Oscar Approved and Accepted Off-label Medical Necessity Criteria for Products, Drugs and Biologicals (PG136) Form

Utilization Management of Off-label Use

The utilization management of off-label use of products is important for ensuring the safety and efficacy of drugs intended for human use. The U.S. FDA evaluates drugs and biologicals to ensure that they are safe and effective prior to marketing for all indications or uses. However, physicians may use a product for an indication not in the approved labeling, called off-label use, when the intent is the "practice of medicine".

FDA-approved drugs and biologicals may be considered for use in off-label indications if determined to be reasonable and necessary by the Plan. However, off-label usage is not supported and, therefore, the drug is not covered if a use is identified as not indicated by the FDA, or if a use is specifically identified as not indicated in one or more of the compendia listed, or if the Plan determines, based on peer-reviewed medical literature, that a particular use of a drug is not safe and effective. Peer-reviewed medical literature is considered when assessing off-label use.

This policy applies to products such as drugs and biologicals that need prior authorization but have no specific guidelines or coverage criteria, or for which product-specific clinical policies are still being updated due to recent changes in labeling. The Plan may review all requests made under the Medical or Pharmacy benefit against specific prior authorization criteria, as applicable and at its discretion. If the Member's Provider requests an off-label use of products or if the Plan requests it, the Provider is responsible for submitting documentation that supports the non-approved use.

Definitions

Biosimilar

refers to copies of biologic drugs. They are similar to an FDA-approved biologic, known as the reference product.

Brand Name Drug

means the first version of a particular medication to be developed or a medication that is sold under a pharmaceutical manufacturer’s own registered trade name or trademark. The original manufacturer is granted a patent, which allows it to be the only company to make and sell the new drug for a certain number of years.

Compendia

are summaries of drug information and medical evidence to support decision-making about the appropriate use of drugs and medical procedures. Examples include, but are not limited to:

1. American Hospital Formulary Service Drug Information
2. Elsevier Clinical Pharmacology
3. National Comprehensive Cancer Network Drugs and Biologics Compendium
4. Thomson Micromedex DrugDex
5. United States Pharmacopeia-National Formulary (USP-NF)

Documentation

refers to written information, including but not limited to:

1. Up-to-date chart notes, relevant test results, and/or relevant imaging reports to support diagnoses;
2. Prescription claims records, and/or prescription receipts to support prior trials of formulary alternatives.

Evidence-based, peer-reviewed medical journals

are publications that publish original research and scholarly articles related to the medical field. These journals use a peer-review process in which submitted articles are reviewed by independent experts in the same field to ensure their scientific accuracy, validity, and reliability before publication. The articles published in these journals are often based on research that uses rigorous scientific methods to provide evidence for medical practices, therapies, and treatments. The goal of evidence-based medicine is to provide the most effective care to patients based on the best available scientific evidence.

FDA, or the Food and Drug Administration,

is an agency of the United States federal government responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter medications, vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, cosmetics, and veterinary products. The FDA's main goal is to ensure that these products are safe and effective for their intended use, and that their labeling and marketing are truthful and not misleading.

Formulary

means a list of medications available to members with or without Prior Authorization.

Generic Drugs

means prescription Drugs that have been determined by the Food and Drug Administration (FDA) to be equivalent to Brand Name Drugs, but are not made or sold under a registered trade name or trademark. Generic Drugs have the same active ingredients, meet the same FDA requirements for safety, purity, and potency and must be dispensed in the same dosage form (e.g., tablet, capsule, cream) as the Brand Name Drug.

High Strength/Quality Evidence

is defined as at least one randomized, double-blind trial without significant limitations and with intent-to-treat analysis, confidence intervals reported, and consistent results from multiple trials or a meta-analysis with low heterogeneity. In some cancer-related cases, a non-blinded or single-blinded trial that meets the study objectives may also be considered as High Strength/Quality Evidence, such as in National Cancer Institute (NCI)-sponsored cooperative group studies or multicenter trials.

Low Strength/Quality Evidence

is defined as evidence that includes observational studies, case reports, or case series, and in some cases, randomized clinical trials with significant limitations. It also encompasses evidence in the form of expert consensus panel reports or expert reviewer comments.

Moderate Strength/Quality Evidence

is defined as at least one non-blinded or single-blinded, randomized or non-randomized clinical trial; a meta-analysis of randomized, controlled clinical trials with heterogeneous results if reasons for heterogeneity are adequately discussed; a randomized, controlled clinical trial with important methodological limitations; or inconsistent evidence from two or more randomized controlled trials with widely varying estimates of treatment effects.

