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Clinical Nutrition (Edinburgh, Scotland) Apr 2020Esophagectomy is associated with high postoperative morbidity rates, which can result in decreased quality of life and impaired recovery. Implementation of enhanced...
BACKGROUND
Esophagectomy is associated with high postoperative morbidity rates, which can result in decreased quality of life and impaired recovery. Implementation of enhanced recovery after surgery (ERAS) protocols have made a great impact in optimizing postoperative recovery. However, the best timing to start oral intake is still unclear. Conservative feeding protocols have been developed with a nil-by-mouth period in the first postoperative days to reduce postoperative complication rates (e.g. anastomotic leakage and pneumonia). This study aimed to evaluate adherence to the feeding protocol following minimal invasive esophagectomy and identify reasons for protocol deviation.
METHODS
All consecutive patients who underwent an esophagectomy with gastric tube reconstruction between 2014 and 2016 in two high-volume hospitals in the Netherlands were retrospectively analyzed. All patients were planned to receive enteral tube feeding via jejunostomy directly after surgery. Data regarding postoperative feeding related symptoms (e.g. nausea, vomiting, regurgitation) and adherence to the postoperative feeding protocol were gathered.
RESULTS
A total of 186 patients were included. Feeding protocol deviation was observed in 109 patients (59%) and was significantly more common in patients with anastomotic leakage, chyle leakage, and acute respiratory distress. Postoperative feeding related symptoms were present in 107 patients (58%) and were significantly more common in female patients and patients with a cervical anastomosis.
CONCLUSION
In this study, more than half of the patients deviated from the intended feeding protocol after esophagectomy. Postoperative complications appeared to be the main reason for feeding protocol deviation. This study shows that a predefined feeding protocol including an oral fasting period is often violated because of complications.
Topics: Administration, Oral; Aged; Clinical Protocols; Enteral Nutrition; Esophagectomy; Female; Humans; Length of Stay; Male; Middle Aged; Netherlands; Postoperative Care; Practice Guidelines as Topic; Prospective Studies; Retrospective Studies; Sex Factors; Treatment Outcome
PubMed: 31174943
DOI: 10.1016/j.clnu.2019.05.018 -
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 -
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 -
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 -
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 -
Therapeutic Innovation & Regulatory... Jul 2021Improving interpretation of existing guidelines and management of protocol deviation processes could increase process efficiencies and help reduce noise to support rapid...
Improving interpretation of existing guidelines and management of protocol deviation processes could increase process efficiencies and help reduce noise to support rapid identification of important protocol deviations. Towards this end, TransCelerate identified key principles to build upon and clarify the definition of a protocol deviation and developed a holistic approach to protocol deviation management. The approaches are flexible to suit a variety of indications, study designs, and investigational agents while also supporting consistent application within a study, program or organization.
Topics: Research Design
PubMed: 33782921
DOI: 10.1007/s43441-021-00269-w -
Therapeutic Innovation & Regulatory... Nov 2016The DIA's Good Clinical Practice and Quality Assurance Community (DIA GCP/QA) created a working group to develop templates for a protocol deviation standard operating...
BACKGROUND
The DIA's Good Clinical Practice and Quality Assurance Community (DIA GCP/QA) created a working group to develop templates for a protocol deviation standard operating procedure (SOP) and protocol deviation handling plan (PDHP).
METHODS
The working group consisted of QA auditors, data managers, statisticians, and clinical monitors from several pharmaceutical companies, academia, and independent auditing firms. Various examples of standard operating procedures, data handling plans, and auditing plans were examined, and the core elements extracted into the initial PD SOP and PDHP templates. The draft templates were presented at a workshop at the DIA 51st Annual Meeting held in June 2015 in Washington, DC, and feedback was incorporated. The workshop came at the heels of a previously published position paper, "The Lifecycle and Management of Protocol Deviations."
RESULTS
The PD SOP and the PDHP templates are presented in this article. They are a starting point, and each company will need to modify to suit its individual needs.
CONCLUSIONS
This article expands on the position paper to include concrete tools for the management of protocol deviations, including best practices for detection, classification, mitigation, and management of protocol deviations with a goal to reduce the impact on subject safety and data integrity.
PubMed: 30231739
DOI: 10.1177/2168479016647987 -
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 -
Arthritis Research & Therapy Mar 2015Treat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve...
INTRODUCTION
Treat-to-target (T2T) strategies using a protocol of pre-defined adjustments of disease-modifying anti-rheumatic drugs (DMARDs) according to disease activity improve outcomes for patients with rheumatoid arthritis (RA). However, successful implementation may be limited by deviations from the protocol. The aim of this study was to determine the prevalence of protocol deviation, explore the reasons and identify subsets of patients in whom treatment protocols are more difficult to follow.
