Medical Policy: 05.01.09 

Original Effective Date: July 2005 

Reviewed: October 2020 

Revised: October 2020 



This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.


This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.



Off-label drug use is the use of a drug approved by the U.S. Food and Drug Administration (FDA) for other uses or in treatment regimens or patient populations that are not included in approved labeling.


The FDA approves drugs or specific indications that are included in the drug's labeling. When a drug is used for an indication other than those specifically included in the labeling, it is referred to as an off-label use. Many off-label uses are effective, well-documented in the literature, and widely used.


Unapproved uses of drugs include a variety of situations ranging from completely unstudied to thoroughly investigated drug uses where the FDA has not been asked for approval, whereas approved uses of drugs have been proved to be safe and effective by the FDA after the review of adequate and controlled clinical trials that have documented their use.


Prior Approval:

Not applicable.



Criteria for Initial Approval

The off-label use of a drug may be considered medically necessary when the following criteria are met:

  1. The requested drug has NOT been excluded from coverage by Wellmark due to lack of demonstrated safety or efficacy, clinical benefit, or administrative program (i.e. exclusion at launch while awaiting P&T review, plan exclusions)
  2. The patient has a documented history of a trial and failure, contraindication, or intolerance to established FDA approved and/or clinical guideline recommended therapies (if applicable) used to treat or manage the disease or condition.
  3. The requested dosing frequency and duration of use falls within the manufacturer’s published dosing guidelines or within dosing guidelines found in the compendia of current literature (examples: package insert, Drug Facts & Comparisons, current accepted consensus-based guidelines).
  4. The diagnosis is clinically supported as a use by at least one of the following: 
    • One of the following compendia:
      • Drug Facts & Comparisons® Level of Evidence A
      • National Comprehensive Cancer Network (NCCN) Drugs and Biologics CompendiumTM Category of Evidence and Consensus 1 or 2A
    • OR
    • Scientific evidence demonstrates efficacy and safety for the requested use. The evidence must:
      • Consist of an adequate number of well-designed studies with sufficient numbers of patients in relation to the incidence of the disease
      • Be published in major peer-reviewed journals that publish original manuscripts only after the manuscripts have been critically reviewed by unbiased independent experts for scientific accuracy, validity, and reliability.
      • Demonstrate consistent results across all studies.
      • Establish appropriate dosing frequency and duration of use.
      • Document positive health outcomes and demonstrate that the drug is as effective as or more effective than established alternatives.
      • Document improvements that are attainable outside the investigational setting. 


If criterion I, II, III and IV have not been satisfied, the requirements of the off-label drug use policy have not been met. 


Approval will be for the duration of prescription/treatment course up to 12 months.


Continuation of Therapy

The request for continuation of therapy may be considered medically necessary when ALL initial authorization criteria are met AND clinical documentation is provided showing the patient has achieved and/or maintained a positive clinical response with the requested therapy.


Approval will be for the duration of prescription/treatment course up to 12 months.


Note: Prescribers must submit clinical documentation supporting the drug's safety and effectiveness in treating the intended indication. 


Dosage and Administration

Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines.


Clinical Rationale

Facts & Comparisons® eAnswers is a drug compendia that provides up-to-date, comprehensive drug information includingoff-label uses. An editorial review panel consisting of practicing physicians and pharmacists assign a documentation level to each monograph with level A being good and level G being poor. According to Facts and Comparisons, this panel critically evaluates monograph data and provides an authoritative consensus about whether the reviewed published information is considered sufficient to warrant prescribing in appropriate populations. For the purpose of this policy, indications listed in Facts and Comparisons® eAnswers is determined medically necessary when the Level of Evidence is A or B.


The National Comprehensive Cancer Network (NCCN) Drug & Biologics Compendium is a listing of agents with both FDA-approved indications and NCCN designated off-label indications derived from the NCCN Clinical Practice Guidelines in Oncology. As stated by NCCN, these off-label uses are based upon evaluation of evidence from literature combined with expert judgment in an evidence-based method. Each recommendation is designated with a Category of Evidence that reflects the quality of evidence and consensus on which the recommendation is based. For the purpose of this policy, indications listed in NCCN Drug and Biologics Compendium with a Category of Evidence and Consensus 1 or 2A are considered medically necessary.


    Procedure Codes and Billing Guidelines:

    • To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.


    Selected References:

    • U.S. Food and Drug Administration (FDA). Off-label and investigational use of marketed drugs, biologics, and medical devices
    • DrugDex® System(database online). Greenwood Village, CO: Thomson Micromedex.
    • Facts and Comparisons® (database online). St. Louis, MO: Wolters Kluwer Health, Inc.
    • National Comprehensive Cancer Network® NCCN Drugs & Biologic Compendium™ (database online).


    Policy History:

    • October 2020 - Annual Review, Policy Revised
    • February 2019 - Annual Review, Policy Revised
    • October 2018 - Annual Review, Policy Renewed
    • September 2017 - Annual Review, Policy Renewed
    • September 2016 - Policy Revised
    • August 2016 - Annual Review, Policy Revised
    • August 2015 - Annual Review, Policy Renewed
    • August 2014 - Annual Review, Policy Revised
    • August 2013 - Annual Review, Policy Revised
    • September 2012 - Annual Review, Policy Renewed
    • September 2011 - Annual Review, Policy Renewed

    Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.


    *CPT® is a registered trademark of the American Medical Association.