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Scientific Reports Jul 2018The traditional quantum secret sharing does not succeed in the presence of rational participants. A rational participant's motivation is to maximize his utility, and...
The traditional quantum secret sharing does not succeed in the presence of rational participants. A rational participant's motivation is to maximize his utility, and will try to get the secret alone. Therefore, in the reconstruction, no rational participant will send his share to others. To tackle with this problem, we propose a rational quantum secret sharing scheme in this paper. We adopt the game theory to analyze the behavior of rational participants and design a protocol to prevent them from deviating from the protocol. As proved, the rational participants can gain their maximal utilities when they perform the protocol faithfully, and the Nash equilibrium of the protocol is achieved. Compared to the traditional quantum secret sharing schemes, our scheme is fairer and more robust in practice.
PubMed: 30042486
DOI: 10.1038/s41598-018-29051-z -
Therapeutic Innovation & Regulatory... Jul 2022Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience.
BACKGROUND
Little to no data exist quantifying and benchmarking the magnitude of protocol deviation experience.
METHODS
Nearly two-dozen companies provided the Tufts Center for the Study of Drug Development (Tufts CSDD) with data on the design and the performance of 187 protocols.
RESULTS
The results of this working group study show that phase II and III protocols have a mean total of 75 and 119 protocol deviations, respectively, involving nearly one-third of all patients enrolled in each clinical trial. Oncology clinical trials have the highest relative mean number of protocol deviations affecting more than 40% of patients enrolled in each trial. The number of endpoints, the number of procedures per visit, and the number of countries were modestly positively associated with and predictive of, the incidence of deviations per protocol. A strong positive relationship was shown between the number of investigative sites and the number of protocol deviations.
CONCLUSION
The results of this initial study provide useful measures that sponsor companies can use to benchmark their own protocol deviation experience, identify factors most associated with protocol deviations, and determine whether remediation is warranted.
Topics: Benchmarking; Humans
PubMed: 35378712
DOI: 10.1007/s43441-022-00401-4 -
Enhanced Recovery Deviation and Failure After Pancreaticoduodenectomy: Causative Factors and Impact.The Journal of Surgical Research Jan 2020Enhanced recovery after surgery (ERAS) following pancreaticoduodenectomy (PD) is popular and safe. This study aimed to describe the incidence, causative factors, and...
BACKGROUND
Enhanced recovery after surgery (ERAS) following pancreaticoduodenectomy (PD) is popular and safe. This study aimed to describe the incidence, causative factors, and clinical impact of deviation from and failure of an ERAS protocol.
MATERIALS AND METHODS
A prospective cohort analysis of elective PD patients managed according to an ERAS protocol between October 2015 and June 2018 was performed. Univariate and multivariate analyses identified variables associated with protocol deviation and failure. The relationship between protocol deviation and failure was also explored.
RESULTS
A total of 97 patients were identified comprising of 46 females and 51 males. The median age was 68 y (range 17-85). Twenty-one patients (21.6%) suffered serious complications, whereas two (2.1%) died perioperatively. The median length of stay (LoS) was 14 d (6-36). In total, 73 (75.3%) patients deviated, whereas 39 (40.2%) failed the protocol. On univariate analysis, protocol deviation was associated with male gender, surgery time ≥270 min, and prolonged LoS. On multivariate analysis only prolonged LoS remained significant. Only serious complications were associated with protocol failure on multivariate analysis. Protocol deviation was not associated with significant complications nor ERAS protocol failure.
CONCLUSIONS
ERAS protocol deviation does not alter the course of those destined to protocol failure. Greater understanding into the causative factors of either protocol deviation or failure may be the only way to personalize care and realize the maximal benefit of ERAS in this specific group of patients.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Elective Surgical Procedures; Enhanced Recovery After Surgery; Female; Hospitals, University; Humans; Incidence; Israel; Length of Stay; Male; Middle Aged; Pancreaticoduodenectomy; Postoperative Complications; Prospective Studies; Treatment Failure; Young Adult
PubMed: 31494390
DOI: 10.1016/j.jss.2019.07.055 -
Gynecologic Oncology Oct 2023Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were...
OBJECTIVE
Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic.
METHODS
Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control.
RESULTS
Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods.
CONCLUSIONS
Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.
PubMed: 37659265
DOI: 10.1016/j.ygyno.2023.08.011 -
Neuroscience and Biobehavioral Reviews Jun 2018The rat intradimensional/extradimensional (ID/ED) task, first described by Birrell and Brown 18 years ago, has become the predominant means by which attentional... (Review)
Review
The rat intradimensional/extradimensional (ID/ED) task, first described by Birrell and Brown 18 years ago, has become the predominant means by which attentional set-shifting is investigated in rodents: the use of rats in the task has been described in over 135 publications by researchers from nearly 90 universities and pharmaceutical companies. There is variation in the protocols used by different groups, including differences in apparatus, stimuli (both stimulus dimensions and exemplars within), and also the methodology. Nevertheless, most of these variations seem to be of little consequence: there is remarkable similarity in the profile of published data, with consistency of learning rates and in the size and reliability of the set-shifting and reversal 'costs'. However, we suspect that there may be inconsistent data that is unpublished or perhaps 'failed experiments' that may have been caused by unintended deviations from effective protocols. The purpose of this review is to describe our approach and the rationale behind certain aspects of the protocol, including common pitfalls that are encountered when establishing an effective local protocol.
