Leveraging the Expertise of the CTSA Program to Increase the Impact and Efficiency of Clinical Trials.

Importance: Multicenter clinical trials play a critical role in the translational processes that enable new treatments to reach all people and improve public health. However, conducting multicenter randomized clinical trials (mRCT) presents challenges. The Trial Innovation Network (TIN), established in 2016 to partner with the Clinical and Translational Science Award (CTSA) Consortium of academic medical institutions in the implementation of mRCTs, consists of 3 Trial Innovation Centers (TICs) and 1 Recruitment Innovation Center (RIC). This unique partnership has aimed to address critical roadblocks that impede the design and conduct of mRCTs, in expectation of accelerating the translation of novel interventions to clinical practice. The TIN's challenges and achievements are described in this article, along with examples of innovative resources and processes that may serve as useful models for other clinical trial networks providing operational and recruitment support. Observations: The TIN has successfully integrated more than 60 CTSA institution program hubs into a functional network for mRCT implementation and optimization. A unique support system for investigators has been created that includes the development and deployment of novel tools, operational and recruitment services, consultation models, and rapid communication pathways designed to reduce delays in trial start-up, enhance recruitment, improve engagement of diverse research participants and communities, and streamline processes that improve the quality, efficiency, and conduct of mRCTs. These resources and processes span the clinical trial spectrum and enable the TICs and RIC to serve as coordinating centers, data centers, and recruitment specialists to assist trials across the National Institutes of Health and other agencies. The TIN's impact has been demonstrated through its response to both historical operational challenges and emerging public health emergencies, including the national opioid public health crisis and the COVID-19 pandemic. Conclusions and Relevance: The TIN has worked to reduce barriers to implementing mRCTs and to improve mRCT processes and operations by providing needed clinical trial infrastructure and resources to CTSA investigators. These resources have been instrumental in more quickly and efficiently translating research discoveries into beneficial patient treatments.

Approaches for enhancing the informativeness and quality of clinical trials: Innovations and principles for implementing multicenter trials from the Trial Innovation Network.

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.

The Trial Innovation Network Liaison Team: building a national clinical and translational community of practice.

In 2016, the National Center for Advancing Translational Science launched the Trial Innovation Network (TIN) to address barriers to efficient and informative multicenter trials. The TIN provides a national platform, working in partnership with 60+ Clinical and Translational Science Award (CTSA) hubs across the country to support the design and conduct of successful multicenter trials. A dedicated Hub Liaison Team (HLT) was established within each CTSA to facilitate connection between the hubs and the newly launched Trial and Recruitment Innovation Centers. Each HLT serves as an expert intermediary, connecting CTSA Hub investigators with TIN support, and connecting TIN research teams with potential multicenter trial site investigators. The cross-consortium Liaison Team network was developed during the first TIN funding cycle, and it is now a mature national network at the cutting edge of team science in clinical and translational research. The CTSA-based HLT structures and the external network structure have been developed in collaborative and iterative ways, with methods for shared learning and continuous process improvement. In this paper, we review the structure, function, and development of the Liaison Team network, discuss lessons learned during the first TIN funding cycle, and outline a path toward further network maturity.

Using gamification to enhance clinical trial start-up activities.

Background: The Trial Innovation Network (TIN) is a collaborative initiative within the National Center for Advancing Translational Science (NCATS) Clinical and Translational Science Awards (CTSA) Program. To improve and innovate the conduct of clinical trials, it is exploring the uses of gamification to better engage the trial workforce and improve the efficiencies of trial activities. The gamification structures described in this article are part of a TIN website gamification toolkit, available online to the clinical trial scientific community. Methods: The game designers used existing electronic trial platforms to gamify the tasks required to meet trial start-up timelines to create friendly competitions. Key indicators and familiar metrics were mapped to scoreboards. Webinars were organized to share and applaud trial and game performance. Results: Game scores were significantly associated with an increase in achieving start-up milestones in activation, institutional review board (IRB) submission, and IRB approval times, indicating the probability of completing site activation faster by using games. Overall game enjoyment and feelings that the game did not apply too much pressure appeared to be an important moderator of performance in one trial but had little effect on performance in a second. Conclusion: This retrospective examination of available data from gaming experiences may be a first-of-kind use in clinical trials. There are signals that gaming may accelerate performance and increase enjoyment during the start-up phase of a trial. Isolating the effect of gamification on trial outcomes will depend on a larger sampling from future trials, using well-defined, hypothesis-driven statistical analysis plans.

