An In-Depth Discussion About FDA Oversight of Diagnostic Tests and the Effect of Inaccurate Tests on Patients


Newly diagnosed patients may decide to either receive medical treatment or forego treatment based on the results of their diagnostic test.  As recently reported in PEW, although it is critical that test results are accurate, there are risks of inaccuracies in every diagnostic test.

For instance, if a patient receives false-positive results, he or she will undergo potentially harmful treatment while their underlying condition is ignored.

On the other hand, if a patient receives false-negative results, and understandably foregoes therapy, the disease will progress untreated.

In Vitro Diagnostics (IVDs)

IVDs are one of the many diagnostic tools used by health care providers. They are the most widely used tests when making treatment decisions. IVDs involve removing and analyzing samples from the human body. These clinical tests are labeled “medical devices”.

Here’s where the system gets compartmentalized. According to the FDA, the manufacturer of medical devices is mandated to confirm the accuracy and usefulness of its tests when it diagnoses a condition before bringing the drug to market.

But the FDA has given an exemption for this requirement to IVDs that have been developed and used in-house by the same laboratory. The term “in-house” encompasses hospitals, doctors’ offices, academic medical centers or large testing facilities. These tests have been labeled “laboratory-developed tests” (LTDs).

About LDTs

Some test developers argue that the LDTs should be under the medical practice umbrella and not labeled as medical devices.

But the FDA insists that LDTs are medical devices and are under its jurisdiction by way of the Medical Device Amendment of 1976. At the time of that bill’s passage, LDTs were primarily used to diagnose rare diseases. The LDT tests were conducted manually rather than analyzed by software programs.

This put LDTs in a low-risk category that exempted them from the more rigid requirements applicable to IVDs. But with advanced technology, such as the advent of genetic sequencing, LDTs have become more complex. They are now being developed to test a much larger number of conditions and are being marketed nationwide.

A Word of Caution

Although some LDTs may perform equally or better than an FDA approved test, it must be noted that in some cases it is possible that LDTs may be produced using components that are not legally marketed for clinical use.

A Huge Discrepancy

Reporting by LDTs is voluntary and there is no central registry. The FDA estimates the existence of approximately 650 LDTs.  On the other hand, the American Clinical Laboratory Association claims that there are about 11,633 laboratories that are permitted to develop LDTs. It suggests that the majority of these LDTs are developing and performing tests.

Precision Medicine

LDTs, just like IVDs, are vitally important in the treatment and diagnosis of many diseases. They are key factors in precision medicine, formally known as personalized medicine.

Precision medicine is still in its early stages. It involves the identification of molecule patterns (molecular profiling) and genetic profiling which is the identification of the characteristics of a person’s DNA.

Yet even with the advances in precision medicine, the FDA exercises a relatively minor amount of oversight of LDTs relative to IVDs.

About Commercial IVDs

IVDs are used by clinicians for diagnosis purposes, for detecting genetic mutations or measuring an immune reaction to infection.

They are also valuable in determining effective therapies and to predict the chances of a patient’s developing a specific disease in the future.

In order to ensure safety and effectiveness, the FDA regulates all commercial IVDs. In accordance with the aforementioned Medical Device Amendment of 1976, that includes products used to diagnose disease and other conditions.

There are three classes of risk-based FDA regulations. Class III poses the highest risk if the tests are not accurate. An example would be genetic testing to determine cancer treatments.

Primary Premarket Reviews

Of the two premarket reviews by the FDA, again the Class III tests relate to the highest risk. This would also include tests that are unique to the market.

The second premarket notification relates to the Food, Drug and Cosmetic Act which is less restrictive. The product must be “substantially equivalent” when compared to other products on the market.

Approval or clearance, in either case, requires that IVDs prove safety and effectiveness through clinical and analytical validation. Both represent FDA standards to determine the accuracy of a test.

Clinical validation is a process which determines whether a test accurately identifies a patient’s clinical condition.

Analytical validation is precise, accurate and reliable. It measures a test’s performance in detecting a hormone, genetic marker or chemical in a sample.

Centers for Medicare & Medicaid Services (CMS)

In accordance with a 1988 amendment, all laboratories that perform tests on human specimens are subject to its regulations. Oversight is conducted through a certification process by the CMS.

The CMS conducts analytical validations every two years on LDTs or other labs that have not received FDA clearance. The analytical validity standards under this process fall short of the standards set by the FDA review.

It May Take a Village

The FDA and congressional members of both parties, along with diagnostic manufacturers and patient organizations, have called for federal oversight reform in connection with LDTs. Technological advances create opportunities for these tests to affect thousands of people.

The Challenge

Regulating LDTs is challenging when attempting to develop and apply regulatory frameworks that both protect a patient’s safety yet still bring innovative tests to market in a reasonable time frame.

The need for reform is evident. Physicians and their patients depend on tests for treatment decisions. Oversight has largely remained unchanged while diagnostic testing has moved forward.

Although IVDs and LDTs often have similar roles within clinical practice, oversight levels are substantially different. This is detrimental to patients who could base their treatment decisions on inaccurate tests.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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