Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.

New technologies and disruptions related to Coronavirus disease-2019 have led to expansion of decentralized approaches to clinical trials. Remote tools and methods hold promise for increasing trial efficiency and reducing burdens and barriers by facilitating participation outside of traditional clinical settings and taking studies directly to participants. The Trial Innovation Network, established in 2016 by the National Center for Advancing Clinical and Translational Science to address critical roadblocks in clinical research and accelerate the translational research process, has consulted on over 400 research study proposals to date. Its recommendations for decentralized approaches have included eConsent, participant-informed study design, remote intervention, study task reminders, social media recruitment, and return of results for participants. Some clinical trial elements have worked well when decentralized, while others, including remote recruitment and patient monitoring, need further refinement and assessment to determine their value. Partially decentralized, or “hybrid” trials, offer a first step to optimizing remote methods. Decentralized processes demonstrate potential to improve urban-rural diversity, but their impact on inclusion of racially and ethnically marginalized populations requires further study. To optimize inclusive participation in decentralized clinical trials, efforts must be made to build trust among marginalized communities, and to ensure access to remote technology.

One challenge for multisite clinical trials is ensuring that the conditions of an informative trial are incorporated into all aspects of trial planning and execution. The multicenter model can provide the potential for a more informative environment, but it can also place a trial at risk of becoming uninformative due to lack of rigor, quality control, or effective recruitment, resulting in premature discontinuation and/or non-publication. Key factors that support informativeness are having the right team and resources during study planning and implementation and adequate funding to support performance activities. This communication draws on the experience of the National Center for Advancing Translational Science (NCATS) Trial Innovation Network (TIN) to develop approaches for enhancing the informativeness of clinical trials. We distilled this information into three principles: (1) assemble a diverse team, (2) leverage existing processes and systems, and (3) carefully consider budgets and contracts. The TIN, comprised of NCATS, three Trial Innovation Centers, a Recruitment Innovation Center, and 60+ CTSA Program hubs, provides resources to investigators who are proposing multicenter collaborations. In addition to sharing principles that support the informativeness of clinical trials, we highlight TIN-developed resources relevant for multicenter trial initiation and conduct.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.

We present a new surface-balance and ice-motion dataset derived from high-precision GPS measurements from a network of steel poles within three icefields of the Allan Hills blue-ice area, Antarctica. The surveys were conducted over a 14 year time period. Ice-flow velocities and mass- balance estimates for the main icefield (MIF) are consistent with those from pre-GPS era measurements but have much smaller uncertainties. The current study also extends these measurements through the near-western icefield (NWIF) to the eastern edge of the mid-western icefield (MWIF). The new dataset includes, for the first time, well-constrained evidence of upward motion within the Allan Hills MIF, indicating that old ice should be present at the surface. These data and terrestrial meteorite ages suggest that paleoclimate reconstructions using the surface record within the Allan Hills MIF could potentially extend the ice-core-based record beyond the 800 000 years currently available in the EPICA Dome C core.

Field experiments were conducted to compare performance of glyphosate with three different boom arrangements in a winter wheat-fallow rotation near North Platte, NE, in 1994 and 1995. One boom was optically controlled, and the other boom was for broadcast herbicide applications. Spraying with both booms at the same time was called “dual boom.” The sprayers were tested during May, June, and July on two weed density levels established by applying glyphosate at 0.42 kg ae/ha with and without atrazine at 0.84 kg ai/ha in October following wheat harvest. The dual-boom and the broadcast herbicide applications were more efficient in controlling weeds than the optically controlled system. The dual boom reduced weed density 4.5-fold compared with the optically controlled sprayer used alone. Horseweed < 8 cm tall was more difficult to control with the optically controlled sprayer than redroot pigweed and kochia because of its cylindrical-shaped growth patterns. Barnyardgrass and green foxtail seedlings with an erect growth pattern were also difficult for the sensors to detect. Poorer control with the optically controlled sprayer was associated with failure to identify small weeds, chlorotic plants, inconsistency among sensors, and too wide a field of view (FOV), as sensors were spaced farther apart than presently recommended. The number of sensors on a boom needs to be increased to improve the performance of the optically controlled sprayer.

