Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Off-label Coverage for Prescription Drugs and/or Biologics

Policy #:08.00.15d

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin 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 Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.

CRITERIA TO ESTABLISH MEDICAL NECESSITY FOR OFF-LABEL COVERAGE OF US FOOD AND DRUG ADMINISTRATION (FDA)--APPROVED DRUGS AND/OR BIOLOGICS

Off-label use of prescription drugs and/or biologics is considered medically necessary and, therefore, covered when the off-label condition is supported by either the Company-recognized prescription drug and/or biologic compendia, or published research, as outlined below.

1. COMPENDIA FOR ONCOLOGIC INDICATIONS (ANTI-CANCER CHEMOTHERAPY)

For coverage of an anti-cancer chemotherapy regimen, the off-label use is considered medically necessary and therefore covered when one of the following criterion is met:
  • The narrative text in American Hospital Formulary Service--Drug Information (AHFS-DI®) is supportive of the use; or
  • The indication is classified as Category 1 or 2A by National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium™; or
  • The indication is classified as Class I or Class IIa in Micromedex® DrugDex® Compendium.

An anti-cancer chemotherapy regimen is considered experimental/investigational even when above criteria have been met, and when one of the following exists:
  • The indication is classified as Category 3 by NCCN® or Class III in Micromedex® DrugDex®.
  • The narrative text in AHFS-DI® is not supportive of the use.
  • Any of the compendia listed above state that the prescription drug and/or biologic is not indicated, is unsupported, is not recommended, or equivalent terms are used regarding the prescription drug and/or biologic.

When a compendia is considered neither supportive nor non-supportive (ie, Category 2B in NCCN, Class IIb in Micromedex® DrugDex®, or an absence of narrative text or evidence classification from any Company-recognized compendium), please refer to the section in this policy entitled Published Clinical Research.

2. COMPENDIA FOR NON-ONCOLOGIC INDICATIONS

For coverage of non-oncologic prescription drugs and/or biologics, the off-label use is considered medically necessary and therefore covered when:
  • The narrative text in American Hospital Formulary Service--Drug Information (AHFS-DI®) is supportive of the use or
  • The indication is classified as Class I or Class IIa in Micromedex® DrugDex® Compendium.

Non-oncologic drugs and/or biologics are considered experimental/investigational and therefore not covered, even when the above criteria have been met, and when one of the following exists:
  • The indication is classified as Class III in Micromedex® DrugDex®.
  • The narrative text in AHFS-DI® is not supportive of the use.
  • Either of the compendia listed above state that the prescription drug and/or biologic is not indicated, is unsupported, is not recommended, or equivalent terms are used regarding the prescription drug and/or biologic.

When a compendia is considered neither supportive nor non-supportive (ie, Category 2B in NCCN, Class IIb in Micromedex® DrugDex®, or an absence of narrative text or evidence classification from any Company-recognized compendium), please refer to the section in this policy entitled Published Clinical Research.

3. PUBLISHED CLINICAL RESEARCH

In order for an off-label use to be supported by published clinical research, all of the following criteria must be met:
  • The prescription drug and/or biologic must have been studied in at least two clinical trials conducted at different centers, and the results must have been published in national or international peer-reviewed journals with an editorial committee composed of physicians. Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications. It does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).
    • A use is considered supported by clinical research when it appears in at least two Phase III clinical trials that have definitively demonstrated its safety and effectiveness as an appropriate medical treatment for the condition. If no Phase III trial evidence is available, at least two Phase II clinical trials with reasonably large patient samples showing consistent results of safety and efficacy may be considered in certain instances (e.g., in rare diseases in which a Phase III study might be difficult to complete in a reasonable period of time after completion of the Phase II studies, or when overwhelmingly good evidence of safety and effectiveness is noted in the Phase II studies).
  • Reliable evidence must demonstrate that the proposed off-label use for the specified medical condition is safe and effective and that the beneficial effects of the treatment outweigh its risks.
  • In determining whether there is supportive clinical evidence for a particular use of a prescription drug and/or biologic, the quality of the evidence in published, peer-reviewed medical literature is considered. Among other things, such consideration involves the assessment of the following:
    • The prevalence and life history of the disease when evaluating the adequacy of the number of subjects and the response rate
    • The effect on the individual's well-being and other responses to therapy that indicate effectiveness (e.g., reduction in mortality, morbidity, and signs and symptoms)
    • Whether the clinical characteristics of the beneficiary and the indication are adequately represented in the published evidence
    • Whether the study is appropriate to address the clinical question, such as:
      • If the study design is appropriate to address investigative questions (e.g., in some clinical studies, it may be unnecessary or not feasible to use randomization, double-blind trials, placebos, or crossover)
      • If non-randomized clinical trials with a significant number of subjects may be a basis for supportive clinical evidence for determining accepted uses of prescription drug and/or biologic
      • Generally, case reports are considered uncontrolled, are based on anecdotal information, and do not provide adequate supportive clinical evidence for determining accepted uses of prescription drugs and/or biologics
  • The off-label use is supported by published clinical research, and the results have been published in major peer-reviewed medical journals such as, but not limited to:
  • American Journal of Medicine
  • Annals of Internal Medicine
  • Annals of Oncology
  • Annals of Surgical Oncology
  • Biology of Blood and Marrow Transplantation
  • Blood
  • Bone Marrow Transplantation
  • British Journal of Cancer
  • British Journal of Hematology
  • British Medical Journal
  • Cancer
  • Clinical Cancer Research
  • Drugs
  • European Journal of Cancer
  • Gynecologic Oncology
  • International Journal of Radiation, Oncology, Biology, and Physics
  • Journal of Clinical Oncology
  • Journal of the National Cancer Institute
  • Journal of the National Comprehensive Cancer Network (NCCN)
  • Journal of Urology
  • Lancet
  • Lancet Oncology
  • Leukemia
  • Radiation Oncology
  • The Journal of the American Medical Association
  • The New England Journal of Medicine


