Clinical Policy Title: Investigational (experimental) health services

Transcription

1 Clinical Policy Title: Investigational (experimental) health services Clinical Policy Number: Effective Date: January 1, 2016 Initial Review Date: August 19, 2015 Most Recent Review Date: September 21, 2016 Next Review Date: September 2017 Policy contains: Clinical trials. Investigational (experimental) services. Related policies: None. ABOUT THIS POLICY: Keystone First has developed clinical policies to assist with making coverage determinations. Keystone First s clinical policies are based on guidelines from established industry sources, such as the Centers for Medicare & Medicaid Services (CMS), state regulatory agencies, the American Medical Association (AMA), medical specialty professional societies, and peer-reviewed professional literature. These clinical policies along with other sources, such as plan benefits and state and federal laws and regulatory requirements, including any state- or plan-specific definition of medically necessary, and the specific facts of the particular situation are considered by Keystone First when making coverage determinations. In the event of conflict between this clinical policy and plan benefits and/or state or federal laws and/or regulatory requirements, the plan benefits and/or state and federal laws and/or regulatory requirements shall control. Keystone First s clinical policies are for informational purposes only and not intended as medical advice or to direct treatment. Physicians and other health care providers are solely responsible for the treatment decisions for their patients. Keystone First s clinical policies are reflective of evidence-based medicine at the time of review. As medical science evolves, Keystone First will update its clinical policies as necessary. Keystone First s clinical policies are not guarantees of payment. The purpose of this policy is to define the medical review decision process for requests for coverage of specific health interventions that are considered investigational or experimental and not contained in a separate clinical policy. Keystone First defines the terms "investigational" or "experimental" as any procedure, test, drug, equipment or facility still undergoing study whose safety or efficacy is not known, or are services that are used in a way that departs from generally accepted standards of practice in the medical community. A service or intervention is considered investigational if it meets any of the following criteria: Criteria for investigational health services or interventions (any of the following criteria must be met) The participant is in ongoing clinical trials or is otherwise under a systematic, intensive investigation to determine its maximum tolerated dose, safety and effectiveness compared with a standard means of treatment or diagnosis. The service cannot be marketed lawfully without approval of the U.S. Food and Drug Administration (FDA). The service is not of proven benefit for the particular diagnosis or treatment of the member s particular condition. 1

2 Criteria for investigational health services or interventions (any of the following criteria must be met) The service is not generally recognized by the medical community as effective and appropriate for the diagnosis or treatment of the member s particular condition. The service is generally recognized, based on reliable evidence* and by the medical community, as a diagnostic or treatment intervention for which additional study regarding its safety and effectiveness for the diagnosis or treatment of the member s particular condition is recommended. Note: If the Pennsylvania TAG recognizes a service to not be investigational or investigational, this judgment takes priority over any corporate policy of Keystone First. If the TAG recognizes a service to be investigational or experimental, the corporate policy may or may not agree. * Reliable evidence describes peer-reviewed reports of clinical studies that have been designed according to accepted scientific standards, such that potential biases are minimized to the fullest extent, and generalizations may be made about safety and effectiveness of the technology outside of the research setting. Studies are to be published or accepted for publication in medical or scientific journals that meet nationally recognized requirements for scientific manuscripts and that are generally recognized by the relevant medical community as authoritative. Keystone First maintains a policy governing the hierarchy of strength of evidence from various sources. Furthermore, evidence-based guidelines from respected professional organizations and governmental entities may be considered reliable evidence if generally accepted by the relevant medical community. Coverage policy Keystone First considers investigational (experimental) health interventions to be not medically necessary and, therefore, not covered, except for requests that meet all of the following criteria: Criteria for medical necessity (all criteria must be met) The member has a current diagnosis that will most likely cause death within one year or less, despite therapy with currently accepted treatment. Standard interventions have been ineffective in significantly improving the member s condition. The risks and benefits are considered reasonable by the treating physicians. The member is to participate in a clinical trial satisfying all of the following criteria: The investigational drug, device or therapy is under current FDA review and has an investigational new drug (IND) number or investigational device exemption (IDE). The clinical trial has passed independent scientific scrutiny and has also been approved by an Institutional Review Board (IRB) that will oversee the investigation. The clinical trial is sponsored by the National Cancer Institute (NCI) or similar national cooperative 2

