Clinical Trial Definitions

The Center for Medicaid and Medicare Services (CMS) will reimburse certain costs associated with a "Qualifying Clinical Trial (QCT)." A QCT is a trial that meets the requirements set forth in the Clinical Trial Policy (NCD 310.1) by the Center for Medicare and Medicaid Service (CMS). Once a trial has been determined to be a QCT, the routine costs associated with it are billable to and reimbursable by Medicare and third party payors.

As outlined below, there are three (3) mandatory criteria and seven (7) desirable characteristics to be designated a QCT.

The "3 requirements":

1. The study evaluates an item/service within a Medicare benefit category that is not statutorily excluded,
2. The study has therapeutic intent, and
3. Trials of therapeutic interventions must enroll patients with diagnosed disease (but may enroll healthy control group.).

And: "Deemed" to meet the additional required 7 Desirable Characteristics because it falls
into one of the following:

4. Funded by NIH, CDC, AHRQ, CMS, DOD, and VA
5. Supported by centers or cooperative groups funded by NIH, CDC, AHRQ, CMS,
   DOD, VA
6. Conducted under an investigational new drug application (IND) reviewed by the FDA
7. Exempt from having an IND under 21 CFR 312.2(b)(1)

7 Desirable Characteristics:

1. The principal purpose of the trial is to test whether the intervention potentially improves the participants' health outcomes;
2. The trial is well-supported by available scientific and medical information or it is intended to clarify or establish the health outcomes of interventions already in common clinical use;
3. The trial does not unjustifiably duplicate existing studies;
4. The trial design is appropriate to answer the research question being asked in the trial;
5. The trial is sponsored by a credible organization or individual capable of executing the proposed trial successfully;
6. The trial is in compliance with Federal regulations relating to the protection of human subjects; and
7. All aspects of the trial are conducted according to the appropriate standards of scientific integrity.

Self-certification by the Principal Investigator was initially contemplated but never implemented by CMS and may not be used to determine whether a study qualifies for coverage.

To learn more about how to register, maintain, or submit results in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

Registration at ClinicalTrials.gov is required for trials that meet the Food and Drug Administration Amendments Act of 2007 (FDAAA) section 801 definition of an “Applicable Clinical Trial”, which includes the following:

1. Controlled clinical investigations (other than phase 1 investigations) of any U.S. Food and Drug Administration (FDA)-regulated drug or biological product for any disease or condition.
2. Certain studies of FDA-regulated medical devices, excluding small clinical trials to determine feasibility and certain clinical trials to test prototype devices, but including FDA-required pediatric post-market surveillances of a device product.*

Applicable clinical trials generally include interventional studies (with one or more arms) of FDA-regulated drugs, biological products, or devices that meet one of the following conditions:

• The trial has one or more sites in the United States;
• The trial is conducted under an FDA investigational new drug application or investigational device exemption;
• The trial involves a drug, biologic, or device that is manufactured in the United States or its territories and is exported for research

Please see the Applicable Clinical Trial Checklist for more guidance regarding this definition.

To learn more about how to register, maintain, or submit results in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

*Early Feasibility trials are typically excluded from this definition. Early Feasibility trials typically have 10 or fewer participants. FDA guidance further states that Early Feasibility trials are limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication. The guidance further defines a “traditional feasibility study” as a clinical investigation that is commonly used to capture preliminary safety and effectiveness information on a near-final or final device design to adequately plan an appropriate pivotal study.

The International Committee of Medical Journal Editors (ICMJE) defines a clinical trial as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the relationship between a health-related intervention and a health outcome. Health-related interventions are those used to modify a biomedical or health-related outcome; examples include drugs, surgical procedures, devices, behavioral treatments, educational programs, dietary interventions, quality improvement interventions, and process-of-care changes. Health outcomes are any biomedical or health-related measures obtained in patients or participants, including pharmacokinetic measures and adverse events.

Please see the ICMJE website for more guidance regarding this definition.

To learn more about how to register, maintain, or submit results in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

The National Institute of Health (NIH) defines a clinical trial as any NIH funded research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.

Note: Basic experimental studies involving humans (BESH) are studies that meet both the definition of basic research and the NIH definition of a clinical trial. BESH therefore are subject to NIH clinical trials policies such as registration and results reporting. More information can be found on the NIH website.

NIH applications/proposals involving clinical trials with due dates on or after January 25, 2018 must be submitted to an FOA or request for proposal (RFP) that explicitly states it will accept clinical trials.

The NIH has special considerations for Training, Fellowship, and Career Development Awards. Please see below:

• Institutional Training awards do not support clinical trials (with the exception of some D43 and K12 awards).
• The NIH encourages fellows to receive training in clinical research, however, NIH supported fellows are not permitted to conduct a clinical trial independently.
• Career Development awards may support either independent clinical trials or a mentored research training experience, depending on the FOA.

Please see the NIH website for more guidance regarding this definition.

To learn more about how to register, maintain, or submit reports in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

The Office of Human Research Protections (OHRP) defines a clinical trials as any "federally funded research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes."

Please see the OHRP website for more guidance regarding this definition.

To learn more about how to register, maintain, or submit reports in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

The Patient-Centered Outcomes Research Institute (PCORI) does not have an explicit definition of what they consider to be a clinical trial. However, PCORI has a process regarding their funding of "comparative clinical effectiveness clinical trials and observational studies" in which registration is required.

Please see the PCORI process document for more guidance regarding this definition.

To learn more about how to register, maintain, or submit reports in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

The Office of Research and Development (ORD) within the Department of Veterans Affairs (VA) defines a clinical trial as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of the interventions on biomedical or behavioral health-related outcomes."

Please see the VA website for more guidance regarding this definition.

To learn more about how to register, maintain, or submit reports in clinicaltrials.gov, please see our Clinical Trials Procedures Page.

The World Health Organization (WHO) defines a clinical trial as "any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Clinical trials may also be referred to as interventional trials. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiologic procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc. This definition includes Phase I to Phase IV trials."

Please see the WHO website for more guidance regarding this definition.

To learn more about how to register, maintain, or submit reports in clinicaltrials.gov, please see our Clinical Trials Procedures Page.