maximum sample size
Recently Published Documents


TOTAL DOCUMENTS

16
(FIVE YEARS 8)

H-INDEX

4
(FIVE YEARS 1)

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13579-e13579
Author(s):  
Diana L Urbauer ◽  
Shannon Neville Westin ◽  
Ying Yuan

e13579 Background: Many trial designs with futility or toxicity monitoring require that accrual halt to wait for currently enrolled patients to complete their assessment window. However, logistics often prevent this. In these cases, the performance of those designs might be compromised. This study examines the performance of 2 popular designs when enrollment is not halted at interim. Methods: Simulations were run to examine the effect of continuous enrollment on the operating characteristics (OCs) of a Simon’s 2-stage design for futility monitoring and a design using Bayesian posterior probabilities for toxicity monitoring. Both sets of 10,000 simulations examined the OCs when accrual rate was 0.5, 1.5, 3 and 5 patients/month with an assessment window of 30, 60 and 180 days. Results: The first scenario examined the OCs of a Simon design with 12 patients in the first stage and 21 at the end of the second stage. Regardless of accrual rate, the expected number of patients (EN0) increased and probability of early termination (PET0) decreased under the null hypothesis. Rate of change increased as assessment window increased. EN0 was 16 and PET0 was 54% when halting enrollment between stages. With continuous enrollment, EN0 ranged from 16-19, 17-21, and 18-21 patients for the 30-, 90- and 180-day assessment windows. PET0 ranged from 54%-50% with a 30-day assessment window. It halved to 24% with 3 patients/month enrolled and a 90-day window. PET0 was essentially 0 with a 180-day window and an enrollment of 3 patients/month. OCs for toxicity monitoring were examined for the early stopping rule Pr(toxicity rate > 0.3 | data) > 0.85 with toxicity rate ̃ beta(1, 1) with a maximum sample size of 20 and cohort size of 5. Expected number of patients (EN) increased and probability of early termination (PET) decreased as accrual rate increased, with rate of change increasing as assessment window increased. When the true probability of toxicity was 50% and enrollment halted between cohorts, EN was 10 patients and PET was 78%. EN was 17 and PET 54% with an assessment window of 30 days and 5 patients were enrolled per month. With a 90-day assessment window and 3 patients/month enrolled, EN was 16 and PET 59%. EN was 20 and PET was 12% with a 180-day assessment window and 3 patients were enrolled per month. Similar results were noted for cohorts of size 10 and a maximum number of 40 patients. Conclusions: The performance of designs that require halting enrollment while waiting for results of an interim analysis can be compromised by continuous accrual when assessment windows are lengthy and the accrual is fast. In these circumstances, consideration should be given to designs, such as Bayesian multiple imputation for delayed outcomes (Cai et al Stat Med 2014) and TOP2 (Lin et al JNCI 2019), that do not require accrual halt to make real-time interim analysis in the presence of pending patients, which protects patients from excessive toxicity or a futile intervention.


Author(s):  
Nicole Viaene ◽  
Johannes Hallmann ◽  
Leendert P. G. Molendijk

Abstract Nematodes can be present in different matrices. This chapter describes several methods to extract nematodes from soil and plant parts. It is crucial that an appropriate method is chosen for the purpose of the research as different types of nematodes, and even different nematode stages, are extracted depending on the method. Factors to consider for choosing the optimal extraction method are the extraction efficiency of the method, the maximum sample size that can be analysed and costs of the extraction equipment. In addition, water consumption, labour and the time needed before nematodes can be examined can be important factors.


Author(s):  
Nicole Viaene ◽  
Johannes Hallmann ◽  
Leendert P. G. Molendijk

Abstract Nematodes can be present in different matrices. This chapter describes several methods to extract nematodes from soil and plant parts. It is crucial that an appropriate method is chosen for the purpose of the research as different types of nematodes, and even different nematode stages, are extracted depending on the method. Factors to consider for choosing the optimal extraction method are the extraction efficiency of the method, the maximum sample size that can be analysed and costs of the extraction equipment. In addition, water consumption, labour and the time needed before nematodes can be examined can be important factors.


