Investigational (Experimental) Services

Description of Service

BCBSNC defines the terms "investigational" or "experimental" as the use of a service that is not recognized by the Plan as standard medical care for the condition, disease, illness or injury being treated. A service includes, but is not limited to the diagnostic service, procedure, test, treatment, facility, equipment, drug or device.

Related policies:

Clinical Trial Services

Medical Necessity

New-To-Market Specialty Drug PPA Requirements

***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician.

Policy

BCBSNC will not provide coverage for Investigational (Experimental) Services, except for covered clinical trial services (see Clinical Trial Services policy). Investigational (Experimental) Services do not meet the criteria for "medically necessary services" because these services are not standard medical practice (see Medical Necessity policy).

Benefits Application

This medical policy relates only to the services described herein. Please refer to the Member's Benefit Booklet for availability of benefits. Member's benefits may vary according to benefit design; therefore member benefit language should be reviewed before applying the terms of this medical policy.

This policy will apply to all product lines of business unless otherwise indicated by the member’s certificate/contract (e.g., self-funded groups).

When Investigational (Experimental) Services are covered

Investigational (Experimental) Services are not covered except as delineated in the Clinical Trial Services medical policy.

**NOTE: Investigational (Experimental) Services may be covered in circumstances related to treatment of the 2019 novel Coronavirus (COVID-19) as outlined above in “Update on Investigational (Experimental) Services for COVID-19 Treatment”.**

When Investigational (Experimental) Services are not covered

Investigational (Experimental) Services are not covered. BCBSNC does not cover Investigational (Experimental) services.

A service is considered Investigational (Experimental) if any of the following criteria are met:

1. The service requiring Federal or other Governmental body approval, does not have unrestricted market approval from the Food and Drug Administration (FDA) or final approval from any other governmental regulatory body for use in treatment of a specified condition. Any approval that is granted as an interim step in the regulatory process is not a substitute for final or unrestricted market approval. 
2. There is insufficient or inconclusive evidence published in peer-reviewed medical literature to permit the Plan to evaluate the clinical effectiveness of the service. “Evidence” means well-designed and well-documented investigations published in peerreviewed medical literature. 
3. There is inconclusive evidence published in peer-reviewed medical literature that the service improves health outcomes and outweighs any harmful effects and/or safety risk. 
4. There is insufficient or inconclusive evidence published in peer-reviewed medical literature that the service under consideration is as beneficial as established alternatives, including insufficient or inconclusive evidence as to whether the service presents harmful effects and/or safety risks that established alternatives do not present. 
5. There is insufficient or inconclusive evidence published in peer-reviewed medical literature that, when used in a non-investigational setting, the service is as beneficial as established alternatives, including insufficient or inconclusive evidence as to whether the service results in a measurable improvement in health outcomes and/or outweighs the risk of the service. 

Note: BCBSNC does not cover investigational, cosmetic or not medically necessary services and will not reimburse for any services associated with those investigational, cosmetic or not medically necessary services.

A requirement in a medical policy for enrollment in a patient registry to prospectively collect clinical outcomes data does not define a service as investigational.

Policy Guidelines

Determinations are made by the Plan after BCBSNC’s review of available Medical and Scientific Evidence as defined below. Evidence-based physician specialty societal guidelines, opinions of experts in a particular field, and opinions and assessments of nationally recognized review organizations may also be considered by the Plan but are not determinative or conclusive.

Medical and Scientific Evidence is defined by BCBSNC as one of the following: 

1. Peer-reviewed scientific studies published in or accepted for publication by medical journals that meet nationally recognized requirements for scientific manuscripts and that submit most of their published articles for review by experts who are not part of the editorial staff. 
2. Peer-reviewed literature or biomedical compendia from such sources as the National Institute of Health’s National Library of Medicine or The Cochrane Library. 
3. An accepted indication for treatment in one of the following standard reference compendia:
   • The American Hospital Formulary Service-Drug Information,
   • The American Medical Association Drug Evaluations, 
   • The American Dental Association Accepted Dental Therapeutics, and
   • The United States Pharmacopoeia Drug Information. 
4. An accepted indication for treatment of cancer in one of the following standard reference compendia, for drugs approved by the FDA for treatment of cancer: 
   • The National Comprehensive Cancer Network Drugs & Biologics Compendium 
   • The Thomson Micromedex ® DRUGDEX ® 
   • The Elsevier Gold Standard’s Clinical Pharmacology 
   • Any other authoritative compendia as recognized periodically by the United States Secretary of Health and Human Services. 
5. Findings, studies, or research conducted by or under the auspices of federal government agencies and nationally recognized federal research institutes including the: 
   • U.S. Department of Health and Human Services, 
   • Federal Agency for Healthcare Research and Quality, 
   • National Institutes of Health, 
   • National Cancer Institute, 
   • National Academy of Sciences, 
   • Center for Medicare and Medicaid Services, and 
   • Any national board recognized by the National Institutes of Health for the purpose of evaluating the medical value of health services.