In some cancer-related cases, a non-blinded, non-randomized trial such as a phase II study may be considered as Moderate Strength/Quality Evidence for rare cancers or cancers with limited treatment options.

Medical Necessity Criteria for Initial Authorization

If there is no product-specific Clinical Guideline or indication-specific clinical criteria, the Plan considers the requested FDA-approved or cleared product medically necessary if ALL the following criteria are met:

1. The product is being prescribed by or in consultation with a specialist or clinician with relevant specialty training IF accurate diagnosis and prescription, determination of risks and benefits of treatment, dosing, monitoring for side effects, or overall care coordination require specialist training to ensure safe and effective use of the product;AND
2. The safety and effectiveness of use for the indication is consistent with ONE of the following:
   1. FDA approved labeling (i.e., product information) for indication, including age, dosing (dosage, frequency, duration of therapy, and site of administration), and contraindications; or
   2. Use is supported with an appropriate level of evidence of efficacy by at least ONE of the following compendia, and not contraindicated or otherwise not recommended in the FDA labeling:
      1. American Hospital Formulary Service-Drug Information (AHFS-DI) and Grades of Recommendation is EITHER "Recommended" OR "Reasonable Choice";or
      2. American Medical Association (AMA) Drug Evaluations, or its successor publication;or
      3. Clinical Pharmacology and the off-label use carries a Strong Recommendation "For" use, with any level of evidence;or
      4. Lexi-Drugs AND the indication is listed as "Use: Off-Label" AND rated as "Evidence Level A";or
      5. Micromedex DrugDex and the Strength of Recommendation for the indication is a Class I, Class IIa, or Class IIb;or
      6. National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium and the level of evidence for the indication is Category 1, 2A, or 2B;or
   3. Evidence-based, peer-reviewed, recognized medical literature meeting ALL of the following:
      1. At least two articles from major peer-reviewed professional medical journals published in the United States or Great Britain have recognized, based on scientific or medical criteria, the drug's safety and effectiveness for treatment of the indication for which the drug has been prescribed;and
      2. No article from a major peer-reviewed professional medical journal has concluded, based on scientific or medical criteria, that the drug is unsafe or ineffective or that the drug's safety and effectiveness cannot be determined for the treatment of the indication for which the drug has been prescribed;and
      3. The use is not listed as unsupported, not indicated, not recommended (or equivalent terms) in any of the medical reference compendia;AND
3. The member must have documented evidence of ALL of the following:
   1. Failure of an adequate trial of at least three FDA-approved or cleared products (if available) that are considered the standard of care, unless:
      1. Clinically significant adverse effects are experienced;or
      2. All FDA-approved or cleared alternatives are contraindicated;or
      3. The request is for a product for treatment associated with cancer for a State with regulations against pre-requisite trial(s) of alternatives in certain oncology settings;and
   2. If the requested product is a Brand drug with a generic or biosimilar available, the member is unable to use or has tried and failed the corresponding generic or biosimilar product from two or more (≥ 2) manufacturers (if available);and
   3. If the drug is to be used in combination with other drugs for a particular indication, the safety and efficacy of use of those drugs in combination must be supported by reliable evidence in peer-reviewed published medical literature;AND
4. The product being requested meets BOTH of the following:
   1. The requested dosage, frequency, duration of therapy, and site of administration are supported by FDA labeling (product information), compendia of current literature, practice guidelines, or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence);and
   2. If the requested dosage exceeds the Plan’s quantity limit AND the prescribed dosage cannot be achieved using a different dose or formulation that is within the Plan’s limit; AND
5. The member has no contraindications to the prescribed agent per FDA labeling;AND
6. Documentation (such as office chart notes, lab results or other clinical information) are provided for review to substantiate the above listed requirements.AND

Medical Necessity Criteria for Reauthorization:

Prior authorization renewals will be reviewed on a case-by-case basis to determine medical necessity. Reauthorization requests will be considered medically necessary if ALL of the following criteria are met:

1. The member meets all Medical Necessity Criteria for Initial Authorization;AND
2. The member is experiencing positive clinical response or benefit from therapy as evidenced by disease stability or disease improvement;AND
3. The member does not have evidence of unacceptable toxicity from the requested product;AND
4. If the request is for a dose increase, it must meet BOTH of the following criteria:
   1. The requested dosage, frequency, duration of therapy, and site of administration are supported by FDA labeling (product information), compendia of current literature, practice guidelines, or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence);and

   2. If the requested dosage exceeds the Plan’s quantity limit AND the prescribed dosage cannot be achieved using a different dose or formulation that is within the Plan’s limit.

