Quality Of Clinical Research Research Articles

Enlightenments of DITTO framework and its application for setting up mock acupuncture in clinical research

How to set up a placebo control scientifically and effectively is a problem in clinical research on acupuncture therapy. In 2020, the UK National Institute of Health Research established a standardized methodological framework DITTO, that is, "Deconstruct""Identify""Take out""Think" and "Optimize" to standardize the setting of invasive console-control intervention. Acupuncture therapy theoretically belongs to the category of invasive therapeutic intervention, and the percutaneous puncture therapy was also considered when the DITTO framework was developed. Therefore, this framework can be applied to clinical research of acupuncture, and may provide a reference for the appropriate setting of simulated acupuncture. In this article, we introduce the formulation process and main contents of the DITTO framework, and analyze the adjustments needed to be made and possible problems encountered in the application of each part of the framework in acupuncture clinical research through medical cases. The DITTO framework can guide and standardize the design of mock acupuncture control in acupuncture clinical research to a certain extent, which is conducive to finding a more suitable implementation method of mock acupuncture, thus promoting the improvement of the quality of acupuncture clinical research. However, because there is no precedent in the field of acupuncture in traditional Chinese medicine, further research is needed in the future practical application so that it can be better combined with the characteristics of acupuncture and the purpose of clinical research.

A Methodological Framework for Investigating Diversity in Clinical Research

AbstractBackgroundMany reports and reviews have been published on best practices in research recruitment, engagement, and retention (RER), yet clinical research broadly lacks identifiable mechanisms to translate these qualitative reports into quantifiable, testable hypotheses on the science of RER. A science of diversity requires precise mechanisms for true efficacy, but before this is possible, we must develop key methodological and ontological frameworks. Thus, we are in dire need a basic sciences approach to identify mechanisms that underpin RER research, and disparities in Alzheimer’s disease and related dementias (ADRD) clinical research more broadly.MethodA science of diversity in clinical trials must ensure research conducted under the umbrella of this discipline is not methodologically confounded. Although researchers studying health inequities have begun to parse health disparitiesfrom health inequities, recruitment into research may still conflate foundational causal concepts, obscuring researchers’ ability to truly determine the nature of group differences. An ordered methodological framework was proposed, formalizing key biases that may confound efforts to diversity clinical research samples, and to determine the nature of health inequities and disparities among marginalized and minoritized populations.ResultIn addition to aspects of biological differences and structural inequities that may inform group differences in both RER and ADRD clinical research, three additional sources of bias were identified: biases of selection and inclusion into research, error and biases of measurement, and biases of implementation of research protocols. Notably, existing tools to measure and mitigate these sources of noise are available, ensuring that detected group differences are not confounded by shortcomings in scientific design.ConclusionI present this novel framework to support a rigorous methodological approach to the study of diversity in ADRD clinical trials, anchoring a formalized science of RER and ensuring that estimates of health disparities and inequities in ADRD research are free of biases introduced by well‐intentioned research teams. Implementing this methodological approach is expected to improve accrual of diverse and representative populations into ADRD research, and to improve the quality and generalizability of ADRD clinical research itself.

Thrombolysis in Stroke Mimics: Comprehensive Stroke Centers vs Telestroke Sites.

Hyperacute treatment of acute stroke may lead to thrombolysis in stroke mimics (SM). Our aim was to determine the frequency of thrombolysis in SM in primary stroke centers (PSC) dependent on telestroke versus comprehensive stroke centers (CSC). Retrospective review of prospectively collected data from the Quality improvement and Clinical Research (QuICR) registry, the Discharge Abstract Database (DAD), and The National Ambulatory Care Reporting System (NACRS) of consecutive patients treated with intravenous thrombolysis for acute ischemic stroke in Alberta (Canada) from April 2016 to March 2021. A total of 2471 patients who received thrombolysis were included. Linking the QuICR registry to DAD 169 (6.83%) patients were identified as SM; however, on our review of the records, only 112 (4.53%) were actual SM. SMs were younger with a mean age of 61.66 (±16.15) vs 71.08 (±14.55) in stroke. National Institute of Health Stroke Scale was higher in stroke with a median (IQR) of 10 (5-17) vs 7 (5-10) in SM. Only one patient (0.89 %) in SM groups had a small parenchymal hemorrhage versus 155 (6.57%) stroke patients had a parenchymal hemorrhage. There was no death among patients of thrombolysed SM during hospitalization versus 276 (11.69%) in stroke. There was no significant difference in the rate of SM among thrombolysed patients between PSC 27 (5.36%) versus CSC 85 (4.3%) (P = 0.312). The most responsible diagnosis of SM was migraine/migraine equivalent, functional disorder, seizure, and delirium. The diagnosis of SM may not always be correct when the information is extracted from databases. The rate of thrombolysis in SM via telestroke is similar to treatment in person at CSC.

