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Journal of Clinical Epidemiology Jan 2021There is considerable actual and potential waste in research. Evidence-based research ensures worthwhile and valuable research. The aim of this series, which this...
OBJECTIVES
There is considerable actual and potential waste in research. Evidence-based research ensures worthwhile and valuable research. The aim of this series, which this article introduces, is to describe the evidence-based research approach.
STUDY DESIGN AND SETTING
In this first article of a three-article series, we introduce the evidence-based research approach. Evidence-based research is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner.
RESULTS
We describe evidence-based research and provide an overview of the approach of systematically and transparently using previous research before starting a new study to justify and design the new study (article #2 in series) and-on study completion-place its results in the context with what is already known (article #3 in series).
CONCLUSION
This series introduces evidence-based research as an approach to minimize unnecessary and irrelevant clinical health research that is unscientific, wasteful, and unethical.
Topics: Biomedical Research; Clinical Trials as Topic; Ethics, Research; Evidence-Based Medicine; Humans; Needs Assessment; Reproducibility of Results; Research Design; Systematic Reviews as Topic; Treatment Outcome
PubMed: 32979491
DOI: 10.1016/j.jclinepi.2020.07.020 -
Frontiers in Public Health 2022Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19... (Review)
Review
Decentralized clinical trials (DCTs) are studies in which the need for patients to physically access hospital-based trial sites is reduced or eliminated. The CoViD-19 pandemic has caused a significant increase in DCT: a survey shows that 76% of pharmaceutical companies, device manufacturers, and Contract Research Organizations adopted decentralized techniques during the early phase of the pandemic. The implementation of DCTs relies on the use of digital tools such as e-consent, apps, wearable devices, Electronic Patient-Reported Outcomes (ePRO), telemedicine, as well as on moving trial activities to the patient's home (e.g., drug delivery) or to local healthcare settings (i.e., community-based diagnosis and care facilities). DCTs adapt to patients' routines, allow patients to participate regardless of where they live by removing logistical barriers, offer better access to the study and the investigational product, and permit the inclusion of more diverse and more representative populations. The feasibility and quality of DCTs depends on several requirements including dedicated infrastructures and staff, an adequate regulatory framework, and partnerships between research sites, patients and sponsors. The evaluation of Ethics Committees (ECs) is crucial to the process of innovating and digitalizing clinical trials: adequate assessment tools and a suitable regulatory framework are needed for evaluation by ECs. DCTs also raise issues, many of which are of considerable ethical significance. These include the implications for the relationship between patients and healthcare staff, for the social dimension of the patient, for data integrity (at the source, during transmission, in the analysis phase), for personal data protection, and for the possible risks to health and safety. Despite their considerable growth, DCTs have only received little attention from bioethicists. This paper offers a review on some ethical implications and requirements of DCTs in order to encourage further ethical reflection on this rapidly emerging field.
Topics: Humans; COVID-19; Delivery of Health Care; Pandemics; Telemedicine; Clinical Trials as Topic
PubMed: 36590004
DOI: 10.3389/fpubh.2022.1081150 -
Diabetes Care Mar 2019This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of...
OBJECTIVE
This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials.
RESEARCH DESIGN AND METHODS
In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications.
RESULTS
Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51-78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25-56), for each 10 percentage points lower TIR ( < 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics.
CONCLUSIONS
Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics-especially when measured with continuous glucose monitoring-add value as outcome measures in many studies.
Topics: Adult; Blood Glucose; Blood Glucose Self-Monitoring; Clinical Trials as Topic; Diabetes Complications; Diabetes Mellitus; Disease Progression; Female; Glycated Hemoglobin; Humans; Longitudinal Studies; Male; Middle Aged; Outcome Assessment, Health Care; Patient Care Planning; Prognosis; Research Design; Time Factors; Treatment Outcome
PubMed: 30352896
DOI: 10.2337/dc18-1444 -
Seizure Jan 2017Status epilepticus (SE) requires not only urgent symptomatic treatment with antiepileptic drugs but also rapid identification and treatment of its cause. This narrative... (Review)
Review
PURPOSE
Status epilepticus (SE) requires not only urgent symptomatic treatment with antiepileptic drugs but also rapid identification and treatment of its cause. This narrative review summarizes the most important advances in classification and treatment of SE.