Team Development Measure in Interprofessional Graduate Education: A Pilot Study.

A faculty team developed the 4-week Recovery-Based Interprofessional Distance Education (RIDE) rotation for graduate students in their disciplines. The evaluation team identified the Team Development Measure (TDM) as a potential alternative to reflect team development during the RIDE rotation. The TDM, completed anonymously online, was piloted on the second student cohort (N = 18) to complete the RIDE rotation. The overall pretest mean was 60.73 points (SD = 11.85) of a possible 100 points, indicating that students anticipated their RIDE team would function at a moderately high level during the 4-week rotation. The overall posttest mean, indicating student perceptions of actual team functioning, was 72.71 points (SD = 23.31), an average increase of 11.98 points. Although not statistically significant, Cohen's effect size (d = 0.43) indicates an observed difference of large magnitude. No other published work has used the TDM as a pre-/posttest measure of team development. The authors believe the TDM has several advantages as a measure of student response to interprofessional education offerings, particularly in graduate students with prior experience on health care teams. Further work is needed to validate and extend the findings of this pilot study. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 18-22.].

Transforming Health Care Through Interprofessional Graduate Education.

PURPOSE: We provide an overview of the Recovery-based Interprofessional Distance Education (RIDE) rotation for graduate students in psychiatric mental health (PMH) nursing, pharmacy, nutrition, and exercise physiology, with faculty from the four professions represented. CONCLUSIONS: Interprofessional education can enhance team concepts in these professions and is viewed positively by students and faculty. PRACTICE IMPLICATIONS: Interprofessional learning opportunities prepare graduates to contribute to team-based care. We urge colleagues to join us in providing meaningful IPE experiences to students at all levels, with the goal of optimizing health care for all persons with mental health treatment needs.

Postprandial walking reduces glucose levels in women with gestational diabetes mellitus.

The purpose of this study was to investigate blood glucose changes, as measured by a continuous glucose monitoring system, that occur in women with gestational diabetes mellitus (GDM) following an acute bout of moderate-intensity walking after consuming a high-carbohydrate/low-fat meal. This study found that moderate-intensity walking induced greater postprandial glucose control compared with sedentary activity and it appears that moderate-intensity activity may be used to reduce postprandial glucose levels in women with GDM.

Recovery-Based Interprofessional Distance Education (RIDE): Graduate Student Responses.

Graduate student attitudes (n = 28) were assessed before and after participation in interprofessional practitioner education (IPE). Twenty-eight graduate students participated (14 mental health nursing, 6 pharmacy, 4 nutrition, 4 exercise physiology); most had at least some health care experience. Posttest scores indicated gains on a majority of constructs measured. These results suggest that online-blended IPE content yields gains in team skills and attitudes. This study adds to a very small body of literature on IPE in graduate programs. More research is needed in examining online versus face-to-face delivery.

Effect of Adding Online Social Support Tools to an Adult Walking Program: A Pilot Randomized Controlled Trial.

This pilot study examined the efficacy of providing access to online social support tools on adults' step counts during a technology-mediated walking intervention. Sixty-three insufficiently active adults were randomized to a 12-week walking intervention with (SUPPORT) or without (NO SUPPORT) access to online social support tools. Both groups received a pedometer, step goals, and access to relevant websites. The SUPPORT group also received access to online social support tools. A mixed-factor analysis of variance was conducted to examine within- and between-group differences in measures of daily steps, psychosocial indicators, and health. Both groups significantly (p < .05) increased their daily steps over time from baseline by 1,401 (SUPPORT) and 2,461 (NO SUPPORT), with no significant differences between groups. Psychosocial and health improvements were no greater for SUPPORT versus NO SUPPORT. The SUPPORT group's use of the online social support tools was low. Results suggest that giving adults access to online social support tools during a technology-mediated walking program did not lead to an enhanced increase in daily steps versus an identical program without these tools; however, the low use of these tools may have weakened their effect. Future studies should examine SUPPORT versus NO SUPPORT among groups with preexisting social ties.

