Innovation for Healthier Americans: Materials from our Senate briefing

Below are the materials from the Senate briefing we hosted with the Patient, Consumer, and Public Health Coalition titled “Innovation for Healthier Americans: The Impact of Proposed Health Bills on Patients & Consumers”.

Lab-Developed Tests (LDTs): A Critical Role for the FDA

Examples that illustrate the need for FDA regulation of LDTs

FDA and Medical Software   


Lab-Developed Tests (LDTs): A Critical Role for the FDA

Laboratory developed tests (LDTs) serve an increasingly important role in health care today. Compared to just a few decades ago, the tests are more complex, and inaccurate results are much more likely to endanger patients. When the FDA was given the responsibility to regulate medical devices in 1976, LDTs were basic laboratory tests, such as a blood sugar test. For that reason, the FDA chose not to regulate most LDTs. But today’s diagnostic tests are more complicated and, for example, may be used to obtain a genetic analysis of a cancer cell to guide treatment decisions. FDA regulation of LDTs will ensure patients and physicians are relying on tests that are safe and effective.

CLIA Cannot Substitute for FDA Assurance of Safety and Effectiveness

The CMS CLIA program does not determine if a test is accurate (which is called clinical validity). It instead ensures quality control mechanisms are in place. In contrast, the FDA review process evaluates the clinical validity of a test before it is approved (premarket) and after it is on the market (post-market surveillance). Clinical validity is essential to understanding the risks and benefits of any test. For example, an ovarian cancer test with a high rate of false positives will result in women receiving unnecessary hysterectomies, whereas a high rate of false negatives will result in cancer going undetected.

Transparency Will Increase Physician and Patient Confidence in LDTs and Encourage Innovation

Faulty tests erode the confidence of physicians and patients, and put patients’ lives at risk. The American Society of Clinical Oncologists (ASCO) has expressed agreement with the FDA’s proposals to improve regulation of LDTs, stating that “a patient’s treatment options are increasingly driven by detection of molecular abnormalities in the tumor that drive treatment selection. ASCO believes that the tests used to detect those abnormalities must be of the highest quality and thoroughly validated before being offered to doctors and patients.” Requiring FDA review prior to allowing a test to be sold and giving FDA the authority to gather and publicly share information about adverse events will give patients and providers the information they need to make informed treatment decisions. Non-LDT in vitro diagnostics (IVDs) are already under FDA regulation. Using the same regulatory processes will ensure higher quality tests for patients. That will stimulate, not hamper, the kind of innovation that saves lives and improves the quality of patients’ lives.

FDA’s Plan Follows a Risk-Based, Phased-In Approach to Ensure Efficiency and Responsiveness

The FDA draft guidance on LDTs lays out a risk-based, phased-in approach that will proceed over several years. This approach allows ample time for laboratories to come into compliance and will also ensure that the highest-risk devices are regulated as quickly as possible. The guidance document also proposes a series of carve-outs, permitting manufacturers of LDTs for unmet needs or rare diseases to escape the most stringent pre-market review requirements. This type of regulatory framework will protect the public health while being flexible enough to encourage the development of new tests for serious conditions.


In response to the FDA’s proposed regulatory framework, NIH Director Dr. Francis Collins stated that “this is good news for all who are working to turn the dream of personalized medicine into a reality.”1 We agree. The FDA’s draft guidance displays the agency’s willingness to balance its goals regarding safety and efficacy with its concerns about innovation and patient access — and all parties should work together to move our regulatory framework for LDTs into the 21st century.


Examples that illustrate the need for FDA regulation of LDTs

OvaSure Ovarian Cancer Test

The OvaSure ovarian cancer test shows the importance of FDA oversight of LDTs in protecting patients’ lives.

  • In June 2008, the test was marketed to screen for early-stage ovarian cancer in high-risk women based on peer-reviewed published data showing it could detect ovarian cancer with a positive predictive value (PPV) of 99.3%.
  • It was later discovered that poor study design led to a falsely high predictive value. The actual PPV was only 6.5%, meaning that only 1 in 15 patients who tested positive actually had ovarian cancer.
  • OvaSure was pulled from the market by October 2008 after a warning letter from the FDA but not before many women underwent unnecessary hysterectomies because of a faulty test.

Oncotype DX HER2 Breast Cancer RT-PCR Test

FDA regulation will help ensure the validity of LDTs that detect genetic tumor markers and guide drug therapy decisions. These LDTs are critical to the success of the Precision Medicine Initiative. Patients and their providers must be able to trust them.

  • The Oncotype DX HER2 breast cancer RT-PCR test was intended to diagnose early stage HER2 receptor positive breast cancers so that the appropriate HER2 targeted drug could be used.
  • In 2011, a group of prominent pathologists from three independent laboratories found discrepancies between this HER2 RT-PCR and other tests that are FDA-approved. They discovered that the test has poor sensitivity, resulting in many false negatives and women not receiving life-saving treatment. Patients died as a result.


FDA and Medical Software

Jay G. Ronquillo, MD, MPH, MMSc, MEng

In a study of FDA reported recalls, completed in 2016, we found:

  • Over the last 5 years, more than 600 different software devices totaling over 1.4 million units were recalled for moderate or high risk patient safety issues.
  • Nearly 200,000 units were recalled for having the most serious (life-threatening) risk to patients. Although recalls are officially considered voluntary, few would take place without FDA regulatory authority.

If MEDTECH becomes law, the FDA would not be gathering adverse event reports and encouraging recalls of many stand-alone IT devices with life-threatening flaws. The results of this study show that software flaws affect millions of patients and removing medical software from FDA regulatory oversight would be dangerous. The Senate can do better.

Medical software represents an increasingly important aspect of medicine. The MEDTECH Act and related bills would remove some health IT entirely from FDA’s regulatory oversight (e.g. electronic health records, clinical decision support). For other types of software, the FDA would be limited in its ability to identify safety risks. Industry says that deregulation would foster the creation of innovative new medical devices. However, the data above indicate that medical software must remain regulated by the FDA in order to protect patients from harm.

Some examples of the devices that were recalled in recent years because of their potential to seriously harm or even kill patients due to software errors include:

  • Oncology electronic medical record systems: recalled because they calculated and recorded incorrect drug dosage treatment.
  • Clinical decision support systems used during surgery: recalled because they erroneously switched patient data and failed to warn physicians about dangerous drug reactions.

Software devices are re-used repeatedly for different patients. A conservative estimate is that millions of patients being treated by hundreds of physicians would have unknowingly been at risk for poor care, serious injury, and even death if the software had not been recalled.

Conclusion: If medical software is removed from FDA regulatory oversight, millions of patients would be at risk from defective software.

  1. FDA’s Proposed Oversight of Laboratory-Developed Tests. National Institutes of Health. Accessed January 13, 2015. 

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