METHODS
In this retrospective cohort study, treatment-naïve patients with RA of less than one year's duration, attending a dedicated early arthritis clinic between 2001 and 2013, were followed for three years from initiation of combination therapy with conventional DMARDs which was subsequently modified according to a T2T protocol. At each clinic visit, whether deviation from the protocol occurred, the type of deviation and the reasons for deviation were assessed. The relationship between protocol deviations and baseline variables was determined using linear regression analysis.
RESULTS
In total, 198 patients contributed 3,654 clinic visits. The prevalence of protocol deviations was 24.5% and deviation in at least at one clinic visit was experienced by 90.4% of patients. The median time to first deviation was 30 weeks. Continuing existing treatment rather than intensifying therapy was the most common type of deviation (59.9%). Patient and physician related factors were the most common reasons for deviation, each accounting for 24.7% of deviations, followed by toxicities (23.3%) and comorbidities (20.0%). The prevalence of protocol deviations was lower among patients who achieved remission after three years (13.1%; 162 deviations out of 1,228 visits) compared with those who were not in remission (30.9%; 523/1692) (P<0.0001). On multivariate analysis, only body mass index (P=0.003) and helplessness score (P=0.04) were independent predictors of protocol deviations although the predictive power of the model was not strong (R2=0.17).
CONCLUSIONS
Deviation from a T2T protocol occurred in one quarter of visits, indicating that applying the T2T approach is feasible in clinical practice. Failure to escalate dose when indicated was commonly encountered, and just under half of the observed deviations were related to either toxicities or comorbidities and were therefore justifiable on clinical grounds.
Topics: Adult; Aged; Antirheumatic Agents; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Male; Middle Aged; Practice Guidelines as Topic; Remission Induction; Retrospective Studies; Severity of Illness Index; Time Factors; Treatment Outcome
PubMed: 25889527
DOI: 10.1186/s13075-015-0562-0 -
Minerva Ginecologica Aug 2011The aim of this paper was to evaluate the didactic protocol on the management of both labour and birth. (Review)
Review
AIM
The aim of this paper was to evaluate the didactic protocol on the management of both labour and birth.
METHODS
Selection criteria were carried out with randomized, quasi-randomized controlled trials and other relevant articles involving a comparison of partogram with no partogram, or comparison between different partogram designs. A printed alert and/or action lines are designed to prevent the deviation. Particularly partograms where divided in: 1) partogram versus no partogram in labour-delivery; 2) partogram with two-hour action line versus partogram with four-hour action line; 3) partogram with two-hour action line versus partogram with three-hour action line; 4) partogram with three-hour action line versus partogram with four-hour action line; 5) partogram with alert line versus partogram with alert and action line; 6) earlier versus later intervention.
RESULTS
We included twenty-eight studies in this review, involving 7 827 women; six studies assessed partogram versus no partogram and the remainder assessed different partogram designs. There was no evidence of significant difference between partogram and no partogram in caesarean section. When compared the use or less of partogram in vaginal deliveries, this tool with defined management protocols prevents obstructed labour (protracted phase or arrest of dilatation). Quality monitoring of the labour with the partogram will reduce the morbidity and mortality in both mother and newborn. Deviation of the curve from the standard partogram is an alert graphic expression of risk and moves forward an adequate management of treatment. Regarding the use of partogram as didactic protocol, it is considered useful in the comprehension of the various evolutions of labor and delivery.
CONCLUSION
On the basis of literature, the data regarding the use of partogram is controversial. Regarding elective caesarean section partogram doesn't give any advantages owing to the absence of labor. Relating the employ of partogram in labour, it is helpful for correcting the deviation from the normality, permitting the opportune use of both drugs (oxytocin) and procedures (amniotomy). Even if the literature does not recommend a routine use of the partogram as part of standard labour management, it always represents an instrument for a better determination of the parameters evaluated (dilatation, mechanical curve, contractions). Both physicians and midwives have to be trained to a correct use the partogram in order to have satisfactory results. A challenge to improve the graph and facilitate the compilation of the model should be addressed. Further trial evidence is required to establish the real and significant utility of partogram. Besides, the partogram is a practical graph for medico-legal evaluation in case of contentiousness.
Topics: Clinical Protocols; Delivery, Obstetric; Female; Humans; Labor, Obstetric; Pregnancy
PubMed: 21747340
DOI: No ID Found