Physical Activity With and Without TV Viewing: Effects on Enjoyment of Physical Activity and TV, Exercise Self-Efficacy, and Barriers to Being Active in Overweight Adults.

BACKGROUND: Physical activity (PA) is enjoyable, but there are barriers to participation. TV viewing is highly enjoyable with limited barriers. Exercising while viewing TV may impact enjoyment, exercise self-efficacy, and barriers to PA, compared with exercising without TV. METHODS: 58 sedentary, overweight adults were randomized to 1 of 2 PA prescriptions: one that increased PA during TV viewing (TV Commercial Stepping), and another that focused solely on PA (Walking). Random effects models tested changes in enjoyment of TV and PA, exercise self-efficacy, and barriers to PA across time (baseline, 3, and 6 months) and PA prescription during a 6-month PA intervention. RESULTS: At baseline, TV was more enjoyable than PA. Over the 6-month intervention, enjoyment of TV viewing did not change, but enjoyment of PA and exercise self-efficacy significantly increased, while barriers to PA significantly decreased for both groups compared with baseline (P < .05). CONCLUSIONS: While enjoyment of TV viewing remained constant, PA became more enjoyable, confidence to exercise increased, and barriers to being active were reduced for previously sedentary adults participating in a behavioral PA intervention. These findings highlight the importance of encouraging inactive adults to engage in some form of PA, whether it occurs with or without TV viewing.

The Recovery-Based Interprofessional Distance Education (RIDE) Rotation: Content and Rationale.

A faculty team of two psychiatric nurse practitioners, an exercise physiologist, a registered dietician and a pharmacist developed the 8-week Recovery-Based Interprofessional Distance Education (RIDE) rotation for graduate students in the four disciplines. Organizing the RIDE rotation around the recovery model ensured an emphasis upon optimal health and quality of life. RIDE faculty engaged in project planning for several months before the RIDE rotation was offered to students. In this paper, we describe details of the 8-week program. Our next step will be to analyze student feedback and de-identified evaluation data from the first student cohort.

Validity of Physical Activity Monitors for Estimating Energy Expenditure During Wheelchair Propulsion.

BACKGROUND: It is unknown if activity monitors can detect the increased energy expenditure (EE) of wheelchair propulsion at different speeds or on different surfaces. METHODS: Individuals who used manual wheelchairs (n = 14) performed 5 wheeling activities: on a level surface at 3 speeds, on a rubberized track at 1 fixed speed and on a sidewalk course at a self-selected speed. EE was measured using a portable indirect calorimetry system and estimated by an Actical (AC) worn on the wrist and a SenseWear (SW) activity monitor worn on the upper arm. Repeated- measures ANOVA was used to compare measured EE to the estimates from the standard AC prediction equation and SW using 2 different equations. RESULTS: Repeated-measures ANOVA demonstrated a significant main effect between measured EE and estimated EE. There were no differences between the criterion method and the AC across the 5 activities. The SW overestimated EE when wheeling at 3 speeds on a level surface, and during sidewalk wheeling. The wheelchair-specific SW equation improved the EE prediction during low intensity activities, but error progressively increased during higher intensity activities. CONCLUSIONS: During manual wheelchair propulsion, the wrist-mounted AC provided valid estimates of EE, whereas the SW tended to overestimate EE.

Physical activity variety, energy expenditure, and body mass index.