Topics: Animals; Attention; Behavior, Animal; Humans; Models, Animal; Rats; Reproducibility of Results; Reversal Learning; Task Performance and Analysis
PubMed: 29474818
DOI: 10.1016/j.neubiorev.2018.02.013 -
Statistical Considerations for Bias and Protocol Deviation in Medical Device Pivotal Clinical Study.Therapeutic Innovation & Regulatory... Sep 2019The gold standard in conducting clinical trials/studies is to follow what is prespecified in the study protocol. However, deviations from the study protocol may occur....
BACKGROUND
The gold standard in conducting clinical trials/studies is to follow what is prespecified in the study protocol. However, deviations from the study protocol may occur. This article discusses the issues of protocol deviation in pivotal clinical trials or studies for medical device and provides statistical approaches to mitigating bias such as selection bias specifically for diagnostic test clinical trials or studies.
METHOD
Bias correction methods are developed for 2 specific types of selection biases, prescreening bias and verification bias. Statistical approaches are discussed on how to estimate device performance adjusted for enrollment enrichment and discrepant testing results. We use an FDA-approved Roche Cobas Human Papillomavirus (HPV) test for detecting high-grade cervical disease (>CIN2) as an example to illustrate how to correct for verification bias. A recently FDA-cleared Microarray Assay in detecting copy number variation is used to illustrate how to properly estimate sensitivity and specificity for the discrepancy analysis.
RESULTS
The unadjusted sensitivity and specificity based on verified samples were 83.2% and 60.4% for the Roche's HPV test. However, using the correction method with the missing-at-random assumption, the verification bias-adjusted sensitivity and specificity were 34.5% and 93.6%, respectively.
CONCLUSION
Protocol deviations can lead to biased estimates of device clinical performance if not handled appropriately. Statistical methods correcting for bias and protocol deviations are recommended in estimating device performance.
Topics: Bias; Clinical Studies as Topic; DNA Copy Number Variations; DNA, Viral; Diagnostic Tests, Routine; Equipment and Supplies; Female; Humans; Papillomaviridae; Papillomavirus Infections; Sensitivity and Specificity; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 30380916
DOI: 10.1177/2168479018804175 -
Respiratory Care Apr 2021Treatments for ARDS that improve patient outcomes include use of lung-protective ventilation, prone ventilation, and conservative fluid management. Implementation of...
BACKGROUND
Treatments for ARDS that improve patient outcomes include use of lung-protective ventilation, prone ventilation, and conservative fluid management. Implementation of ARDS protocols via educational programs might improve adherence and outcomes. The objective of this study was to investigate the effects of an ARDS protocol implementation on outcomes and adherence with ARDS guidelines.
METHODS
This was a single-center, interventional, comparative study before and after protocol implementation. Staff education for the ARDS protocol was implemented between June 2014 and May 2015. A retrospective cohort analysis was conducted during between January 2012 and May 2014 (pre-protocol) and between June 2015 and June 2017 (post-protocol). A total of 450 subjects with ARDS were included. After propensity score matching, 432 subjects were analyzed. Of those, 330 subjects were treated after protocol implementation.
RESULTS
The median (interquartile range [IQR]) plateau pressure and tidal volume over the first 3 d decreased significantly after protocol implementation (30.5 [IQR 24.2-33] vs 25.5 [IQR 21.7-30], = .01 and 7.65 vs 7.4 mL/kg predicted body weight, = .032, respectively). The percentage of subjects with unsafe tidal volume (> 10 mL/kg predicted body weight) decreased (14.4% vs 5.8%, = .02). The percentage of subjects with safe plateau pressure (≤ 30 cm HO) increased (47.4% vs 76.5%, < .001). PEEP deviation from the ARDSNet PEEP/[Formula: see text] table was significantly lower after the implementation. Mortality at 28 and 90 days improved after implementation (53.9% vs 41.8% and 61.8% vs 48.2%, respectively). Adjusted odds ratios for 28-d and 90-d mortality were 0.47 (95% CI 0.28-0.78) and 0.45 (95% CI 0.27-0.76), respectively.
CONCLUSIONS
ARDS protocol implementation was associated with improved survival and rate of adherence.
Topics: Humans; Lung; Respiration, Artificial; Respiratory Distress Syndrome; Retrospective Studies; Tidal Volume
PubMed: 33051253
DOI: 10.4187/respcare.07999 -
3 Biotech Mar 2022Maize possesses wide variation in amylose and amylopectin which assumes significance as a part of both food-chain and different industrial applications. Estimation of...