3 Criteria for medical necessity (all criteria must be met) body (e.g., Department of Defense, Department of Veterans Affairs) and conforms to the rigorous independent oversight criteria as defined by the NCI for the performance of clinical trials. The clinical trial is not a single institution or investigator study (NCI-designated Comprehensive Cancer Center trials are exempt from this requirement). The member must: Not be treated off protocol. Actually be enrolled in the trial. Note: Some investigational studies are not conducted under FDA scrutiny, but meet all the other criteria. For example, new uses of old technologies, new uses of drugs already approved by FDA (as these would not have an IND number). All other policies required for such treatment as defined by state and federal regulatory bodies, including the Centers for Medicare & Medicaid Services (CMS), pertinent state department of insurance, and department of Medicaid policy are met. For Medicare members only Keystone First considers investigational (experimental) interventions to be medically necessary when compliance with the following regulations is met: 42CFR405b Federal Health Insurance for the Aged and Disabled. Guidance for the Public, Industry, and CMS Staff Coverage with Evidence Development Document Issued on November 20, National Coverage Determination for Routine Costs in Clinical Trials (310.1). All requests for coverage of clinical trials, including routine costs, for Medicare members must be referred to the Part A/Part B Medicare administrative contractor (A/B MAC) for the geographic jurisdiction where the services will be rendered, unless it is a request involving a Category B IDE trial. Limitations: Keystone First considers all other investigational (experimental) interventions to be not medically necessary. All requests for coverage of medical services of a non-medicare member enrolled in a clinical trial and for Medicare Category B IDE clinical trials require review by a medical director. Keystone First will cover routine costs of medical care incurred while participating in clinical trials. Routine costs include: Medically necessary treatments for conditions that result as unexpected consequences (complications) of a clinical trial. 3

4 Items or services required solely for the provision of the investigational item or service (e.g., the administration of a noncovered chemotherapeutic agent), the clinically appropriate monitoring of the effects of the item or service, or the prevention of complications. Items or services that are typically provided for conventional care, regardless of whether a member is enrolled in a clinical trial. Keystone First will deny coverage for: Any clinical trial that is not related to the treatment of cancer or other life threatening disease or condition. Cost of the investigational item or service itself. Costs for data collection. Items and services customarily provided by the research sponsors free of charge for any enrollees in the trial. Items and services provided solely to satisfy data collection and analysis needs that are not used in the direct clinical management of the patient (e.g., monthly computed tomography, or CT, scans for a condition usually requiring only a single scan). Non-health care items and services (e.g., transportation, lodging, meals, special food products and personal care services) required as a result of the member s enrollment in the clinical trial. Services that are clearly inconsistent with widely accepted and established standards of care for a particular diagnosis. Note: All applicable plan limitations for coverage of out-of-network care will apply to routine patient care costs in clinical trials. Alternative covered services: Accepted standard medical practices. Background Health care providers are responsible for determining which interventions are considered proven, appropriate and accepted (standard of care or best practice) and which are not (investigational or experimental) (Steinberg, 1995; Reiser, 1994). Such determinations help distinguish interventions whose likely benefits and harms can be described and anticipated from those whose effects are unpredictable and lack adequate scientific validation. Some organizations incorporate concepts of medically necessary or medical necessity. Definitions of medically necessary vary but generally integrate legal and evidence-based concepts of appropriate and essential medical care with some required demonstration of clinical benefit (EBM, 1992; CMS, 2015; AMA, 2015). 4

5 By definition, investigational services would be considered not medically necessary. However, these decisions are not always clear cut. Frequently, providers must decide what to do when promising new innovations exist that have a defensible rationale but depart from the standard of care or lack sufficient evidence of benefit from rigorous scientific review. Interventions may move between the two categories as new knowledge and uses evolve, blurring the boundaries between research and clinical care. Historically, health plans have covered medical services considered standard or medically necessary, but have been inconsistent in their coverage for services deemed investigational. Whether plans should cover some investigational services and under what circumstances is a constant debate. Increasing costs and a desire for accessible and equitable quality care impose greater scrutiny on resource allocation, which may threaten to curtail development of, and access to, medical innovation (Reiser, 1994; Steinberg, 1995; Agich, 2001; Kamerow, 2007; Taylor, 2010). In addition, variation in state requirements for coverage for clinical trials and the willingness to require such coverage for Medicaid recipients on the same terms as private payers must be considered (Taylor, 2010). Ultimately, for an investigational service to be considered medically necessary and made available to patients, it must be introduced and tested in a rational, efficient and safe manner. Systematic data collection of safety and efficacy in human participants and protection of those participants are essential to achieving these goals (Agich, 2001; Silberman, 2011). Consistent with deeply rooted ethical principles for human participant protections, clinical trials rely on a research protocol with formal mechanisms of voluntary informed consent. The protocol requires independent institutional review board (IRB) approval or equivalent, and must be conducted according to accepted methodological standards of scientific research. Conditions for use of an investigational service may include participation in a clinical study to determine its safety, effectiveness or comparative effectiveness, or for FDA approval. FDA extends access to investigational drugs and devices through investigational new drug (IND) and investigational device exemption (IDE) authorizations, respectively (21CFR 312; 21 CFR 812). These authorizations permit an investigational drug or device to be used in clinical studies for collecting safety and efficacy data. An IND authorizes use of: 1) an investigational drug for patients with serious or immediately life-threatening diseases or conditions who lack other therapeutic options and who may benefit from such therapies; and 2) an approved drug product for a new indication or in a new patient population (21CFR 312). An IDE permits the study of an investigational device not approved for marketing, or to study certain modifications or new intended uses of legally marketed devices (21 CFR 812). The FDA further classifies IDEs as: Category A (experimental or investigational) device for which absolute risk has not been established (i.e., initial questions of safety and effectiveness have not been resolved and the FDA is unsure whether the device type can be safe and effective). Category B (investigational or non-experimental) device for which underlying questions of safety and effectiveness of the device have been resolved or the risk is considered nonsignificant. 5