OBJECTIVES: To examine if physical activity (PA) variety was associated with moderate- to vigorous-intensity PA (MVPA) energy expenditure and body mass index (BMI) at 18 months during an obesity intervention. METHODS: Participants with ≥ 10 minutes/week of MVPA at 6 months and complete PA data were included. Participants were classified into Variety (N = 30), ≥ 2 different activities/week, or Less Variety (N = 65), only 1 activity/week. RESULTS: Weekly MVPA-related energy expenditure was higher for Variety than Less Variety (3674.7 ± 1934.6 kcal/week vs 2197.3 ± 1841.4 kcal/week, p < .05) at 18 months, with no difference in BMI. CONCLUSIONS: Greater weekly PA variety during obesity treatment was related to greater 18-month MVPA energy expenditure.

Monitoring capabilities of the Omron HJ-720ITC pedometer.

PURPOSE: The purpose of our study was to examine the monitoring capabilities of the Omron HJ-720ITC pedometer and determine the feasibility of using it in physical activity interventions. METHODS: Using data from an 8-week lifestyle-intervention study, we tested the capabilities of the pedometer for recording physical activity data. Data from a total of 28 subjects were used in our analysis. The total number of patient steps per day was recorded over the duration of an intervention, as well as "aerobic steps per day" (ie, those taken at a cadence of > 60 steps per minute for ≥ 10 consecutive minutes). Daily wear time was computed in order to ascertain participant compliance in wearing the pedometer. In addition, aerobic steps per minute were computed, providing an assessment of activity intensity during continuous walking bouts. RESULTS: Total steps per day and aerobic steps per day increased from baseline assessment to Week 8. Participants exceeded 100 steps/minute for 89% of their aerobic minutes, suggesting that they were in the moderate-intensity range (3-6 metabolic equivalent tasks) when performing continuous bouts of walking (> 10 minutes). CONCLUSION: The new pedometer is a reasonably priced, wearable activity monitor that is feasible for use in clinical and research settings.

Reducing TV watching during adult obesity treatment: two pilot randomized controlled trials.

The more time adults spend being sedentary, the greater the risk of obesity. The effect of reducing television (TV) watching, a prominent sedentary behavior, on weight loss has not been tested in an adult standard behavioral obesity intervention, and the mechanisms by which reducing TV watching influences energy balance behaviors are not well understood. Two, 8-week, pilot, randomized controlled trials were conducted examining the effect of a reduced TV watching prescription on energy balance behaviors and weight loss within an adult standard behavioral obesity intervention. In the first study, participants (n=24) were randomized into one of two conditions: (a) reduce energy intake and increase moderate to vigorous physical activity (MVPA) (INCREASE PA); or (b) reduce energy intake and decrease TV watching (DECREASE TV). As findings from the first pilot study did not show an increase in MVPA in the DECREASE TV group, the second study was designed to examine the effect of adding a reduced TV prescription to a standard intervention to optimize outcomes. In Pilot Study 2, participants (n=28) were randomized to INCREASE PA or to INCREASE PA+DECREASE TV. Outcomes included objectively measured TV watching and MVPA, self-reported light physical activity (LPA-Pilot Study 2 only), self-reported dietary intake while watching TV, and weight. Conditions with TV watching prescriptions significantly reduced TV watching. Both studies showed medium to large effect sizes for conditions with TV watching prescriptions to show greater reductions in dietary intake while watching TV. Pilot Study 1 found a trend for an increase in MVPA in INCREASE PA and Pilot Study 2 found significant increases in MVPA in both conditions. Pilot Study 2 found a significant increase in LPA in the INCREASE PA+DECREASE TV. Results indicate adding a TV watching prescription to a standard obesity intervention did not enhance increases in MVPA, but may assist with reducing dietary intake while TV watching and increasing LPA. Future research should examine the effect of reducing TV watching during obesity treatment over a longer time frame in a larger sample.

Classification accuracy of the wrist-worn gravity estimator of normal everyday activity accelerometer.

