Impediments to Clinical Research in the United States

Abstract

Clinical trials are essential to the evaluation of promising scientific discoveries, but they are becoming unsustainably burdensome, threatening to deprive patients and health-care providers of new therapies and new evidence to guide the use of existing treatments. Regulations are often blamed for impeding clinical research, but there are other elements of the clinical trials enterprise that also have the potential to add burdens, through either imposed requirements or incentives that do not favor clinical research (Figure 1).

Progress toward the prevention and treatment of atrial fibrillation: A summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, December 9–10, 2013

“…The current clinical trials system is encumbered by regulatory and administrative burdens. 144 Trial startup is hampered by poorly coordinated institutional review board (IRB) activities, lack of standardized data collection (with limited reusability of case report forms), and institution-specific contract requirements. Trial monitoring often uses retrospective evaluation rather than building quality into study design.…”

U.S. Food and Drug Administration Inspections of Clinical Investigators: Overview of Results from 1977 to 2009

“…Getz and colleagues (11) reported that between 1999 and 2005, the number of study procedures per protocol for all phases and therapeutic areas increased by an average of 6.5% annually, and the number of procedures per protocol for gastrointestinal, anesthesia, and ophthalmology protocols increased annually by 30.5%, 22.5%, and 21.2%, respectively. A separate study found that the average number of protocol- (10,11). One of the reasons for this increase is that current regulatory practices often demand excessively detailed recording of imprecise symptoms, such as start and stop dates of subjective low-grade adverse events, for example, fatigue.…”

“…In recent years, the complexity of clinical trials has increased (9-13). For instance, eligibility criteria for industry-sponsored clinical trials have increased greatly; the Tufts Center for the Study of Drug Development found that 48% of patients screened for clinical trials over the period from 1990 to 1999 went on to complete the trial, whereas only 23% did so for the period from 2000 to 2009 (10,13). Assuming that the decrease is at least partly due to screen failures, this may be because the average number of inclusion criteria increased from 10 in 1999 to 26 in 2005.…”

“…It has been well documented that the complexity of clinical trials has increased substantially in this period of time (9)(10)(11)(12)(13)(14)(15). Hence, the purpose of this review was to describe the frequency with which compliance problems are observed, with the rationale for the study being that compliance in the face of increasing protocol complexity might present challenges that should be ascertained, so that they can be addressed.…”

A qualitative study on clinical research in Finland: fragmented governance and volume in the 2000s

“…Academic institutions and researchers in North America and later in Europe have expressed concerns over clinical research, with various initiatives attempting to overcome those problems. [1][2][3][4][5][6][7][8][9][10] One initiative in Europe is the network of European academic infrastructures (ECRIN, The European Clinical Research Infrastructure Network), which is a part of the European research infrastructures (ESFRI). Concerns expressed include the poor availability of medically trained researchers, a lack of time among clinicians, the low quality of research, patients not getting the new therapies in a timely fashion, commercial biases in the funding and conducting of research and the shifting of drug trials to low income countries.…”