Purpose
The purpose of this Appendix is to ensure an understanding of DoD policy and practice regarding inclusion in CPGs of “off- label” uses of U.S. Food and Drug Administration (FDA)–approved products and use of antivenoms that are not FDA-approved. This applies to patients who are armed forces members and select DoD civilian employees and contractor personnel.
BACKGROUND
Unapproved (i.e., “off-label”) uses of FDA-approved products are extremely common in American medicine and are usually not subject to any special regulations. However, under Federal law, in some circumstances, unapproved uses of approved products are subject to FDA regulations governing “investigational new drugs.” These circumstances include such uses as part of clinical trials, and in the military context, command required or requested, unapproved uses such as investigational medical products requesting Assistant Secretary of Defense for Health Affairs approval to be used under a force health protection (FHP) program as described in DoD Instruction 6200.02. Some command requested unapproved uses may also be subject to special regulations. Antivenoms not FDA-approved and used by the DoD outside the United States are regulated using a unique investigational new drug (IND) program by FDA through the FHP Division of U.S. Army Medical Materiel Development Activity (USAMMDA) in accordance with AR 40-7.
ADDITIONAL INFORMATION REGARDING OFF-LABEL AND IND USES IN CPGS
The inclusion in CPGs of off-label and IND uses is not a clinical trial, nor is it a command request or requirement. Further, it does not imply that the Military Health System requires DoD health care practitioners use nor considers it to be the “standard of care.” Rather, the inclusion in CPGs of off-label and IND uses is to inform the clinical judgment of the responsible health care practitioner by providing information regarding potential risks and benefits of treatment alternatives. The decision is for the clinical judgment of the responsible health care practitioner within the practitioner-patient relationship.
ADDITIONAL PROCEDURES
Balanced Discussion
Consistent with this purpose, CPG discussions of off-label and IND uses specifically state that their uses are not approved by the FDA. Further, such discussions are balanced in the presentation of appropriate clinical study data, including any such data that suggest caution in the use of the product and specifically including any FDA-issued warnings.
Quality Assurance Monitoring
With respect to such off-label and IND uses, DoD procedure is to maintain a regular system of quality assurance monitoring of outcomes and known potential adverse events. For this reason, the importance of accurate clinical records is underscored.
Per AR 40-7, use of antivenoms not approved by FDA must be reported within 14 days to the pharmacy service, pharmacy staff officer, and FHP, USAMMDA (usarmy.detrick.medcom-usammda.mbx.force-health-protection@mail.mil). The following information is required:
Information to Patients
Good clinical practice includes the provision of appropriate information to patients. Each CPG discussing an unusual off- label or IND use will address the issue of information to patients. When practicable, consideration will be given to including in an appendix an appropriate information sheet for distribution to patients, whether before or after use of the product.
Information to patients should address in plain language: a) that the use is not approved by the FDA; b) the reasons why a DoD health care practitioner would decide to use the product for this purpose; and c) the potential risks associated with such use.
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