PURPOSE: The purpose of this study was to determine whether the published left-wrist cut points for the triaxial Gravity Estimator of Normal Everyday Activity (GENEA) accelerometer are accurate for predicting intensity categories during structured activity bouts. METHODS: A convenience sample of 130 adults wore a GENEA accelerometer on their left wrist while performing 14 different lifestyle activities. During each activity, oxygen consumption was continuously measured using the Oxycon mobile. Statistical analysis used Spearman's rank correlations to determine the relationship between measured and estimated intensity classifications. Cross tabulations were constructed to show the under- or overestimation of misclassified intensities. One-way χ2 tests were used to determine whether the intensity classification accuracy for each activity differed from 80%. RESULTS: For all activities, the GENEA accelerometer-based physical activity monitor explained 41.1% of the variance in energy expenditure. The intensity classification accuracy was 69.8% for sedentary activities, 44.9% for light activities, 46.2% for moderate activities, and 77.7% for vigorous activities. The GENEA correctly classified intensity for 52.9% of observations when all activities were examined; this increased to 61.5% with stationary cycling removed. CONCLUSIONS: A wrist-worn triaxial accelerometer has modest-intensity classification accuracy across a broad range of activities when using the cut points of Esliger et al. Although the sensitivity and the specificity are less than those reported by Esliger et al., they are generally in the same range as those reported for waist-worn, uniaxial accelerometer cut points.

The influence of commercially-available carbohydrate and carbohydrate-protein supplements on endurance running performance in recreational athletes during a field trial.

BACKGROUND: It is recommended that endurance athletes consume carbohydrate (CHO) supplements, providing 6-8% CHO concentration, during exercise > 60 minutes to improve athletic performance. Recently research has compared carbohydrate-protein (CHO-P) supplementation to the traditionally used CHO supplementation during endurance exercise, following these supplementation recommendations, in controlled settings, but not under simulated applied conditions such as a field trial. Therefore, the purpose of the present investigation was to test CHO and CHO-P supplementation under applied conditions such that commercially-available isocaloric (CHO-P & double-carbohydrate [CHO-CHO]) and isocarbohydrate (CHO-P & CHO) supplements were compared to a placebo (PLA), within an outdoor running field trial > 60 minutes in order to asses their influence on endurance performance. METHODS: Twelve male recreational runners completed four, 19.2 km runs, where they were instructed to run at a pace similar to race pace including a final sprint to the finish, which in this case was the final two laps of the course (1.92 km). Supplementation was provided before the start and in 4 km increments. Performance was measured by time to complete the 19.2 km run and last 1.92 km sprint. RESULTS: Analyses found no difference between supplements in time to complete the 19.2 km run (PLA = 88.6 ± 11.6 min, CHO = 89.1 ± 11.3 min, CHO-P = 89.1 ± 11.8 min, CHO-CHO = 89.6 ± 11.9 min) or last 1.92 km sprint to the finish (PLA = 8.3 ± 1.2 min, CHO = 8.2 ± 1.2 min, CHO-P = 8.2 ± 1.2 min, CHO-CHO = 8.4 ± 1.5 min). CONCLUSIONS: When following recommendation for supplementation within a field trial, commercially available CHO and CHO-P supplements do not appear to enhance performance in male recreational runners.

The ability of the PACER to elicit peak exercise response in youth [corrected].

PURPOSE: A graded exercise test (GXT) is the standard laboratory method of determining peak aerobic fitness (V˙O2peak). The FITNESSGRAM's Progressive Aerobic Cardiovascular Endurance Run (PACER) test is commonly used to estimate the peak oxygen consumption in the youth in the field.The objective of this study is to compare the peak physiological variables and RPEpeak during a treadmill GXT and the PACER test in 10- to 15-yr-old youths. METHODS: Participants (20 boys and 25 girls, 12.7 ± 1.7 yr) completed the PACER and treadmill GXT in a randomized order, separated by at least 24 h. HRpeak was measured via telemetry, V˙O2peak and RERpeak were measured using a portable metabolic system, and participants reported RPEpeak at the end of each test. RESULTS: No significant differences were found between the GXT and PACER HRpeak (197 vs 197 beats·min), RERpeak (1.13 vs 1.12), V˙O2peak (45.0 vs 45.9 mL·kg·min), and RPEpeak (8.4 vs 8.3). The SE of the measurement between the GXT V˙O2peak and PACER V˙O2peak was 1.4 mL·kg·min. CONCLUSIONS: It appears that the PACER elicits similar peak exercise responses compared with a treadmill GXT. The PACER can also be administered for fitness and functional capacity assessments in healthy and clinical populations.

