Routine patient care in clinical trials: whose cost is it anyway?

• Author: Berlyn, Dina

1. INTRODUCTION

   On June 07, 2000, President William J. Clinton issued an Administrative Declaration (hereinafter "the Declaration") to then Health and Human Services Secretary Donna Shalala requiring Medicare to pay for the routine medical costs for Medicare recipients who were patients in clinical trials. (2) There were, at the time, pending in Congress, several bills which would have required Medicare to pay these expenses, but all except one only required coverage of these expenses in clinical trials for cancer. The "for cancer only" provision would create an irrational public policy that could in fact be harmful to progress against diseases other than cancer. The Declaration and its resulting regulations are not so limited; the President made the Declaration as a result of a report from the Institute of Medicine which argued that the President had the authority to make this change administratively. (3)

   There were also several pending proposals, differing in scope, before Congress which would have mandated private third party payers to cover routine care costs for clinical trial patients. These proposals differed in that some were limited as to trial sponsor and some to trials for cancer therapy. The two that passed their house of origin in Congress will be discussed in some detail. The Bipartisan Patient Protection Act of 2001 (commonly referred to as McCain/Kennedy) (4) was considered by the 107th Congress; it was nearly as broad in scope to private third party payers as the Clinton Declaration was regarding Medicare. Some state legislatures have recently addressed the issue as well, and this article discusses their differing approaches. Connecticut examined this issue, and the ease study of this process supports the need for congressional action to create a uniform standard.

   This article examines the issue of coverage for routine medical expenses for clinical trial patients by third party payers from both a medical and political policy perspective. It is critical for patients, investigators, and sponsors to know who is responsible for paying these costs. This issue affects the willingness of patients to enter clinical trials and has the potential to affect which diseases will be the subjects of clinical trials. This presentation first summarizes the basics of clinical trials and then explores the definition of routine care in clinical trials. Medicare reimbursement, an issue that has been the subject of recent decisive action, is the starting point. The article provides explanation and discussion of the possible models, federal and state, for mandated coverage by other third party payers of routine patient care in clinical trials. A policy discussion and analysis follow, which includes information on the potential effects of this change on third party payers as well as researchers and patients. The placement of the cost liability for these expenses is related to other issues of patient protection; there is a brief discussion of the dangers of research on human subjects past and present to place this issue within the larger context of patient protection. In general, this mandated coverage is sensible and would create good public policy. However, it is important that patient protection remain the top priority in what could be an increased number of trials. The wording of the mandate should be careful not to shift costs that are rightfully borne by the trial sponsor to others.

2. WHAT ARE CLINICAL TRIALS?

   Clinical trials are part of the process that a new medical therapy (usually a drug or device) must undergo prior to approval by the Food and Drug Administration (FDA) and approved use by patients. This is the part of the approval process in which the therapy is tested on human subjects. The clinical trials generally have four phases. Phase I is concerted primarily with safety; it requires only a small number of patients (generally 20-80) and determines safe dosage and monitors side effects. If the drug or device is found to be acceptably safe, the study moves to a Phase II trial which uses a larger number of patients (usually 100-300) and studies efficacy as well as safety. Phase II does not compare the experimental therapy to any control group. If Phase II shows a promising effect and does not appear to uncover any previously undetected safety issues, the trial moves to Phase III.

   Phase III is the mainstay of the clinical trial process. In Phase III the treatment is given to a large number of patients (generally 1,000-3,000) often at multiple locations, and the new therapy's effectiveness is compared either to a placebo or to the current standard treatment for the particular condition. This phase monitors safety, confirms effectiveness, and compares the new therapy to those currently available (or to a placebo) in terms of both safety and efficacy. This Phase is of extraordinary importance to the FDA when it decides whether to approve a new medical therapy. Phase IV is conducted after the therapy is approved, and this Phase simply monitors the patients on the new therapy for a specified period of time after approval. (5)

3. WHAT ARE ROUTINE PATIENT CARE COSTS IN CLINICAL TRIALS?

   There are three basic types of costs associated with clinical trials: the cost of the investigational drug or device, the cost of data collection and analysis, and the cost of routine care for patient enrollees. (6) The first two types of costs are traditionally borne by the clinical trial sponsor and this model is generally accepted with little disagreement. The question of who should assume the routine care costs for patients in clinical trials remains a contentious issue in both medicine and politics.

   In order to implement President Clinton's order, The Health Care Financing Administration (HCFA) posted a National Coverage Decision (NCD) for Medicare coverage of clinical trials. After the posting the NCD and allowing comment, HCFA amended the Medicare Manual in September 2000 to include section 30-1. According to section 30-1:

   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 a clinical trial except:

   *the investigational item or service, itself,

   *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); and

   *items and services customarily provided by the research sponsor 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; and

   *Items or service 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. (7)

   HCFA's definition is at the broad end of the spectrum and includes significantly more coverage than some other suggested definitions of routine care. Not all of the proposed definitions are this clear. HCFA was influenced by the Institute of Medicine (IOM) which supports a broad meaning of the term and defines routine patient care as, "Care that would be received by a patient undergoing 'standard treatment.' This would include such items as room and board for patients who are hospitalized, diagnostic and laboratory tests and monitoring appropriate to the patient's condition, post surgical care when indicated, office visits, and so on." (8) Section 30-1 simply expands on IOM's suggested definition and adds details which provide clarity.

   Many of the definitions of routine care in proposed federal legislation as well as enacted by state legislation are consistent with HCFA's definition, but less detailed. The varying versions of the Patients' Bill of Rights that were proposed in the 106th Congress offered little detail. The language from the House version of the Patients' Bill of Rights in the 106th Congress is identical to that in the Bi-Partisan Patient Protection Act of the 107th Congress regarding clinical trial coverage. That congressional language leaves significant discretion to the future rule making process: the plan or issuer "may not deny (or limit or impose additional conditions on) the coverage of routine patient costs for items and services furnished in connection with participation in the trial." (9) The legislation that was proposed also offered a definition of what is net part of routine care: "Routine patient costs do not include the cost of the tests or measurements conducted primarily for the purpose of the clinical trial involved." (10) The regulations that would have been required to implement this kind of federal legislation would have significantly affected the ultimate outcome of the policy.

   Generally the state statutes have taken a middle ground--not as much detail as the Medicare Manual, but more guidance than the Congressional proposals. For example, New Hampshire's statutes define routine care as, "The cost of any medically necessary health care service that is incurred as a result of the treatment being provided to a member of a health plan. Routine costs are those for which the health plan regularly reimburses its members, health care providers, or health care institutions subject to the terms and conditions of the member's policy and the provider's service agreement with the insurer." (11) The New Hampshire statute also defines non-routine costs:

   1. the cost of an investigational new drug or...