2020 ◽  
pp. 096228022098078
Author(s):  
Bosheng Li ◽  
Liwen Su ◽  
Jun Gao ◽  
Liyun Jiang ◽  
Fangrong Yan

A delayed treatment effect is often observed in the confirmatory trials for immunotherapies and is reflected by a delayed separation of the survival curves of the immunotherapy groups versus the control groups. This phenomenon makes the design based on the log-rank test not applicable because this design would violate the proportional hazard assumption and cause loss of power. Thus, we propose a group sequential design allowing early termination on the basis of efficacy based on a more powerful piecewise weighted log-rank test for an immunotherapy trial with a delayed treatment effect. We present an approach on the group sequential monitoring, in which the information time is defined based on the number of events occurring after the delay time. Furthermore, we developed a one-dimensional search algorithm to determine the required maximum sample size for the proposed design, which uses an analytical estimation obtained by the inflation factor as an initial value and an empirical power function calculated by a simulation-based procedure as an objective function. In the simulation, we tested the unstable accuracy of the analytical estimation, the consistent accuracy of the maximum sample size determined by the search algorithm and the advantages of the proposed design on saving sample size.


Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Julia M. Edwards ◽  
Stephen J. Walters ◽  
Cornelia Kunz ◽  
Steven A. Julious

Abstract Introduction Sample size calculations require assumptions regarding treatment response and variability. Incorrect assumptions can result in under- or overpowered trials, posing ethical concerns. Sample size re-estimation (SSR) methods investigate the validity of these assumptions and increase the sample size if necessary. The “promising zone” (Mehta and Pocock, Stat Med 30:3267–3284, 2011) concept is appealing to researchers for its design simplicity. However, it is still relatively new in the application and has been a source of controversy. Objectives This research aims to synthesise current approaches and practical implementation of the promising zone design. Methods This systematic review comprehensively identifies the reporting of methodological research and of clinical trials using promising zone. Databases were searched according to a pre-specified search strategy, and pearl growing techniques implemented. Results The combined search methods resulted in 270 unique records identified; 171 were included in the review, of which 30 were trials. The median time to the interim analysis was 60% of the original target sample size (IQR 41–73%). Of the 15 completed trials, 7 increased their sample size. Only 21 studies reported the maximum sample size that would be considered, for which the median increase was 50% (IQR 35–100%). Conclusions Promising zone is being implemented in a range of trials worldwide, albeit in low numbers. Identifying trials using promising zone was difficult due to the lack of reporting of SSR methodology. Even when SSR methodology was reported, some had key interim analysis details missing, and only eight papers provided promising zone ranges.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Tunde Lawrence ◽  
Marjo Hahka-Kemppinen ◽  
Jonathon B. Cohen ◽  
Marek Kania

