It's Time to Harmonize Clinical Trial Site Standards

Abstract

Climbing costs and lengthy time frames of clinical trials are significant bottlenecks in medical product development. Despite the fact that scientific discoveries yield many new possible targets for developing into therapies, the capacity and resources with which to develop these targets are limited, thereby leaving potentially valuable discoveries undeveloped and unrealized. Under the aegis of the Clinical Trial Site Standards Harmonization Action Collaborative ("the Collaborative") of the Forum on Drug Discovery, Development, and Translation of the National Academies of Sciences, Engineering, and Medicine, clinical research stakeholders set out to discuss opportunities to improve clinical trial site functioning, with the goal of increasing productivity in medical product development. Our conclusion: harmonization of standards for clinical trial sites has significant promise in improving clinical trials. Standards would also be essential to the formation of a site accreditation system in the United States, should a consensus emerge on the need for such a system. This paper synthesizes the results of the work conducted to inform discussions of the Collaborative. This paper may serve as a launching point for harmonizing requirements applied to clinical trial sites and the development of standards. A clinical trial infrastructure that reduces redundancies and increases efficiencies would, in turn, accelerate the pace and productivity of new product development, to the benefit of patients and society. DISCUSSION PAPER Perspectives | Expert Voices in Health & Health Care Investing More, Producing Less Patients are in need of new medicines to treat an array of rare, common, and complex diseases. By its nature, the development of a new medicine, vaccine, device, or diagnostic is a careful process, one executed in keeping with the cardinal rule of medicine: "First, do no harm." Today, however, biopharmaceutical development faces an efficiency crisis, and the stakes for reform are high. Without a substantial increase in the rate of clinical success and subsequent drug approvals, many observers believe innovators will be unable to bring forward enough new medicines to sustain investment in research and development (R&D) activities [1]. The costs of development have skyrocketed, but

Research methodology and practical issues relating to the conduct of a medical device registry

“…83,84 Thoughtful review of clinical investigation plans should ensure standardized data collection to facilitate comparisons between the findings of different registries. 46,61,85…”

“…90 Specialists can help by trying to adapt their respective standard practices to the wider international community and strive for cross-sector alignment with common protocols for patient follow-up and surveillance as well as harmonization of investigative site standards. 85,91 With regard to safety reporting, centralized, risk-based monitoring is required to avoid too many data and too much workload obscuring relevant information. 92…”

“…At risk are the advantages of registries and, worse, seeing medical devices become victim to Eroom’s law (a backwards Moore’s Law) that has made drug discovery slower and more expensive despite technological improvements. 85,93 Scientific evaluation of surgical innovation is more difficult and needs to be considered separately. It took 20 years for randomized trial data to demonstrate the safety and efficacy of laparoscopic cholecystectomy, by which time the procedure was already standard practice worldwide.…”

More than a Box to Check: Research Sponsor and Clinical Investigator Perspectives on Making GCP Training Relevant

“…Concerns have been raised over the current structure and delivery of GCP training to prepare clinical investigators and their delegates to conduct registrational clinical trials [1,2]. GCP training has been described as timeconsuming [3], emphasizing trial activities unrelated to research validity [4] and providing only the minimum of what is needed in the quality conduct of clinical trials [1]; redundant [1]; lacking specificity about the definition of site quality or clinical investigators' perspectives on site [5]; and having monitoring standards that vary widely across research studies and sites [6,7]. Despite being the industry standard, there is little evidence that completion of GCP training alone sufficiently qualifies investigators and their delegates in the quality conduct of clinical trials [1].…”

More than a box to check: Research sponsor and clinical investigator perspectives on making GCP training relevant

“…Concerns have been raised over the current structure and delivery of GCP training to prepare clinical investigators and their delegates to conduct registrational clinical trials [ 1 , 2 ]. GCP training has been described as time-consuming [ 3 ], emphasizing trial activities unrelated to research validity [ 4 ] and providing only the minimum of what is needed in the quality conduct of clinical trials [ 1 ]; redundant [ 1 ]; lacking specificity about the definition of site quality or clinical investigators’ perspectives on site quality [ 5 ]; and having monitoring standards that vary widely across research studies and sites [ 6 , 7 ]. Despite being the industry expectation, there is little evidence that completion of GCP training alone sufficiently qualifies investigators and their delegates in the quality conduct of clinical trials [ 1 ].…”