Clinical Trials

Number 11.01.503*

Effective Date September 3, 2014

Revision Date(s) 08/11/14; 08/12/13; 11/13/12; 03/23/12; 09/13/11; 10/12/10 ; 01/13/09; 01/08/08; 05/08/07; 05/09/06; 05/10/05; 03/18/05

Replaces 2.03.503

*Medicare has a policy.



(This policy is specific to Washington state mandates for clinical trials. See Benefit Application for state mandates for Alaska and Oregon members)

Member participation in a qualifying clinical trial that is researching an emerging technology that has been deemed investigational by the Company may be eligible for coverage of routine costs (see Policy Guidelines) when ALL of the following criteria are met:

  • The technology must be a treatment for a life-threatening condition that has a poor prognosis with the most effective treatment currently available.
  • The term “life-threatening condition” means any disease or condition from which the likelihood of death is probable unless the course of the disease or condition is interrupted. (1)
  • The clinical trial must have “therapeutic intent”, with the aim to potentially improve health outcomes, and not for diagnosis or supportive care.
  • The study in which the patient requests participation is a Phase I, Phase II, Phase III or Phase IV clinical trial (see Description section) that is conducted in relation to the prevention, detection or treatment of cancer or other life-threatening disease or condition funded or approved by:
  • One of the National Institutes of Health (NIH); OR
  • An NIH cooperative group or center which is a formal network of facilities that collaborate on research projects and have an established NIH-approved peer review program operating within the group including, but not limited to, the NCI Clinical Cooperative Group and the NCI Community Clinical Oncology Program; OR
  • The federal Departments of Veterans Affairs or Defense OR
  • An institutional review board (IRB) of an institution in Washington state that has a multiple project assurance contract approval by the Office of Protection for the Research Risks of the NIH; OR
  • A qualified research entity that meets the criteria for NIH Center Support Grant eligibility.
  • A signed, informed consent form is in the member’s medical record for the clinical trial.
  • The technology must have approval from the appropriate government regulatory bodies, if applicable:
  • Devices must be FDA-approved via one of the following processes:
  • PMA (Premarket Approval)
  • 510(k)
  • HDE (Humanitarian Device Exemption)
  • IDE (Investigational Device Exemption)
  • Drugs must have one of the following:
  • Final FDA approval for marketing for at least one indication via the NDA (New Drug Application) process
  • IND (Investigational New Drug) approval

Related Policies



Off Label Use of Drugs and Biologic Agents


Intraoperative Radiation Therapy (IORT)


Hematopoietic Stem-Cell Transplantation for Primary Amyloidosis


Hematopoietic Stem-Cell Transplantation for Waldenstrom Macroglobulinemia


Noncovered Services and Procedures

Policy Guidelines


To be eligible for coverage of routine costs the member must be enrolled in the qualifying clinical trial at the time coverage of routine costs is requested. Search for a registry of federally and privately supported clinical trials conducted in the United States and around the world.

Routine costs in clinical trials eligible for coverage, when the criteria in the Policy statement are met, include:

  • Items or services that are typically covered by the health plan contract for a member who is not enrolled in a clinical trial (e.g., conventional care);
  • Items or services necessary to provide the investigational item or service being studied, the clinically appropriate monitoring of the effects of the item or service, or the prevention of complications;
  • Items or services needed for reasonable and necessary care arising from the provision of an investigational item or service – in particular, for the diagnosis or treatment of complications.

Investigational costs not eligible for coverage include:

  • The investigational item or service itself (whatever is being studied), unless the investigational item or service is covered outside a clinical trial;
  • Items and services solely for data collection and analysis that are not used in the direct clinical management of the patient outside of the clinical trial (e.g., monthly CT scans for a condition where a one single scan is the standard of care);
  • Items and services provided free of charge by the research sponsors for anyone enrolled in the trial.



The Company may be asked to cover services that are provided within the context of clinical trials. These requests often represent relatively new technology or therapies or application of established therapies to treat new or rare diagnoses. Under certain controlled situations it may be appropriate to approve coverage for these services on a case by case basis.

Clinical trials are designed and used to research one or more interventions for treating a disease, syndrome, or condition before they are made available to the general public. Examples of these interventions, though not all inclusive, are medical products, drugs, devices, radiation therapy or surgical procedures. Services, supplies and drugs that are a standard of care throughout the medical community may have a clinical trial designed to demonstrate their efficacy for a different diagnosis or when they are used in combination with other therapeutic agents. Many clinical trials are designed to study and report therapeutic effectiveness over a prolonged period of time.

Phases of Clinical Trials

The progress of a clinical trial is categorized by the “phase” category assigned. Most trials can be categorized into one of four phases. A generally accepted categorization follows. Note that the cohort size is not absolute and there are exceptions.

Phase I

The therapeutic intervention is tested in a small group of people (20-80) for the first time to evaluate its safety and effectiveness. Phase 1 studies may determine the metabolic mechanism of action of the treatment in humans. In the case of drug trials, the side effects associated with increasing doses, drug metabolism and structure-activity relationships. They are primarily focused on safety.