      Table 1: Level of Evidence Definitions

      • AHFS Grades of Recommendation
        • Recommended (Accepted) - The drug or biologic should be used, is recommended/indicated, or is useful/effective/beneficial in most cases.
      • (Accepted, with Possible Conditions) (e.g., treatment option) - The drug or biologic is reasonable to use under certain conditions (e.g., in certain patient groups), can be useful/effective/beneficial, or is probably recommended or indicated.
      • Not Fully Established (Unclear Risk/Benefit, Equivocal Evidence, Inadequate Data and/or Experience) - Usefulness and/or effectiveness is unknown, unclear, or uncertain or is not well established relative to the standard of care.
      • Not Recommended (Unaccepted) - The drug or biologic is considered inappropriate, obsolete, or unproven; is not recommended, is not indicated, or is not useful/effective/beneficial; or may be harmful.
      • Elsevier Clinical Pharmacology (quality of evidence rating and strength of recommendation)
      • Strong Recommendation - An off-label use that carries a Strong Recommendation "For" or "Against" use, with any level of evidence, should be considered binding and reflect that Elsevier recommends or does not recommend, respectively, the use of the drug for that indication in the situation described. All off-label uses with a strong level of recommendation will appear in the referential database and be clearly identified as recommended or not recommended; however, a strong recommendation “Against use” will not be found within the clinical decision support data.
      • Equivocal/Weak Recommendation - Off-label uses that have inconclusive data "For" or "Against" use carry a Weak Recommendation. A Weak recommendation, with any level of evidence, reflects a neutral or equivocal position (i.e., neither for or against use) by Elsevier. All off-label uses with a weak level of recommendation will appear in the referential database and be clearly identified as equivocal; however, a weak recommendation "Against use" will not be found within the clinical decision support data.
      • Lexi-Drugs Level of Evidence Scale
        • A - Consistent evidence from well-performed randomized, controlled trials or overwhelming evidence of some other form (e.g., results of the introduction of penicillin treatment) to support the off-label use. Further research is unlikely to change confidence in the estimate of benefit.
        • B - Evidence from randomized, controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise), or very strong evidence of some other research design. Further research (if performed) is likely to have an impact on confidence in the estimate of benefit and risk and may change the estimate.
        • C - Evidence from observational studies (e.g., retrospective case series/reports providing significant impact on patient care), unsystematic clinical experience, or from potentially flawed randomized, controlled trials (e.g., when limited options exist for condition). Any estimate of effect is uncertain.
        • G - Use has been substantiated by inclusion in at least one evidence-based or consensus-based clinical practice guideline.
      • Micromedex DrugDex Strength of Recommendation
        • Class Ila - Recommended, Most Cases - The given test, or treatment is generally considered to be useful, and is indicated in most cases.
        • Class IIb - Recommended, Some Cases - The given test, or treatment may be useful, and is indicated in some, but not most, cases.
        • Class III - Not Recommended - The test or treatment has not been proven to be useful, and should not be administered.
      • Class Indeterminate
        • Evidence Inconclusive
      • NCCN Categories of Evidence and Consensus
        • Category 1 - Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
        • Category 24 - Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
        • Category 2B - Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
        • Category 3 - Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

      Table 2: Peer-reviewed Professional Medical Journals

      NOTE: The list of medical journals provided as an example is not intended to be an all-inclusive or comprehensive list. Numerous other credible medical journals exist that are not included here, and this list should not be considered a complete representation of the medical journal landscape.