The Canadian Consortium for Research in Pediatric Surgery: Roadmap for Creation and Implementation of a National Subspecialty Research Consortium.

Clinical practice should be driven by high-quality research that produces evidence to inform best practices. Generation of such evidence is often challenging, particularly for smaller specialties, such as pediatric surgery, that treat many patients with rare diseases. Multi-institutional collaboration is seen as a major strategy to address these challenges. We have recently created the Canadian Consortium for Research in Pediatric Surgery, a national consortium that includes all major pediatric surgical services across Canada. The mission of the Consortium is to improve pediatric surgical care through high-quality collaborative research. In this article, we describe the rationale and methodology for creation of the Canadian Consortium for Research in Pediatric Surgery, demonstrate its achievements to date, and share a number of foundational concepts that are integral to its success. Our aim is to provide a model for creation of such consortia, ultimately leading to improvements in the quality of clinical research and patient care.

QLTI-08. SURVEY OF CANADIAN NEURO-ONCOLOGY CLINICIANS ABOUT THE TREATMENT OF ADULT MEDULLOBLASTOMA

Abstract BACKGROUND Given the rarity of medulloblastoma in adults (fewer than 50 incident cases annually across Canada), the optimal chemotherapy strategy in this population is unknown. The management of adult medulloblastomas is thought to vary from institution to institution. Guidelines often omit suggestions for specific chemotherapy regimens, reflecting the lack of high quality evidence in this population. We sought to understand Canadian adult medulloblastoma practice patterns, hoping to inform future quality metrics and guidelines. METHODS In March 2022 a 30-question survey was sent out to 71 adult neuro-oncology clinicians on the Canadian Adolescent and Young Adult national rounds mailing list. Snowball sampling was permitted. RESULTS There were 25 responses (up to 35% response rate). Radiation oncologists (11), neuro-oncologists (8), medical oncologists (4), and neurosurgeons (2) responded from 6/10 Canadian provinces. They each treated on average 1.6 medulloblastoma patients per year. Most (61% of respondents) said that medulloblastoma molecular subgrouping was always done at their centre. Half (50%) indicated that cerebrospinal fluid testing was always done at diagnosis. The most common (64%) radiation regimen was 36 Gy (in 20 fractions) craniospinal irradiation + 18 Gy (in 10 fractions) boost. Concomitant chemotherapy was rarely given (75% of respondents included chemotherapy less than half of the time). Adjuvant chemotherapy was frequently administered (79% of respondents give it more than half of the time). The most common adjuvant chemotherapy was Cisplatin/Lomustine/Vincristine (57%), but other regimens included Cisplatin/Lomustine/Vincristine alternating with Cyclophosphamide/Vincristine (21%), Cisplatin/Cyclophosphamide/Vincristine (14%), and carboplatin-based regimens (14%). Respondents noted challenges prescribing chemotherapy in this population: drug toxicities, limited resources, and clinical uncertainty. There was support for standard of care adult medulloblastoma guidelines in 92% of respondents. CONCLUSIONS There is significant practice variation among Canadian neuro-oncology centres treating adult medulloblastoma. This variation can serve as an opportunity for quality improvement and clinical research.

Harnessing the nursing and midwifery workforce to boost Australia's clinical research impact.

Harnessing the nursing and midwifery workforce to boost Australia's clinical research impact.

Does Central Monitoring Lead to Higher Quality? An Analysis of Key Risk Indicator Outcomes

BackgroundCentral monitoring, which typically includes the use of key risk indicators (KRIs), aims at improving the quality of clinical research by pro-actively identifying and remediating emerging issues in the conduct of a clinical trial that may have an adverse impact on patient safety and/or the reliability of trial results. However, there has to-date been a relative lack of direct quantitative evidence published supporting the claim that central monitoring actually leads to improved quality.Material and MethodsNine commonly used KRIs were analyzed for evidence of quality improvement using data retrieved from a large central monitoring platform. A total of 212 studies comprising 1676 sites with KRI signals were used in the analysis, representing central monitoring activity from 23 different sponsor organizations. Two quality improvement metrics were assessed for each KRI, one based on a statistical score (p-value) and the other based on a KRI’s observed value.ResultsBoth KRI quality metrics showed improvement in a vast majority of sites (82.9% for statistical score, 81.1% for observed KRI value). Additionally, the statistical score and the observed KRI values improved, respectively by 66.1% and 72.4% on average towards the study average for those sites showing improvement.ConclusionThe results of this analysis provide clear quantitative evidence supporting the hypothesis that use of KRIs in central monitoring is leading to improved quality in clinical trial conduct and associated data across participating sites.

Large Surgical Databases with Direct Data Abstraction: VASQIP and ACS-NSQIP.

Direct data abstraction from a patient's chart by experienced medical professional data abstractors has been the historical gold standard for quality and accuracy in clinical medical research. The limiting challenge to population-wide studies for quality and public health purposes is the high personnel costs associated with very large-scale efforts of this type. Two historically related programs that are at least partially able to successfully circumvent this problem and provide high-quality data relating to surgical procedures and the early postoperative period are reviewed in this article. Both utilize similar data abstraction efforts by specially trained and qualified medical abstractors of a sample subset of the total procedures performed at participating hospitals.The Veterans Affairs Surgical Quality Improvement Program (VASQIP), detailed by Nicholas J. Giori, MD, PhD, in the first section of this article, makes use of trained abstractors and has undergone recent additions and updates, including the development of an associated total hip registry for the VA system. The data elements and data integrity provided by both of these programs establish important benchmarks for other "big data" efforts, which often attempt to use alternative less-expensive methods of data collection in order to achieve more widespread or even nationwide data collection.In the second section, Elizabeth B. Habermann, PhD, MPH, provides a detailed review of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), the data elements collected, and examples of the range of quality improvement and outcomes studies in orthopaedic surgery that it has made possible, along with information on data that have not been collected and the resulting limitations. The ACS NSQIP was actually modeled after the very similar earlier effort started by the United States Department of Veterans Affairs (VA).

Strong and high-quality evidence synthesis needs Cochrane: a statement of support by the GRADE Guidance Group

Cochrane is widely recognized for its pioneering efforts in promoting and producing high quality systematic reviews as the basis of evidence-based decision-making and advancing the underlying methods of evidence synthesis. The GRADE Working Group has developed the most widely used approach to rating the certainty of evidence, to ensure that users of the reviews understand how much trust to put in findings of research and to then use this evidence for decision-making.For decades, both organizations have been closely aligned through their mutual goal of providing trustworthy healthcare related information to allow individuals, guideline developers, and policy makers to make decisions grounded in evidence.Beyond the concepts of SoF table, the joint experience in rating the certainty of evidence and the application of GRADE in Cochrane reviews strengthened the reviews and GRADE’s conceptual developments, and, ultimately, becoming the internationally accepted approach for rating certainty of evidence.The work of the two groups is also aligned with the mission of the Journal of Clincial Epidemiology’s (JCE) promotion of the quality of clinical and patient-oriented health care research. These alignments are one of the reasons for submitting this commentary to the JCE in support of Cochrane.A strong Cochrane is not only in the interest of GRADE and the entire evidence-based healthcare community, but also of the future of trusted evidence, informed decisions, and a better health.

Development of an Electronic Health Record Registry to Facilitate Collection of Commission on Cancer Metrics for Patients Undergoing Surgery for Breast Cancer.

