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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 -
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 -
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 -
CoDAS 2022Verify and compare vocal deviation in quality, vocal symptoms and reflux symptom index in patients with clinical diagnosis of laryngopharyngeal reflux (LPR).
PURPOSE
Verify and compare vocal deviation in quality, vocal symptoms and reflux symptom index in patients with clinical diagnosis of laryngopharyngeal reflux (LPR).
METHODS
100 individuals of both genders participated in this prospective study, aged between 18 and 60 years old, who presented signs of LPR in the nasofibrolaryngological exam. Participants answered the Reflux Symptom Index (RSI) questionnaire to determine the reflux index and the Voice Symptom Scale (VoiSS). Their voices were recorded for the auditory-perceptual assessment. Three speech therapists with voice experience were contacted and the most reliable one was maintained.
RESULTS
100 examined voices, 34 were classified as adapted and 66 as deviated. The predominant vocal quality type was rough and a slight degree of deviation. The average score on VoiSS and RSI of individuals with deviated voice is significantly higher than the adapted voice group on both protocols (p<0.01). The symptom reported with most frequency and intensity, in both analyses, was throat clearing. There were statistically significant differences once analyzed the vocal quality types by pairs: rough-adapted (p=0.0021) and tense-adapted (p=0.0075) on VoiSS, and rough-adapted (p=0.001) on RSI.
CONCLUSION
Individuals with deviated voice reported higher occurrence of LPR related vocal signals and symptoms measured by VoiSS and RSI. The numerous theories about the disease do not make possible a single conclusion on the subject. Further studies are needed in the area to assist the professional in the diagnosis and treatment of the RLF patient.
Topics: Adolescent; Adult; Female; Humans; Laryngopharyngeal Reflux; Male; Middle Aged; Prospective Studies; Surveys and Questionnaires; Voice; Voice Quality; Young Adult
PubMed: 35239772
DOI: 10.1590/2317-1782/20212019065 -
BMC Oral Health Aug 2022Accurate integration of the dentitions with the face is essential in dental clinical practice. Here we introduce a noninvasive and efficient protocol to integrate the...
BACKGROUND
Accurate integration of the dentitions with the face is essential in dental clinical practice. Here we introduce a noninvasive and efficient protocol to integrate the digitized maxillary dentition with the three-dimensional (3D) facial photo using a prefabricated modified computer-aided design/computer-aided manufacture (CAD/CAM) facebow.
METHODS
To integrate the maxillary dentition with the 3D facial photo, the CAD/CAM facebow protocol was applied to 20 patients by taking a series of 3D facial photos in the clinic and integrating them in the laboratory. The integration accuracy of this protocol was compared with that of a valid 3D computed tomography (CT)-aided protocol concerning translational deviations of the landmarks representing maxillary incisors and maxillary first molars as well as the rotational deviation of the maxillary dentition. The intra- and inter-observer reproducibility was assessed, and the time of clinical operation and laboratory integration was recorded.
RESULTS
This facebow-aided protocol generated 3D fused images with colored faces and high-resolution dentitions, and showed high reproducibility. Compared with the well-established CT-aided protocol, the translational deviations ranged from 0 to 1.196 mm, with mean values ranging from 0.134 to 0.444 mm, and a relatively high integration error was found in the vertical dimension (Z) with a mean ± standard deviation (SD) of 0.379 ± 0.282 mm. Meanwhile, the rotational deviations ranged from 0.020 to 0.930°, with mean values less than 1°, and the most evident deviation was seen in pitch rotation with a mean ± SD of 0.445 ± 0.262°. The workflow took 4.34 ± 0.19 min (mins) for clinical operation and 11.23 ± 0.29 min for laboratory integration.
CONCLUSION
The present radiation-free protocol with the modified CAD/CAM facebow provided accurate and reproducible transfer of the digitized maxillary dentition to the 3D facial photo with high efficiency.
Topics: Computer-Aided Design; Dentition; Humans; Imaging, Three-Dimensional; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 36028874
DOI: 10.1186/s12903-022-02394-w -
Radiotherapy and Oncology : Journal of... Jan 2022Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT).