Billing/Coding/Physician Documentation Information

This policy may apply to the following codes. Inclusion of a code in this section does not guarantee that it will be reimbursed. For further information on reimbursement guidelines, please see Administrative Policies on the Blue Cross Blue Shield of North Carolina web site at www.bcbsnc.com. They are listed in the Category Search on the Medical Policy search page.

Applicable service codes: See procedure code for the specific procedure or service.

BCBSNC may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included. 

Scientific Background and Reference Sources

BCBSA Medical Policy Reference Manual

Specialty Matched Consultant Advisory Panel - 11/1999

Medical Policy Advisory Group - 12/2/1999

Medical Policy Advisory Group - 9/2001

Medical Policy Advisory Group - 2/2002

Medical Policy Advisory Group - 3/2002

Medical Policy Advisory Group - 10/2003

Medical Policy Advisory Group - 9/2005

Senior Medical Director review 1/2017

Medical Director review 4/2020

Specialty Matched Consultant Advisory Panel 11/2020

Medical Director review 11/2021

Specialty Matched Consultant Advisory Panel 11/2021

Medical Director Review 12/2021

Specialty Matched Consultant Advisory Panel 11/2022

Medical Director Review 11/2022

Medical Director Review 3/2023

Specialty Matched Consultant Advisory Panel 11/2023

Medical Director Review 11/2023

Specialty Matched Consultant Advisory Panel 11/2024

Medical Director Review 11/2024

Policy Implementation/Update Information

1/96 Original Policy issued

8/96 Revised: Updated list with removal of the following policies: Laser Prostatectomy, Terbutaline Infusion Pump, and TIPS.

6/97 Policy revised to include non-FDA approved drugs, devices, equipment, and supplies.

11/98 Revised to remove the list of procedures considered investigational. Check specific policy for proper coverage guidelines.

9/99 Reformatted, Medical Term definitions added.

12/99 Reaffirmed, Medical Policy Advisory Group

4/01 S9990, S9991 removed from coding section.

9/01 Medical Policy Advisory Group review. No change to policy.

4/02 Medical Policy Advisory Group review 2/02 and 3/02. Policy revised based on clinical trials mandate and medical consultant recommendations. Revised the definition for Medical and Scientific Evidence to include review from The Cochrane Library.

10/03 Medical Policy Advisory Group review. Information added in Benefits Application and Billing and Coding sections of the policy. No change in criteria. Format change.

11/03 Corrected Benefit Application Section.

3/04 Policy Number changed from ADM9060 to MED1263.

10/8/05 Medical Policy Advisory Group review on 09/08/2005. No changes to policy coverage criteria.

4/9/07 Policy Number changed from MED1263 to ADM9051.

05/05/08 Policy reviewed 4/4/2008 by Vice President and Senior Medical Director of Provider Partnerships, Medical and Reimbursement Policy. No changes to policy criteria.

09/28/09 Under the section, “When Investigational (Experimental) Services are not covered” added the following: Note: BCBSNC does not cover investigational, cosmetic or not medically necessary services and will not reimburse for any services, procedures, drugs or supplies associated with those investigational, cosmetic or not medically necessary services.” for clarification purposes. Active policy, no longer scheduled for routine review.

6/22/10 Policy Number(s) removed (amw)

7/1/2014 Policy category changed from Medical Policy to Reimbursement policy. No change to current policy statement. (adn)

7/15/2014 Policy category name returned to “Corporate Medical Policy.” (adn)

11/24/15 Review dates removed from policy header. No change to policy content. (adn)

1/27/17 Added Appendix to the policy on pages 5-7. Under “Medical and Scientific Evidence as defined by BCBSNC on page 3, added accepted compendia for oncology drugs statement: “An accepted indication for treatment of cancer in one of the following standard reference compendia, for drugs approved by the FDA for treatment of cancer:The National Comprehensive Cancer Network Drugs & Biologics Compendium, The Thomson Micromedex ® DRUGDEX ®, The Elsevier Gold Standard’s Clinical Pharmacology, and Any other authoritative compendia as recognized periodically by the United States Secretary of Health and Human Services. Senior Medical Director review 1/2017. (lpr)

4/1/19 Added Avalon tag AHS-B0005 to policy name. (lpr)

10/15/19 Removed Avalon tag “AHS” from policy name to clarify this is a BCBSNC policy that applies to all medical coverage policies. (eel)

12/31/19 Description section updated. Definition of service added for clarity. Evidence based physician specialty societal guidelines added to Policy Guidelines. Added to when not covered section #2 “Evidence that permits conclusions concerning the effect on health outcomes is generally considered to be of moderate to high strength, based on welldesigned and well-conducted studies.“ Added to when not covered section #3 “The services’ beneficial effects on health outcomes does not outweigh any harmful effects on health outcomes.” Added to when not covered section note “A requirement in a medical policy for enrollment in a patient registry to prospectively collect clinical outcomes data does not define a service as investigational.“ Specialty Matched Consultant Advisory Panel review 11/19/2019. No change to policy statement. (eel)