EXPERIMENTAL/INVESTIGATIONAL

Prescription drugs and/or biologics that are considered experimental/investigational are not covered because the safety and/or effectiveness of the prescription drug and/or biologic cannot be established by a review of the available published peer-reviewed literature. Prescription drugs and/or biologics are considered experimental/investigational for any of the following:
  • The prescription drug and/or biologic has not received US Food and Drug Administration (FDA) approval for any indication.
  • The off-label use of the prescription drug and/or biologic does not meet the medical necessity criteria listed in this policy or in any other specific Company Medical Policy addressing a drug and/or biologic (ie, the off-label use is not recognized by the appropriate compendia or published clinical research).
  • The FDA determines a prescription drug and/or biologic to be contraindicated for specific condition(s) or specific off-label use(s).
  • The off-label use is not medically accepted or not indicated by a compendium for specific conditions (ie, the indication is a Category 3 in NCCN, Class III in Micromedex® DrugDex®, or when the narrative text in AHFS-DI® is not supportive.)
    • The absence of narrative text for an off-label use is considered neither supportive nor non-supportive.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the prescription drug and/or biologic.
Guidelines

While the Company does not require precertification/preapproval for all prescription drugs and/or biologics, all off-label uses are subject to retrospective review and audit.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, the prescription drug and/or biologic is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

A medication or class of medications may be a product or group contract exclusion. Individual benefits must be verified.

Description

An off-label or unlabeled use of a prescription drug and/or biologic is a use that has not been approved by the US Food and Drug Administration (FDA). Use of a prescription drug and/or biologic for any indication, patient population, or route of administration other than those approved by the FDA and listed on the label or packaging insert is considered an off-label or unlabeled use.

Off-label uses are generally recognized as medically accepted indications if they are supported in either 1) one or more authoritative compendia, and none list it as not indicated, unsupported, not recommended, or equivalent terms; or 2) in peer-reviewed medical literature. Reliable evidence must demonstrate that the proposed off-label use to treat the specified medical condition is safe and effective, and that the beneficial effects of the treatment outweigh its risks.

Peer-reviewed medical literature includes scientific, medical, and pharmaceutical publications in which original manuscripts are published only after having been critically reviewed for scientific accuracy, validity, and reliability by unbiased, independent experts prior to publication. In order for a use to be supported by clinical research, it must have been studied in at least two clinical trials conducted at different centers, and the results must have been published in national or international peer-reviewed journals with an editorial committee composed of physicians. Peer-reviewed medical literature does not include in-house publications of pharmaceutical manufacturing companies or abstracts (including meeting abstracts).

According to the National Cancer Institute, clinical trials are usually conducted in a series of steps called phases. These are outlined as follows:
    Phase 0 trials are the first step in testing a new agent in people. Phase 0 trials will evaluate how the new agent is processed in the body and how it exerts its clinical effects in the body. Phase 0 trials enroll a small number of individuals (10-15 individuals) who are administered a very small amount of the new agent.
    Phase I trials evaluate what dose is safe, how a new agent should be given (by mouth, injected into a vein, or injected into the muscle), and how often. Researchers watch closely for any harmful side effects. Phase I trials usually enroll a small number of individuals (20 or more individuals) and take place at only a few locations. The dose of the new therapy or technique is increased a little at a time. The highest dose with an acceptable level of side effects is determined to be appropriate for further testing.
    Phase II trials study the safety and effectiveness of an agent or intervention, and evaluate how it affects the human body. Phase II studies usually focus on a particular aspect of a disease, and include fewer than 100 patients.
    Phase III trials compare a new agent or intervention (or new use of a standard one) with the current standard therapy. Participants are randomly assigned to the standard group or the new group, usually by computer. This method, called randomization, helps to avoid bias and ensures that human choices or other factors do not affect the study's results. In most cases, studies move into Phase III testing only after they have shown promise in Phases I and II. Phase III trials often include large numbers of individuals across the country.
    Phase IV trials are conducted to further evaluate the long-term safety and effectiveness of a treatment. They usually take place after the treatment has been approved for standard use. Several hundred to several thousand people may take part in a Phase IV study. These studies are less common than Phase I, II, or III trials.

