scholarly journals phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0256391
Author(s):  
Jun Yin ◽  
Yu Du ◽  
Rui Qin ◽  
Shihao Shen ◽  
Sumithra Mandrekar
Keyword(s):  
Phase I ◽  
Repeated Measures ◽  
Real Life ◽  
R Package ◽  
Dose Finding ◽  
Repeated Measure ◽  
Design Parameters ◽  
Multiple Treatment ◽  
Repeated Measures Design ◽  
Late Treatment

Traditional dose-finding designs are substantially inefficient for targeted agents and cancer immunotherapies by failing to incorporate efficacy signals, mild and moderate adverse events, and late, cumulative toxicities. However, the lack of user-friendly software is a barrier to the practical use of the novel phase I designs, despite their demonstrated superiority of traditional 3+3 designs. To overcome these barriers, we present an R package, phase1RMD, which provides a comprehensive implementation of novel designs with repeated toxicity measures and early efficacy. A novel phase I repeated measures design that used a continuous toxicity score from multiple treatment cycles was implemented. Furthermore, in studies where preliminary efficacy is evaluated, an adaptive, multi-stage design to identify the most efficacious dose with acceptable toxicity was demonstrated. Functions are provided to recommend the next dose based on the data collected in a phase I trial, as well as to assess trial characteristics given design parameters via simulations. The repeated measure designs accurately estimated both the magnitude and direction of toxicity trends in late treatment cycles, and allocated more patients at therapeutic doses. The R package for implementing these designs is available from the Comprehensive R Archive Network. To our best knowledge, this is the first software that implement novel phase I dose-finding designs that simultaneously accounts for the multiple-grade toxicity events over multiple treatment cycles and a continuous early efficacy outcome. With the software published on CRAN, we will pursue the implementation of these designs in phase I trials in real-life settings.

scholarly journals The Effect of Binaural Beamforming Technology on Speech Intelligibility in Bimodal Cochlear Implant Recipients

2018 ◽  
Vol 23 (1) ◽  
pp. 32-38 ◽  
Author(s):  
Jantien L. Vroegop ◽  
Nienke C. Homans ◽  
André Goedegebure ◽  
J. Gertjan Dingemanse ◽  
Teun van Immerzeel ◽  
...  
Keyword(s):  
Cochlear Implant ◽  
Repeated Measures ◽  
Speech Intelligibility ◽  
Real Life ◽  
Speech Comprehension ◽  
Noise Sources ◽  
Additional Advantage ◽  
Listening Condition ◽  
Repeated Measures Design ◽  
Speech Reception Thresholds

Although the benefit of bimodal listening in cochlear implant users has been agreed on, speech comprehension remains a challenge in acoustically complex real-life environments due to reverberation and disturbing background noises. One way to additionally improve bimodal auditory performance is the use of directional microphones. The objective of this study was to investigate the effect of a binaural beamformer for bimodal cochlear implant (CI) users. This prospective study measured speech reception thresholds (SRT) in noise in a repeated-measures design that varied in listening modality for static and dynamic listening conditions. A significant improvement in SRT of 4.7 dB was found with the binaural beamformer switched on in the bimodal static listening condition. No significant improvement was found in the dynamic listening condition. We conclude that there is a clear additional advantage of the binaural beamformer in bimodal CI users for predictable/static listening conditions with frontal target speech and spatially separated noise sources.

scholarly journals Foods for Health: An Integrated Social Medical Approach to Food Insecurity Among Patients With Diabetes

2020 ◽  
pp. 089011712096414
Author(s):  
Jonathan L. Blitstein ◽  
Danielle Lazar ◽  
Kathleen Gregory ◽  
Colleen McLoughlin ◽  
Linda Rosul ◽  
...  
Keyword(s):  
Food Security ◽  
Glycemic Control ◽  
Food Insecurity ◽  
Nutrition Education ◽  
Repeated Measures ◽  
Repeated Measure ◽  
Care Practice ◽  
Mixed Effect ◽  
Repeated Measures Design ◽  
Patients With Diabetes

