On-Label and Off-Label Use
On-label drugs are those prescribed and used in accordance with their license. If a drug is used not in accordance with its license it is considered “off label.”
Off-label drugs can be classified in two ways:
- “Off-label on-guideline” use is when the drug is not prescribed for a condition for which it has been licensed but for a use which has been peer-reviewed for efficacy and recommended by recognized guideline-issuing organizations (such as the National Cancer Comprehensive Network [NCCN], the European Society for Medical Oncology [ESMO], or a specialty medical college or society). RGA recommends that off-label on-guideline use not be classified as experimental by health insurers.
- “Off-label off-guideline” use is when a drug prescribed is for a use for which it is not licensed and where said use has not been incorporated into an appropriate clinical guideline such as that described above. These drugs are classed as experimental and should not be covered.
There may be occasions when insurers are asked to cover the cost of drugs or medical devices that are off-label off-guideline or where studies on potential treatment indications are still in Phase I, II, or III clinical trials and therefore classified as experimental. In these cases, an insurer may wish to consider paying a portion of the claim if the treatment is part of a specific clinical trial by an appropriate governing or regulatory body within a controlled framework or is part of a strictly monitored compassionate use or expanded access program for patients with a life-threatening condition who lack further treatment options. Since such drugs are considered experimental, all contributions towards costs should be paid on an ex-gratia basis and, if appropriate, with the concurrence of the insurer’s reinsurer.
In the event of a public health emergency, an emergency use authorization (EUA) for a specific drug or treatment (e.g., a vaccine) may be granted by authorities such as the FDA or EMA. despite the drug or treatment not yet being out of clinical trials. During the EUA period, claims for the drug or treatment should be processed as if on-label and not experimental.
Non-Pharmacological Therapies and Techniques
Innovation in non-pharmacological therapies and surgical techniques is continuous and key to improving patient outcomes. However, unlike drugs and devices, recognition of novel therapies and techniques are not subject to the same governance and review required to license new drugs and devices.
In addition, recognition of new treatments as “standard of care” is usually condition-specific and are adopted by specialists in the same clinical field and/or approved by a hospital’s ethics committee, based either on outcomes of clinical trials or sufficient evidence of treatment results.
When determining if a new non-pharmacological treatment is experimental, insurers may not be able to rely on the authorization of a regulatory body. They may need to make their own assessments and determinations, and so should use consistent assessment criteria.
Insurers should also be willing to consider additional evidence to substantiate appropriate use of an experimental treatment but should continue to apply available established guidelines.
Sample policy language for assessment criteria:
To NOT be classed as experimental, a claimed treatment must either have received final approval from an appropriate government or regulatory body, or all of the following criteria must be met:
- There is sufficient scientific evidence to draw conclusions about the treatment’s effect on patient health outcomes
- It must be shown to improve net health outcomes
- It must be shown to be as beneficial as any established alternative
- Health outcomes must be consistent and repeatable
- Improvement attributable to the treatment must be attainable in non-investigational settings
Occasions when an insurer may wish to consider cover for Experimental Treatment:
- If required to by law or regulation: Local laws or insurance regulations may mandate what treatments insurers are allowed to cover or exclude. For example, the U.S. Affordable Care Act requires insurers to cover costs associated with any portion of a clinical trial that falls under a standard treatment protocol. This would include drugs as well as associated laboratory or radiological tests generally associated with care.
- If used as a replacement for an established treatment: An insurer may wish to contribute the amount it would have paid towards the cost of the conventional covered treatment, with the understanding that the claimant cannot then revert to the standard treatment protocol.
- Based on clinical outcome: An insurer may agree with a care provider to cover an experimental treatment based on a successful outcome. In such an arrangement, criteria for success would need to be defined up front. The insure would cover the cost of treatment but would receive a rebate from the provider if the pre-agreed success criteria were not achieved.
- Compassionate grounds: An insurer may also, via a strict pre-authorization process, cover certain experimental treatments on compassionate grounds. Such grounds may include a patient suffering a serious or immediately life-threatening condition for which there are no comparable or satisfactory alternative therapies to treat or diagnose the condition.
There may also be circumstances where a treatment, or a course of treatment, may not strictly adhere to guidelines but may be appropriate for certain patients based on their diagnoses and comorbidities. An insurer may want to employ the services of external experts to assess such cases if the expertise needed to assess the situation is not available internally.
If a novel treatment is proven to be effective but is more expensive, an insurer should not rely on the experimental treatment exclusion but instead should look to limit reimbursement based on policy wording pertaining to reasonable and customary costs, which should ideally preclude treatment that is more expensive than an equally effective treatment.
All payments outside of policy terms and conditions should be made ex-gratia, so as not to set precedent or prejudice the insurer’s use of policy terms in the future.
If an insurer is considering paying for an experimental treatment that would be outside of the terms and conditions of the insurer’s policy, the insurer should, if required by their reinsurance arrangement, seek reinsurance support in advance of making payment.
- “On-Label” drug use is not experimental, even if the drug is new and expensive
- “Off-Label On-Guideline” drug use is not experimental
- “Off-Label Off-Guideline” drug use is experimental, and claims should be subject to experimental treatment exclusions
- Non-pharmacological treatment, therapies, or techniques are not experimental if they have undergone appropriate studies, there is sufficient peer reviewed evidence, and they are part of clinical guidelines/pathways from an appropriate body
It is not appropriate for insurers to reimburse claims based on the concept that “the treating doctor knows best” or “because the treating doctor says so.” Treatment should be provided in accordance with best practice guidelines, and if subject to a challenge, insurers should seek to establish if there are any unique circumstances in relation to the claimant that justify deviation from best practice.