Background: The B-cell receptor (BCR) signaling pathway plays a critical role in the pathogenesis of lymphomas, particularly in non-Hodgkin lymphomas (NHL). Despite availability of therapeutic agents targeting BCR pathway, there is an unmet medical need for more effective and well-tolerated therapeutic agents for patients with advanced relapsed, refractory, or resistant NHL. HMPL-689 is a novel, orally available, highly selective, and potent small molecule inhibitor of phosphosinositide 3 kinase-delta (PI3Kδ), a crucial signaling transduction molecule in the BCR signaling pathway. A global clinical study of HMPL-689 is currently ongoing in the USA and the EU countries of France, Italy, Poland, and Spain. Preliminary results from dose escalation and expansion stages of this study are expected soon. Herein is the description of an ongoing phase 1, open-label, multi-center, single-arm study of HMPL-689 in patients with advanced relapsed, refractory, or resistant (R/R) NHL (NCT03786926). Study Population: Target patient population is adult patients with histologically confirmed advanced relapsed, refractory, or resistant NHL. To be eligible for enrollment, patients must have exhausted all approved therapeutic options available. Patients are ineligible for the study if they have primary central nervous system lymphoma. Objectives and Endpoints: The primary objective is to determine the maximum-tolerated dose (MTD)/recommended phase 2 dose (RP2D) of HMPL-689. The primary endpoints are the incidence of dose-limiting toxicity (DLT) and safety parameters, including treatment-emergent adverse events and laboratory abnormalities The secondary objective is to evaluate the pharmacokinetic (PK) parameters and preliminary efficacy. The secondary endpoints include concentration-time profiles, PK parameters, and efficacy parameters, including objective response rate, time to response, duration of response, and progression-free survival. Study Design: Study consists of a dose escalation and dose expansion stages. The dose-escalation stage utilizes a mTPI-2 design, with anticipated enrollment of approximately 24 patients until MTD is reached, and RP2D is determined. The proposed doses for escalation cohorts are 10, 15, 20, 25, 30, 35, 40, 45, and 50 mg, QD, PO in a 28-day cycle. Patients will be treated until disease progression, intolerable toxicity, no further benefit, withdrawal, end of study, or death. The expansion stage will be dosed at the MTD. Approximately 10 patients will be enrolled in each of the following cohorts: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),Mantle cell lymphoma (MCL),Follicular lymphoma (FL)Marginal zone lymphoma (MZL)Peripheral T-cell lymphoma (PTCL)Cutaneous B-cell lymphomaWaldenström's macroglobulinemia / lymphoplasmacytic lymphoma (WM) Statistical Methods: The maximum sample size in the dose-escalation stage will be determined based on the accumulated safety data and the mTPI-2 design. The maximum sample size under the mTPI-2 method is k × (d + 1), where k denotes the cohort size and d denotes the number of doses. The minimum cohort size in this study is 3 patients per cohort. To ensure that the highest dose (if needed) is reached, it is estimated that approximately 33-39 patients will be needed in this study. For dose expansion, approximately 70 patients (10 in each cohort) will provide robust safety data in the patient populations studied. For a given AE with a true rate of 10%, 5%, or 1%, the probability of observing at least one such AE in 70 patients is 99.9%, 97.2%, and 50.5%, respectively. For preliminary assessment of anti-tumor activity based on ORR, if at least 8 patients in a specific lymphoma subtype are evaluable for tumor response, the chance of observing at least one response is 94.2%, if the true ORR is 30%. Data will be summarized by dose level, subtype of malignancy, and overall as appropriate. Continuous assessments will be summarized by number of patients (n), mean, standard deviation, median, minimum and maximum. Significance: This study is the first global clinical study of HMPL-689, a novel inhibitor of the BCR signaling pathway, which is currently enrolling patients with advanced relapsed, refractory, or resistant NHL who have exhausted all approved therapeutics options available. Disclosures Lawrence: Hutchison MediPharma International, Inc:Current Employment, Current equity holder in publicly-traded company.Hahka-Kemppinen:Hutchison MediPharma International, Inc:Current Employment, Current equity holder in publicly-traded company.Cohen:Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo:Consultancy;Genentech, BMS, Novartis, LAM, BioInvent, LRF, ASH, Astra Zeneca, Seattle Genetics:Research Funding.Kania:Hutchison MediPharma International, Inc:Current Employment, Current equity holder in publicly-traded company.


2020 ◽  
Vol 11 (1) ◽  
pp. 262
Author(s):  
Donatus Mugisha Rulangaranga ◽  
Mellan Basemera ◽  
Alain Vilard Ndi Isoh

This study was carried out to establish whether structure of government support has any association or influence onto sustainability of SMEs in Uganda. The focus was to ascertain whether there is a link between how government provides support to SMEs and sustainability of these SMEs. A maximum sample size of 384 SMEs was selected. Questionnaire approach was used to collect data from the owners and or managers of SMEs. Based on factor analysis, two components of structure of government support were established namely; quality of structure of government support and extent of policy implementation. To test the association of the variables, correlation analysis was carried out. The results from this analysis indicated that both components of structure of government support had significant association with SME sustainability in Uganda. Quality of structure however, had higher degree of association as compared to extent of policy implementation. Structural Equation Modeling (SEM) analysis was carried out to check the degree of influence of structure of government support onto SME sustainability. The results indicated that both components of structure of government support have influence onto SME sustainability. Based on this, it was concluded that structure of government support has a significant association with and influence onto SME sustainability in Uganda. It was therefore recommended that there was need for government support towards SMEs to be properly structured in order to realize SME sustainability. The structuring needs to take into consideration the quality of the structure as well as extent to which SME policy is implemented.