Accurate and efficient data collection is a challenge for quality improvement initiatives and clinical research. We describe the development of a custom electronic health record (EHR)-based registry to automatically extract structured Commission on Cancer axillary surgery-specific metrics from a custom synoptic note template included in the operative reports for patients with breast cancer undergoing surgery. The smart functionality of our enterprise-based EHR system was leveraged to create a custom smart phrase to capture axillary surgery-specific variables. A multidisciplinary team developed structured data elements correlating to each axillary surgery-specific variable. These data elements were then included in a note template for the operative report. Each variable could be aggregated and converted into a single flat database through the EHR's reporting workbench and serve as a live, prospective registry for all users within the EHR. The final axillary surgery-specific note template in a synoptic format allowed for efficient and easy entry and automatic collection of breast cancer-specific metrics. From initial adoption in February 2021-December 2021, there were 1,254 patients who underwent breast surgery with axillary surgery. The operative notes allowed for automatic capture of metrics from 60.5% (n = 759) of patients. Data capture improved from 37.6% in the initial adoption period of 6 months to 86.2% in the last 5 months. We were able to demonstrate successful implementation of provider-driven structured data entry into EHR systems that permits automatic data capture. The end result is a custom synoptic note template and a real-time, prospective registry of breast cancer-specific Commission on Cancer metrics that are robust enough to use for quality improvement initiatives and clinical research.

Academic program recommendations for graduate degrees in medical physics: AAPM Report No. 365 (Revision of Report No. 197).

Academic program recommendations for graduate degrees in medical physics: AAPM Report No. 365 (Revision of Report No. 197).

The NIDDK Diabetic Foot Consortium.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Foot Consortium (DFC) was established in September 2018 by the NIDDK to build an organization to facilitate the highest quality of clinical research on diabetic foot ulcers (DFUs) that will answer clinically significant questions to improve DFU healing and prevent amputations. The initial focus of the DFC is to develop and validate biomarkers for DFUs that can be used in clinical care and research. The DFC consists of a data coordinating center (DCC) for operational oversight and statistical analysis, clinical sites for participant recruitment and evaluation, and biomarker analysis units (BAUs). The DFC is currently studying biomarkers to predict wound healing and recurrence and is collecting biosamples for future studies through a biorepository. The DFC plans to address the challenges of recruitment and eligibility criteria for DFU clinical trials by taking an approach of "No DFU Patient Goes Unstudied." In this platform approach, clinical history, DFU outcome, wound imaging, and biologic measurements from a large number of patients will be captured and the in-depth longitudinal data set will be analyzed to develop a computational-based DFU risk factor profile to facilitate scientifically sound clinical trial design. The DFC will expand its platform to include studies of the role of social determinants of health, such as food insecurity, housing instability, limited health literacy, and poor social support. The DFC is starting partnerships with the broad group of stakeholders in the wound care community.

A robust knockoff filter for sparse regression analysis of microbiome compositional data

Microbiome data analysis often relies on the identification of a subset of potential biomarkers associated with a clinical outcome of interest. Robust ZeroSum regression, an elastic-net penalized compositional regression built on the least trimmed squares estimator, is a variable selection procedure capable to cope with the high dimensionality of these data, their compositional nature, and, at the same time, it guarantees robustness against the presence of outliers. The necessity of discovering “true” effects and to improve clinical research quality and reproducibility has motivated us to propose a two-step robust compositional knockoff filter procedure, which allows selecting the set of relevant biomarkers, among the many measured features having a nonzero effect on the response, controlling the expected fraction of false positives. We demonstrate the effectiveness of our proposal in an extensive simulation study, and illustrate its usefulness in an application to intestinal microbiome analysis.

Transitioning to the clinical research nurse role - A qualitative descriptive study.

