scholarly journals Exact confidence limits for the response rate in two-stage designs with over- or under-enrollment in the second stage

2016 ◽  
Vol 27 (4) ◽  
pp. 1045-1055 ◽  
Author(s):  
Guogen Shan
Keyword(s):  
Study Design ◽  
Response Rate ◽  
Sample Space ◽  
P Value ◽  
Two Stage ◽  
Stage Design ◽  
Second Stage ◽  
Point Estimates ◽  
Exact Confidence Intervals ◽  
Early Phase Clinical Trials

Simon’s two-stage design has been widely used in early phase clinical trials to assess the activity of a new investigated treatment. In practice, the actual sample sizes do not always follow the study design precisely, especially in the second stage. When over- or under-enrollment occurs in a study, the original critical values for the study design are no longer valid for making proper statistical inference in a clinical trial. The hypothesis for such studies is always one-sided, and the null hypothesis is rejected when only a few responses are observed. Therefore, a one-sided lower interval is suitable to test the hypothesis. The commonly used approaches for confidence interval construction are based on asymptotic approaches. These approaches generally do not guarantee the coverage probability. For this reason, Clopper-Pearson approach can be used to compute exact confidence intervals. This approach has to be used in conjunction with a method to order the sample space. The frequently used method is based on point estimates for the response rate, but this ordering has too many ties which lead to conservativeness of the exact intervals. We propose developing exact one-sided intervals based on the p-value to order the sample space. The proposed approach outperforms the existing asymptotic and exact approaches. Therefore, it is recommended for use in practice.

scholarly journals Two-Stage Single-Arm Trials Are Rarely Analyzed Effectively or Reported Adequately

2021 ◽  
pp. 1813-1820
Author(s):  
Michael J. Grayling ◽  
Adrian P. Mander
Keyword(s):  
Final Stage ◽  
Interim Analysis ◽  
Primary Outcome ◽  
Point Estimate ◽  
Two Stage ◽  
Stage Design ◽  
Patient Subgroup ◽  
Future Studies ◽  
Point Estimates ◽  
Outcome Trial

PURPOSE Two-stage single-arm designs have historically been the most common design used in phase II oncology. They remain a mainstay today, particularly for trials in rare subgroups. Consequently, it is imperative such studies be designed, analyzed, and reported effectively. We comprehensively review such trials to examine whether this is the case. METHODS Oncology trials that used Simon's two-stage design over a 5-year period were identified and reviewed. They were evaluated for whether they reported sufficient design (eg, required sample size) and analysis (eg, CI) details. Articles that did not adjust their inference for the incorporation of an interim analysis were also reanalyzed. RESULTS Four-hundred twenty-five articles were included. Of these, just 47.5% provided the five components that ensure design reproducibility. Only 1.2% and 2.1% reported an adjusted point estimate or CI, respectively. Just 55.3% provided the final stage rejection bound, indicating many trials did not test a hypothesis for their primary outcome. Trial reanalyses suggested reported point estimates underestimated treatment effects and reported CIs were too narrow. CONCLUSION Key design details of two-stage single-arm trials are often unreported. Their inference is rarely performed such as to remove bias introduced by the interim analysis. These findings are particular alarming when considered against the growing trend in which nonrandomized trials make up a large proportion of all evidence on a treatment's effectiveness in a rare biomarker-defined patient subgroup. Future studies must improve the way they are analyzed and reported.

A Two-Stage Design Method for Compliant Mechanisms Having Specified Non-Linear Output Paths

2006 ◽  
Author(s):  
Masakazu Kobayashi ◽  
Hiroshi Yamakawa ◽  
Shinji Nishiwaki ◽  
Kazuhiro Izui ◽  
Masataka Yoshimura
Keyword(s):  
Topology Optimization ◽  
Shape Optimization ◽  
Compliant Mechanisms ◽  
Compliant Mechanism ◽  
Design Method ◽  
Two Stage ◽  
Traditional Methods ◽  
Stage Design ◽  
Second Stage ◽  
Additional Constraints

Compliant mechanisms generated by traditional topology optimization methods have linear output response, and it is difficult for traditional methods to implement mechanisms having non-linear output responses, such as nonlinear deformation or path. To design a compliant mechanism having a specified nonlinear output path, a two-stage design method based on topology and shape optimization is constructed here. In the first stage, topology optimization generates an initial and conceptual compliant mechanism based on ordinary design conditions, with “additional” constraints that are used to control the output path at the second stage. In the second stage, an initial model for the shape optimization is created, based on the result of the topology optimization, and the additional constraints are replaced by spring elements. The shape optimization is then executed, to generate a detailed shape of the compliant mechanism having the desired output path. In this stage, parameters that represent the outer shape of the compliant mechanism and the properties of spring elements are used as design variables in the shape optimization. In addition to configuration of the specified output path, executing the shape optimization after the topology optimization also makes it possible to consider the stress concentration and large displacement effects. This is an advantage offered by the proposed method, since it is difficult for traditional methods to consider these aspects, due to inherent limitations of topology optimization.

