Clinical trials are scientific investigations of treatment alternatives designed to help compare the safety and efficacy of new, untested or nonstandard treatments to standard, currently accepted treatments. Clinical trials are intended to improve the clinician’s knowledge about a treatment to improve clinical outcomes for future patients.
Clinical trials have inclusion and exclusion criteria to assist in determining who is qualified to participate. These criteria frequently include factors like age, gender, disease type, stage of disease, medical history and previous disease treatment. These criteria allow the most appropriate candidates to participate in a clinical trial.
Participants enrolled in clinical trials must be given information regarding the trial from the health care providers administering the trial. The potential trial participant needs to be provided with the risks and potential benefits of the study so that written informed consent can be given. They must be informed that they may be receiving standard treatment, investigational treatment, placebo treatment or no treatment. Trial participants may withdraw from a trial at any time.
Protocols are the plan the clinical trials are based on. They are designed to safeguard the health of the participants and describe the candidates appropriate for the trial. They also contain a description and schedule for all aspects of the study. This includes, but is not limited to, testing required, drugs and drug dosing and the length of time the study is anticipated to take. The research team regularly monitors the health and response to treatment of the trial participants.
Phases of Clinical Trials
Clinical trials generally proceed through four phases:
Phase I trials: Researchers test an experimental drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range and to identify side effects. Typically, none of these individuals have the condition that is the treatment subject of the trial.
Phase II trials: The experimental study drug or treatment is given to a larger group of people (100-300) to see if it is effective for the disease or condition under investigation and to further evaluate its safety.
Phase III trials: The experimental study drug or treatment is usually given to a large group of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments and collect information that will allow the experimental drug or treatment to be used safely.
Phase IV trials: Post-marketing studies collect additional information, including the drug's effects in various populations, as well as risks, benefits and side effects associated with long-term use.
Medically necessary routine patient care costs for clinical trials for cancer and life-threatening conditions for members of non-grandfathered Plans are covered according to the criteria below and consistent with the Plan’s medical coverage. All reimbursement policies for members in clinical trials are consistent with policies for members NOT in clinical trials.
Routine costs in clinical trials include:
Services rendered by a physician, diagnostic or laboratory tests and other services provided during the course of treatment for a disease or condition or one of its complications that are consistent with the usual and customary standard of care.
Routine costs of a clinical trial DO NOT INCLUDE:
The investigational item, device, equipment, drug or service that is being studied.
Items and services provided solely to satisfy data collection and analysis needs and that are not used in the direct clinical management of the beneficiary (i.e., "protocol-induced costs").
Items and services customarily provided by the research sponsors without cost for the enrollee in the trial.
Items or services that are clearly inconsistent with the widely accepted and established standards of care for the disease or condition under investigation.
The costs of data collection and record-keeping that would not be required but for the clinical trial.
Here are the criteria for coverage of clinical trial services for cancer and life-threatening conditions:
- The trial is identified in one of these ways: The clinical trial must be a phase I, phase II, phase III or phase IV patient research study approved by centers or cooperative groups that are funded by the National Institutes of Health, the Food and Drug Administration, the Centers for Medicare & Medicaid Services, the Centers for Disease Control and Prevention, the Agency for Health Care Research and Quality, the Department of Defense or the Department of Veterans Affairs.
- Referral of a participating health care provider who has concluded that the individual’s participation in such a trial would be appropriate based upon the individual meeting the entry criteria of the clinical trial protocol.
- Medical and scientific information provided by the beneficiary establishing that the individual’s participation in such trial would be appropriate based upon the individual meeting the entry criteria of the clinical trial protocol.
- The member has a current diagnosis with a grave or terminal prognosis, as determined by member’s physician within a reasonable degree of medical certainty, and has failed or is refractory to all known effective interventions.
- The clinical trial must be conducted in a setting and by personnel who maintain a high level of expertise because of their training, experience and volume of patients and have a written protocol that describes a scientifically sound study that has been approved by all relevant institutional review boards (IRBs) before participants are enrolled.
- The trial must have therapeutic intent, and must not be designed exclusively to test toxicity or disease pathophysiology.
- Trials of therapeutic intent must enroll patients diagnosed with the disease or condition under investigation rather than healthy volunteers (trials of diagnostic interventions may enroll healthy patients in order to have a proper control group).
- The principal purpose of the trial is to test whether the intervention potentially improves the participant’s health outcomes and does not unjustifiably duplicate interventions in common clinical use.
- There is no alternative non-investigational therapy that is clearly superior to the treatment being received in the trial.
- The participation of the member has been prior authorized and a complete trial protocol has been provided TO THE PLAN identifying therapies, devices, services, testing and imaging that are required as part of the investigational study.
- The beneficiary must:
- Be enrolled in the trial.
- Provided documented informed consent to participate in the trial.
- Be treated according to trial protocol.
Benefit Application: This policy is specific to NON-grandfathered lines of business only.
High-Quality Clinical Trials are those whose rationale and methodology have been subjected to independent peer review; that are sponsored by an entity with a recognized program in clinical research that conducts its activities according to all appropriate federal and state regulations and generally accepted standard operating procedures governing the conduct of participating investigators; and whose results will be reported upon completion of the trial, regardless of their positive or negative nature.
High-quality clinical trials generally have the following characteristics:
- Therapeutic intent. The protocol treatment is appropriate for the patient's disease, condition and risk state, and is undertaken with therapeutic intent.
