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Investigational Criteria

Policy Number: MP-495

Latest Review Date: October 2019

Category: Administrative                                                      

Policy Grade: N/A


Investigational (experimental) services/supplies are considered not medically necessary.


Investigational is defined as any treatment, procedure, facility, equipment, drug, drug usage or supplier that either the plan has not recognized as having scientifically established medical value, or does not meet generally accepted standards of medical practice. Information is reviewed from the published peer-reviewed literature, recognized standards of practice and technology assessments to determine if the service in question meets specific criteria to determine coverage.


The following criteria are used to determine if a service or supply will be considered non-investigational:

  • The technology must have final approval from the appropriate government regulatory bodies.
  • The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
  • The technology must improve the net health outcome;
  • The technology must be as beneficial as any established alternatives; AND,
  • The improvement must be attainable outside the investigational setting.


When we make determinations about the investigational nature of a service or supply we are making them solely for the purpose of determining whether to pay for the service or supply under a member’s contract coverage. All decisions concerning treatment should be made solely by the physician or other medical providers.


The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services. The FDA is responsible for protecting and promoting health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs, vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices, veterinary products and cosmetics.

New drugs receive extensive scrutiny before FDA approval in a process called a New Drug Application or NDA. New drugs are available only by prescription by default. A change to over-the-counter (OTC) status is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be “safe and effective when used as directed.”

The term “off-label” refers to drug usage for indications other than those approved by the FDA. Drug companies may not submit for a separate FDA approval for their drugs for new indications. Many times drugs will be used off-label for other conditions based on the hypothesis that the mechanism of action will also work for this condition. When published literature or other pharmacopedia reviews show that the off-label use is effective the drug may be used as a treatment option and become a standard of care.

After approval of an NDA, the sponsor must review and report to the FDA every patient adverse drug experience of which it learns. Unexpected serious and fatal adverse drug events must be reported within 15 days, and other events on a quarterly basis. The FDA also receives directly adverse drug event reports through its MedWatch program. These reports are called “spontaneous report” because reporting by consumers and health professionals is voluntary. While this remains the primary tool of postmarket safety surveillance, FDA requirements for postmarketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials, called Phase IV trials. In some cases, the FDA requires risk management plans for some drugs that may provide for other kinds of studies, restrictions, or safety surveillance activities.

The Center for Biologics Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process similar to that for drugs.

The Center for Devices and Radiological Health (CDRH) is the branch of the FDA responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices. The definition of a medical device is given in the FD&C Act, and it includes products from the simple toothbrush to complex devices such as implantable brain pacemakers. CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment, television receivers, microwave ovens, tanning booths, and laser products.

CDRH regulatory powers include the authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or non-compliant products. CDRH also conducts limited amounts of direct product testing.

Clearance requests are for medical devices that prove they are “substantially equivalent” to the predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate “safety and efficacy”, for example it may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed.

All five criteria referenced in the policy description must be met before a service or device is determined not to be investigational. The FDA status is only one of the criteria which must be met.

The following descriptions may assist in determining if a service should be questioned as possibly investigational or experimental.

  • Very few providers perform this procedure.
  • The patient may have to travel to another area of the Country to receive this treatment and the condition is not extremely rare.
  • The treatment is not performed in the United States.
  • There is not a Current Procedural Terminology (CPT) code for the service, or the only code assigned is a category III tracking code.
  • There is not a specific HCPCS code to report the service or supply.
  • The only clinical studies published are not peer-reviewed or are sponsored by the manufacturer or developer.
  • The device has to be approved by an Institutional Review Board or is part of a clinical trial.


Investigational, Experimental


This includes product approvals issued by the Food and Drug Administration, an agency of the United States Department of Health & Human Services.


Coverage is subject to member’s specific benefits.  Group specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply.

FEP:  Special benefit consideration may apply.  Refer to member’s benefit plan.  FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.


CPT Codes:     Not applicable


  1. website.
  2. Blue Cross and Blue Shield Association, the Technology Evaluation Center (TEC): Evidence-based Practice Center. October 2007. Agency for Healthcare Research and Quality, Rockville, MD.


Medical Policy Group (3), April 2012

Medical Policy Administration Committee, May 2012

Available for comment May 10 – June 25, 2012

Medical Policy Group, March 2015 (3):  2015 Update – no new literature or information to reference; verbiage update to policy statement - no change in intent of policy statement; References updated

Medical Policy Group, August 2017 (3):  2017 Update – no new literature or information to reference; reviewed by consensus; no change in policy statement

Medical Policy Group, October 2019 (7):  2019 Update – no new literature or information to reference; reviewed by consensus; no change in policy statement.


This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

  1. The technology must have final approval from the appropriate government regulatory bodies;
  2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
  3. The technology must improve the net health outcome;
  4.  The technology must be as beneficial as any established alternatives;
  5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

  1. In accordance with generally accepted standards of medical practice; and
  2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
  3. Not primarily for the convenience of the patient, physician or other health care provider; and
  4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.