ModifiedUnitedHealthcarePolicy CSIND0054.05

Off-Label/Unproven Specialty Drug Treatment (for Indiana Only)

Criteria and evidentiary standards UnitedHealthcare uses to determine medical necessity for off‑label or unproven indications of FDA‑approved specialty drugs administered or supervised under the medical benefit for Indiana members.

Policy Summary

PayerUnitedHealthcare

PolicyOff-Label/Unproven Specialty Drug Treatment (for Indiana Only)

Policy CodePolicy CSIND0054.05

Change TypeCoverage rationale and definition updates

Effective Date08/01/2025

Next Review DateN/A

Key ActionObtain prior authorization and document FDA approval, state Medicaid coverage, diagnostic support from compendia or two peer‑reviewed articles, and history of failure/intolerance to standard therapies.

SourceLink

POLICY UPDATE CHANGES

Removed notation indicating evidence limited to case studies or case series is not sufficient to meet the standard of this criterion (for peer-reviewed articles presented in a major peer-reviewed medical journal).

Updated definition of 'Serious Rare Disease'.

Updated References section to reflect the most current information.

Archived previous policy version CSIND0054.04.

Indiana-onlystate applicability

FDA‑approvedFDA requirement

Compendia/evidencediagnosis support

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Serious Rare Disease

CSIND0054.04prior version archived

08/01/2025effective date

Coverage Criteria

Initial coverage criteria

Covered when ALL of the following are met:

Primary conditions: The drug is approved by the U.S. Food and Drug Administration; the requested drug is a covered benefit by the member's state Medicaid agency; and one of: the requested drug is considered 'unproven' per UnitedHealthcare drug policy, the indication for the requested drug is not addressed by a UnitedHealthcare drug policy, or a UnitedHealthcare drug policy does not exist for the requested drug.

Source: Indications of Coverage

Clinical severity and prior use: The requested drug is intended to treat a chronic and seriously debilitating condition or a Serious Rare Disease; the patient has not failed a previous course or trial of the requested drug; the patient is not currently enrolled in an eligible clinical trial; and there is documented history of failure, contraindication, or intolerance to standard, conventional therapies to treat or manage the disease or condition, where available.

Source: Indications of Coverage

Support for diagnosis/use: Diagnosis is clinically supported by at least one of the following: (1) AHFS-DI Therapeutic Uses; (2) Elsevier Gold Standard Clinical Pharmacology under Indications; (3) DRUGDEX with Strength of Recommendation Class I, IIa, or IIb under Therapeutic Uses; (4) InterQual Specialty Rx clinical indications; or (5) two articles from major peer-reviewed medical journals demonstrating the proposed off-label use is generally safe and effective (unless there is validated and uncontested contradictory evidence in a major peer-reviewed journal).

Acceptable evidence sources listed in policy

This policy applies to provider‑administered or supervised specialty drugs, and patient self‑administered specialty drugs when covered under the medical benefit, for off‑label or unproven indications as described in the policy. It does not addressself‑administered medications covered under the pharmacy benefit; those are managed under the pharmacy benefit. It also excludes oncology medications covered under the medical benefit that are addressed by the NCCN Compendium (see the Medical Benefit Drug Policy titled Oncology Medication Clinical Coverage for Indiana), and excludes vaccines.

Policy revision effective 08/01/2025 includes an operational change: the previous explicit notation that evidence limited to case studies or case series is not sufficient to meet the published evidence standard for peer‑reviewed articles in major medical journals has been removed. This change modifies how submitted peer‑reviewed evidence may be evaluated under the Coverage Rationale.

Use of a specialty drug for an off‑label or unproven indication is not medically necessary when the policy’s required conditions are not met. Key required elements include that the drug be FDA‑approved, be a covered benefit by the member’s state Medicaid agency, be intended to treat a chronic and seriously debilitating condition or a Serious Rare Disease, and that there be documented failure, contraindication, or intolerance to standard therapies when available. Additionally, the diagnosis/use must be supported by acceptable sources such as listed compendia, InterQual Specialty Rx, or two peer‑reviewed journal articles demonstrating safety and effectiveness; absence of these evidentiary supports is a basis for noncoverage.

Provider Actions and Authorization

Prior Authorization

Prior Authorization Required

Prior Authorization Required. Prior authorization is required for medical-benefit specialty drugs when requested for off-label or unproven indications covered by this policy. Submit prior authorization requests per plan procedures before administration to avoid payment denial.

