In addition to patient recruitment, difficulty finding investigators and sites was one of the issues most frequently raised by industry representatives in discussions with ERG. According to some, the problem is not a lack of researchers overall but rather a lack of highly qualified researchers who are consistently able to enroll high-quality patients in sufficient numbers. As a result, sponsors compete with each other for these top investigators, creating the impression that there is a shortage even though less well-qualified investigators might be available.
Whether and how sponsors experience this competition is based, to some degree, on their companies’ size and disease specialties. Many of the larger CROs have strategic partnerships with large drug companies, which provide the CROs with a consistent revenue stream. In exchange, the drug companies get priority access to staff, data management resources, and investigators. This allocation of resources to big drug companies further intensifies resource competition for small companies. Companies pursuing drugs in the same therapeutic areas at the same time will also face more competition, not only for patients, as discussed in the Section 4.3, but also for investigators and sites. For highly specialized treatment areas such as anti-fungals, sponsors may have a very limited universe of qualified investigators to choose from in the first place.
Other experts frame the problem somewhat differently, asserting that this barrier stems not simply from competition for top investigators but also from an actual overall shortage of biostatisticians and clinical informaticists across academic medicine, industry, and government (Bonham, Califf, Gallin, & Lauer, 2011). In support of this claim, there is evidence to suggest that the rate of attrition among U.S. investigators is increasing. The proportion of clinical investigators who are from North America has been falling since 1997, while the proportions of investigators from Western Europe and the rest of the world have been increasing (English, Lebovitz, & Giffin, 2010).
There is reason to believe that this trend will persist and the pool of investigators in this country will continue to shrink. It is very challenging to conduct clinical trials and establish a successful career as a clinical investigator in the U.S (English, Lebovitz, & Giffin, 2010); 45 percent of first-time investigators quit the field after their first clinical trial (Califf, Filerman, Murray, & Rosenblatt, 2011), and there is little motivation for new investigators to replace them. The clinical investigator track is, in many ways, less appealing than other options available to researchers, who would prefer to publish results more easily and avoid the hassles of getting a clinical trial protocol approved. Furthermore, conducting clinical trials does not earn researchers much respect among academics, and academic institutions often provide little support in the design and initiation of trials. Although community physicians and practitioners represent a large pool of potential investigators, they are generally uninvolved in the clinical trial process (for reasons discussed in Section 4.7) (English, Lebovitz, & Giffin, 2010). In this shrinking pool of resources, competition for resources will likely continue to intensify as increasing numbers of trials are conducted in orphan/low-prevalence diseases.
The outlook for resources at the investigative site level is similarly bleak. Many veteran sites in the U.S. have been struggling financially in recent years, forcing some to shift resources to more profitable enterprises or even cease their clinical research activities altogether (Getz K. A., 2010a). While some of this financial hardship can be attributed to the global economic downturn—the number of new trials being initiated declined, and many trials have been delayed or terminated—much of it is due to industry practices. For one thing, protocols have grown increasingly complex (in terms of the number of procedures and amendments and amount of effort required to execute them), to the point of becoming unmanageable (discussed in more detail in Section 4.6). Recruitment is also very difficult in the United States (see Section 4.3), which increasingly drives sponsors to sites overseas. Furthermore, sponsors and CROs are responding to the unpredictability of site performance with a practice called “hedging,” in which trials are spread across larger numbers of sites, each with smaller numbers of patients, an economically unfavorable arrangement for many sites. Finally, sites face serious cash flow problems. In general, sponsors try to defer payment to later in the study; it takes an average of approximately 120 days for sites to receive payment from sponsors and CROs for work that they have already completed. Many experienced investigative sites need to borrow money in order to stay afloat, with the average U.S.-based site carrying a debt of $400,000. If these factors remain unaddressed, more sites can be expected to permanently close their doors to clinical research (Getz K. A., 2010a).