Studies have reported on the important role of the clinical research nurse in clinical studies. Yet, there is no international consensus about the role's competencies and tasks. Furthermore, the literature offers a little description of the career pathway from a ward-based registered nurse to a clinical research nurse. More knowledge about this specific role could benefit the nursing profession as well as increase the quality of clinical research. The aim of the study was to explore Swedish registered nurses' experiences transitioning into the clinical research nurse role. The study had a qualitative design. Data were collected via semi-structured interviews. Inductive qualitative content analysis was employed. Ten participants (i.e., clinical research nurses) were interviewed in the spring of 2017. A semi-structured interview guide was used to address the transition into the clinical research nurse role, experience working in a new role, experience of ethical dilemmas and experience of organizational and professional issues related to the role. The interviews were analysed inductively using qualitative content analysis. The registered nurses described experiencing reality shock when they became clinical research nurses; that is, it was a challenging and transforming experience. The main theme, a challenging transition, was developed from the four subthemes highlighting that it defied their previous nursing role. They experienced an unclear professional identity, extended professional mandate, increased professional status and growing ethical consciousness in their new role. The results highlight that registered nurses who became clinical research nurses had needs that were both distinct from and overlapped with those of their former professional role as registered nurses. To avoid reality shocks, the development of clear competence pathways for nurses to become clinical research nurses, including introduction, mentorship and continued support, is necessary. Making their professional title more homogeneous, nationally and internationally, would facilitate role identification and comparisons in research.

Prediction of 90 day home time among patients with low baseline ASPECTS undergoing endovascular thrombectomy: results from Alberta’s Provincial Stroke Registry (QuICR)

BackgroundThe benefit of endovascular thrombectomy (EVT) in stroke patients with a low baseline Alberta Stroke Program Early CT Score (ASPECTS, ≤5) is uncertain. We aim to use random forest regression...

Colchicine as a Modulator of Platelet Function: A Systematic Review.

The microtubule inhibitor and anti-inflammatory agent colchicine is used to treat a range of conditions involving inflammasome activation in monocytes and neutrophils, and is now known to prevent coronary and cerebrovascular events. In vitro studies dating back more than 50 years showed a direct effect of colchicine on platelets, but as little contemporary attention has been paid to this area, we have critically reviewed the effects of colchicine on diverse aspects of platelet biology in vitro and in vivo. In this systematic review we searched Embase, Medline, and PubMed for articles testing platelets after incubation with colchicine and/or reporting a clinical effect of colchicine treatment on platelet function, including only papers available in English and excluding reviews and conference abstracts. We identified 98 relevant articles and grouped their findings based on the type of study and platelet function test. In vitro, colchicine inhibits traditional platelet functions, including aggregation, clotting, degranulation, and platelet-derived extracellular vesicle formation, although many of these effects were reported at apparently supraphysiological concentrations. Physiological concentrations of colchicine inhibit collagen- and calcium ionophore-induced platelet aggregation and internal signaling. There have been limited studies of in vivo effects on platelets. The colchicine-platelet interaction has the potential to contribute to colchicine-mediated reduction in cardiovascular events, but there is a pressing need for high quality clinical research in this area.

Development of an electronic health record registry to facilitate collection of Commission on Cancer (CoC) metrics for patients undergoing surgery for breast cancer.

1549 Background: Accurate and efficient data collection is a challenge for quality improvement initiatives and clinical research. We describe the development of a custom electronic health record (EHR) based registry to automatically extract structured Commission on Cancer (CoC) axillary surgery specific metrics from a custom synoptic note template included in the operative reports for breast cancer patients undergoing surgery. Methods: The “Smart” functionality of our enterprise-based EHR system was leveraged to create a custom Smart phrase to capture axillary surgery specific variables. A multidisciplinary team developed structured data elements correlating to each axillary surgery-specific variable. These data elements were then included in a note template for the operative report. Each variable could be aggregated and converted into a single flat database through the EHR’s reporting workbench and serve as a live, prospective registry for all users within the EHR. Results: The final axillary surgery-specific note template in a synoptic format allowed for efficient and easy entry and automatic collection of breast cancer specific metrics. From initial adoption in February 2021 through December 2021, there were 1,254 patients who underwent breast surgery with axillary surgery. The operative notes allowed for automatic capture of metrics from 60.5% (n = 759) of patients. Data capture improved from 37.6% in the initial adoption period of six months to 86.2% in the last five months. Capture rate in December 2021 was 98%. Conclusions: We were able to demonstrate successful implementation of provider driven structured data entry into EHR systems that permits automatic data capture. The end result is a custom synoptic note template and a real-time, prospective registry of breast cancer-specific CoC metrics that are robust enough to use for quality improvement initiatives and clinical research.