6 Clinical evaluation of such devices requires all of the following: IRB approval of an IDE. FDA approval is also required for Category A devices, as they present a potential for serious risk to the health, safety or welfare of a subject. Informed consent from all patients. Labeling for investigational use only. Monitoring of the study. Required records and reports. For services not under the legal restraint of FDA regulation, providers may consider evaluations contained in studies by authoritative and independent public bodies such as the National Institutes of Health and the Agency for Healthcare Research and Quality (Reiser, 1994). Both ethical principles of research and regulatory requirements assume that a degree of standardization of device, technique or procedure exists for a scientific research protocol to be feasible (Agich, 2001). However, compliance with IRB protocols and regulations that serve to protect human participants can challenge study design, recruitment and retention of trial participants, especially for underserved and vulnerable populations, and may lead to fewer therapeutic choices for patients and clinicians (Agich, 2001; Wipke-Tevis, 2008; DuBois, 2012; Kuthning, 2013; Thompson, 2013). Clinicians, clinical researchers and payers of health services share the burden of providing access to innovation and quality care. They must balance several important but, at times, conflicting social objectives, as they can influence rates of innovation, timing of access to promising technology, patient safety and health care costs (Steinberg, 1995). The paramount priority must be protecting patients from undue harm. Searches Keystone First searched PubMed and the databases of: UK National Health Services Center for Reviews and Dissemination. Agency for Healthcare Research and Quality s National Guideline Clearinghouse and other evidence-based practice centers. The Centers for Medicare & Medicaid Services (CMS). We conducted searches on August 10, Search terms were: "human experimentation [Mesh]," "compassionate use trials [Mesh]," "therapies, investigational [Mesh]," and "drugs, investigational" [Mesh]. We included descriptive articles and regulatory documents relevant to this policy. We included: 6

7 Systematic reviews, which pool results from multiple studies to achieve larger sample sizes and greater precision of effect estimation than in smaller primary studies. Systematic reviews use predetermined transparent methods to minimize bias, effectively treating the review as a scientific endeavor, and are thus rated highest in evidence-grading hierarchies. Guidelines based on systematic reviews. Economic analyses, such as cost-effectiveness, and benefit or utility studies (but not simple cost studies), reporting both costs and outcomes sometimes referred to as efficiency studies which also rank near the top of evidence hierarchies. Findings N/A. Policy Updates: None. CMS policy CMS policy Investigational devices 42CFR405b Federal Health Insurance for the Aged and Disabled Summary CMS may consider for Medicare coverage certain devices with an FDA-approved investigational device exemption (IDE) that have been categorized as non-experimental or non-investigational (Category B). Medicare payment may be made for: Covered services to treat a condition or complication that arises due to the use of a noncovered device or a noncovered device-related service. Routine care services related to experimental or investigational (Category A) devices as defined in (b); and furnished in conjunction with an FDA-approved clinical trial. The trial must meet criteria established through the National Coverage Determination (NCD) process; and if the trial is initiated before January 1, 2010, the device must be determined as intended for use in the diagnosis, monitoring or treatment of an immediately life-threatening disease or condition. Routine care services related to a non-experimental or non-investigational (Category B) device defined in (b) that is furnished in conjunction with an FDA-approved clinical trial. Medicare contractors may approve coverage for any device with an FDA-approved IDE categorized as a non-experimental or non-investigational (Category B) device if all other coverage requirements are met. Medicare contractors must consider whether any restrictions concerning site of service, indications for use or any other list of conditions for coverage have been placed on the device s use. 7