Association of physical activity, fitness, and race: NHANES 1999­2004.

PURPOSE: Regular physical activity (PA) can be used to improve cardiorespiratory fitness (CRF). Previous research has shown differences in CRF (VO2max) among racial groups, but it is unclear how much of these differences can be explained by PA. Thus, we sought to examine the association between PA and CRF in different racial groups. METHODS: As a part of the National Health and Nutrition Examination Survey (1999­2004), 3115 adults (18­49 yr) completed a submaximal graded treadmill exercise test to estimate VO2max. Independent variables were demographics (race, education, sex, partner status, and waist circumference), behavioral measures (smoking and alcohol consumption), self-reported PA from three domains (leisure-time, domestic, and transportational PA (MET x min x wk(-1)), and the proportion of PA at a vigorous intensity (VMET). CRF was the dependent variable. Multiple linear regression was performed using SUDAAN statistical software. RESULTS: Results indicated that VO2max was significantly higher for Mexican Americans (40.9 T 0.5 mL x kg(-1) x min(-1)) and non-Hispanic whites (40.2 +/- 0.3 mL x kg(-1) x min(-1)) compared with non-Hispanic blacks (37.9 +/- 0.6 mL x kg(-1) x min(-1)) (P = 0.01). Demographics including race explained 18.5% of the variance in VO2max, with race being significant (P < 0.01) in the model. When PA was added to the model, the explained variance in VO2max increased to 19.3% (P = 0.001). VMET was more predictive of VO2max than total PA, and the model including VMET explained 20.4% of the variance in VO2max. Race remained a significant, independent predictor of VO2max after VMET and overall PA were added to the model. CONCLUSION: Race, PA, and exercise intensity are important factors in explaining differences in CRF. After accounting for demographics, PA, and VMET, a large proportion of the variance in CRF remains unexplained. Thus, other factors should also be considered when examining racial/ethnic differences in CRF.

Effect of BMI on pedometers in early adolescents under free-living conditions.

PURPOSE: Pedometers may provide valuable information regarding the ambulatory patterns of adolescents, but the effects of body mass index (BMI) on pedometer accuracy in this population are unknown.The purpose of this study was twofold: 1) to determine whether the New Lifestyles NL-2000 (NL) and the Digi-Walker SW-200 (DW) (New Lifestyles, Inc., Lees Summit, MO) yield similar step counts as compared with an ankle-mounted criterion, StepWatch 3, when worn by early adolescents in a free-living environment and 2) to study whether BMI percentile affects the accuracy of waist-mounted pedometers in adolescents. METHODS: Seventy-four early adolescents (13.0 ± 1.1 yr) wore the devices during one weekday. The study population included 33 normal weight, 21 overweight, and 20 obese participants. Two-way repeated-measures ANOVA was used to determine whether the BMI and the device were related to the number of steps per day and percentage of actual steps. RESULTS: The NL and DW recorded fewer steps than the StepWatch 3 in each BMI category (P < 0.05). In the obese group, the DW underestimated the steps more than the NL (P < 0.001). For the normal weight, overweight, and obese groups, the NL counted 89.1%, 89.1%, and 91.6% of the steps, respectively, whereas the DW counted 86.7%, 84.6%, and 72.7%, respectively. CONCLUSION: Researchers must be cognizant of the limitations of waist-mounted pedometers and carefully choose a device that suits the needs of their investigations. Because of the inaccuracies of the DW when measuring steps in obese adolescents, careful consideration must be given before choosing this device for research and interventions. The NL is a better device for assessment of adolescents' steps than the DW, especially for those who are obese.