METHODS AND MATERIALS
We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson's Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials.
RESULTS
Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p = 0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p < 0.001).
CONCLUSIONS
There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.
Topics: Credentialing; Humans; Neoplasms; Quality Assurance, Health Care; Radiation Oncology
PubMed: 34838891
DOI: 10.1016/j.radonc.2021.11.018 -
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 -
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 -
Nihon Hoshasen Gijutsu Gakkai Zasshi Oct 2022There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose...
PURPOSE
There are problems with dose management in X-ray computed tomography (CT) because the protocol used for any examination is not always in the same scan range. The purpose of this study was to investigate the usefulness of setting the CT protocol based on the scan range.
METHODS
We evaluated the examination data of patients who underwent plain CT based on a scan range of chest to pelvis and abdomen to pelvis. The previous protocol [Chest-Abdomen Routine] was changed to the current protocols [Chest_Abdomen] and [Chest_Pelvis], and the previous protocol of [Abdomen Routine] was changed to the current protocols [Abdomen] and [Abdomen_Pelvis]. Examination data of height, scan length, volume CT dose index (CTDI), and dose length product (DLP) were obtained from digital imaging and communications in medicine, and radiation dose structured report using Radimetrics. The relationship between patient height and scan range, and CTDI and DLP was indicated in a scatter plot. Standard deviation (SD) of scan length and DLP were compared between current and previous protocols. Outliers were defined as the data exceeding average ±2SD.
RESULTS
The SD of scan length decreased by 77.1% on abdomen to pelvis, and the SD of DLP decreased by 65.2% on abdomen to pelvis. The causes of the outliers were CT scan range, scan parameter, arm position, metal implants, and body thickness of patients.
CONCLUSION
Setting CT protocols based on the scan range reduced SD of scan length and DLP. It was helpful for reducing the number of scan range outliers and analyzing the cause of outliers.
Topics: Humans; Radiation Dosage; Tomography, X-Ray Computed; Pelvis; Thorax; Abdomen
PubMed: 36031372
DOI: 10.6009/jjrt.2022-1131 -
Frontiers in Reproductive Health 2022Prospective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences...
BACKGROUND
Prospective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences reproductive outcomes. While web-based research methods provide efficient and effective strategies to collect questionnaire-based data, few of these studies incorporate biospecimen collection, which can enhance the validity of exposure assessment. There is limited literature on the feasibility and cost-effectiveness of collecting biospecimens in web-based preconception cohort studies.
METHODS
We evaluated the feasibility and cost-effectiveness of in-clinic and mail-based biospecimen collection in Pregnancy Study Online (PRESTO), a North American web-based preconception cohort study. Both members of the couple were eligible to participate if their conception attempt time was ≤3 months at enrollment. We invited study participants from the Boston, MA and Detroit, MI metropolitan areas to attend a study visit and provide urine and blood (hereafter "in-clinic protocol"). We invited all other participants to complete mail-based collection of urine and blood spots (hereafter "mail-based protocol"). We compared overall consent and protocol completion rates, demographic characteristics of those who consented and completed either of the protocols, and costs between mail-based and in-clinic protocols for biospecimen collection. Finally, we described logistical challenges pertaining to reliance on mail-based delivery of time-sensitive biospecimens compared with in-clinic methods.
RESULTS
During January 2022-July 2022, 69% of female participants (134/195) and 42% of male participants (31/74) consented to participate in the mail-based protocol. Consent rates for the in-clinic protocol were 39% for female participants (289/739 during March 2014-July 2022) and 25% for male participants (40/157 during March 2017-July 2022). Participants who consented to participate were generally of higher socioeconomic position than non-participants. Deviations from the protocol occurred more frequently within the mail-based protocol but were easily corrected. The cost per participant enrolled was similar across protocols (mail-based: $276.14 vs. in-clinic: $270.38).
CONCLUSIONS
Our results indicate that mail-based collection of biospecimens may create opportunities to recruit a larger and more geographically diverse participant population at a comparable cost-per-participant enrolled to in-clinic methods.
PubMed: 36699143
DOI: 10.3389/frph.2022.1052231