8 CMS policy NCD for Routine Costs in Clinical Trials (310.1) Summary Medicare covers the routine costs of qualifying clinical trials, as such costs are defined below, as well as reasonable and necessary items and services used to diagnose and treat complications arising from participation in all clinical trials. All other Medicare rules apply. Routine costs of a clinical trial include all items and services that are otherwise generally available to Medicare beneficiaries (i.e., there exists a benefit category, it is not statutorily excluded, and there is not a national noncoverage decision) that are provided in either the experimental or the control arms of a clinical trial except all of the following: The investigational item or service, itself unless otherwise covered outside of the clinical trial. Items and services provided solely to satisfy data collection and analysis needs and that are not used in the direct clinical management of the patient (e.g., monthly CT scans for a condition usually requiring only a single scan). Items and services customarily provided by the research sponsors free of charge for any enrollee in the trial. Routine costs in clinical trials include: Items or services that are typically provided absent a clinical trial (e.g., conventional care). Items or services required solely for the provision of the investigational item or service (e.g., administration of a noncovered chemotherapeutic agent), 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. Any clinical trial receiving Medicare coverage of routine costs must meet the following three requirements: The subject or purpose of the trial must be the evaluation of an item or service that falls within a Medicare benefit category (e.g., physicians' service, durable medical equipment or diagnostic test) and is not statutorily excluded from coverage (e.g., cosmetic surgery or hearing aids). The trial must not be designed exclusively to test toxicity or disease pathophysiology. It must have therapeutic intent. Trials of therapeutic interventions must enroll patients with diagnosed disease rather than healthy volunteers. Trials of diagnostic interventions may enroll healthy patients to serve as a proper control group. The three requirements above are insufficient by themselves to qualify a clinical trial for Medicare coverage of routine costs. Clinical trials also should have the following desirable characteristics; however, some trials, as described below, are presumed to meet these characteristics and are automatically qualified to receive Medicare coverage: The principal purpose of the trial is to test whether the intervention potentially improves the participants' health outcomes. 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 8

9 CMS policy CMS Coverage with Evidence Development (CED) guidance Summary clinical use. The trial does not unjustifiably duplicate existing studies. The trial design is appropriate to answer the research question being asked in the trial. The trial is sponsored by a credible organization or individual capable of executing the proposed trial successfully. The trial is in compliance with federal regulations relating to the protection of human participants. All aspects of the trial are conducted according to the appropriate standards of scientific integrity. Governing principles: CED will occur within the coverage determination process, which is transparent and open to public comment. CED will not be used when less restricted coverage is justified by the available evidence. CED will generally expand access to medical technologies for beneficiaries. CED will lead to the production of evidence complementary to existing medical evidence. CED will not duplicate or replace the FDA s authority in assuring the safety, efficacy, and security of drugs, biological products, and devices. CED will not assume the National Institute of Health s role in fostering, managing or prioritizing clinical trials. CED will be consistent with federal laws, regulations and patient protections. Glossary Clinical trial Research studies that explore whether a medical strategy, treatment or device is safe and effective for humans. Clinical trials follow strict scientific standard to protect patients and help produce reliable study results. Coverage with evidence development (CED) Medicare coverage for a treatment or technology on the basis of data collection through a clinical trial or registry to assess the appropriateness of an item or service for use with a particular beneficiary. Good clinical practices (GCP) Refers to the regulations and requirements that must be complied with while conducting a clinical study. These regulations apply to the manufacturers, sponsors, clinical investigators, institutional review boards and the medical device. Institutional review board (IRB) Any board, committee or other group formally designated by an institution to review biomedical research involving human subjects to determine whether or not research should be done. Also called an ethics review board. 9

10 Investigational or experimental services Any procedure, study, test, drug, equipment or facility of unknown safety or efficacy that is still undergoing study, or services used in a way that departs from generally accepted standards of practice in the medical community. Investigational but non-experimental service A term designated by the FDA to distinguish a device with underlying questions of safety and effectiveness that have been resolved (e.g., newer generations of legally marketed devices) or the risk is considered non-significant. Investigational device exemption (IDE) Request for FDA authorization to allow an investigational device to be used in a clinical study to collect safety and effectiveness data. The FDA further divides this classification into two categories: Category A (experimental or investigational) device whose absolute risk has not been established. Category B (investigational or non-experimental) device whose underlying questions of safety and effectiveness have been resolved or the risk is considered non-significant. Investigational new drug application (IND) A request for FDA authorization to administer an investigational drug or biological product to humans in the context of a clinical trial for collecting safety and effectiveness data. Three types are: Investigator INDs are submitted by a physician who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND to propose studying an unapproved drug, or an approved product for a new indication or in a new patient population. Emergency use INDs allow the FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with 21CFR, Sec or Sec This is also used for patients who do not meet the criteria of an existing study protocol, or if an approved study protocol does not exist. Treatment INDs are submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place. Medically Necessary A service or benefit is Medically Necessary if it is compensable under the MA Program and if it meets any one of the following standards: The service or benefit will, or is reasonably expected to, prevent the onset of an illness, condition or disability. The service or benefit will, or is reasonably expected to, reduce or ameliorate the physical, mental or developmental effects of an illness, condition, injury or disability. The service or benefit will assist the Member to achieve or maintain maximum functional capacity in performing daily activities, taking into account both the functional capacity of the Member and those functional capacities that are appropriate for Members of the same age. 10