2019 ◽  
Author(s):  
Rob Cribbie ◽  
Nataly Beribisky ◽  
Udi Alter

Many bodies recommend that a sample planning procedure, such as traditional NHST a priori power analysis, is conducted during the planning stages of a study. Power analysis allows the researcher to estimate how many participants are required in order to detect a minimally meaningful effect size at a specific level of power and Type I error rate. However, there are several drawbacks to the procedure that render it “a mess.” Specifically, the identification of the minimally meaningful effect size is often difficult but unavoidable for conducting the procedure properly, the procedure is not precision oriented, and does not guide the researcher to collect as many participants as feasibly possible. In this study, we explore how these three theoretical issues are reflected in applied psychological research in order to better understand whether these issues are concerns in practice. To investigate how power analysis is currently used, this study reviewed the reporting of 443 power analyses in high impact psychology journals in 2016 and 2017. It was found that researchers rarely use the minimally meaningful effect size as a rationale for the chosen effect in a power analysis. Further, precision-based approaches and collecting the maximum sample size feasible are almost never used in tandem with power analyses. In light of these findings, we offer that researchers should focus on tools beyond traditional power analysis when sample planning, such as collecting the maximum sample size feasible.


Author(s):  
Harish Chandra Tiwari ◽  
Sudhir Kumar Gupta

Background: Postnatal care is crucial in maintaining and promoting the health of the woman and the newborn baby. Despite the known benefits of the postnatal care, there are many access and utilization barriers to care. The present study was conducted on postnatal care and its correlates among recently delivered women visiting to BRD Medical College Gorakhpur. Methods: For present cross-sectional study recently delivered women (RDW) defined as a post natal woman who had a baby between two months to six months of age at the time of data collection were taken as the study subjects. Complete post natal care was considered if RDWs had received post natal check-up (Post natal day -1, day-3, day-7,) along with immunization of child with BCG, OPV and three doses of DPT/Pentavalent vaccine. Sample size was calculated as 275 by using the formula 4PQ/L2 with an allowable error (L) of 20% including 10% extra for non/incomplete responders. The proportion of women receiving postnatal care was considered as 50.0% as by this proportion maximum sample size is arrived. Results: A total of 269 recently delivered women (RDW) were taken as the study subjects. They belonged to age group 19-29 year (Mean age 23.7±6.7 year), either educated up to 12th standard and only few were graduate or post graduate. Majority of them belonged to middle or lower middle class. Conclusions: Postpartum care utilization was associated with socioeconomic status, antenatal care received or not, planned pregnancy or not. Interestingly, access to care was not perceived as a top reason for not obtaining PPC. 


2016 ◽  
Vol 12 (4) ◽  
pp. 430-437 ◽  
Author(s):  
Rainer Dziewas ◽  
Satish Mistry ◽  
Shaheen Hamdy ◽  
Jens Minnerup ◽  
Ingeborg Van Der Tweel ◽  
...  

Rationale Ongoing dysphagia in stroke patients weaned from mechanical ventilation often requires long-term tracheotomy to protect the airway from aspiration. In a recently reported single-centre pilot study, a significantly larger proportion (75%) of tracheotomized dysphagic stroke patients regained sufficient control of airway management allowing tracheotomy tube removal (decannulation) 24–72 h after pharyngeal electrical stimulation (PES) compared to controls who received standard therapy over the same time period (20%). Aim To assess the safety and efficacy of PES in accelerating dysphagia rehabilitation and enabling decannulation of tracheotomized stroke patients. Design International multi-centre prospective randomized controlled single-blind trial in approximately 126 ICU patients (the 90th percentile of the calculated maximum sample size). Study outcomes Primary outcome: proportion of stroke patients considered safe for decannulation 24–72 h after PES compared to control patients who do not receive PES. Key secondary outcomes focus on: dysphagia severity, decannulation rates, decannulation rate after a repeat PES treatment in patients persistently dysphagic after an initial PES treatment, stroke severity, duration of ICU-stay, occurrence of adverse events including pneumonia and need for recannulation over 30 days or until hospital discharge (if earlier). Discussion Dysphagia and related airway complications are reported as one of the main reasons for stroke patients remaining tracheotomized once successfully weaned from ventilation. This study will evaluate if PES can improve airway safety sufficiently enough to allow earlier tracheotomy tube removal.


Sign in / Sign up

Export Citation Format

Share Document