Tag Archives: FDA

FDA’s Wish List: Regulatory Authority for Lab-Developed Tests

By ThinkReliability Staff

Laboratory testing is incredibly important to health care – it is thought to be an influence in about 70% of health decisions. Results of testing will often be used to diagnose a patient, or select a treatment plan. Thus, inaccurate testing results can lead to inappropriate, sometimes even dangerous, treatments. However, diagnostic tests manufactured and used within a single laboratory, known as laboratory developed tests, or LDTs, are not subject to regulation by the FDA.

This has led to significant concern by the FDA, outlined in a report making the case for FDA oversight for these tests. Their concerns can be diagrammed in a Cause Map, or visual root cause analysis, allowing us to see how the specific concerns are related and impact patient safety and other regulatory goals.

The first step in any problem solving method is to determine the problem that is to be solved. Using the Cause Mapping method, the “problem” is defined as an impact to an organization’s goals. In this case, patient safety is impacted because of the possibility for insufficient treatment of life-threatening disease and the potential for patients to undergo unnecessary dangerous procedures. Additionally, patient services are impacted because of the threat to the scientific integrity of clinical trials using these tests.

The second step in the Cause Mapping method is the analysis. Beginning with one of the impacted goals and asking ‘why’ questions develops the cause-and-effect relationships involved in the issue. In this case, we begin with the patient safety goal that is impacted due to insufficient treatment for life-threatening disease. This is due to either a failure to detect the disease and/or to patients choosing to undergo unproven therapies. We address each cause in turn.

The failure to detect a disease is caused by inaccurate test results and/or insufficient interpretation of test results. Inaccurate test results can be caused by tests not being clinically valid (one of the FDA’s prime concerns) because the test is not regulated by the FDA. The test is not required to be regulated by the FDA, which is the addressed in the FDA’s report. The argument against requiring FDA regulation for tests is that the laboratories that create and use the tests are regulated under the Clinical Laboratory Improvement Amendments (CLIA). However, according to the FDA, CLIA is intended to regulate the operators of laboratories, not diagnostic devices. The report provides multiple case studies of problematic LDTs, which were offered from laboratories “following the minimum requirements of CLIA.”

Inaccurate test results are also caused by not identifying adverse events, which are not systematically reported for these tests (another of the FDA’s prime concerns). An additional prime concern of the FDA is that performance data is not required to be reviewed prior to marketing these devices. Not only is FDA approval not required, but there is an incentive for companies not to seek FDA approval of LDTs, leading to an uneven playing field (another of the FDA’s prime concerns) for companies who do seek FDA approval of laboratory tests. Insufficient interpretation of test results occurs because testing labels do not provide adequate information on interpretation (another of the FDA’s prime concerns).   Again, these causes are due to not requiring regulation by the FDA.

The FDA is concerned that results from unapproved testing may result in patients choosing to undergo unproven therapies. Misleading manufacturer’s claims and/or lack of transparency can mean patients are unaware that the tests have not been cleared or approved by the FDA. These causes are both listed as prime concerns of the FDA. Patients are unable to assess tests available because there is no comprehensive listing of tests currently being used (the last prime concern of the FDA).

Because of these reasons (causes), the FDA is requesting oversight of LDTs. The oversight provided by the FDA would ideally provide solutions to these issues by addressing each of the concerns (causes) listed in the report. To learn more, click here to read the report. Or, click on “Download PDF” above to view the cause-and-effect relationships including the FDA’s concerns about LDTs.

Price of Daraprim jumped ~5,000%

By Kim Smiley

The cost of prescription drugs have been in the news the last several years as the United States struggles to deal with rising health care costs, but few stories have come close to generating as much outrage as the recent massive price increase of Daraprim.  As new specialty drugs hit the market, they are often expensive as drug companies recoup the costs of development and maximize profits while the drug is covered by patents, which may be frustrating but is understandable.  That is not what happened in the case of Daraprim, a lifesaving drug used as an antimalarial drug and to treat toxoplasmosis.  The medication has been around since the 1950s and isn’t covered by any patents.

So why has the price of Daraprim suddenly increased about 5,000 percent?  A Cause Map, or visual root cause analysis, can be used to intuitively show the causes that contributed to the issue.  (To view an outline and a High Level Cause Map, click on “Download PDF” above.) This is one of those issues where it may be tempting to identify the “root cause” or focus on a single cause that contributed to the issue, but there are many factors that need to be considered.  The piece of the puzzle that is probably the easiest to focus on is the fact that a new company bought the only company with regulatory approval to sell the drug in the United States and significantly raised the price.  Basically, there is demand for the drug and the company which has a monopoly on the supply in the US took advantage of it by increasing the price per pill from $13.50 to about $750.

The CEO of the company has been widely villainized for what many consider a predatory price increase, but it is important to remember that the Daraprim price increase was legal.  Many find the price increase distasteful, but there are currently no laws or regulations that prevent huge medication price increases, which is another cause that contributed to the issue.

While a generic version of the drug is available in many other countries for less than a dollar a pill, it cannot be sold in the US without going through a lengthy and expensive approval process. Possible solutions to prevent similar price increases in the future could be to create laws that limit price increases on drugs without patents on them or to increase the supply of medications sold in the US by allowing some sort of reciprocal approvals with countries that have strong regulatory systems in place.  A senate committee is requesting documents and information relating to the pricing of Daraprim and several other medications and there are lawmakers pushing to create legislation that would limit price hikes.

Another enterprising company seems to have found their own solution to the problem of the high cost of Daraprim – creating a cheaper alternative. Imprimis Pharmaceuticals has stated that they will produce a substitute drug that will be priced as low as $99 for a 100 pills.  The alternative drug isn’t a generic version of Daraprim, but rather a compounded drug that combines two FDA approved drugs (pyrimethamine, the only ingredient in Daraprim, and leucovorin) that are often used together.  The compounded drug would not be FDA approved, but doctors can prescribe it specifically for a patient based on the rules governing compounded medications.

It isn’t as elegant as having another FDA-approved supplier of Daraprim, but it seems like a viable work-around for many patients.  It also seems like satisfactory justice for the price of 60-year-old pyrimethamine drugs to end up cheaper in the US after they were hiked up to such high levels.