As a biomedical engineer, consultant, and manager during the last 14 years I have been responsible for varying aspects of research, development, and investigational use of mechanical circulatory support and other cardiovascular devices at the University of Utah, Veterans Affairs’, and LDS Hospital Medical Centers in Salt Lake City, Utah.
Reshaping of our Environment
The health care environment in which we work today is being reshaped by many factors including cost–containment, managed care, limitations on resources, restrictive insurance plans, increased competition, regulation, and concern with legal risks. This unsettled environment is influencing the design of clinical trials and the role of institutions in the conduct of those trials. While many factors are contributing to the need for clinical trials that are more complex and expensive to conduct, at the same time health care organizations and other sources of financial support are limiting resources for the conduct of these trials. The objectives of this presentation are, first, to discuss issues affecting clinical trials; second, to emphasize how these primarily administrative and financial issues influence participation in a clinical trial; and, finally to encourage discussions between investigators and sponsors about these factors and how to deal with them.
Motives for Participation
The traditional, often altruistic, motives for participation in clinical trials are still relevant today. Clinical investigators are motivated to seek out the most effective therapies for their patients, take great pride in providing state–of–the–art therapies, in the resultant positive publicity, and in influencing the development of new products. Being able to provide the newest and best therapies helps in attracting and retaining good employees, is attractive to referring physicians, and enables physicians to provide cost–effective care to their patients. Seldom, in earlier years, were they asked to quantify the value of these benefits. Now, investigators are increasingly being asked to weigh the financial and other benefits of participation in a clinical trial against risks for the investigator, the institution, a parent corporation, and even affiliated third party payers. Investigators are frequently being required to prepare detailed risk-benefit analyses to justify participation in clinical trials. Although the traditional motives (Table 1 ) for participation in clinical trials are still important considerations, we are witnessing an increasing trend toward requirements for financial justification and oversight of the decision making process for participation in clinical trials.
Table 1: Motivating Factors for Participation in Trials
Disincentives
Financial and other risks are strong disincentives for participation in clinical trials. Health care corporations are increasingly wary of trials that cannot be clearly shown to support the corporation’s bottom line. Investigators must compete for limited funds and resources against a variety of other programs considered “essential” in a leaner, more cost–conscious organization. Resources for “nonessential” activities may be limited, resulting in potential for “burn–out” of the research staff. Within some corporations, participation in clinical trials is even viewed as a detraction from the performance of essential, profit producing activities. The potential for negative publicity is considered very real, as evidenced by adverse publicity on subjects such as runaway health care costs, selective access to expensive therapies, and courtroom battles over treatment choices. Health Maintenance Organizations may be reluctant to contract for services at facilities that they perceive as promoting expensive, investigational procedures. Investigators are increasingly finding their ability to influence the design of new devices limited by a trend toward development and testing of new devices in Europe and other parts of the world.
Although these issues contribute to an environment in which the conduct and participation in clinical trials can be exceptionally challenging, they are problems that the combined efforts of sponsors and investigators can effectively address. For example, cooperatively developed publications and public relations materials (intended for health care professionals as well as the general public, insurance groups, and health care organizations) are essential to maintaining support for research activities. Collaborative studies addressing cost–effectiveness of new therapies can be conducted concurrently with clinical trials, providing essential data needed to convince parent corporations and insurance groups of the value of new therapies. Participation in and sponsorship of conferences is essential to disseminate knowledge on all aspects of device use, and to provide a forum for discussions on device refinement and generational succession. The consolidation and dissemination of this knowledge in the form of educational materials, protocols, reimbursement manuals, sample cost–benefit analyses, and other guiding documents can substantially ease the transition to use of new technologies.
Cost–Benefit Analysis
Preparation and periodic revision of cost–benefit analyses are proving to be one of the challenging tasks investigators are being asked to add to their responsibilities. To present a favorable analysis to support participation in a clinical trial, an investigator must carefully consider both tangible and intangible potential costs and benefits. The experiences of other investigators and of the study sponsor’s staff are valuable sources of information to assist in this task. It is also helpful to review the animal and human experience with specific and similar devices, to better understand the state of development and potential resource requirements for device use. A device with a track record of effective clinical use is likely to involve fewer risks and require correspondingly fewer resources to plan for, fund, and manage.
A cost analysis usually includes the expenses for all resources (personnel, facilities, equipment, and supplies) required for the trial, education requirements, anticipated maintenance, and system upgrades. Educational costs may include initial training and continuing education, such as attendance at conferences and periodic refresher training for staff. The costs related to entering a patient into the trial will include the costs of evaluation of the patient, patient care (in–patient, out–patient, and follow–up), re–admissions, professional fees, and support services. Some institutions may require inflation, administrative, and overhead costs to be included.
The financial benefits for participation in a clinical trial are often more difficult to explain or quantify than the costs. Although funding or reimbursement for patient and device charges are considered the minimal necessary benefits to be attained, other benefits may be of equal or greater importance. These include the ability to provide state of the art care, the best possible outcomes at the lowest cost, in short, factors that have traditionally motivated professionals to participate in clinical trials (a partial listing of which may be found in Table 1 ). Although these benefits can yield financial gains for a corporation, they are admittedly more difficult to quantify. Nevertheless, estimates can be made and the intangible benefits emphasized. Improved outcomes (clinical and financial) can be estimated by comparisons to published results from studies conducted with similar devices. Tracking of referrals can highlight the value of clinical trials in increasing patient volumes, use of ancillary services, and potential cash flow to an institution. Experienced public relations staff can often estimate the advertising value of publicity obtained or anticipated from participation in a clinical trial. Human resource studies can be used to support the retention value of challenging projects for quality employees and contrasted with the high cost of personnel turnovers. These are but a few examples of approaches for presenting the benefits of trials, similar approaches need to be discussed and developed to aid in justifying the commitment for participation in a clinical trial.
