The core and essence of the conventional practice of medicine have been a physician’s creative use of medications, devices, and therapies that in the best knowledge of that physician has the possibility of treating a patient’s disease. In the 1950s this long-standing international tradition was renamed “the off-label” practice of medicine in the United States (only).
The term “off-label” was birthed with the creation of the Food and Drug Administration (FDA). As all medical drugs and devices to be used in the United States henceforth required FDA approval, manufacturers submitted applications for approval of their drug or device and the FDA subsequently labeled the drug or device for one or more uses (indications). This is called the FDA label. Once approved or labeled the device or drug could be used by any physician in any manner to treat any disease or patient, i.e., the practice of medicine. The practice of medicine in the United States thus was divided between on-label and off-label.
The off-label practice of medicine is ethically underpinned by the Hippocratic Oath which states that as a physician- in the classic version “…I will apply dietetic measures for the benefit of the sick according to my ability and judgment; I will keep them from harm and injustice” or in the modem version, “I will apply, for the benefit of the sick, all measures which are required.”
The ethics of Off-Label Hyperbaric Oxygen Therapy (HBOT) were strengthened and reaffirmed by the findings of the Ethics Task Force of the Undersea and Hyperbaric Medical Society in 1998. The Ethics Task Force found that the off-label use of HBOT was entirely ethical, and a scholarly rendition of this opinion by the two bioethicists was published in the journal Undersea and Hyperbaric Medicine. Hyperbaric physicians in the United States can offer their patients the benefits of HBOT for a wide variety of conditions for which their international colleagues also prescribe HBOT. Furthermore, the legality of treating off-label was established as an important part of the practice of medicine in the USA 26 years ago in United States v. Evers, 453 F. Supp. 1141, 1149 (M.D. Ala. 1978).
In conclusion, the off-label use of HBOT is the ethical application of the principles of the Hippocratic Oath buttressed by recent bioethical research and legal rulings.
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When a ventilator was first approved by the FDA, it had a list of indications with it. However, upon further reflection, it was recognized that the need to get oxygen to someone who could not breathe without assistance did not need an indication, in other words, the requirement to list all potential uses and indications was waived for this device. Discussions with the FDA on this topic lead the Environmental Tectonics Corporation to submit a 501 (k:) for delivery of hyperbaric oxygen under a physician’s prescription without indications listed (6/26/2002). This means that the FDA has taken the first step in putting hyperbaric chambers in the same class of devices as ventilators – a device that requires no indications to be listed.
When a drug or device is approved for marketing by the FDA, it normally has to state a list of indications of use. The list would include what diagnoses this drug or device would be used to treat. When the drug or device is used for a particular diagnosis that does not appear on the original list then the indication is considered “Off-Label”. (Device Labeling Guidance, FDA Guidance Doc. No. G-91, pt. III May 8, 1991) Off-Label uses are neither risky nor investigational; they constitute the traditional practice of medicine that has existed long before the FDA. The off-label designation by the FDA is simply a term they use to mean they are silent on the indicated use. The off-label use of a drug or medical device may be less risky than the approved indications. All drugs and devices contain inherent risks. The labeled indication may just be the one that had the strongest evidence for approval or, in the case of the 13 FDA labeled indications for HBOT, indications, the result of accepting a list without the FDA insisting on scientific due diligence.
In their article “FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions” Beck and Azari state the following: there is a belief that all off-label treatment is ipso facto “investigational” or “experimental.” It is an accepted principle that once the FDA determines that a drug or device can be marketed, a physician’s discretionary use of that product (the practice of medicine) is not restricted to the uses indicated on FDA-regulated labels. Off-label use is widespread in the medical community and often is essential to giving patients optimal medical care, both of which medical ethics, FDA, and most courts recognize. Even so, the public (and an occasional court) mistakenly presumes that all off-label treatment is investigational or experimental. (Beck, James, and Azari. “FDA, Off-Label Use, and Informed Consent: Debunking Myths and Misconceptions.” Food and Drug Law Journal, 53 (1998): 71- 104).
The FDA considers a drug or device “investigational” once the drug or device has been submitted for FDA approval. It then must go through three phases of clinical testing known as the investigational new drug (IND) process. If the IND testing proves a drug or device is safe and effective then the manufacturer would submit a new drug application (NDA). After the FDA approves an NDA for a device or a drug it then can be marketed by the manufacturer for the indications for which it was approved. The point is that approval means it can be marketed (by the manufacturer) for those uses only. A device or drug can never be marketed for off-label uses (by the manufacturer) but can be prescribed for off-label uses (Beck, p.75).
According to FDA documents and regulations and the Food and Drug Journal, just because the indications of use were approved by the FDA: “the FDA never has had the authority to regulate the practice of medicine; physicians may use legally marketed drugs or devices in any way that they believe, in their professional judgment, will best serve their patients. Courts have repeatedly recognized the propriety of off-label use, and several states statutorily recognize off-label use in various contexts.”
The term investigational only applies when a new drug or device has been submitted for approval or when a manufacturer wants to market an approved drug or device for off-label use. The FDA regulates the marketing of approved drugs and devices but not the prescribing of those drugs or devices. Furthermore, the Food and Drug Law Journal states the following:
“Off-label uses of medical devices and drugs perform an important therapeutic role in many, if not most, areas of medical practice. Prescriptions for off-label uses of drug products “may account for more than 25% of the approximately 1.6 billion prescriptions written each year, with some recent estimates running as high as 60%.” Pediatric uses also are mostly off-label. Thus, “in some cases, if you didn’t use the drug in an off-label way, you’d be guilty of malpractice.”(Beck, p. 80)
HBOT for brain injuries, for example, is simply the off-label use of an FDA-approved drug and device. The Food and Drug Law Journal further states the following in reference to off-label uses being neither “research” nor “experimental”: The mere fact that a product is used off-label to treat a patient does not make that use research. As a matter of medical ethics, there is a distinction between the “practice of medicine” and “research.” Certain third-party payers have used the FDA label indications as a means for determining reimbursement, which, in practice, results in the untoward restriction of a physician’s ability to use an approved drug or device off-label. Again, the FDA label was never intended to influence the practice of medicine, but the poor understanding of what the FDA was doing has been opportunistically used by third-party payers to restrict reimbursement.
Finally, it is the practice of certain third-party payers to use CMS National Coverage Indications (NCI) as the determining factor for reimbursement for any and all patients regardless of the age of the patient and to call any indication not on this list as either research or an experimental indication. Doing so is a misuse of NCIs which are only intended to apply to 65-year-old Medicare recipients and not, for example, Medicaid recipients.
* Disclaimer: In Full Support of the FDA., Hyperbaric Oxygen Therapy for indications other than the UHMS-approved indications is considered Off Label. The content and information provided within this site are for informational and educational purposes only. Consult a doctor before pursuing any form of medical treatment, including Hyperbaric Oxygen Therapy. The Information provided on this site is not to be considered Medical Advice. Please consult with your Treating Medical Physician.