In the field of oncology, there are many reasons to consider a medically supported off-label use of a prescription drug and/or biologic for a cancer chemotherapy agent. Prescription drugs and/or biologics may be effective for many other cancers in addition to those that were considered in the primary labeling of the prescription drug and/or biologic, and many chemotherapeutic agents are given in combinations (regimens). Any of the prescription drugs and/or biologics in the combination may not have been approved in the initial labeling of the products. In addition, the combination of effective chemotherapeutic agents changes over time. Healthcare providers are often left with few approved treatment options if initial treatment regimens have failed.
References


American Hospital Formulary Service (AHFS). Drug Information 2016. [Lexicomp Online Web site]. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed October 14, 2016.

Centers for Medicare & Medicaid Services (CMS). Agency for Healthcare Research and Quality (AHRQ) Technology Assessment Program. Technology assessment: Compendia for coverage of off-label uses of drugs and biologics in an anticancer chemotherapeutic regimen. Final report. [CMS Web site]. 05/07/07. Available at: http://www.cms.gov/medicare-coverage-database/details/technology-assessments-details.aspx?TAId=46&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=Pennsylvania&KeyWord=compendia&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAAAAAAA%3d%3d& . Accessed October 14, 2016.

Centers for Medicare & Medicaid Services (CMS). Medicare Benefit Policy Manual.Chapter 15: Covered medical and other health services. §50.4.5: Off-Label Use of Drugs and Biologicals in an Anti-Cancer Chemotherapeutic Regimen. Rev 212, Issued: 11/06/15, Effective: 08/12/15. Implementation 02/10/16. [CMS Web site]. Available at:
https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/Internet-Only-Manuals-Ioms-Items/Cms012673.html and
https://www.cms.gov/Regulations-and-Guidance/Guidance/Transmittals/Downloads/R212BP.pdf . Accessed October 14, 2016.

Centers for Medicare & Medicaid Services (CMS). National Coverage Determination (NCD). 110.17: NCD for anti-cancer chemotherapy for colorectal cancer & Publication 100-04: Medicare Claims Processing. Transmittal 588: Coverage of colorectal anti-cancer drugs included in clinical trials. [CMS Web site]. 01/28/05. Available at:http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=291&ncdver=1&bc=BAABAAAAAAAA& . Accessed October 14, 2016.

Centers for Medicare & Medicaid Services (CMS). NCA for anticancer chemotherapy for colorectal cancer (CAG-00179N). [CMS Web site]. 01/28/05. Available at: https://www.cms.gov/medicare-coverage-database/details/nca-details.aspx?NCAId=90&ver=23&NcaName=Anticancer+Chemotherapy+for+Colorectal+Cancer&bc=BEAAAAAAAAAA&Accessed October 14, 2016.

Company Benefit Contracts.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology™. [NCCN Web site]. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp [via subscription only]. Accessed October 14, 2016.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium™.[NCCN Web site]. Available at: http://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed October 14, 2016.

Novitas Solutions, Inc. Local Coverage Article A53049. Approved Drugs and Biologicals; Includes Cancer Chemotherapeutic Agents. [Novitas Solutions, Inc. Medicare Services Web site]. Original 10/01/2015; Revised: 01/01/2016. Available at:
https://www.cms.gov/medicare-coverage-database/details/article-details.aspx?articleId=53049&ver=34&Cntrctr=319&ContrVer=1&CntrctrSelected=319*1&bc=AgABAAEAAAAAAA%3d%3d& . Accessed October 14, 2016.

Truven Health Analytics. Micromedex® DrugDex® Compendium. [Internet database]. Greenwood Village, CO. [Micromedex® Solutions Web site]. Available at: http://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed October 14, 2016.

US Food and Drug Administration (FDA). Regulatory Information. Federal Food, Drug, and Cosmetic Act. [FDA Web site]. 10/05/15. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/FDCActChapterVDrugsandDevices/default.htm. Accessed October 14, 2016.





Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

N/A


HCPCS Level II Code Number(s)

N/A


Revenue Code Number(s)

N/A

Coding and Billing Requirements


Cross References


Policy History

Revisions from 08.00.15d:
09/12/2018This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 11/30/2016
Version Issued Date: 11/30/2016
Version Reissued Date: 09/12/2018

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Independence Blue Cross is an independent licensee of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.