Purpose: Examine a clinic-based approach to improve food security and glycemic control among patients with diabetes. Design: One-group repeated-measures design. Setting: Federally Qualified Health Centers in a large Midwest city. Sample: Of the 933 patients with diabetes who consented at baseline, 398 (42.66%) returned during the follow-up period for a visit that included Hemoglobin A1c (HbA1c) results. Intervention: Integrated social medicine approach that includes food insecurity screening, nutrition education, and assistance accessing food resources as a standard-of-care practice designed to minimize disruptions in how patients and providers experience medical care. Measures: HbA1c collected as part of a standard blood panel. Analysis: Repeated-measure, mixed-effect linear regression models. Results: There was a decrease in mean HbA1c (Δ = −0.22, P = 0.01) over the study period. The model examining change over time, glycemic control (GC), and food security status (F1, 352 = 5.80, P = 0.02) indicated that among participants with poor GC (33.12%), food secure (FS) participants exhibited significantly greater levels of improvement than food insecure (FI) participants (Δ = −0.55, P = 0.04). Among participants with good GC, changes in HbA1c were not significantly different between FS and FI participants (Δ = 0.23, P = 0.21). Conclusion: Providing nutrition education and food assistance improved HbA1c profiles among FS and FI participants, but FI participants may face social and structural challenges that require additional support from health care teams.

scholarly journals Functional Connectivity and Networks Underlying Complex Tool-Use Movement in Assembly Workers: An fMRI Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Seira Taniguchi ◽  
Yuichiro Higashi ◽  
Hirotaka Kataoka ◽  
Hiroshi Nakajima ◽  
Tetsuya Shimokawa
Keyword(s):  
Functional Connectivity ◽  
Tool Use ◽  
Repeated Measures ◽  
Inferior Frontal Gyrus ◽  
Real Life ◽  
Analysis Of Covariance ◽  
Repeated Measure ◽  
Angular Gyrus ◽  
Middle Temporal Gyrus ◽  
Resting State Functional Connectivity

The aim of this study was to identify the functional connectivity and networks utilized during tool-use in real assembly workers. These brain networks have not been elucidated because the use of tools in real-life settings is more complex than that in experimental environments. We evaluated task-related functional magnetic resonance imaging in 13 assembly workers (trained workers, TW) and 27 age-matched volunteers (untrained workers, UTW) during a tool-use pantomiming task, and resting-state functional connectivity was also analyzed. Two-way repeated-measures analysis of covariance was conducted with the group as a between-subject factor (TW > UTW) and condition (task > resting) as a repeated measure, controlling for assembly time and accuracy as covariates. We identified two patterns of functional connectivity in the whole brain within three networks that distinguished TW from UTW. TW had higher connectivity than UTW between the left middle temporal gyrus and right cerebellum Crus II (false discovery rate corrected p-value, p-FDR = 0.002) as well as between the left supplementary motor area and the pars triangularis of the right inferior frontal gyrus (p-FDR = 0.010). These network integrities may allow for TW to perform rapid tool-use. In contrast, UTW showed a stronger integrity compared to TW between the left paracentral lobule and right angular gyrus (p-FDR = 0.004), which may reflect a greater reliance on sensorimotor input to acquire complex tool-use ability than that of TW. Additionally, the fronto-parietal network was identified as a common network between groups. These findings support our hypothesis that assembly workers have stronger connectivity in tool-specific motor regions and the cerebellum, whereas UTW have greater involvement of sensorimotor networks during a tool-use task.

Evaluation of a Wind Noise Attenuation Algorithm on Subjective Annoyance and Speech-in-Wind Performance

2017 ◽  
Vol 28 (01) ◽  
pp. 046-057 ◽  
Author(s):  
Petri Korhonen ◽  
Francis Kuk ◽  
Eric Seper ◽  
Martin Mørkebjerg ◽  
Majken Roikjer
Keyword(s):  
Hearing Aids ◽  
Repeated Measures ◽  
Hearing Aid ◽  
Real Life ◽  
Subjective Rating ◽  
Noise Attenuation ◽  
Wind Noise ◽  
Wind Speeds ◽  
Repeated Measures Design ◽  
Phoneme Identification

AbstractWind noise is a common problem reported by hearing aid wearers. The MarkeTrak VIII reported that 42% of hearing aid wearers are not satisfied with the performance of their hearing aids in situations where wind is present.The current study investigated the effect of a new wind noise attenuation (WNA) algorithm on subjective annoyance and speech recognition in the presence of wind.A single-blinded, repeated measures design was used.Fifteen experienced hearing aid wearers with bilaterally symmetrical (≤10 dB) mild-to-moderate sensorineural hearing loss participated in the study.Subjective rating for wind noise annoyance was measured for wind presented alone from 0° and 290° at wind speeds of 4, 5, 6, 7, and 10 m/sec. Phoneme identification performance was measured using Widex Office of Clinical Amplification Nonsense Syllable Test presented at 60, 65, 70, and 75 dB SPL from 270° in the presence of wind originating from 0° at a speed of 5 m/sec.The subjective annoyance from wind noise was reduced for wind originating from 0° at wind speeds from 4 to 7 m/sec. The largest improvement in phoneme identification with the WNA algorithm was 48.2% when speech was presented from 270° at 65 dB SPL and the wind originated from 0° azimuth at 5 m/sec.The WNA algorithm used in this study reduced subjective annoyance for wind speeds ranging from 4 to 7 m/sec. The algorithm was effective in improving speech identification in the presence of wind originating from 0° at 5 m/sec. These results suggest that the WNA algorithm used in the current study could expand the range of real-life situations where a hearing-impaired person can use the hearing aid optimally.

Basic Study Designs

2018 ◽  
pp. 68-86
Author(s):  
Alexandra Gomez ◽  
Felipe Fregni ◽  
Vera Novak ◽  
Andre Brunoni
Keyword(s):  
Repeated Measures ◽  
Real Life ◽  
Basic Study ◽  
Repeated Measures Design ◽  
Parallel Group ◽  
Control Comparison ◽  
Quasi Experimental ◽  
Comparison Trial ◽  
Study Designs

This chapter on basic study designs provides an overview of the most common design methodologies used in interventional studies. The chapter discusses both the advantages and limitations of parallel group designs (placebo or active control comparison trial, factorial design), repeated measures design (cross-over or between-subjects design), and quasi-experimental designs. It provides examples and discusses designs that are used in specific settings (for example, rare diseases, phases of dug development, and interventions in real life, including large simple trials, N-of-1). The chapter ends with a case study that illustrates the in-depth application of the available options into practice.

Visual Word Recognition in Two Facial Motion Conditions: Full-Face Versus Lips-Plus-Mandible

1995 ◽  
Vol 38 (6) ◽  
pp. 1387-1394 ◽  
Author(s):  
Lynn K. Marassa ◽  
Charissa R. Lansing
Keyword(s):  
Repeated Measures ◽  
Visual Recognition ◽  
Repeated Measure ◽  
Video Sequences ◽  
Exposure Condition ◽  
Repeated Measures Design ◽  
Open Set ◽  
Full Face ◽  
Face Exposure ◽  
Exposure Conditions

The present study used a new method to develop video sequences that limited exposure of facial movement. A repeated-measures design was used to investigate the visual recognition of 60 monosyllabic spoken words, presented in an open set format, for two face exposure conditions (full-face vs. lips-plus-mandible). Twenty-six normal hearing college students and 4 adults with bilateral sensorineural hearing loss speechread a video laserdisc presentation of a male talker under the two face exposure conditions. Percent phoneme correct scores were similar in the part-face and full-face conditions. However, scores significantly improved for the repeated measure independent of the face exposure condition observed. The results suggested that speechreaders (a) can recognize monosyllabic words in video sequences that provide information only about movements of the lips-plus-mandible region and (b) are sensitive to practice effects.

scholarly journals Adaptive Dose-Finding Studies: A Review of Model-Guided Phase I Clinical Trials

2014 ◽  
Vol 32 (23) ◽  
pp. 2505-2511 ◽  
Author(s):  
Alexia Iasonos ◽  
John O'Quigley
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Dose Escalation ◽  
Late Onset ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Design Parameters ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Trial Duration

Purpose We provide a comprehensive review of adaptive phase I clinical trials in oncology that used a statistical model to guide dose escalation to identify the maximum-tolerated dose (MTD). We describe the clinical setting, practical implications, and safety of such applications, with the aim of understanding how these designs work in practice. Methods We identified 53 phase I trials published between January 2003 and September 2013 that used the continual reassessment method (CRM), CRM using escalation with overdose control, or time-to-event CRM for late-onset toxicities. Study characteristics, design parameters, dose-limiting toxicity (DLT) definition, DLT rate, patient-dose allocation, overdose, underdose, sample size, and trial duration were abstracted from each study. In addition, we examined all studies in terms of safety, and we outlined the reasons why escalations occur and under what circumstances. Results On average, trials accrued 25 to 35 patients over a 2-year period and tested five dose levels. The average DLT rate was 18%, which is lower than in previous reports, whereas all levels above the MTD had an average DLT rate of 36%. On average, 39% of patients were treated at the MTD, and 74% were treated at either the MTD or an adjacent level (one level above or below). Conclusion This review of completed phase I studies confirms the safety and generalizability of model-guided, adaptive dose-escalation designs, and it provides an approach for using, interpreting, and understanding such designs to guide dose escalation in phase I trials.