11 Standard of care Items and services whose likely benefits and harms can be described and anticipated and are considered proven, appropriate and accepted. For Medicare beneficiaries, services for which a benefit category exists, is not statutorily excluded, and no national non-coverage decision exists; a legal term firmly established in law and defined as the caution that a reasonable person in similar circumstances would exercise in providing care to a patient. Also called best practices. References Professional society guidelines/other: Code of Federal Regulations (2014 Annual Edition). U.S. Government Printing Office website. Accessed August 8, Applicable regulations include: 21CFR312 Investigational New Drug Application. 21CFR812 Investigational Device Exemptions. 21CFR50 Protection of Human Subjects. 21CFR56 Institutional Review Boards. 21CFR54 Financial Disclosure by Clinical Investigators. 21CFR820 Design Controls of the Quality System Regulation. 42CFR405.2 Federal Health Insurance for the Aged and Disabled. Peer-reviewed references: H Definitions of "Screening" and "Medical Necessity". American Medical Association (AMA) website. Accessed August 8, Comparative effectiveness: its origin, evolution and influence on health care. J Oncol Pract. 2009;5(2): Agich GJ. Ethics and innovation in medicine. J Med Ethics. 2001; 27(5): DuBois JM, Beskow L, Campbell J, et al. Restoring balance: a consensus statement on the protection of vulnerable research participants. Am J Public Health. 2012; 102(12): Evidence-Based Medicine Working Group. Evidence-based medicine. A new approach to teaching the practice of medicine. JAMA. 1992;268(17): Kamerow D. Paying for promising but unproven technologies. BMJ (Clinical Research Ed.). November ;335(7627):

12 Kuthning M, Hundt F. Aspects of vulnerable patients and informed consent in clinical trials. Ger Med Sci. 2013;11: Doc03. Reiser SJ. Criteria for standard versus experimental therapy. Health affairs (Project Hope). 1994; 13(3): Silberman G, Kahn KL. Burdens on research imposed by institutional review boards: the state of the evidence and its implications for regulatory reform. Milbank Q. 2011;89(4): Steinberg EP, Tunis S, Shapiro D. Insurance coverage for experimental technologies. Health Aff (Millwood). 1995;14(4): Taylor PL. State payer mandates to cover care in US oncology trials: do science and ethics matter? J Natl Cancer Inst. 2010;102(6): Thompson HS, Shelton RC, Mitchell J, Eaton T, Valera P, Katz A. Inclusion of underserved racial and ethnic groups in cancer intervention research using new media: a systematic literature review. J Natl Cancer Inst. Monographs. 2013;2013(47): Wipke-Tevis DD, Pickett MA. Impact of the Health Insurance Portability and Accountability Act on participant recruitment and retention. Western J Nurs Res. 2008;30(1): CMS National Coverage Determinations (NCDs): National Coverage Determinations (NCD) for Routine Costs in Clinical Trials (310.1). Centers for Medicare & Medicaid Services website. Accessed August 10, Guidance for the Public, Industry, and CMS Staff: Coverage with Evidence Development. Centers for Medicare & Medicaid Services website. +Coverage+with+Evidence+Development. Published Updated November 20, Accessed August 10, Local Coverage Determinations (LCDs): No LCDs identified as of the writing of this policy. Commonly submitted codes 12

13 Below are the most commonly submitted codes for the service(s)/item(s) subject to this policy. This is not an exhaustive list of codes. Providers are expected to consult the appropriate coding manuals and bill in accordance with those manuals. CPT Code Description Comment N/A There are no applicable CPT codes for this policy ICD 10 Code Description Comment Z00.6 Encounter for examination for normal comparison and control in clinical research program HCPCS Code N/A Description There are no applicable HCPCS codes for this policy Comment 13