Maize possesses wide variation in amylose and amylopectin which assumes significance as a part of both food-chain and different industrial applications. Estimation of amylose and amylopectin in maize kernels is important for developing suitable hybrids. The existing protocols for estimation of amylose and amylopectin in maize are elaborate and lengthy, and involve high cost. Here, we developed a rapid and cost-effective method for estimation of amylose and amylopectin in maize kernels. 10% toluene and 80% ethanol were used for removal of proteins (~ 10%) and lipids (~ 4%) from maize flour. The over-estimation of amylose was minimized using NaOH with KI to stop free KI to bind with amylopectin. Standards were improved by mixing amylose and amylopectin in different concentrations (0-100%), rather than using amylose or amylopectin alone. Standard curve generated regression equation of = 90.436 + 0.8535 with = 0.9989. Two types of samples viz., (1) protein, amylose and amylopectin (2) amylose and amylopectin, showed that starch fractions were highly comparable to expected values with correlation coefficient () of 0.9998 and mean standard deviation of 0.54. The protocol successfully estimated wide range of amylose (2.79-50.04%) and amylopectin (59.96-97.21%) among diverse maize inbreds including () and () mutants. Present protocol required 75% less time and 92.5% less cost compared to existing protocols. The newly developed method would be highly useful in developing maize hybrids high in amylose or amylopectin. This is the first report of rapid and cost-effective protocol for estimation of starch fractions in maize kernels.
PubMed: 35186659
DOI: 10.1007/s13205-022-03128-z -
Perspectives in Clinical Research 2023Failure to stay within an ethics committee (EC)-approved protocol limits is termed protocol deviation or violation (PD/PV), depending on the seriousness of the...
INTRODUCTION
Failure to stay within an ethics committee (EC)-approved protocol limits is termed protocol deviation or violation (PD/PV), depending on the seriousness of the transgression and its attendant risks and/or harms. PD/PVs arise in the post-approval phase of the research and are often missed. Current guidelines expect ECs to detect, report and recommend suitable actions such that research participants' risks and harms are mitigated, to the extent possible.
OBJECTIVE
Yenepoya Ethics Committee-1 conducted an internal audit of ongoing postgraduate dissertations involving human participants to assess the occurrence of PD/PVs.
MATERIALS AND METHODS
54 out of 80 postgraduates responded to our request for filling out a self-reported checklist. These responses were followed up with physical verification of the protocol-related documents.
RESULTS
Protocol transgressions were classified as non-compliance (administrative issues), protocol deviations (minor transgressions with minimal or less than minimal increase in attendant risk to participants) and protocol violations (serious transgressions with more than minimal increase in attendant risk to participants). The non-compliances included non-reporting for audit and non-reporting of PDs. Protocol deviations included non-conformance to EC validity, sample size, approved methodology, informed consent process and documentation and suboptimal data storage. No protocol violations were observed.
CONCLUSION
We report PD/PVs from these 54 protocols - with our assessment on the negative impact it may have on scientific validity, harm to participants, EC functioning and credibility of the institution - in the hope that our readers appreciate this important aspect of the post-approval process in the functioning of an EC.
PubMed: 37325575
DOI: 10.4103/picr.picr_235_21 -
Journal of Atrial Fibrillation Dec 2019Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of...
BACKGROUND
Manufacturer/federal drug administration (FDA) recommends inpatient initiation of dofetilide with the manufacturer providing an initiation algorithm. The outcomes of algorithm deviation have not been reported outside of clinical trials.
OBJECTIVE
We sought to perform a chart review of all the patients admitted for inpatient initiation of dofetilide to report on the incidence of protocol deviations and their implications.
METHODS
We performed a retrospective review of all patients over a 15-month periodwho were initiated on dofetilide for the very first time or reinitiated on dofetilide after a break of three months or more at our institution. We assessed data about patients who were given dofetilide without adherence to the protocol (i.e. protocol deviation).
RESULTS
A total of 189 patients were included in the study with a median age of 66 ± 9 years. Mean baseline QTc interval was 436 ± 32 msec, and 61% (116/189) were in atrial fibrillation (AF) at the time of dofetilide initiation. In 9% (17/189) of patients, the drug was discontinued due to intolerance or inefficacy. Therapy in 49% (93/189) of patients was noted to deviate from manufacturer recommended protocol with deviations more than once in some patients during the same hospitalization. Baseline QTc exceeding 440 msec(>500msec in conduction abnormalities) was the most frequent deviation (25%; 47/189).Ventricular tachyarrhythmia occurred in 4% (7/189) of patients, did not differ between patients, and occurred with and without protocol deviations (5% vs 2%; p = 0.27).
CONCLUSIONS
In our retrospective study, there were frequent deviations from the manufacturer-recommended algorithm guidelines for dofetilideinitation, primarily due to prolonged baseline QTc interval. The impact of these protocol deviations on drug discontinuation was uncertain; however, significant adverse events were higher in the deviation group compared to the group that fully adhered to the protocol. Further multicenter studies are warranted to clarify our findings.
PubMed: 32435348
DOI: 10.4022/jafib.2265