The Cost of Research: A Survey of Participating Sites in a Nationwide Registry

DISCUSSION

The CARRA registry is the first to attempt to record longitudinal data on pediatric subjects with rheumatologic diseases. It is considered an important first step in the natural observation of the course of pediatric rheumatic disease, as well as a bank of potential subjects to approach for new studies. However, the implementation of the registry was fraught with difficulties, largely because of costs that were not realized at inception. This survey supported what we expected: that the cost to enroll a subject into the registry far exceeded what was provided in the grants, and therefore most sites had to supplement what was given to them with either their own research money or divisional funds.

Because we allowed responders to keep the sites anonymous, we were unable to determine whether there was a cost difference between small and large sites. Our large site, for example, was able to hire a research assistant to recruit and enter data using our own funds, resulting in a reduced hourly cost and increased number of children entered (453). Our calculated per-patient cost was $88 per subject enrolled, which is a good deal less than the average of $102. Although we had a lower per-subject cost, we still had a total deficit of $19,932. We speculate that small centers would not have access to a research assistant, and would therefore incur higher costs and enroll fewer subjects. The use of resources varies from site to site owing to several factors, including the role of the research person. The use of a dedicated research person facilitates recruitment, although that was not specifically studied. Most rheumatology centers are stretched too thin regarding personnel to justify using their time for studies that are in addition to their clinical responsibilities. Adequate funding could help support paid research assistants whose job it is to carry out most of the research activities.

We knew that more complicated diseases tended to take longer to abstract, yet payment was the same. As a result, we postulated there would be an enrollment bias favoring subjects whose data were more easily abstracted because of their disease diagnosis or length of disease. Indeed, 33% of responders reported subject selection, most commonly against enrolling subjects with SLE and FM. However, children with SLE and JDMS were enrolled at a higher rate than the survey by Bowyer and Roettcher would predict⁹. This higher enrollment rate may have been observed because these children came to the clinic more often, were more willing to participate in research, or were more interesting to rheumatologists as potential research subjects. More notable is the marked dearth of children entered into the CARRA registry with FM, an absence that may reflect either the long and complicated histories of children with FM, or researcher bias against noninflammatory conditions.

This registry brings to the forefront what is often the case in academic research: that government and foundation funding is inadequate to cover the actual costs to the site for successful implementation. This is unfortunate because it prevents potentially beneficial research from being properly completed and may result in underpowered studies. It also creates an ethical dilemma in the recruitment of subjects because of the possibility that subject data may ultimately be unusable as a result of recruitment and enrollment issues. Underfunding studies creates significant barriers to investigators doing clinical research who need additional funds, either from their research monies or from divisional funds, to complete sponsored studies. Losing money to participate in funded research cannot be long tolerated in this economic climate, nor should it be. There are advantages to participation in collaborative studies, including advances in disease understanding, comparison of care and treatment, and publications. However, relying on colleagues to be good citizens in the research community is not an adequate reason to perpetuate underfunding recruitment and enrollment costs.

We did not compare our enrollment in our study to industry sponsors. It may be that reimbursement is greater in studies in which industry has vested interests and thus recruitment may be enhanced. Using a budget template that is based on industry-sponsored trials may provide a more realistic appraisal when working on budgets for registry and other non-industry trials.

In the future, all parties must make an increased mutual effort to ensure that clinical research requiring the recruitment and enrollment of subjects is properly funded so that valid and evaluable results are obtained. Investigators need to more accurately estimate the time and effort that will be necessary for the successful implementation of a trial. If the grant is a multisite protocol, sites should be required to fully estimate the costs for their own site, because these can vary greatly. We speculate that smaller sites may have increased costs. Additionally, if a grant comes in for a specific amount, the funder needs to understand that budget justifications for recruitment and enrollment are likely to vary significantly from site to site based on the circumstances that exist among pediatric rheumatology centers. Ultimately, these steps will improve the implementation of studies and the quality of the data obtained.