Sources of Funding
Financial support necessary for participation in a clinical trial usually is obtained from a variety of sources. These sources include the study sponsor, departmental development funds, a parent corporation, research grants, philanthropic sources, and reimbursement from third party payers. Although previously institutions and their parent corporation were better positioned to provide support for the introduction of new technologies, this is becoming more difficult. From an institutional perspective, often the most important funding for participation in a device trial is support or reimbursement for patient and device charges. Unfortunately, at the same time insurance groups are becoming increasing restrictive in their reimbursement for investigational therapies. Confidence in the potential for cost reimbursement is an important factor in the decision to participate in a clinical trial.
A track record in reimbursement for the use of a device or similar devices at other centers increases the likelihood for reimbursement. Other centers’ experiences may suggest effective approaches to reimbursement that a new sponsor or investigator could use. HICFA Category B (non–experimental/investigational) classification for a device increases the likelihood for success, but does not guarantee either Medicare or private reimbursement. Without a track record or HICFA class B classification, reimbursement is often dependent upon acceptance of the device within the medical community as a standard of care for treatment of a specific condition.
A standard of care argument can include the use of favorable published results from similar studies, studies with similar devices, and any legal precedence for use or reimbursement that may exist. A “silver lining” in the trend toward foreign trials of devices preceding U.S. trials is that for many devices, trials in the U.S. are now trials of proven devices and therapies. This opens the door for the presentation of arguments, with legal precedence, that proven standards of care are being applied by study investigators. Unless a specific exclusion is written into an insurance contract, reimbursement for an accepted standard of care is difficult to deny. In a clinical trial involving a device accepted as “standard of care” for a disease, it is not uncommon for all reasonable patient expenses (not specific to the conduct of the trial) to be included in insurance coverage.
Support from Study Sponsor
The amount and type of support available from a study sponsor will vary considerably among sponsors and even between studies with the same sponsor. Factors influencing the level of a sponsor’s financial assistance include: the financial strength of the sponsor, development costs, the potential for third party reimbursement, the experience of the investigator, the state of development of the device, and traditional factors of supply and demand. Sponsors are invariably caught in a balancing act between taking care of their investigators and their investors, with the inevitable cost of clinical trials often extending into millions of dollars. The support expected from sponsors is most often assistance with equipment, supplies, and patient care expenses, particularly expenses specific to the study protocol. Products and services may be provided at no charge, at a discount, on consignment, by lease or rental, at cost, or with the possibility of no discounts at all. All of these options are usually open for discussion, and need to be addressed early in the planning stages of a trial.
Patient care, equipment, and supplies are the cost issues most frequently discussed, but there are a number of other less obvious but significant areas where assistance may be available from the sponsor. For example, sponsors often provide initial and ongoing education and educational materials free of charge or at minimal expense. Sponsor funded users meetings, surveys, and study summaries are invaluable sources of information for clinicians and staff learning the nuances of successful device use. Additionally, study sponsors often provide clinical, technical, statistical, maintenance, networking, reimbursement, and organizational assistance to their trial centers, with technical and clinical support usually available on a 24 hour basis. Discussions of the type and quantity of support and assistance a sponsor and investigator can provide one another are best not limited to financial issues, but should include how collaboration can contribute to the achievement of mutually beneficial goals.
Collaboration, Cost Sharing
Just as investigators are finding increasing financial pressures in their environment, so too are sponsors of trials. Regulatory and legal issues contribute to the design of larger, more complex, expensive trials. A collaborative, cost sharing arrangement may be a feasible alternative, in which sponsors and investigators each assume responsibility for costs. For example: institutions may be most capable of shouldering the cost of patient care, if a collaborative effort has laid the groundwork for reimbursement for this care. Similarly, industry is best positioned to support the investigators with expertise, reasonably priced equipment, and supplies. Expertise may be best packaged as consolidated educational, reimbursement, cost–effectiveness, and other materials that will ease the challenges of introducing new technologies into a health care environment already stressed in recent years by multiple organizational and operational changes.
Summary
Prior to initiating a clinical trial, many issues need to be discussed to insure an adequate understanding of the investigators’ and sponsors’ limitations, capabilities, and expectations. Many of these issues are addressed in contracts and agreements, the formats for which have evolved over many years. In these documents, issues such as publication rights, access to results, confidentiality, conditions for termination, compensation, and indemnification are covered. However, other essential, although noncontractual issues that reflect upon trends in and the climate of the health care system, need to be discussed. Issues such as the development of collaborative cost–effectiveness studies, public relations plans, content of a cost–benefit analysis, results of other trials, reimbursement strategies, and the development of resources that contribute to the ease, safety, and efficacy of device use. With the increasing expense, oversight, and administrative burden for the conduct and participation in clinical trials, there is a correspondingly greater need for sponsor and investigator communication, collaboration, and risk and cost sharing to ensure the successful outcome of clinical trials today.
