offer additional legal and privacy protections to patients:
  • The Privacy Act of 1974 allows for some privacy protection for medical records.
  • The Americans with Disabilities Act (ADA) addresses similar issues regulating medical information about disabilities by protecting both privacy and discrimination (employment, public services and public accommodations; genetic illnesses are not specifically referenced, however).
  • The Health Insurance Portability and Accountability Act, passed in 1996, upholds some restrictions on the use of genetic information in setting premiums and determining eligibility for benefits in health insurance.
  • The Patient Protection and Affordable Care Act, passed in 2010, states that health insurance providers cannot deny coverage or set rates based upon any pre-existing medical condition.