Phase II

The treatment is applied to a larger group of people (100-300) to further evaluate effectiveness and safety. In drug studies, this phase often consists of pilot studies, which may be open label, single or double blind.

Phase III

The treatment is applied to large groups of people (1000-3000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments and collect information that will allow the treatment to be used safely.

Phase IV

The treatment continues to be tested after marketing approval of the device or drug by the Food and Drug Administration (FDA). This testing is performed to collect information about the effect in various populations and any side effects associated with long term use.

Note: In any phase of a treatment clinical trial, the FDA can impose a clinical hold if the treatment is found to be unsafe or if the protocol is clearly deficient in design in meeting its stated objectives. Institutional Review Boards (IRBs)* also may cause a trial to be suspended if some aspect of the study is found to be unsafe.

Types of U.S. Food and Drug Administration (FDA) Approval – Devices and Drugs

Clinical trials may investigate drugs or devices that have received different types of FDA approval. Some approvals may allow marketing of drugs or devices; some may approve their use only in investigational settings.  The various FDA approvals are described below.


  • PMA (Premarket Approval)
  • PMA approval by the FDA is the required process of scientific review to ensure the safety and effectiveness of Class III devices, which are defined as devices that support or sustain human life or are of substantial importance in preventing impairment of human health or present a potential, unreasonable risk of illness or injury.
  • 510(k)
  • 510(k) approval is granted by the FDA for devices that are determined to be substantially equivalent to devices already placed into one of three classification categories.
  • HDE (Humanitarian Device Exemption)
  • A humanitarian use device (HUD) is a device that is intended to benefit patients by treating or diagnosing a disease or condition that affects fewer than 4,000 individuals in the United States per year. A device manufacturer’s research and development costs could exceed its market returns for diseases or conditions affecting small patient populations. The FDA, therefore, developed and published this regulation to provide an incentive for the development of devices for use in the treatment or diagnosis of diseases affecting these populations.
  • The regulation provides for the submission of an HDE application, which is similar in both form and content to a PMA application, but is exempt from the effectiveness requirements of a PMA. An HDE application is not required to contain the results of scientifically valid clinical investigations demonstrating that the device is effective for its intended purpose. The application, however, must contain sufficient information for the FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices or alternative forms of treatment. Additionally, the applicant must demonstrate that no comparable devices are available to treat or diagnose the disease or condition, and that they could not otherwise bring the device to market.
  • An approved HDE authorizes marketing of the HUD. However, an HUD may only be used after IRB approval has been obtained for the use of the device for the FDA approved indication. The labeling for an HUD must state that the device is a humanitarian use device and that, although the device is authorized by Federal Law, the effectiveness of the device for the specific indication has not been demonstrated.
  • IDE (Investigational Device Exemption)
  • An IDE allows an investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a PMA application or a 510(k) submission to the FDA. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.


  • IND (Investigational New Drug)
  • In an IND application, sponsors — companies, research institutions, and other organizations that take responsibility for marketing a drug — must show the FDA results of pre-clinical testing they’ve done in laboratory animals and what they propose to do for human testing. At this stage, the FDA decides whether it is reasonably safe to move forward with testing the drug on humans. Drug studies in humans can begin only after an IND is reviewed by the FDA and a local institutional review board (IRB)*. Drugs with a treatment IND may not be marketed.
  • Approved NDA (New Drug Application)
  • An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured. While the NDA process includes a number of review steps, approval is considered final for the purposes of this policy once full approval is granted by the FDA.

*An Institutional Review Board (IRB) is a panel of scientists and non-scientists in hospitals and research institutions that oversees clinical research. IRBs approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study’s objectives, and other details. IRBs make sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm.

Note: This policy is specific to Washington state mandates for clinical trials. See Benefit Application section for links for state mandates regarding clinical trials for Alaska and Oregon members.



Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

Benefit Application


Services provided in a qualifying clinical trial that are approved for coverage under this medical policy will have benefits provided as detailed in the applicable benefit category (such as pharmacy, durable medical equipment (DME), medical care, etc.) that would typically be covered by the health plan for a member who is not enrolled in a clinical trial. Services provided in a clinical trial that are fully funded by another source may not be covered by the plan.


Effective September 29, 2010, Alaska has a specific state statute (Senate Bill 10) that requires health care insurers to provide insurance coverage for medical care received by a patient during certain approved clinical trials designed to test and improve prevention, diagnosis, treatment or palliation of cancer. More information regarding covered and non-covered services and other administrative criteria can be found at the following link: (Last accessed July 17, 2014.)

Note: This mandate addresses clinical trials related only to cancer.


Effective January 1, 2010, Oregon has a specific state statute (Senate Bill 316) that mandates benefit coverage for the routine costs of the care of patients enrolled in and participating in qualifying clinical trials. More information regarding covered and non-covered services and other administrative criteria can be found at the following link: . (See section 743A.192 Clinical Trials). (Last accessed July 17, 2014.)

Note: This mandate address clinical trials related to cancer or other life-threatening disease or condition.


Effective November 8, 2012, Washington has a specific Washington Administrative Code (WAC  284-43-850) that mandates benefit coverage for the routine costs of patients enrolled in and participating in qualifying clinical trials for Phases I - IV. More information regarding covered and non-covered services and other administrative criteria can be found at the following link: (Last accessed July 17, 2014.)

Note: This mandate addresses clinical trials related to cancer or other life-threatening disease or condition.

Patient Protection and Affordable Care Act (PPACA)

Effective March 23, 2010, and upheld June 28, 2012 the Patient Protection and Affordable Care Act (PPACA) has specific mandates for the routine costs of the care of patients enrolled in and participating in qualifying clinical trials. More information regarding covered and non-covered services and other administrative criteria can be found at the following link: (Last accessed July 17, 2014.)

Note: This mandate addresses clinical trials related to cancer or other life-threatening disease or condition.

Alaska and Oregon State Mandates and Self-Funded Groups

These state mandates do not generally apply if the group is self-funded. However, some self-funded groups may elect to add state mandates or similar provisions to their contracts. If the member is in a self-funded group, please check the member contract for benefits regarding clinical trials or how the group defines experimental and investigational services. The provisions for clinical trials or definitions of what is considered experimental and investigational should be administered as outlined in the group’s health plan contract.

In the absence of contract language addressing clinical trials, the criteria of this policy should be applied to members covered by self-funded group health plan contracts.



Some life threatening malignant conditions, when the currently available interventions are not known to be effective, are the subject of clinical trials. During the consecutive phases of some clinical trials, evidence emerges which strongly suggests that the services under study may be as effective, or more effective, than conventional treatment.

In addition, when clinical trials offer medical outcomes that are at least comparable to standard treatment, there may be quality of life considerations. These may include reduction of treatment side effects and treatment strategies which are more compatible with higher level functionality. In some circumstances the preliminary data from trials may provide strong indications that quality of life and longevity will likely be increased over more conventional therapy.

By providing coverage for members who chose to participate in the qualifying trials, the member benefits from having access to new technology with early evidence of efficacy, often in circumstances where no effective alternative treatments are available.



  1. Sec. 2709. Coverage for individuals participating in approved clinical trials. (2010). Patient Protection and Affordable Care Act. Retrieved from Last accessed July 17, 2014.






ICD-9 Procedure


Examination of participant in clinical trial



Services provided as part of a Phase I clinical trial



Services provided as part of a Phase II clinical trial



Services provided as part of a Phase III clinical trial



Transportation costs to and from trial location and local transportation costs (e.g., fares for taxicab or bus) for clinical trial participant and one caregiver/companion



Lodging costs (e.g., hotel charges) for clinical trial participant and one caregiver/companion



Meals for clinical trial participant and one caregiver/companion

Type of Service



Place of Service



Physician office










Add to Administrative Section - New Policy


Replace Policy and move to Medicine, sub-section Oncology - Policy title and policy number changed for clarification purposes.


Replace Policy - Policy reviewed; no change to policy statement.


Replace Policy - Policy reviewed; no changed to policy statement.


Replace Policy - Policy updated with literature review. Policy statement clarified for ease of use, but no substantial change to criteria. Criteria for devices added. Description and Rationale revised. HCPCS codes added.


Cross Reference Update - No other changes.


Replace Policy - Policy statement and guidelines clarified to define routine costs eligible for coverage and costs not eligible for coverage. Intent of policy statement unchanged.


Replace Policy - Benefit Application revised to include Oregon mandate to provide coverage for all clinical trials and links to AZ and OR mandates.


Minor update - Note added at the top of the description section regarding Arizona and Oregon Members to view benefit application.


Replace Policy - Benefit Application revised to add Alaska mandate for cancer clinical trials and delete Arizona mandate.


Minor update - Benefit Application clarified regarding AK and OR mandates and self-funded groups.


Replace Policy – Policy reviewed; no change in policy statements.


Related Policies updated; new title for 5.01.01.


Replace Policy. Policy reviewed; no change in policy statements.


Replace policy. Policy title changed to “Clinical Trials”. All references to “oncology” clinical trials changed to “Clinical Trials”. Policy statements revised to meet Washington state specific mandates which require coverage of routine costs of all qualifying clinical trials phases I-IV when criteria are met. (The prior policy related only to clinical trials phase II-III). Used the PPACA definition of “life threatening condition”. Added statement about the PPACA to the benefit application section. Reference 1 added. Added code V70.7. Policy moved to the UM section of the Medical Policy classification index and renumbered; previously 2.03.503, the policy is now 11.01.503.


Replace policy. Policy reviewed; no change in policy statements.


Update Related Policies. Delete 5.01.01 and replace with 5.01.549.


Update Related Policies. Add 8.01.530 and 8.01.531.


Annual Review. Policy reviewed. Literature search through June 2014 did not prompt addition of new references. In Benefit Application section the hyperlink to Oregon State law is revised. Policy Statement unchanged.


Update Related Polices. Add 10.01.517.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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