scholarly journals dfpk: An R-package for Bayesian dose-finding designs using pharmacokinetics (PK) for phase I clinical trials

2018 ◽  
Vol 157 ◽  
pp. 163-177 ◽  
Author(s):  
A. Toumazi ◽  
E. Comets ◽  
C. Alberti ◽  
T. Friede ◽  
F. Lentz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
R Package ◽  
Dose Finding ◽  
Phase I Clinical Trials

scholarly journals Effective sample size for computing prior hyperparameters in Bayesian phase I–II dose-finding

2014 ◽  
Vol 11 (6) ◽  
pp. 657-666 ◽  
Author(s):  
Peter F Thall ◽  
Richard C Herrick ◽  
Hoang Q Nguyen ◽  
John J Venier ◽  
J Clift Norris
Keyword(s):  
Phase I ◽  
Sample Size ◽  
Dose Finding ◽  
Design Parameters ◽  
Effective Sample Size ◽  
Operating Characteristics ◽  
Trade Off ◽  
Design Elements ◽  
Practical Usefulness ◽  
Practical Guidelines

Background: The efficacy–toxicity trade-off based design is a practical Bayesian phase I–II dose-finding methodology. Because the design’s performance is very sensitive to prior hyperparameters and the shape of the target trade-off contour, specifying these two design elements properly is essential. Purpose: The goals are to provide a method that uses elicited mean outcome probabilities to derive a prior that is neither overly informative nor overly disperse, and practical guidelines for specifying the target trade-off contour. Methods: A general algorithm is presented that determines prior hyperparameters using least squares penalized by effective sample size. Guidelines for specifying the trade-off contour are provided. These methods are illustrated by a clinical trial in advanced prostate cancer. A new version of the efficacy–toxicity program is provided for implementation. Results: Together, the algorithm and guidelines provide substantive improvements in the design’s operating characteristics. Limitations: The method requires a substantial number of elicited values and design parameters, and computer simulations are required to obtain an acceptable design. Conclusion: The two key improvements greatly enhance the efficacy–toxicity design’s practical usefulness and are straightforward to implement using the updated computer program. The algorithm for determining prior hyperparameters to ensure a specified level of informativeness is general, and may be applied to models other than that underlying the efficacy–toxicity method.

scholarly journals Self-Confidence and Perceptions of Athletic Training Students Following Simulated Experiences: A Mixed-Methods Pilot Study

2021 ◽  
Author(s):  
Hannah Stedge ◽  
Valerie Herzog
Keyword(s):  
Mixed Methods ◽  
Athletic Training ◽  
Clinical Education ◽  
Repeated Measures ◽  
Real Life ◽  
Future Research ◽  
High Fidelity ◽  
Athletic Training Students ◽  
Repeated Measures Design ◽  
Self Confidence

Purpose: Athletic training clinical education provides students with a variety of real-life patient encounters under the supervision of a credentialed athletic trainer. However, clinical education experiences may not allow for all students to practice more invasive or less common skills such as rectal thermometry. The purpose of this study was two-fold: 1) determine the effect of a series of low to high-fidelity simulated rectal thermometry experiences on athletic training students’ self-confidence scores; and 2) through a phenomenological qualitative approach, explore athletic training students’ perceptions following the simulated rectal thermometry experiences. Method: This study used a quasi-experimental, mixed methods, one-group repeated measures design. Participants were nine first year professional Master of Athletic Training students who completed four simulated experiences on the skill of rectal thermometry. The outcome measures were The Athletic Trainer’s Self-Confidence Scale (ATSCS) and qualitative semi-structured open-ended interviews. Results: Friedman’s ANOVA revealed a statistically significant improvement from the participant’s baseline ATSCS scores to the last post-test scores. We identified three major themes following qualitative interviews: 1) Perception changes before and after participation; 2) Benefits of a series of four simulations; 3) Explanations for the improvements in confidence and competence. Conclusions: A series of simulated learning activities using high-fidelity and standardized patient interactions can help improve athletic training students’ self-confidence. Though future research is needed, athletic training education programs should consider implementing simulated experiences to equip athletic training students to transition to practice.

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