4/3/20 “Update on Investigational (Experimental) Services for COVID-19 Treatment” temporarily added to policy with the following statements: “BCBSNC recognizes the need for safe and effective, potentially life-saving treatments for COVID-19, including use of drugs approved for indications other than COVID-19 (off-label use) or investigational drugs for which data does not exist to inform clinical use in patients with COVID-19. BCBSNC may consider coverage of investigational (experimental) services in the absence of efficacy data for patients with confirmed COVID-19 disease if the potential for benefit is felt to outweigh the risk. BCBSNC will not provide coverage for COVID-19 treatments which the FDA has deemed unsafe for use, or has prohibited use for safety reasons. BCBSNC encourages participation in COVID-19-related clinical trials and prospective registries when possible.” Added the following statement to “When Covered” section: “NOTE: Investigational (Experimental) Services may be covered in circumstances related to treatment of the 2019 novel Coronavirus (COVID-19) as outlined above in “Update on Investigational (Experimental) Services for COVID-19 Treatment.” The expansion is limited to the timeframe outlined within the policy and subject to defined extensions as needed. Medical Director review 4/2020. (krc)

5/1/20 COVID-19 related changes extended “effective from March 6, 2020 until June 5, 2020, and then will be re-evaluated for extension every 30 days thereafter.” (eel)

6/5/20 COVID-19 related changes extended “effective from March 6, 2020 until July 5, 2020, and then will be re-evaluated for extension every 30 days thereafter.” (eel)

6/26/20 COVID-19 related changes extended “effective from March 6, 2020 until August 4, 2020, and then will be re-evaluated for extension every 30 days thereafter.” (eel)

7/30/20 COVID-19 related changes extended “effective from March 6, 2020 until September 30, 2020. We will reevaluate if an additional extension is needed as we approach September 30.” (eel)

9/29/20 COVID-19 related changes extended “effective from March 6, 2020 through December 31, 2020. We will reevaluate if an additional extension is needed as we approach December 31.” (eel)

11/20/20 COVID-19 related changes extended “effective from March 6, 2020 through June 30, 2021. We will reevaluate if an additional extension is needed as we approach June 30.” (eel)

12/8/20 Specialty Matched Consultant Advisory Panel review 11/18/2020. No change to policy statement. (cw)

2/9/21 Last CAP Review date corrected from 2019 to 2020. (bb)

6/1/21 COVID-19 related changes extended “effective from March 6, 2020 through December 31, 2021. We will reevaluate if an additional extension is needed as we approach December 31.” (bb)

11/30/21 Specialty Matched Consultant Advisory Panel review 11/2021. No change to policy statement. (tt)

12/31/21 COVID-19 related changes removed for 12/31/2021 deadline. Medical Director review. (tt)

1/11/22 COVID-19 related changes extended “effective from March 6, 2020 through June 30, 2022. We will reevaluate if an additional extension is needed as we approach June 30.” (tt)

6/30/22 COVID-19 related changes extended “effective from March 6, 2020 through September 30, 2022. We will reevaluate if an additional extension is needed as we approach September 30.” Medical Director review. (tt)

9/30/22 COVID-19 related changes extended “effective from March 6, 2020 through December 31, 2022. We will reevaluate if an additional extension is needed as we approach December 31.” Medical Director review 9/2022. (tt)

11/29/22 Specialty Matched Consultant Advisory Panel review 11/2022. COVID-19 related changes extended “effective from March 6, 2020, through March 31, 2023. We will reevaluate if an additional extension is needed as we approach March 31.” When Not Covered and Policy Guidelines sections updated for clarity. Medical Director review 11/2022. (tt)

3/7/23 COVID-19 related changes removed due to PHE expiration on 5/11/2023. Medical Director review 3/2023. Notification given 3/7/2023 for effective date 5/16/2023. (tt)

12/5/23 Specialty Matched Consultant Advisory Panel review 11/2023. Medical Director review 11/2023. No change to policy statement. (tt)

12/17/24 Specialty Matched Consultant Advisory Panel review 11/2024. Medical Director review 11/2024. No change to policy statement. (tt)

Appendix: Evidence Standards from NCCN, DrugDex ®, and Clinical Pharmacology/Gold Standard

NCCN

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is (non-uniform) 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.

DRUGDEX

Strength of recommendation

Strength of evidence

Efficacy

Clinical Pharmacology/Gold Standard

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.

The GRADE system provides guidelines for evaluating and rating the quality of evidence and utilizes four (4) quality of evidence levels:

• High 
• Moderate 
• Low 
• Very Low