Two-Stage Design for Cellular Manufacturing System

2012 ◽  
Vol 220-223 ◽  
pp. 137-140
Author(s):  
Ling Gou ◽  
Cong Lu ◽  
Jun Feng Fei
Keyword(s):  
Genetic Algorithm ◽  
Manufacturing System ◽  
Cellular Manufacturing ◽  
Cell Formation ◽  
Layout Design ◽  
Cellular Manufacturing System ◽  
Two Stage ◽  
Stage Design ◽  
Second Stage ◽  
Handling Cost

Cell formation（CF）and cellular layout design are the two main steps in designing a cellular manufacturing system (CMS). Efficient grouping is the prerequisite of a successful Cellular Manufacturing, and it is too hard to obtain a perfect consequence of CF and layout simultaneously. In this paper, a two-stage strategy is used to solve CF problem and layout sequentially. At the first stage, the cells are formed based on the part-machine clustering results obtained through the genetic algorithm, to get the initial inter-cell layout. At the second stage, the genetic algorithm is used to improve the solution obtained, to minimize the handling cost and maximize the utility of the machines.

Efficiency-based recruitment plan for chained quick-service enterprise

2006 ◽  
Vol 25 (3) ◽  
pp. 197-209
Author(s):  
Chun-Hsiung Lan ◽  
Yu-Hua Lan ◽  
Chi-Chung Chang ◽  
Liang-Lun Chuang
Keyword(s):  
Production Efficiency ◽  
Quantitative Approach ◽  
Scale Efficiency ◽  
Data Envelopment ◽  
Two Stage ◽  
Stage Design ◽  
Second Stage ◽  
Two Stage Design ◽  
Using Data ◽  
Quick Service

This paper describes a research method called two-stage design consisting of the determination of the efficiency for each quick-service restaurant of chained enterprise at the first stage by using Data Envelopment Analysis (DEA), and then proposes an approach of Recruitment and Allocation (RA) plan for supporting the everlasting running of the enterprise in the second stage. The technical efficiency, the scale efficiency, the production efficiency, and the return to scale are conducted in the first stage of this two-stage research design. In addition, this study also proposes the potentially improved value to promote the relative efficiency of each chained restaurant through the improvement of inputs or outputs items. Besides, the RA plan is proposed in the second stage of the two-stage design. The RA plan is an efficiency-based quantitative approach to recruit employees as well as to determine the allocation of those recruited employees. This study indeed provides a constructive and quantitative approach of solving the dilemma issue “how to reasonably recruit and allocate employees” for decision makers with profound insight in the quick-service enterprise.

scholarly journals Optimal two-stage design of single arm Phase II clinical trials based on median event time test

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246448
Author(s):  
Yeonhee Park
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Therapeutic Efficacy ◽  
Response Rate ◽  
Two Stage ◽  
Stage Design ◽  
Event Time ◽  
Phase Ii Clinical Trials ◽  
Time Test ◽  
Two Stage Design

The Phase II clinical trials aim to assess the therapeutic efficacy of a new drug. The therapeutic efficacy has been often quantified by response rate such as overall response rate or survival probability in the Phase II setting. However, there is a strong desire to use survival time, which is the gold standard endpoint for the confirmatory Phase III study, when investigators set the primary objective of the Phase II study and test hypotheses based on the median survivals. We propose a method for median event time test to provide the sample size calculation and decision rule of testing. The decision rule is simple and straightforward in that it compares the observed median event time to the identified threshold. Moreover, it is extended to optimal two-stage design for practice, which extends the idea of Simon’s optimal two-stage design for survival endpoint. We investigate the performance of the proposed methods through simulation studies. The proposed methods are applied to redesign a trial based on median event time for trial illustration, and practical strategies are given for application of proposed methods.

The Prevalence of Insecticide Treated Net/malaria :cross section study (Preprint)

2019 ◽  
Author(s):  
Chanda Chalela
Keyword(s):  
Study Design ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Malaria Prevalence ◽  
Malaria Patient ◽  
P Value ◽  
Sectional Study ◽  
Cross Sectional ◽  
Itn Use ◽  
Structured Questionnaire

BACKGROUND ABSTRACT Introduction a study on prevalence of ITN use was carried out in Buchi community Kitwe Zambia from August to October 2019 OBJECTIVE Prevalence of ITN in BUchi METHODS Methodology: This was a cross sectional study design. A structured questionnaire was used to ascertain ownership and utilization and oral interviews, 200 households were targeted 844 individual covered across the 200 households. Data was analyzed with SPSS version 23. RESULTS ABSTRACT Introduction a study on prevalence of ITN use was carried out in Buchi community Kitwe Zambia from August to October 2019 Methodology: This was a cross sectional study design. A structured questionnaire was used to ascertain ownership and utilization and oral interviews, 200 households were targeted 844 individual covered across the 200 households. Data was analyzed with SPSS version 23. Findings: household ownership of at least an ITN was 52% and individual utilization at 37.6%, with 0.825 ITN/households and 0.195ITN /individual. Malaria prevalence of 52.4% /household and a 12.4% of the population. With 47.6% malaria patient coming from households with ITN and 60% of households with ITN have insufficient coverage.61% of malaria patient were female and 31 % male. however there was no significant relation between Gender and malaria prevalence in study area (p value was >0.05). Malaria cases distribution with age groups, 0-15yrs old represented 49.5%, 16-30 yrs., was at 27.6% and the over 30 yrs. case were at 22.9% .use of other preventive measures 23% used mosquito repellent ,others methods 1% with those not using any other methods 76%. CONCLUSIONS Conclusion The study showed clearly that malaria still poses a problem .the prevalence rate of malaria was still high 12.4% of the population and 52.4% of households. With high prevalence of malaria of 49.5% for 0-15yrs.the difference between ownership 52% and Utilization 37.6% showed that even household with ITN, the ITN were not sufficient.60% of households with ITN, the ITN were not sufficient for all occupants