Applies to provider-administered or supervised specialty drugs and patient self-administered specialty drugs covered under the medical benefit
Check plan-specific PA submission channels and timelines

Step Therapy

Step Therapy and Prior Treatment

Step therapy / prior treatment requirement. Documented failure, contraindication, or intolerance to standard or conventional therapies is required where available before coverage of an off-label or unproven indication will be approved.

Record prior medications, dates, dosages, and clinical response or reasons for discontinuation

Background

Off‑label use is defined as an indication or use that deviates from the FDA‑approved prescribing information. This policy applies to medical‑benefit specialty drugs (provider‑administered or supervised and patient self‑administered) when a UnitedHealthcare drug policy does not address the requested indication, lists the requested indication as unproven, or no UnitedHealthcare drug policy exists for the drug.

Definitions

Serious Rare Disease — definition

Serious (definition)Life threatening or accompanied by significant major disability or imminent threat of major disability (examples: paralysis or limb amputation).

Rare (definition)Affects fewer than 200,000 people in the United States at any given time.

Implication for evidenceEvidence from high‑quality clinical studies may not exist or is not likely to exist for Serious Rare Diseases.

Serious Rare Disease — updated definition note

Policy updateDefinition of 'Serious Rare Disease' was updated in this policy version (effective 08/01/2025).

Revision contextUpdate noted in Policy History/Revision Information alongside other changes to Coverage Rationale and References.

Revision History and Policy Changes

2025-08-01policy_revisionLatest

Removed explicit notation that evidence limited to case studies or case series is not sufficient to meet the Coverage Rationale standard; updated the definition of 'Serious Rare Disease' and updated References; archived prior policy version CSIND0054.04.

Policy Summary

PayerUnitedHealthcare

PolicyOff-Label/Unproven Specialty Drug Treatment (for Indiana Only)

Policy CodePolicy CSIND0054.05

Change TypeCoverage rationale and definition updates

Effective Date08/01/2025

Next Review DateN/A

SourceLink

On This Page

If standard therapies are not available or not appropriate, include clinical justification

Documentation Required

Documentation Requirements

Required documentation. Providers must supply documentation that supports FDA approval status, state Medicaid coverage (if applicable), and clinical evidence for the requested diagnosis and off-label use.

Evidence of FDA approval for the drug (labeling) where applicable
Documentation that the drug is a covered benefit by the member's state Medicaid agency when required
Clinical support: compendia citations (AHFS-DI, Clinical Pharmacology, DRUGDEX strength of recommendation), InterQual Specialty Rx, or two peer-reviewed articles demonstrating safety and effectiveness
Records showing prior treatment trials, contraindications, or intolerances

Note

Reference Benefit Plan Requirements

Reference benefit plan requirements. Always reference the member's federal, state, or contractual benefit plan terms when determining coverage; plan-specific requirements may differ from this policy and govern in the event of a conflict.

Verify applicable federal/state/contractual coverage rules before submitting authorization requests
This policy assists in interpreting UnitedHealthcare standard benefit plans but does not override plan-specific terms

Note

Conflicts with Plan or Regulatory Requirements

Conflicts with plan or regulatory requirements. If federal, state, or contractual benefit plan requirements conflict with this policy, the federal/state/contractual requirements govern. Confirm and follow those requirements prior to requesting coverage.

When in conflict, federal/state/contractual requirements take precedence over this policy
Contact the plan administrator or consult the member's contract for definitive coverage determination

Note

Use of InterQual and Plan Tools

Use of third-party criteria and provider action. UnitedHealthcare may use third-party tools (for example, InterQual) to assist in coverage determinations; providers should follow plan rules and supply any additional information those tools require.

If InterQual or other criteria are applied, include documentation aligned to those criteria in the authorization request
Ensure clinical notes and evidence directly address the criteria used for the determination

Denial Risk

Triggers for Denial

Triggers for denial. Coverage may be denied when the request does not meet policy criteria or plan requirements.

Drug is not FDA-approved where approval is required by this policy
Requested indication is not supported by accepted compendia, InterQual, or peer-reviewed literature as specified
Drug is not a covered benefit under the member's applicable state Medicaid or contractual plan
Insufficient documentation of prior treatment failure, contraindication, or intolerance

Note

Provider Action Summary

Provider action callout. Before submitting requests, confirm the member's benefit plan terms, assemble all required documentation, and ensure prior authorization is obtained when required.

Confirm member eligibility and benefit design (federal/state/contractual)
Attach compendia citations, InterQual references, or peer-reviewed articles supporting the indication
Document prior therapies and reasons for failure/intolerance in the medical record
Indicate if the patient is enrolled in an eligible clinical trial (coverage is not available under this policy if enrolled)

Prior versionPrevious policy version CSIND0054.04 was archived during this update.