Clinical trials: a golden opportunity for laboratories?

You need the Midas touch: You've streamlined your laboratory to make it as efficient and cost-effective as possible, but you're still seeking additional sources of revenue. Could drug trials provide a lucrative answer?

For many clinical laboratories, the drive for cost-effectiveness first spurred by managed ore is approaching a point of diminishing returns. Developing alternative revenue sources has become a vital strategy for survival and prosperity. Clinical trials provide one promising option for new or expanded business, particularly in markets where hospital-based and commercial laboratories compete for both inpatient and outpatient testing.

Providing services to clinical trial investigators, however, is not a recipe for success for every laboratory. This type of testing differs in some important ways from a routine patient workload, and these distinctive challenges may or may not make clinical trial participation a cost-effective enterprise for a particular laboratory.

Types of clinical trials

Clinical trials typically include 2 kinds of activity:

* evaluation and validation of new clinical laboratory testing systems or

* laboratory evaluation of patients subjected to new clinical products or protocols, particularly those related to new drug development.

The first type of trial is an extension of a traditional laboratory function. As research and development has moved from hospital laboratories to the diagnostics industry, companies have had to seek partners in the clinical laboratory setting to evaluate their new products using the samples for which they were designed. This kind of "real-world," or field testing, of new equipment or systems is well suited to the environment of a clinical service laboratory. It requires space for the necessary equipment and facilities as well as laboratory personnel with the appropriate skills to develop protocols, collect and analyze specimens, critique the new system's design and operation, and analyze the results for clinical relevance and adequacy. Financial gain isn't the chief motivating factor for laboratories to field test new systems and products. Rather, labs may wish to attain early access to and experience with a novel testing system or to pursue an academic or research-related interest in the technology.

Regarding revenue enhancement for the laboratory, clinical trials of new drugs present the greatest opportunity, and that type of trial is the focus of this discussion.

Clinical trial basics

New drugs and medical devices must undergo a lengthy approval process by the Food and Drug Administration. The clinical laboratory provides objective data in this evaluation process. For some clinicians and institutions, clinical trials have provided a brisk source of revenue. However, laboratorians who are considering entering this complex field should examine very carefully all aspects of this endeavor.

To bring a new drug to market, the manufacturer must first demonstrate that the agent is both safe and effective. Administering the drug to a selected population under controlled conditions and documenting the effects accomplishes this. Laboratory evaluation of these patients is an integral part of the process. In general, the tests are similar to those employed in routine patient care to evaluate specific organ system functioning or detect other physiologic changes - although special protocols may sometimes be required.

The FDA's stringent requirements apply to the clinical trial sponsors; participating laboratories do not need special certification or permits beyond those required for their routine activities, although any recognized certification enhances a laboratory's competitive edge.

The laboratory's relationship may be with the trial sponsor (usually the pharmaceutical company that is developing the drug) or with an intermediary. Many clinical trials are now managed by contract research organizations, which facilitate interaction among the trial sponsor, other participants such as the researchers in a medical center's academic departments, and the enrolled patients. These and other intermediaries function as patient managers, identifying and managing patients throughout the project. Laboratories should be aware of issues of enrolled patient confidentiality and of ethics with regard to patient enrollment and billing.

The clinical trial process for FDA approval of a new drug involves the following:

Screening. The initial stage usually requires medical histories, physical examinations, and established criteria for inclusion to select and qualify participants for a trial. Laboratory testing at this stage is usually in the outpatient setting.

Phase 1. This phase involves specific objectives that establish safe dosage limits and investigate the drug's pharmacokinetic, metabolic, and adverse effects.

Phase 2. This step focuses on identifying a biological response associated with the drug for a particular disease state or patient characteristic.

Phase 3. The final phase takes place in a much larger test population where the drug is compared to standard treatments and/or treatment with a placebo to demonstrate and quantify its efficacy and safety. It may be a multicenter or even a multinational trial and represents the last phase of data development before the new drug application is submitted to the FDA for review.

Phase 4. After approval, the study's length may be measured in years and serves to verify the safety of the product.

Consider the variables

Look carefully at several major factors when deciding whether your laboratory can handle a particular clinical trial workload. When dealing with clinical trials, if you've seen one, you haven't seen them all. The drug under investigation, its metabolic impact, the stage of the trial, and the drug's anticipated effect determine the protocol of each trial and its test mix. One trial might involve a very basic panel of tests such as a complete blood count, glucose, or serum cholesterol. Another might call for more esoteric tests such as flow cytometry or complex coagulation analyses.

Every type of laboratory, whether a large reference facility or an acute-care hospital laboratory, has its own workload pattern and "rhythm" that must be taken into account before its services are marketed to clinical trial managers. The addition of clinical trial-related testing may have an impact on staffing patterns, instrument use, hours of operation, and scheduling demands.