An Enhanced Two Stage MMSE Equalizer for Coded FBMC/OQAM Systems

2019 ◽  
Vol 10 (1) ◽  
pp. 69-82 ◽  
Author(s):  
Mohammad Rizk Assaf ◽  
Abdel-Nasser Assimi
Keyword(s):  
Error Propagation ◽  
Channel Model ◽  
Error Correcting Codes ◽  
Two Stage ◽  
Probability Of Error ◽  
Second Stage ◽  
Different Types ◽  
Mmse Equalizer ◽  
And Performance ◽  
Ici Cancellation

In this article, the authors investigate the enhanced two stage MMSE (TS-MMSE) equalizer in bit-interleaved coded FBMC/OQAM system which gives a tradeoff between complexity and performance, since error correcting codes limits error propagation, so this allows the equalizer to remove not only ICI but also ISI in the second stage. The proposed equalizer has shown less design complexity compared to the other MMSE equalizers. The obtained results show that the probability of error is improved where SNR gain reaches 2 dB measured at BER compared with ICI cancellation for different types of modulation schemes and ITU Vehicular B channel model. Some simulation results are provided to illustrate the effectiveness of the proposed equalizer.

scholarly journals A survey of the knowledge and attitudes of Egyptian healthcare professionals towards the application of Health Information Technology to optimize antibiotic therapy

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i28-i28
Author(s):  
N Hassan ◽  
R Slight ◽  
S P Slight
Keyword(s):  
Information Technology ◽  
Developing Countries ◽  
Antimicrobial Resistance ◽  
Health Information Technology ◽  
Health Information ◽  
Antimicrobial Stewardship ◽  
Healthcare Professionals ◽  
Response Rate ◽  
Public Healthcare ◽  
P Value

Abstract Introduction Antimicrobial resistance is a global health problem, especially in developing countries. Antimicrobial Stewardship Programmes (AMS) have been shown to be effective at reducing antimicrobial resistance and hospital patient stays. Health information technology (HIT) can support Outpatient Parenteral Antimicrobial Therapy (OPAT) through more accurate diagnosis and management of infectious diseases. Aim To evaluate the knowledge and attitude of Egyptian healthcare professionals towards the application of HIT to optimize OPAT. Methods Healthcare professionals who worked in either private or public sectors of Egyptian healthcare system were emailed and asked if they would be willing to complete an electronic questionnaire (using google forms). One reminder was sent by email each week for two weeks (two in total) from the first invitation. The survey was laid out in four sections. The first section included specific details about the healthcare professional’s current employment and role, the second related to HIT services available in their organisations, the third covered their training in HIT and antimicrobial stewardship programmes, and the fourth included their use of HIT to optimize OPAT. Ethical approval was obtained from National Heart Institute, Egypt. Descriptive analysis was carried out for all the variables. One-way ANOVA testing at level of significance P-value <0.05, was used to compare numerical variables. SPSS version 26 was used for statistical analysis. Results Three hundred and eighty-five healthcare professionals were invited to respond to the questionnaire. (The response rate was 75.34% (290)). Of these, 152 (52.6%) were pharmacists, 134 (46.4%) physicians, and 3 (1%) nurses, and many participants (30.8%) had between 6 to 10 years of experience working in either outpatient or in-patient units. Only 15.2% of respondents mentioned that they have access to OPAT in their organizations, 51.2% did not have the service, while 33.6% responded that they did not know if the service was available. However, 27.3% had a training on ASP and 18.3% had a training on HIT. Mean scores for both knowledge (14.31±5.49) and attitude (14.67±2.53) were significantly higher in professionals who had received training in HIT (p = 0.003 & 0.006 respectively). However, scores for attitude were better than scores for knowledge. Conclusions In developing countries, HIT applications in OPAT are still in their infancy with only a few organisations adopting them. Egyptian healthcare professionals showed positive attitudes towards HIT use, especially when their knowledge was improved through training. Two strengths of this study include our high response rate and the wide breadth of different healthcare professionals who responded from both private and public healthcare settings. However, being a questionnaire, some questions were left unanswered and some respondents may not have been aware of their reasons for a particular answer. That said, this study has important implications for practice, with more awareness amongst healthcare professionals required on the availability of HIT services in their hospitals and how further training may be needed on the applications of HIT in optimizing OPAT.

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