A.1 Changes in ischemic stroke presentations and associated workflow during the first wave of the COVID-19 pandemic: A population study

Background: Pandemics may promote hospital avoidance among patients with emergencies, and added precautions may exacerbate treatment delays. Methods: We used linked administrative data and data from the Quality Improvement and Clinical Research Alberta Stroke Program – a registry capturing stroke-related data on the entire Albertan population (4.3 million) – to identify all patients hospitalized with stroke in the pre-pandemic (01/01/2016-27/02/2020) and COVID-19 pandemic (28/02/2020-30/08/2020) periods. We examined changes in stroke presentation rates and use of thrombolysis and endovascular therapy (EVT), adjusted for age, sex, comorbidities, and pre-admission care needs; and in workflow, stroke severity (National Institutes of Health Stroke Scale/NIHSS), and in-hospital outcomes. Results: We analyzed 19,531 patients with ischemic stroke pre-pandemic versus 2,255 during the pandemic. Hospitalizations/presentations dropped (weekly adjusted-incidence-rate-ratio[aIRR]:0.48,95%CI:0.46-0.50), as did population-level incidence of thrombolysis (aIRR:0.49,0.44-0.56) or EVT (aIRR:0.59,0.49-0.69). However, proportions of presenting patients receiving thrombolysis/EVT did not decline (thrombolysis:11.7% pre-pandemic vs 13.1% during-pandemic, aOR:1.02,0.75-1.38). For out-of-hospital strokes, onset-to-door times were prolonged(adjusted-coefficient:37.0-minutes, 95%CI:16.5-57.5), and EVT recipients experienced greater door-to-reperfusion delays (adjusted-coefficient:18.7-minutes,1.45-36.0). NIHSS scores and in-hospital mortality did not differ. Conclusions: The first COVID-19 wave was associated with a halving of presentations and acute therapy utilization for ischemic stroke at a population level, and greater pre-/in-hospital treatment delays. Our data can inform public health messaging and stroke care in future pandemic waves.

Avoided Costs and Economic Benefits Associated with Sponsored Clinical Trials


 
 
 
 The benefits associated with randomized clinical trials (RCTs) for patients, investigators, and sponsors are well known. However, little has been done to estimate the economic benefits related to spon- soring a RCT. Herein, a methodological analysis is proposed to assess the economic benefits and cost-savings of a RCT, namely the trial avoided costs (TAC). The TAC was considered to be cost-saving for the investigational medicinal product (IMP) (i.e., the drug adverted cost) and the diagnostic tests (i.e., procedure adverted cost) in a RCT. This tool is potentially helpful in understanding the financial impact of RCTS on healthcare institutions and provides the opportunity to invest budgets in other resources (i.e., core facilities, research infrastructure, human resources) that can increase the quality of clinical research. 
 
 
 

Clinical annotations for prostate cancer research: Defining data elements, creating a reproducible analytical pipeline, and assessing data quality.

Routine clinical data from clinical charts are indispensable for retrospective and prospective observational studies and clinical trials. Their reproducibility is often not assessed. We developed a prostate cancer-specific database for clinical annotations and evaluated data reproducibility. For men with prostate cancer who had clinical-grade paired tumor-normal sequencing at a comprehensive cancer center, we performed team-based retrospective data collection from the electronic medical record using a defined source hierarchy. We developed an open-source R package for data processing. With blinded repeat annotation by a reference medical oncologist, we assessed data completeness, reproducibility of team-based annotations, and impact of measurement error on bias in survival analyses. Data elements on demographics, diagnosis and staging, disease state at the time of procuring a genomically characterized sample, and clinical outcomes were piloted and then abstracted for 2261 patients (with 2631 samples). Completeness of data elements was generally high. Comparing to the repeat annotation by a medical oncologist blinded to the database (100 patients/samples), reproducibility of annotations was high; T stage, metastasis date, and presenceand date of castration resistance had lower reproducibility. Impact of measurement error on estimates for strong prognostic factors was modest. With a prostate cancer-specific data dictionary and quality control measures, manual clinical annotations by a multidisciplinary team can be scalable and reproducible. The data dictionary and the R package for reproducible data processing are freely available to increase data quality and efficiency in clinical prostate cancer research.