The development of a successful pre-award infrastructure within a climate where clinical trials sponsored by pharmaceutical industry have decreased since 2001--a large multi-specialty academic medical center case study.

Introduction: The Shape of Research

The landscape of research is constantly changing, and by its very nature is characterized by changing systems, procedures, and new technology (Murray, McAdam, Burke 2004). Investigative sites and investigators must have foresight and flexibility to participate competitively. Industry-funded research is a multi-billion dollar business. Pharmaceutical and device companies are extending boundaries into peri- and post-approval activities. More companies are going abroad for clinical trial sites as financial considerations make decreasing pre-clinical costs imperative. By going abroad, pharmaceutical companies find sites that will accept lower payment for research in order to secure a study. Fewer regulations, because of the absence of regulatory oversight agencies such as the Food and Drug Administration (FDA), simplify conduct of the research. Sites abroad also have larger potential subject pools (Shah, 2003).

In a business where, according to industry estimates, a single day's delay in bringing a drug to market can cost as much as $1.3 million, finding a ready source of trial subjects is an advantage (Rowland, 2004). This atmosphere demands that research sites develop and showcase their increased success rates in subject recruitment and retention; accurate, timely data; diverse subject population, and institutional resources, thus ensuring their identity as a niche provider among their competitors. Sites in the United States (U.S.) defend their subject costs by providing quality centered on the Iron Triangle of research. The Iron Triangle (Figure 1) is composed of three points: Good, Fast, and Cheap. When conducting research one can achieve any two of these, but never all three. (Chasse, 2004) In the U.S., one can get data Good and Fast, but not Cheap. Abroad, one can get data that are Fast and Cheap, but not Good, or Good and Cheap, but not Fast. Data obtained in this manner jeopardize the integrity of study results, as information could be inaccurate or not provided expeditiously.

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To become successful niche providers, sites must think "outside the box" of historical site management infrastructures. This case study highlights a successful model for pre-award within a large, multi-specialty academic medical center involved in multi-partite research activities ranging from bench research and animal studies to human trials. The model allows for abbreviated timelines on contract and budget negotiation and execution, enabling viability within a highly competitive marketplace. A Circle of Support (Figure 2) is a strategic plan focusing on customer service and satisfaction, which provides resources necessary for expeditious pre-award processes. Beginning with an entry portal, this dynamic schema illustrates a fluid representation of resources such as feasibility, biostatistics, information systems, budget development and negotiation, and legal review. Additional institutional resources can be pulled into the circle as necessary. Outside of pre-award, examples of institutional resources utilized are regulatory review board (Institutional Review Board) and post-award. With increased scrutiny (Congressional and otherwise) of research ethics, financial management, and conflict of interest, the centralization of the pre-award infrastructure allows for establishment of controls to address these issues. In an industry fraught with opportunities for improvement, geometric consideration of available resource allocation is an exciting concept application (Figure 3).

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According to the May 4, 2005, Kaiser Daily Health Policy Report, the number of clinical trials sponsored by the pharmaceutical industry has decreased "significantly" since 2001, and the number of principal investigators for trials in the U.S. has "declined even more steeply." These results are reflected in a study conducted by the Tufts Center for the Study of Drug Development and reported in the Washington Post (Kaiser Daily Health Policy Report, 2005). Using information collected by the FDA, researchers at Tufts found that after a major expansion during the 1990s, the number of pharmaceutical industry-sponsored clinical trials leveled off in 2000 and began to drop after 2002. The number of principal investigators for trials in the U.S. decreased by 11% between 2001 and 2003, while the number for trials abroad increased by 8%. Discontinuation of trials before they reached their final phase contributed greatly to the decrease. In addition, trials are becoming less lucrative for doctors and researchers; thus, more trials are being conducted at cheaper sites abroad. Researchers are frustrated by increased costs, poor communication, and fragmented organizational infrastructures. Available information increasingly reflects that new clinical trials are increasingly being done abroad. Statistics show that the number of U.S. sites where clinical trials were under-way declined from approximately 51,000 in 2001 to 48,000 in 2003. During that same period, the number of FDA-approved investigational drug studies in all phases of research rose from approximately 3,900 to 4,500, but with less research being done at U.S. sites (Kaiser Daily Health Policy Report, 2005). Although ongoing clinical trials in the United States are generally not being moved overseas, the lower costs abroad and the often greater professional and public interest are leading many companies to set up new trials in Eastern Europe, South America, and India (Kaiser Daily Health Policy Report, 2005).

Ongoing clinical trials are not significantly affected by the current trend of selecting sites overseas because pharmaceutical and device companies realize the cost-effectiveness of letting a study continue to completion at a site where research support is already in place. However, studies indicate that industry looks at locating Phase I studies overseas for several reasons, such as increased potential subject pool, cheaper overall costs, and less governmental regulation. Overseas, there is a larger pool of potential subjects, many of whom are medication naive (Shah, 2003.). Populations in countries with underdeveloped economies usually cannot afford healthcare services or medications. Trials in the U.S. are highly regulated--experiments on human subjects must undergo reviews by government-regulated institutional or central review boards, and are under increased scrutiny to protect participants. Studies conducted overseas and then moved to the U.S. are only required by the FDA to conform to the World Medical Association's Declaration of Helsinki, which is a series of recommendations that critics call rudimentary, nonbinding, and ambiguous. There is no oversight or auditing to ensure that these recommendations have indeed been followed prior to moving the trial to the U.S (Shah, 2003).

To position an institution competitively within the market and meet institutional mandates, departmental objectives should include establishing an internal infrastructure that will streamline and ensure quality processes and determine current and future productivity needs. This case study discusses the evaluation and identification of opportunities for improvement within an active infrastructure of a grants administration office, specifically, contracts administration. Changes were implemented in processes and infrastructure to facilitate flow and timelines for clinical trial agreement processing, budget development and negotiation, monitoring and oversight and timeline tracking for the duration of project administrative set-up.

Materials and Methods

Evaluation of the pre-award process flow indicated a need for contract administration and budgeting to increase functionality via closer proximity and elimination of departmental boundaries. The Circle of Support (Figure 2) lends itself to the creation of a separate contracts and budgets office within grants administration, utilizing a contracts manager and budget manager working in tandem. The Contracts Manager from the Clinical Research Projects Office was moved to Grants Administration, and a Senior Financial Analyst was moved from Research & Education (R&E) Fiscal to Grants Administration in the capacity of Budgeting Manager (Figure 4). The previous configuration consisted of a Contracts Manager interacting with the R&E Fiscal Senior Financial Analyst. Differences in departments and inconvenient physical locations caused fragmentation of processes, resulting in increased processing timelines. Realignment was implemented in March 2004 (Figure 4). Restructuring allowed for abbreviated timelines on contract and budget negotiation and preparation, enabling the institution to be considered an increasingly viable site for highly competitive studies.

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Results

The following data support the contention that restructuring successfully increased both the number of clinical trials and revenues for the institution:

Numbers increased significantly while utilizing the Contracts Administration model (Figure 4) within the Circle of Support (Figure 2). Notable were a 37.6% increase in total funding and 26.8% increase in average funding per contract (Table 1). The flexibility of this configuration facilitates effective communication among the critical path components of contracting, budgeting, and institutional regulatory approval. As illustrated in Chart 1 and Chart 2, significant increase in overall dollars and number of contracts is credited to the restructuring.

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Conclusion

A speaker at a recent conference summed it up nicely: