FDA Approval and Recommendations in the VA/DoD Clinical Practice Guidelines: How Can They Differ?

pills in orange prescription bottles
U.S. Air Force photo by Senior Airman Hailey R. Staker
By Don Workman, Ph.D.
July 9, 2018

You’re likely familiar with PHCoE’s Psych Health Evidence Briefs, which summarize available scientific evidence and clinical guidance on treatments for psychological health conditions commonly experienced by service members. Interestingly, a brief posted recently on using vagus nerve stimulation (VNS) for major depressive disorder (MDD) noted the intervention has Food and Drug Administration (FDA) approval for treatment-resistant depression in adults, yet the VA/DoD Clinical Practice Guideline (CPG) for the Management of Major Depressive Disorder includes a “strong against” strength of recommendation for using VNS in patients with MDD. The CPG recommended against clinical use of VNS because of a lack of published evidence of efficacy for this disorder, safety concerns, and associated costs.

Another brief on the use of topiramate for alcohol use disorder (AUD) pointed out that FDA has not approved topiramate for use in the treatment of AUD, but the VA/DoD CPG for the Management of Substance Abuse Disorders gives a “strong for” strength of recommendation for use in treating patients with AUD. The drug was approved by FDA for another indication, but it has been subsequently found to be useful for the treatment of AUD. For financial reasons, the sponsor (the company making a drug or device) will likely never apply to FDA for relabeling of the drug to include an indication for this new use. In each of these cases, the FDA approval status and the CPG recommendation appear to be at odds with one another. How can that be?

In order to understand how this can be a reasonable difference in the actions of two different government agencies, we need to review the meaning and procedures behind FDA approval and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group recommendations being made by the VA/DoD CPG review committees.

FDA approves drugs and devices when they are determined to be safe and effective for treating a medical disease or condition. If a drug company wants to sell a drug or device in the U.S., they must have FDA approval for the marketing of the item including approval of information related to the effectiveness and safety of the drug or device (the handout with very small print that is included with medications and devices) and the advertising claims that are made about a product. The sponsor submits information, including data from clinical trials, to FDA in order to try and win approval to market the product or to move onto the next step in research development. FDA keeps that research information confidential, and it is often never published by the sponsor or its researchers. 

Of note, clinicians are permitted to use clinical judgment and often engage in “off-label” use of drugs or devices for indications that FDA did not consider when originally approving a drug or device. As long as there is a reasonable medical or scientific justification for this off-label use, it is an acceptable medical practice. Sponsors may provide funding to support research that gets published and supports these additional uses even when they do not wish to take on the expensive proposition of having FDA consider the new indication for this product (because of the time and expense involved).

The VA/DoD clinical practice guidelines are developed as tools to assist clinicians with recommendations about various evidence-based interventions. They begin with an extensive review of the relevant clinical research published in peer reviewed journals, and then apply GRADE categories to indicate the strength and direction of their recommendation regarding the use of the intervention with VA and DoD patient populations. Of note, the subject matter experts who conduct the CPG reviews do not have access to FDA’s information, but only to published research results. And their recommendations take into account factors other than the safety and effectiveness of the products. They are also concerned about how one product compares to others when being considered for treatment for a disease or condition, about the unique needs of their patient populations, and sometimes about the costs associated with an intervention.

With this background information, you can see it’s quite reasonable for the FDA approval status of a product and the VA/DoD CPG recommendations to differ, and sometimes differ dramatically. Clinicians can rely on the CPGs for guidance on when a product should or should not be used off label for service members, as the guideline writers consider both the scientific evidence to support the recommendation and the context of the Military Health System. Clinicians can also rely on their own review of the scientific literature and their knowledge of medicine when considering off-label uses, but in general they should not use treatments that are not supported by the CPGs.

Workman is a contracted licensed clinical psychologist on the research team at the Psychological Health Center of Excellence. He has a doctorate in clinical psychology and a master’s degree in theology.

The views expressed in Clinician's Corner blogs are solely those of the author and do not necessarily reflect the opinion of the Psychological Health Center of Excellence or Department of Defense.

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