      • Academic Emergency Medicine
        • Emergency medicine
        • Publisher Wiley-Blackwell
      • American Journal of Respiratory and Critical Care Medicine
        • Respiratory and critical care
        • American Thoracic Society
      • Annals of Emergency Medicine
        • Emergency medicine
        • Elsevier
      • Annals of Internal Medicine
        • Internal medicine
        • American College of Physicians
      • Annals of Oncology
        • Oncology
        • Elsevier
      • Annals of Surgery
        • Surgery
        • Lippincott Williams & Wilkins
      • Archives of Disease in Childhood
        • Pediatrics
      • Biology of Blood and Marrow Transplantation
        • Hematology/Oncology
      • Blood
        • Hematology
        • American Society of Hematology
      • BMJ Open
        • General medicine
        • BMJ Group
      • Bone Marrow Transplantation
        • Hematology/Oncology
        • Springer Nature
      • British Journal of Cancer
        • Oncology
        • Springer Nature
      • Cancer
        • Oncology
        • Wiley
      • Circulation
        • Cardiology
        • American Heart Association
      • Clinical Cancer Research
        • Oncology
        • American Association for Cancer Research
      • Clinical Infectious Diseases
        • Infectious diseases
        • Oxford University Press
      • Diabetes Care
        • Diabetes
        • American Diabetes Association
      • Emerging Infectious Diseases
        • Infectious diseases
        • Centers for Disease Control and Prevention
      • European Journal of Cancer (formerly the European Journal of Cancer and Clinical Oncology)
        • Oncology
        • Elsevier
      • Gastroenterology
        • Gastroenterology
        • Elsevier
      • Gynecologic Oncology International Journal of Cancer
        • Gynecologic oncology | Oncology
        • Elsevier | Wiley-Blackwell
      • International Journal of Radiation Oncology, Biology, Physics
        • Radiation oncology
        • Elsevier
      • JAMA: The Journal of the American Medical Association
        • General medicine
        • American Medical Association
      • Journal of Clinical Oncology
        • Oncology
        • American Society of Clinical Oncology
      • Journal of Neurology, Neurosurgery, and Psychiatry
        • Neurology and psychiatry
        • BMJ Publishing Group
      • Journal of the National Cancer Institute
        • Oncology
        • Oxford University Press
      • Journal of the National Comprehensive Cancer Network
        • Oncology
        • NCCN
      • Leukemia
        • Hematology/oncology
        • Nature
      • Nature
        • Multidisciplinary sciences
        • Nature Publishing Group
      • Nature Communications
        • Multidisciplinary sciences
        • Nature Publishing Group
      • Nature Medicine
        • General medicine
        • Nature Publishing Group
      • Neurology
        • Neurology
        • American Academy of Neurology
      • Neuropharmacology
        • Pharmacology
        • Elsevier
      • New England Journal of Medicine
        • General medicine
        • Massachusetts Medical Society
      • Obstetrics and Gynecology
        • Obstetrics and gynecology
        • Wolters Kluwer
      • Pediatrics
        • Pediatrics
        • American Academy of Pediatrics
      • PLOS One
        • Multidisciplinary sciences
        • PLOS
      • Radiation Oncology
        • Oncology
        • BioMed Central Ltd.
      • Stroke
        • Neurology
        • American Heart Association
      • The American Journal of Clinical Dermatology
        • Dermatology
        • Springer
      • The American Journal of Clinical Nutrition
        • Nutrition
        • Oxford University Press
      • The American Journal of Gastroenterology
        • Gastroenterology
        • Wolters Kluwer

      Experimental or Investigational / Not Medically Necessary

      The use of products, drugs and biologicals are considered contraindicated, experimental, investigational, or unproven in the following cases:

      1. When no valid scientific evidence exists that demonstrates the efficacy of the product for a particular diagnosis or clinical condition.
      2. The FDA determined a product, drug or biologic to be contraindicated for a specific condition or off-label use.
      3. The Pharmacy and Therapeutics (P&T) Committee classifies it as experimental, investigational, or unproven because the safety and/or efficacy cannot be established after reviewing the published scientific literature.

      Indications or diagnoses in which the drug has been shown to be unsafe or ineffective.

      5. Continued therapy for members who have developed an absolute contraindication or intolerance to the product, or who have failed to respond or who have lost response to the product.
      6. Not "medically accepted" by a Compendium:
      • AHFS-DI or Clinical Pharmacology: The narrative text is "not supportive" (or equivalent term).
      • DrugDex: The level of evidence for the indication is Class III in DrugDex.
      • Lexi-Drugs: Indication is listed as "Use: Unsupported."
      • NCCN: The level of evidence for the indication is Category 3 in NCCN.

      The quality of evidence provided or reviewed is poor (i.e., Low Strength/Quality Evidence), as it primarily consists of:

      • Observational studies: These are studies where the researchers observe a group of people without any intervention, and then analyze the data collected. These studies are prone to bias and confounding variables.
      • Case reports and case series: These are studies that describe the medical history and treatment of one or more individual patients. These studies do not have a control group and are therefore not able to show cause-and-effect relationships.
      • Non-randomized studies: These are studies where the participants are not randomly assigned to different groups. This can introduce bias into the study and make it difficult to draw reliable conclusions.
      • Studies with serious deficiencies or limitations: These are studies that have flaws in their design, execution, or analysis that make it difficult to trust their findings.
      • Expert consensus panel reports or expert reviewers' comments: These are opinions or experiences of experts in the field and are not based on empirical evidence.

      Clinical Guideline Revision / History Information

      Original Date: 3/23/2023
      Reviewed/Revised: