Clinical Trials  Medical Policy Article

**Abstract:**  
  
From the inception of the Medicare program, items and services that were
deemed "experimental or investigational" were statutorily excluded from
Medicare coverage. In recent years, there has been a growing number of
exceptions to this statutory exclusion, and the rules for coverage under these
exceptions have become increasingly complex. Currently, Medicare coverage is
available for Category B Investigational Devices, services under CMS' Coverage
with Evidence Development trials, and other qualifying clinical trials. CMS
National Coverage Determination (NCD) for Routine Costs in Clinical Trials
(CMS Pub.100-03, Section 310.1) provides instructions for coverage of these
clinical trials. This article summarizes and discusses Medicare coverage of
the routine costs of these other qualifying trials.  
  
In 2000, President Clinton issued an executive order directing CMS to cover
the "routine costs" of clinical trials for Medicare beneficiaries. These
routine costs include the provision of the investigational item, but not the
investigational item itself, the prevention, diagnosis, and treatment of
complications, and generally all items and services that would be covered for
a Medicare beneficiary absent the clinical trial.  
  
 **Indications:**  
  
There are several criteria for which clinical trials are eligible for coverage
of their routine costs.  
  
Trials that are deemed to be automatically qualified include:

  * trials funded by NIH, CDC, AHRQ, CMS, DOD, and VA;
  * trials supported by centers or cooperative groups that are funded by NIH, CDC, AHRQ, CMS, DOD, and VA;
  * trials conducted under an investigational new drug application (IND) reviewed by the FDA; or
  * IND exempt drug trials under 21 CFR 312.2(b)(1) will be deemed automatically qualified until the self-certification process is in place.</ul type=disc>
  * Other clinical trials, not falling into the above categories, must meet all the following requirements: 
    * The trial must evaluate an item or service that falls within a Medicare benefit category
    * The trial must not be designed exclusively to test toxicity or disease pathophysiology. It must have a therapeutic intent
    * Trials of therapeutic interventions must enroll patients with diagnosed disease, not healthy volunteers</ul type=disc>
    * Note: Trials of diagnostic interventions may enroll healthy patients as a control group.  
  
In addition to these requirements, covered clinical trials should have the
following desirable characteristics:

      * Tests whether the intervention potentially improves the participants' health outcomes
      * Is well supported by available scientific literature, or is intended to clarify the health outcomes of interventions already in common clinical use
      * Does not unjustifiably duplicate existing studies
      * Design is appropriate to answer the research question
      * Is sponsored by a credible organization or individual
      * Is in compliance with Federal regulations on protection of human subjects
      * All aspects are conducted according to the appropriate standards of scientific integrity</ul type=disc>
      * The local contractor may provide assistance in determining whether a clinical trial that is not automatically deemed to qualify meets Medicare requirements for coverage of routine costs.  
  
In general, the routine costs of a clinical trial include those costs that a
Medicare beneficiary would be eligible for if there were no clinical trial.
This principle tries to ensure that Medicare beneficiaries are not penalized
nor have items or services taken away from them if they participate in a
qualifying clinical trial. These routine costs include:

        * Items or services typically provided absent a clinical trial (e.g., conventional care);
        * Items or services required solely for the provision of the investigational item or service;
        * Clinically appropriate monitoring of the effects of the investigational item or service;
        * Prevention of complications; and
        * Items or services for reasonable and necessary care arising from the provision of an investigational item or service, especially for the diagnosis and treatment of complications.</ul type=disc>
        * **Limitations:**  
  
Items and services not covered as "routine services" in a clinical trial
include:

          * The investigational item or service itself, unless otherwise covered outside the clinical trial;
          * Items and services for the purpose of determining eligibility for the study not related to medically necessary clinical care;
          * Items and services provided solely to satisfy data collection and not necessary for clinical management; and
          * Items and services customarily provided by the research sponsors free of charge for any enrollee in the trial.</ul type=disc>
          * The investigational items or services themselves are not covered as routine costs, unless those items or services are available to Medicare beneficiaries absent a clinical trial. For instance, if a qualifying clinical trial is studying a drug for a non-FDA approved indication, the drug is not covered because it is not otherwise available to Medicare beneficiaries for that experimental indication, even if the drug is FDA approved for other indications. Conversely, if an investigator is doing a head-to-head study of two standard-of-practice procedures to see which one is superior in a given circumstance, then the procedures under study are also covered, even though they are the "experimental service," because these services are otherwise covered for Medicare beneficiaries.   
  
Items and services provided solely for data collection are important non-
routine costs to separate out from the costs constituting the standard of
care. Patients in clinical trials often have laboratory and radiological
studies which exceed the requirements for the ordinary clinical care of a
patient because the requirements for the study's data collection are higher
than what is required for the clinical care of the patient (e.g., monthly CT
scans for a condition usually requiring only a single scan). All the tests and
services in excess of what is required for ordinary clinical care are
considered non-routine, and are not covered. Providers should document which
items and services are required as a part of ordinary clinical care, which are
required in addition to meet the data collection requirements of the study,
and should bill these respectively as covered or noncovered, respectively.
Documentation of covered vs. noncovered services for each study will support
the appropriateness of the bills submitted to Medicare, should these services
be reviewed.  
  
Items and services customarily provided by the research sponsors free of
charge for any enrollee in the trial should likewise not be billed to
Medicare. Items and services provided regularly free of charge to any segment
of the study's enrollees are not included as routine costs and are not
dependent on payer type. For example, because Medicare may pay for certain
costs in the study, but other payers will not and the study sponsor provides
those items or services for free to those study participants, then Medicare
likewise must not be billed for those items and services. Medicare's potential
willingness to pay for an item or service does not determine whether that item
or service is covered. Medicare must be on a level playing field with all
payer types regarding billing for the routine costs in clinical trials. The
one exception to this rule is for patients who are indigent and for whom the
hospital routinely offers care without payment. Services to such individuals
who do not have the ability to pay and for whom the hospital policy is to
provide free care would not inhibit the hospital from billing Medicare for
those same items and services it has furnished to these individuals without
reimbursement.  
  
Other items and services not covered as routine costs include otherwise non-
covered items and services, including items and services for which payment is
statutorily prohibited, unless required for the treatment of complications.
Guidance from the contractor may be required to determine if such treatment of
complications are covered. Also, investigational items and services in a
qualifying clinical trial that are not covered by virtue of a NCD remain not
covered for patients in the trial, although the routine costs may still be
covered. In addition, coverage of routine costs in a clinical trial is subject
to any applicable coverage provisions in the contractor's local coverage
determinations that may be in effect.  
  
Providers are expected to review the items and services that may be billed to
Medicare for each qualifying clinical trial they participate in and to make a
determination for each item and service, whether it is covered or not covered
under these rules. For unusual situations for which the provider may be unable
to make their own determination, the Medicare contractor to which you submit
your claims may be of assistance.  
  
 **Utilization:**  
Not applicable  
  
 **Documentation Requirements:**  
  
The medical record must contain documentation that the services billed to
Medicare meet the criteria defined in the Indications and Limitations section
of this article.  
  
In addition, documentation must be available in the medical record of covered
vs. noncovered services for each study that will support the appropriateness
of the bills submitted to Medicare, should these services be reviewed.  
  
**Coding Guidelines:  
  
General Guidelines for claims submitted to Part A or Part B MAC:**  
  
Procedure codes may be subject to National Correct Coding Initiative (NCCI)
edits or OPPS packaging edits. Refer to NCCI and OPPS requirements prior to
billing Medicare.  
  
For services requiring a referring/ordering physician, the name and NPI of the
referring/ordering physician must be reported on the claim.  
  
The diagnosis code(s) must best describe the patient's condition for which the
service was performed.  
  
A claim submitted without a valid ICD-10-CM diagnosis code will be returned to
the provider as an incomplete claim under Section 1833(e) of the Social
Security Act.  
  
Providers should enter clinical trial and non-clinical trial services on
separate lines when both types of services are submitted on the same claim
form.  
  
Items and services provided free of charge by research sponsors should not be
billed to Medicare. If these items are required for payment of another payable
service, providers should submit the items as non-covered (use modifiers FB
and GX or GY). For OPPS claims, a token charge must be entered on the line for
a no-cost item.  
  
 _Advance Beneficiary Notice of Noncoverage (ABN) Modifier Guidelines_  
An ABN may be used for services which are likely to be non-covered, whether
for medical necessity or for other reasons. Refer to CMS Publication 100-04,
Medicare Claims Processing Manual, Chapter 30, for complete instructions.  
  
Effective from April 1, 2010, non-covered services should be billed with
modifier -GA, -GX, -GY, or -GZ, as appropriate.  
  