Other relevant considerations regarding clinical research projects include:

Duration. "Short" investigations can last for months; long ones may stretch over years or even decades. One example is the Framingham Study, the landmark epidemiology project that examined several generations of a Massachusetts town for cardiovascular disease and other findings. Another example is follow-up testing for the delayed effects of radiation exposure on nuclear plant workers, their families, and area residents. The record keeping and other logistical demands of such long-term investigations are specific and demanding and may include issues such as long-term reconciliation of patient results to quality control changes across reagent lots or other unavoidable testing system changes. Testing methodologies that have been replaced in clinical service labs may need to be retained in service and supported through the end of a study.

Complexity. How many different kinds of tests will each subject undergo, and what kind of sampling protocol and patient management will be required? Does the study call for periodic sampling of a free-living population or for documentation of patients living under controlled conditions? Are the subjects acutely ill hospital inpatients, chronically ill outpatients, healthy volunteers, or a combination of these groups?

Table

Clinical trials testing: Another world

Here is how the demands of routine clinical laboratory operations
and clinical trials testing may differ:

Routine clinical laboratory operations   Clinical trials testing

Standardized protocols and techniques    Variable protocols and
                                         techniques

Standardized report format               Variable report format

Reference ranges based on patient        Reference ranges may differ
population                               from patient population

Highly discounted prices                 Minimal discounts

Difficult collection, multiple payers    Simpler collection, single
                                         payer

Specimen handling. Transporting specimens may be an issue, depending on the location and timing of testing for the patient cohort. Collection, pick-up, delivery, and stabilization of specimens may present challenges.

Technical demands. The testing required in clinical trials most often uses standard methodologies and instrumentation. However, some investigations may require the use of new or revised procedures. For example, a laboratory involved in the investigation of thalidomide and its effects on autoimmune response had to develop improved assays to monitor levels of the drug, which had been off the market for decades since its infamous association with birth defects. A laboratory's ability to provide customized assays and to determine the drug's stability both in vitro and in biological samples places it at a competitive advantage.

In addition, the sensitivity of a laboratory's assays may be appropriate for routine clinical use but not adequate for a particular research protocol. Methodology may have to be revised to provide the information needed in a clinical trial, requiring flexibility on short notice - not a strong point for the many clinical laboratories that depend on highly standardized procedures to keep things running smoothly. A clinical laboratory thrives on routine and consistency, whereas the clinical trials environment is variable and protocol-specific.

Reference ranges. The reference ranges required for laboratory results in clinical trials may vary from those commonly employed in clinical practice. Normal or abnormal thresholds used by a hospital or a reference laboratory for the general population may not be adequate to detect a therapeutic benefit or an adverse effect on a research population or to screen for qualified candidates. Can the laboratory manage multiple reference ranges without risking mix-ups?

Information management. Report formatting in most clinical laboratories is highly standardized, whereas the reporting format may vary from one clinical trial to the next. Can the laboratory generate multiple report formats and change them from one month to the next without disrupting basic service?

The economics of clinical trials

Before getting involved in this type of work, it is essential to do your homework and decide beforehand exactly what the laboratory is prepared to handle and how much of its resources can be allotted to the new workload. How long will the laboratory have to maintain a particular methodology? How will the consistency of data be assured during that time frame? It's reasonable to set boundaries on the type of clinical trial testing your laboratory is prepared to handle and to market only certain services to this sector - for example, only flow cytometry studies.

Clearly, there is no one ideal laboratory to meet the needs of clinical trial clients, given the enormous range in the scope, subject, and complexity of clinical trials. Some characteristics, however, can give a laboratory the edge in seeking business from the research community.

Proximity. It's obviously a big advantage if the laboratory happens to be in a geographic area with a high concentration of clinical trial research organizations, academic medical centers, or pharmaceutical giants or if the laboratory is affiliated with an institution or system that participates in such research.

Flexibility. Meeting the needs of clinical trial clients may require technical versatility, managerial flexibility, and the information-handling resources to manage complex, varied, or long-term databases.

Customized service. The laboratory's appeal is enhanced if it can offer added value to trial sponsors - for example, by developing an algorithm for a more efficient screening process requiring fewer tests.

Participation in clinical trials offers some potential economic benefits to the laboratory beyond a simple increase in test volume. Clinical trial sponsors tend to be less demanding in terms of discounts and more prompt in payment than many hospitals and third-party payers. Billing may be simpler with a single payer.

Increasingly, economic evaluations of a drug's potential cost-effectiveness are being structured into Phase 3 testing (testing within a larger population). The fewer restrictions on a laboratory's technology and the greater its capacity for multidisciplinary service - in advanced statistical management, for instance - the more attractive it will be to pharmaceutical corporations and other potential clinical trial partners. The key issues for laboratory decision makers are to identify opportunities in this new market and to evaluate whether they will be profitable as well as compatible with a lab's operation.

Wendell O'Neal is vice president of Alliance Laboratory Services in Cincinnati, OH.