Risk and benefit are nothing if not relative concepts. A product can have a laundry list of dangerous side effects, but so long as it treats an even more dangerous indication, it can still be approved by regulators. Conversely, a product may present no side effects whatsoever, but if it lacks efficacy, it might still be rejected by regulators.
The very heart of the regulatory process is determining which products ought to be approved, and which ones don't quite pass muster.
And if you're looking for a case study in tough calls—a product which, but for its indication, might never have been approved—an approval late last week by the US Food and Drug Administration (FDA) might be as good as you'll see this year.
NephroCheck: Questionable Effectiveness
FDA's 5 September 2014 approval of Astute Medical's NephroCheck is not an example of the most effective product to be approved by the agency this year. The laboratory testing product is intended to assess critically ill patients for moderate to severe acute kidney injury (AKI), a condition which can rapidly cause permanent damage to a patient's kidneys.
FDA's approval notice focuses in part on the device's efficacy. The device, FDA said, was between 76% and 92% accurate at detecting patients with AKI in its studies of more than 500 patients—not great, but not out of the ordinary either. For example, FDA approved a type 1 diabetes test in August 2014 that has a 65% rate of accuracy.
But another statistic mentioned in FDA's press release is out of the ordinary: the rate at which the device returned false positive results. "NephroCheck incorrectly gave a positive result in about half of patients without AKI," FDA explained in its approval announcement.
A coin flip's worth of accuracy isn't usually worth much for the purposes of obtaining an FDA approval. The aforementioned Type 1 diabetes test, for example, has just a 2% rate of false positive results.
So with such an astonishingly high rate of false positive readings, why did FDA ever allow this device to come to market through its de novo pathway? Simple: a lack of other adequate options.
As FDA explains in its notice, "Current laboratory tests can only assess whether a patient may already have AKI; often, the patient has progressed to moderate to severe AKI before the test results confirm the clinical diagnosis."
NephroCheck differs from existing standards by detecting a patient's risk of developing AKI within the next 12 hours, hopefully prior to the onset of symptoms. That would be especially helpful to those patients most at risk for AKI, which FDA notes are typically those who are already "critically ill." Patients who develop AKI have "worse outcomes" than those suffering from a heart attack, Astute Medical, the device's sponsor, said in a statement.
“Early assessment and timely treatment for AKI can help prevent kidney damage and potential associated complications,” said Alberto Gutierrez, director of FDA's Office of In Vitro Diagnostics and Radiological Health, in a statement. “The NephroCheck provides health care providers with a quick, validated method of assessing a patient’s AKI risk status which may inform patient management decisions.”
In other words, it might not be the ideal treatment tool, but it's still a sizeable advancement over the current standard of care.
Appropriate Risk Hedges
Another reason for approval: FDA's apparent belief that the risks associated with improper diagnosis were low or moderate, as evidenced by the device's approval through the de novo pathway. Because the device has no already-approved predicate, it would ordinarily have been required to go through the premarket approval (PMA) pathway, which is meant for high-risk devices. The de novo pathway, by contrast, is used for new devices which are not thought to represent a high risk to patients.
Astute Medical said the tool will hopefully allow care providers to allow them to transition to a preventative model of treatment as opposed to a "wait and see" approach. The test, the company said, is "the first real improvement in renal testing in over 60 years."
Also limiting potential risk is the intended patient population. "The test is limited for use in patients who have or have had within the past 24 hours acute cardiovascular and or respiratory compromise and are ICU patients as an aid in the risk assessment for moderate or severe acute kidney injury (AKI) within 12 hours of patient assessment," Astute Medical wrote in a statement.