Phase II clinical trials are commonly conducted as pilot studies to evaluate the efficacy and safety of the investigational drug in the targeted patient population with the disease or condition to be treated or preven...Phase II clinical trials are commonly conducted as pilot studies to evaluate the efficacy and safety of the investigational drug in the targeted patient population with the disease or condition to be treated or prevented.When designing such a trial considering efficacy conclusions,people natu-rally think as follows:if efficacy evidence is very strong,a go decision should be made;if efficacy evidence is very weak,a no-go decision should be made;if the efficacy evidence is neither strong nor weak,no decision can be made(inconclusive).The designs presented in this paper match this natural thinking process with go/no-go/inconclusive outcomes.Both two-/three-stage designs are developed with three outcomes.Additionally,a general approach based on conditional error function is implemented such that new decision boundaries can be calculated to handle mid-course sample size change which results in either‘over-running’or‘under-running’and ensure the control of overall type I error.A free open-source R package tsdf that calculates the proposed two-/three-stage designs is available on CRAN.展开更多
Background:Behavioral inhibitory control(BIC)depicts a cognitive function of inhibiting inappropriate dominant responses to meet the context requirement.Despite abundant research into neural substrates of BIC during t...Background:Behavioral inhibitory control(BIC)depicts a cognitive function of inhibiting inappropriate dominant responses to meet the context requirement.Despite abundant research into neural substrates of BIC during the go/no-go and stop signal tasks,these tasks were consistently shown hard to isolate neural processes of response inhibition,which is of primary interest,from those of response generation.Therefore,it is necessary to explore neural substrates of BIC using the two-choice oddball(TCO)task,whose design of dual responses is thought to produce an inhibition effect free of the confounds of response generation.Objective:The current study aims at depicting neural substrates of performing behavioral inhibitory control in the two-choice oddball task,which designs dual responses to balance response generation.Also,neural substrates of performing BIC during this task are compared with those in the go/no-go task,which designs a motor response in a single condition.Methods:The present study integrated go/no-go(GNG)and TCO tasks into a new Three-Choice BIC paradigm,which consists of stan-dard(75%),deviant(12.5%),and no-go(12.5%)conditions simultaneously.Forty-eight college students participated in this experiment,which required them to respond to standard(frequent)and deviant stimuli by pressing different keys,while inhibiting motor response to no-go stimuli.Conjunction analysis and ROI(region of interest)analysis were adopted to identify the unique neural mechanisms that subserve the processes of BIC.Results:Both tasks are effective in assessing BIC function,reflected by the significantly lower accuracy of no-go compared to standard condition in GNG,and the significantly lower accuracy and longer reaction time of deviant compared to standard condition in TCO.However,there were no significant differences between deviant and no-go conditions in accuracy.Moreover,functional neuroimaging has demonstrated that the anterior cingulate cortex(ACC)activation was observed for no-go vs.standard contrast in the GNG task,but not in deviant vs.standard contrast in the TCO task,suggesting that ACC involvement is not a necessary component of BIC.Second,ROI analysis of areas that were co-activated in TCO and GNG showed co-activations in the right inferior frontal cortex(triangle and orbital),with the signals in the TCO task significantly higher than those in the GNG task.Conclusions:These findings show that the designed responses to both standard and deviant stimuli in the TCO task,compared to the GNG task,produced a more prominent prefrontal inhibitory processing and extinguished an unnecessary component of ACC activation during BIC.This implies that prefrontal involvement,but not that of ACC,is mandatory for the successful performance of inhibiting prepotent behaviors.展开更多
文摘Phase II clinical trials are commonly conducted as pilot studies to evaluate the efficacy and safety of the investigational drug in the targeted patient population with the disease or condition to be treated or prevented.When designing such a trial considering efficacy conclusions,people natu-rally think as follows:if efficacy evidence is very strong,a go decision should be made;if efficacy evidence is very weak,a no-go decision should be made;if the efficacy evidence is neither strong nor weak,no decision can be made(inconclusive).The designs presented in this paper match this natural thinking process with go/no-go/inconclusive outcomes.Both two-/three-stage designs are developed with three outcomes.Additionally,a general approach based on conditional error function is implemented such that new decision boundaries can be calculated to handle mid-course sample size change which results in either‘over-running’or‘under-running’and ensure the control of overall type I error.A free open-source R package tsdf that calculates the proposed two-/three-stage designs is available on CRAN.
基金supported by the national natural science foundation of China (NSFC31971018)Sichuan distinguished young scholar fund (2023NSFSC1938).
文摘Background:Behavioral inhibitory control(BIC)depicts a cognitive function of inhibiting inappropriate dominant responses to meet the context requirement.Despite abundant research into neural substrates of BIC during the go/no-go and stop signal tasks,these tasks were consistently shown hard to isolate neural processes of response inhibition,which is of primary interest,from those of response generation.Therefore,it is necessary to explore neural substrates of BIC using the two-choice oddball(TCO)task,whose design of dual responses is thought to produce an inhibition effect free of the confounds of response generation.Objective:The current study aims at depicting neural substrates of performing behavioral inhibitory control in the two-choice oddball task,which designs dual responses to balance response generation.Also,neural substrates of performing BIC during this task are compared with those in the go/no-go task,which designs a motor response in a single condition.Methods:The present study integrated go/no-go(GNG)and TCO tasks into a new Three-Choice BIC paradigm,which consists of stan-dard(75%),deviant(12.5%),and no-go(12.5%)conditions simultaneously.Forty-eight college students participated in this experiment,which required them to respond to standard(frequent)and deviant stimuli by pressing different keys,while inhibiting motor response to no-go stimuli.Conjunction analysis and ROI(region of interest)analysis were adopted to identify the unique neural mechanisms that subserve the processes of BIC.Results:Both tasks are effective in assessing BIC function,reflected by the significantly lower accuracy of no-go compared to standard condition in GNG,and the significantly lower accuracy and longer reaction time of deviant compared to standard condition in TCO.However,there were no significant differences between deviant and no-go conditions in accuracy.Moreover,functional neuroimaging has demonstrated that the anterior cingulate cortex(ACC)activation was observed for no-go vs.standard contrast in the GNG task,but not in deviant vs.standard contrast in the TCO task,suggesting that ACC involvement is not a necessary component of BIC.Second,ROI analysis of areas that were co-activated in TCO and GNG showed co-activations in the right inferior frontal cortex(triangle and orbital),with the signals in the TCO task significantly higher than those in the GNG task.Conclusions:These findings show that the designed responses to both standard and deviant stimuli in the TCO task,compared to the GNG task,produced a more prominent prefrontal inhibitory processing and extinguished an unnecessary component of ACC activation during BIC.This implies that prefrontal involvement,but not that of ACC,is mandatory for the successful performance of inhibiting prepotent behaviors.