Winter wheat cultivars that are competitive with weeds help control weeds in crop rotations. Ten winter wheat cultivars were evaluated for interference with summer annual grasses in the wheat and the subsequent grain sorghum crop in a winter wheat-ecofallow sorghum-fallow rotation in which there are two 10–mo fallow periods and two crops in 3 yr during 1983 to 1987. The medium–tall (100 to 109 cm tall) and medium–statured (90 to 99 cm tall) winter wheat cultivars (‘Buckskin’, ‘Siouxland’, ‘Lancota’, ‘Centurk 78’, and ‘Brule’) were more competitive than medium-short (80 to 89 cm tall) and short (68 to 79 cm tall) cultivars (‘Eagle’, ‘Homestead’, ‘Colt’, ‘Vona’, and ‘TAM 101’). Atrazine plus paraquat was applied to all cultivars 30 d after wheat harvest. When grain sorghum was planted in areas previously seeded with medium–tall and medium-statured winter wheat, summer annual grass weed biomass in sorghum was 61% less than in grain sorghum seeded into areas previously planted with medium-short and short wheat cultivars. Use of pendimethalin plus 2,4–D in winter wheat and glyphosate plus alachlor in grain sorghum eliminated differences in summer annual grass weed density and weed biomass among wheat cultivars. Sorghum grain yields were improved 7% when herbicides were used in the winter wheat and sorghum but value of the increase was less than cost of herbicides. Substituting less costly herbicides for herbicides used in this study still would not have been enough to pay for cost of herbicides for five cultivars. Grain sorghum grown on weed–free stubble of medium–tall and medium–statured winter wheat produced more grain than grain sorghum grown after medium–short and short-statured winter wheat by 5%. Volunteer wheat density during the fallow period following grain sorghum was lower in areas originally seeded to Centurk 78 and Siouxland wheat while volunteer wheat density was higher in areas planted to Homestead and Vona.

Weed-detecting reflectance sensors were modified to allow selective interrogation of the near infrared–red ratio to estimate differences in plant biomass. Sampling was programmed to correspond to the forward movement of the field of view of the sensors. There was a linear relationship (r 2 > 0.80) between actual biomass and crop canopy analyzer (CCA) values up to 2,000 kg/ha for winter wheat sequentially thinned to create different amounts of biomass and up to 1,000 kg/ha for spring wheat sampled at different stages of development. At higher amounts of biomass the sensors underestimated the actual biomass. A linear relationship (r 2 = 0.73) was obtained with the CCA for the biomass of 76 chickpea cultivars at 500 growing degree days (GDD500). The reflectance sensors were used to determine differences in the herbicide response of soybean cultivars sprayed with increasing rates of herbicides. The CCA data resulted in better dose–response relationships than did biomass data for bromoxynil at 0.8 kg ai/ha and glyphosate at 1.35 kg ai/ha. There was no phytotoxicity to soybean with imazethapyr at 1.44 kg ai/ha. The method offers a quick and nondestructive means to measure differences in early-season crop growth. It also has potential in selecting crop cultivars with greater seedling vigor, as an indicator of crop nutrient status, in plant disease assessment, in determining crop cultivar responses to increasing herbicide dose rates, in weed mapping, and in studying temporal changes in crop or weed biomass.

Production systems based on reduced-tillage practices account for over 60% of the cropped land on the Canadian Prairies. Concerns have been expressed regarding potential shifts in weed communities as a result of changing tillage practices. Study objectives were to (1) determine the feasibility of combining and analyzing weed abundance data from 10 medium- to long-term studies on the Canadian Prairies that compared conventional-, reduced-, and zero-tillage systems, (2) identify species that are associated with specific tillage systems, and (3) place species into plant response groups according to the similarity of their tillage system response. Conventional-tillage systems were defined as including both a fall and spring sweep-plow operation before seeding spring crops, whereas reduced tillage consisted of only one sweep-plow operation shortly before seeding. Crops within zero-tillage systems were planted directly into the previous crop's stubble. The association between weed species and tillage systems was investigated using indicator species analysis. Species were assigned to tillage response groups on the basis of the results of the analysis and the expertise of the project scientists. Perennial species such as Canada thistle and perennial sowthistle were associated with reduced- and zero-tillage systems, but annual species were associated with a range of tillage systems. Field pennycress was placed in the conventional-tillage response group, Russian thistle in the zero-tillage group, and wild buckwheat and common lambsquarters were equally abundant in all tillage systems. The goal of classifying weed species based on common functional traits in relation to responses to tillage systems was not realized, in part, because the required information on species biology and ecology was either unavailable or not applicable to local conditions.

We describe a versatile infrared camera/spectrograph, IRIS, designed and constructed at the Anglo-Australian Observatory for use on the Anglo-Australian Telescope. A variety of optical configurations can be selected under remote control to provide several direct image scales and a few low-resolution spectroscopic formats. Two cross-dispersed transmission echelles are of novel design, as is the use of a modified Bowen-Burch system to provide a fast f/ratio in the widest-field option. The drive electronics includes a choice of readout schemes for versatility, and continuous display when the array is not taking data, to facilitate field acquisition and focusing.

The linearity of the detector has been studied in detail. Although outwardly good, slight nonlinearities prevent removal of fixed-pattern noise from the data without application of a cubic linearising function.

Specific control and data-reduction software has been written. We describe also a scanning mode developed for spectroscopic imaging.