Off-Label Use of Drugs and Biologic Agents
Off- label use of a drug or biologic agent may be considered medically necessary if the indication for the use is supported by at least one of the following compendia:
The scientific evidence indicates the drug/biologic agent is effective for the off-label indication. The evidence must:
Prescription drugs and biologic agents are considered investigational or experimental in the following situations:
Drugs or biologic agents that are considered experimental/investigational are not covered because the safety and/or efficacy cannot be established after reviewing the published scientific literature.
Note: Medical policies that address individual drugs/biologic agents may override this policy. (See Related Policies)
Compendium - A comprehensive listing of FDA approved drugs and biologic agents that includes:
Drug - A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease; a substance (other than food) intended to affect the structure or any function of the body; biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process).
Off-label - Use of a drug or biologic agent for indications or conditions other than those specifically approved by the U.S. Food and Drug Administration (FDA). The FDA approved use for drugs/biologic agents are stated in the package insert and available on the FDA website: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Last accessed October, 2014.
Approved indications or the labeled indications for drugs/biologic agents have been proven to be safe and effective by the FDA after the review of adequate and controlled clinical trials. Unapproved or unlabeled uses of drugs include a variety of situations ranging from completely unstudied to thoroughly investigated uses of the drug/biologic agent, yet approval from the FDA has not been requested. Many off-label uses are effective, well documented in the literature, and widely used.
Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.
Health plan contracts may address off-label use of drugs/biologic agents and refer to various compendia. Over time, compendia merge, change names or cease to exist. The clinical review team uses compendia endorsed by the Secretary of HHS and CMS to support coverage decisions when the compendia referenced in individual health plans are no longer in business.
A product or group’s health plan contract may exclude coverage of a medication or a class of medications, such exclusion would override any review for a medical necessity determination or off-label use of drugs/biologic agents, addressed in a Medical Policy.
This policy adheres to the laws set forth in the Alaska state statutes AS 21.07.020 Required contract provisions for health care insurance policy. Accessed October, 2014.
This policy adheres to the laws set forth in the Oregon state revised statutes, Health insurance: Required reimbursements. Accessed October, 2014.
This policy adheres to the laws set forth in the Washington state administrative code, WAC 284-30-450, Insurance Policies and Contracts – Coverage for Drugs. Accessed October, 2014.
The off-label or unapproved use of any drugs/biologic agents dispensed within an approved clinical trial may be covered if the member contract allows for coverage of clinical trials or if the criteria are met as set forth in the Clinical Trials policy. (See Related Policies.)
The National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium is based directly on the NCCN Clinical Practice Guidelines in Oncology. The compendium lists specific panel recommendations for off-label uses of drugs, and each recommendation is supported by a level of evidence category.
The NCCN Categories of Evidence and Consensus used in the recommendations are:
The accepted level of evidence for an off-label clinical indication is Category 1 or 2A; not 2B. (If a provider chooses to use NCCN level 2B evidence in support of a chemotherapeutic drug used for an off-label indication, The Company expects that the provider will make available for review, copies of significant peer-reviewed Phase II or Phase III studies demonstrating such support.)
Centers for Medicare and Medicaid Services (CMS) Compendia List
In 2008 CMS developed an annual review process (including criteria for transparency in the selection process) to recognize compendia. CMS may internally generate changes to the list at any time following investigation and public comment. The following are recognized as authoritative CMS compendia at this time:
Place of Service
New policy. Replaces BC policy 5.01.01. Coverage remains unchanged.
Annual Review. Policy reviewed. Definition of terms moved to Policy Guidelines section. In the Benefit Application section hyperlinks added to state statutes. No new references added reference 10 removed. Policy statements unchanged.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).