The -GA modifier ("Waiver of Liability Statement Issued as Required by Payer
Policy") should be used when physicians, practitioners, or suppliers want to
indicate that they anticipate that Medicare will deny a specific service as
not reasonable and necessary and they **do have** an ABN signed by the
beneficiary on file. Modifier GA applies only when services will be denied
under reasonable and necessary provisions, sections _1862(a)(1), 1862(a)(9) ,
1879(e), or 1879(g)_ of the Social Security Act. Effective April 1, 2010, Part
A MAC systems will automatically deny services billed with modifier GA. An
ABN, Form CMS-R-131, should be signed by the beneficiary to indicate that
he/she accepts responsibility for payment. The -GA modifier may also be used
on assigned claims when a patient refuses to sign the ABN and the latter is
properly witnessed. For claims submitted to the Part A MAC, occurrence code 32
and the date of the ABN is required.  
  
Modifier GX ("Notice of Liability Issued, Voluntary Under Payer Policy")
should be used when the beneficiary has signed an ABN, and a denial is
anticipated based on provisions _other_ than medical necessity, such as
statutory exclusions of coverage or technical issues. An ABN is not required
for these denials, but if non-covered services are reported with modifier GX,
Part A MAC systems will automatically deny the services.  
  
The -GZ modifier should be used when physicians, practitioners, or suppliers
want to indicate that they expect that Medicare will deny an item or service
as not reasonable and necessary and they **have not** had an ABN signed by the
beneficiary.  
  
If the service is statutorily non-covered, or without a benefit category,
submit the appropriate CPT/HCPCS code with the -GY modifier. An ABN is not
required for these denials, and the limitation of liability does not apply for
beneficiaries. Services with modifier GY will automatically deny.  
  
**For claims submitted to the Part B MAC:**  
  
Routine costs of a clinical trial should be submitted to the Part B MAC as
follows:

            * For dates of service on or after January 1, 2008, report modifier "Q1" with each service. The primary diagnosis must be Z00.6.
            * For dates of service prior to January 1, 2008, report modifier "QV" with each service. The primary diagnosis on the claim must be Z00.6
            * As of April 1, 2008, providers have the option of reporting the 8-digit clinical trial number on the claim in item 19 of the CMS 1500 or electronic equivalent. However, this number is not required.</ul type=disc>
            * **For claims submitted to the Part A MAC**  
  
Routine costs of a clinical trial should be submitted to the Part A MAC as
follows:

              * Diagnosis Z00.6 must be reported
              * Condition code 30 is also required on institutional claims, regardless of whether all services on the claim are related to the clinical trial or not.
              * Modifiers QV or Q1 are not required on institutional claims, unless the claim includes clinical trial and non-clinical trial services (for outpatient claims). In this case, modifiers Q1 (on or after January 1, 2008) or QV (prior to January 1, 2008) must be reported with the clinical trial related services.
              * As of April 1, 2008, providers have the option of reporting the 8-digit clinical trial number on the claim in FL 39-41 of the UB-04 or electronic equivalent. However, this is not required.</ul type=disc>
              * _Hospital Inpatient Claims:_
                * The hospital should report the patient's principal diagnosis in Form Locator (FL) 67 of the UB-04. _The principal diagnosis is the condition established after study to be chiefly responsible for this admission._ For routine costs associated with clinical trials, this diagnosis will be Z00.6.
                * _The hospital enters ICD-10-CM codes for up to eight additional conditions in FLs 67A-67Q if they co-existed at the time of admission or developed subsequently, and which had an effect upon the treatment or the length of stay. It may not duplicate the principal diagnosis listed in FL 67._
                * For inpatient hospital claims, the admitting diagnosis is required and should be recorded in FL 69. (See CMS Publication 100-04, _Medicare Claims Processing Manual_ , Chapter 25, Section 75 for additional instructions.)</ul type=disc>
                * _Hospital Outpatient Claims:_
                  * _The hospital should report the full ICD-10-CM code for the diagnosis shown to be chiefly responsible for the outpatient services in FL 67._ If no definitive diagnosis is made during the outpatient evaluation, the patient's symptom is reported. If the patient arrives without a referring diagnosis, symptom or complaint, the provider _should report an ICD-10-CM code for Persons Without Reported Diagnosis Encountered During Examination and Investigation of Individuals and Populations (Z00.00-Z13.9)_. For routine costs associated with clinical trials, this diagnosis will be Z00.6.
                  * _The hospital enters the full ICD-10-CM codes in FLs 67A-67Q for up to eight other diagnoses that co-existed in addition to the diagnosis reported in FL 67._ </ul type=disc>   
  
For dates of service prior to April 1, 2010, FQHC services should be reported
with bill type 73X. For dates of service on or after April 1, 2010, bill type
77X should be used to report FQHC services.