- Peer-reviewed protocol. The trial is based on a peer-reviewed written protocol with clear definitions and statements on study objectives.
- Inclusion criteria. The trial includes clear criteria for patient eligibility, including inclusion and exclusion criteria.
- Study design. The trial specifies study size (target accrual number and rate), study duration, statistical requirements and endpoints.
- National IRB-approved. The trial is approved by a federally registered Institutional Review Board (IRB).
- Review committee-monitored. The trial is overseen by a group or review committee experienced in data monitoring and management that is provided regular updates.
Informed Consent is the process of learning the key facts about a clinical trial before deciding whether to participate. The following facts must be included:
- Why the research is being done
- What the researchers want to accomplish
- What will be done during the trial and for how long
- What risks are involved in the trial
- What benefits can be expected from the trial
- What other treatments are available
- The right of the patient to ask questions or to leave the trial at any time
Informed consent must be documented in written form.
Institutional Review Board (IRB) is a duly constituted board, committee or other group formally designated by an institution to review, to approve the initiation of or to conduct periodic review of, biomedical health services research involving human subjects to ensure the protection of the safety, welfare and rights of those subjects and that meets or exceeds the requirements of Title 21, Part 50 and 56 (FDA) and Title 45, Part 46 (DHHS) of the Code of Federal Regulations (CFR) and is registered with the Office of Human Research Protection of the U.S. Department of Health and Human Services.
Program Participants are individuals who have been diagnosed with the disease being studied and who:
- Are enrolled in a non-grandfathered Plan.
- Have signed an informed consent to participate in a clinical trial.
- Have signed the necessary authorization or other appropriate privacy consent to allow for release of information to allow communication among the parties for payment, statistical analysis and administrative issues related to the clinical trial program.
Protocol-Induced Costs are costs incurred in the administration of any item or service that is required for the completion of the protocol treatment but is not usual, customary and appropriate for the patient's condition and would not typically be provided to that patient when cared for outside of a clinical trial. Examples of protocol-induced costs include:
- Items or services specified as necessary in the protocol document but delivered solely to satisfy data collection and analysis needs of the clinical trial and not used in direct clinical management of patients.
- Items or services provided by the trial sponsor without charge and the cost of the investigational item and service itself.
- Costs associated with fulfillment of regulatory requirements or contractual processes.
- Costs incurred during development of publications or travel to meetings to report protocol results.
Protocol Treatment means those items, drugs, procedures, services and schedules for administration described or specified in the IRB-approved protocol document. In the case of comparative studies, protocol treatment refers to all arms in the protocol document.
Routine Care Costs are costs incurred through the administration or performance of items or services that:
- Are required in the written protocol treatment in a high-quality clinical trial.
- Are usual, customary and appropriate to the patient's condition or disease.
- Would typically be provided for the patient's condition when cared for outside of a high-quality clinical trial, including items or services needed for the prevention, diagnosis or treatment of adverse effects and complications of the written protocol treatment.
Therapeutic Intent, as defined in the Office for Human Research Protections (OHRP) IRB Handbook, means high-quality clinical trials that "provide some benefit to improving a subject's condition" (e.g., prolongation of life, shrinkage of tumor or improved quality of life, even though cure or dramatic improvement cannot necessarily be effected.). Therapeutic intent does not include clinical trials intended to solely test toxicity.
Life-Threatening Condition is defined as any disease or condition from which, with reasonable medical certainty, the likelihood of death is probable within the next 12 months unless the course of the disease or condition is interrupted.
MANAGEMENT OVERSIGHT PROCESSES:
The request to participate in the clinical trial must be pre-certified. The clinical trial protocol is required. Services submitted for review will be evaluated on an ongoing basis for those that are standard of care for the condition investigated and those that would be considered uniquely investigational trial-related services.
The White House, Office of the Press Secretary. President Clinton takes new action to encourage participation in clinical trials. Medicare will reimburse for all routine patient care costs for those in clinical trials. White House Press Release. Washington, DC: Office of the Press Secretary, The White House; June 7, 2000.
- National Academy of Sciences, Institute of Medicine. Extending Medicare Reimbursement in Clinical Trials. Committee on Routine Patient Care Costs in Clinical Trials for Medicare Beneficiaries. Aaron HJ, Gelband H, eds. Washington, DC: National Academy Press; 2000.
- U.S. Department of Health and Human Services, Health Care Financing Administration (HCFA). Medicare coverage of clinical trials. Proposed National Coverage Decision. Baltimore, MD: HCFA; 2000. Available at: http://www.hcfa.gov/quality/8d1.htm. Accessed August 15, 2000.
- U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services (CMS). Decision Memorandum for the Clinical Trials Policy (CAG-00071R). Baltimore, MD: CMS; July 9, 2007.
- Palackdharry CS, Evans DL, McDonough RS, et al. Payer coverage for patients enrolled onto clinical trials: Making the process easy and transparent for everyone. Am J Manag Care. 2012;18(2 Spec No.):SP91-SP97.
This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.
"Current Procedural Terminology© American Medical Association. All Rights Reserved"
History From 2014 Forward
Annual review, no change to policy intent.
Annual review, no change to policy intent.
Annual review, no change to policy intent. Adding definition of "life threatening condition" and management oversight processes.
Annual review, no change to policy intent.