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Streptococcus bovis NEM760 was isolated from a stool swab collected on admission from a patient as surveillance for vancomycin-resistant enterococci. Strain NEM760 was identified as S. bovis by conventional biochemical methods and partial sequence analysis of its 16S rRNA. This strain was resistant to a low level of vancomycin (MIC, 64 micrograms/ml) but was susceptible to teicoplanin (MIC, 1 micrograms/ml), and vancomycin induced resistance to both glycopeptides. The presence of a vanB-related gene in NEM760 was demonstrated in a PCR assay which enabled specific amplification of a 635-hp internal segment of vanB. Sequence analysis of the corresponding PCR product revealed that it was highly homologous (96% identity) to the prototype vanB sequence of Enterococcus faecalis V583. The VanB resistance of determinant of S. bovis NEM760 was transferred by conjugation to E. faecalis and Enterococcus faecium at a similar frequency of 2 x 10(-5) per donor. SmaI-digested genomic DNAs of independently obtained transconjugants of E. faecalis and E. faecium were analyzed by pulsed-field gel electrophoresis and Southern hybridization with a vanB DNA probe. The electrophoretic and hybridization patterns obtained with all transconjugants of the same species were indistinguishable and revealed vanB-containing chromosomal insertions of approximately 100 kb. These results suggest that the genes mediating VanB-type resistance in S. bovis NEM760 are part of large transferable genetic elements. The results presented in the report demonstrate for the first time the role of streptococci in the dissemination of vancomycin resistance among gram-positive bacteria.

Concerns have been raised over the high turnover rate for clinical investigators. Using the U.S. Food and Drug Administration's (FDA) Bioresearch Monitoring Information System database, we conducted an online survey to identify factors that affect principal investigators' (PIs) decisions to conduct only a single FDA-regulated drug trial. Of the 201 PIs who responded, 54.2% were classified as “one-and-done.” Among these investigators, 28.9% decided for personal reasons to not conduct another trial, and 44.4% were interested in conducting another trial, but no opportunities were available. Three categories of broad barriers were identified as generally burdensome or challenging by the majority of investigators: 1) workload balance (balancing trial implementation with other work obligations and opportunities) (63.8%); 2) time requirements (time to initiate and implement trial; investigator and staff time) (63.4%); and 3) data and safety reporting (56.5%). Additionally, 46.0% of investigators reported being generally unsatisfied with finance-related issues. These same top three barriers also affected investigators' decisions to no longer conduct FDA-regulated trials. Our findings illuminate three key aspects of investigator turnover. First, they confirm that investigator turnover occurs, as more than half of respondents were truly “one-and-done.” Second, because a large proportion of respondents wanted to conduct more FDA-regulated trials but lacked opportunities to do so, mechanisms that match interested investigators with research sponsors are needed. Third, by focusing on the barriers we identified that affected investigators' decisions to no longer conduct FDA-regulated trials, future efforts to reduce investigator turnover can target issues that matter the most to investigators.

Conducting randomized controlled trials entails a prolonged, costly study start-up (SSU) process that may create significant delays. Optimizing the operational aspects of multisite trials requires identifying benchmarks in the SSU process and the potential delays associated with them. We engaged in a collaborative effort to identify and describe key SSU intervals that correspond with necessary procedures and processes for activating multisite clinical trials in the US. After developing definitions for SSU benchmarks and obtaining data from research coordinating entities, we identified factors that were significantly associated with reduced cycle times, including the use of central institutional review boards for study approval and status as a private practice or independent research site. However, small sample sizes and large proportions of missing data hamper the interpretability of our results. Future development of standard measures of SSU efficiency will be critical to analyzing and improving study initiation processes at US research sites.

Background High turnover rates among clinical trial investigators contribute to inefficiency, instability, and increased costs for the clinical research enterprise; however, factors contributing to investigator turnover have not been well characterized. Methods Using information from the U.S. Food and Drug Administration's Bioresearch Monitoring Information System (BMIS), we examined trends in the overall clinical investigator workforce and within specific “phenotypes” as well as differences by investigator location (U.S.-based vs. non-U.S.-based). We identified unique investigators within the database, stratifying them into one of three “phenotypes”: those with one Form FDA1572 submission across the study interval (“one-and-done”); those with two or more submissions but with substantial intervals between trials (“stop-and-go”); and those with two or more submissions and continuous involvement in multiple trials (“stayers”). Results Of the 172,453 unique investigators who submitted a Form FDA 1572 during the study interval (1999–2015), 85,455 were classified as “one-and-done” investigators; 21,768 as “stop-and-go” investigators; and 65,231 as “stayer” investigators. The total number of investigators declined across the study interval. Among all subgroups, only “one-and-done” investigators showed growth across the study period, largely driven by increases in non-U.S.-based investigators. “Stop-and-go” investigators showed declines for both U.S.-based and non-U.S.-based investigators, as did “stayers,” who showed the largest absolute and proportional declines of all subgroups. Conclusions From 1999 to 2015, investigators submitting a Form FDA 1572 to the BMIS database declined by approximately one-third and the proportion of investigators involved in only one trial increased, signaling potential adverse trends in the clinical investigator workforce. Strategies for sustaining investigator engagement warrant further exploration.

Making information about financial interests in research readily available to clinical research coordinators, as well as providing education and training, should facilitate the disclosure of financial interests in research to potential research participants during the informed consent process.