METHOD
Data sources included MEDLINE, EMBASE, ClinicalTrials.gov, and back tracking of references in pertinent studies, reviews, and books.
RESULTS
SE is now defined as "a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures." A new diagnostic classification system of SE introduces four axes: semiology, aetiology, EEG correlates, and age. For the acute treatment intravenous benzodiazepines (lorazepam, diazepam, clonazepam) and intramuscular midazolam appear as most effective treatments for early SE. In children, buccal or intranasal midazolam are useful alternatives. In established SE intravenous antiepileptic drugs (phenytoin, valproate, levetiracetam, phenobarbital, and lacosamide) are in use. Treatment options in refractory SE are intravenous anaesthetics; ketamine, magnesium, steroids and other drugs have been used in super-refractory SE with variable outcomes.
CONCLUSION
Over the past 25 years major advances in definition, classification and understanding of its mechanisms have been achieved. Despite this up to 40% of patients in early status cannot be controlled with first line drugs. The treatment of super-refractory status is still an almost evidence free zone.
Topics: Clinical Trials as Topic; Databases, Factual; Electroencephalography; History, 20th Century; History, 21st Century; Humans; Status Epilepticus
PubMed: 27890484
DOI: 10.1016/j.seizure.2016.11.001 -
Current Treatment Options in Oncology Jul 2021Clinical trials play a critical role in discovering new treatments, but the path to regulatory approval can be cumbersome and time consuming. Efforts to increase the... (Review)
Review
Clinical trials play a critical role in discovering new treatments, but the path to regulatory approval can be cumbersome and time consuming. Efforts to increase the efficiency and interpretability of clinical trials within the neuro-oncology community have focused on standardization of response assessment, development of consensus guidelines for clinical trial conduct, decentralization of clinical trials, removal of barriers to clinical trial accrual, and re-examination of patient eligibility criteria.
Topics: Clinical Trials as Topic; Humans; Medical Oncology; Nervous System Neoplasms; Outcome Assessment, Health Care; Practice Guidelines as Topic; Research Design
PubMed: 34213625
DOI: 10.1007/s11864-021-00875-8 -
The Quarterly Journal of Nuclear... Dec 2019In radiomics, quantitative features that describe phenotypic tumor characteristics are derived from radiographic images. Because radiomics generates information from... (Review)
Review
In radiomics, quantitative features that describe phenotypic tumor characteristics are derived from radiographic images. Because radiomics generates information from routine medical images, it is a powerful way to non-invasively examine the spatial and temporal heterogeneity of disease, and thus has potential to significantly impact clinical trial design, execution, and ultimately patient care. The aim of this review article is to discuss how radiomics may address some of the current challenges in clinical randomized control trials, and the difficulties of integrating robust and repeatable radiomics analysis into trial design. Each step of the radiomics process, including image acquisition and reconstruction, image segmentation, feature extraction, and computational analysis, requires extensive standardization in order to be successfully incorporated into clinical trials and inform clinical decision making. By addressing these challenges, the potential of radiomics may be realized.
Topics: Clinical Trials as Topic; Diagnostic Imaging; Humans; Image Processing, Computer-Assisted; Neoplasms
PubMed: 31527581
DOI: 10.23736/S1824-4785.19.03217-5 -
Clinical Microbiology and Infection :... Jan 2019The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step. (Review)
Review
BACKGROUND
The development of an in vitro diagnostic test from a good idea to a clinically relevant tool takes several steps, with more stringent requirements at every step.
OBJECTIVES
This article aims to summarize the necessary questions to be asked about a test and to illustrate study designs answering these questions. We also aim to relate Regulation (EU) 2017/746 to the needs of evidence-based diagnostic testing, where applicable.
SOURCES
We used literature on evidence-based diagnostics, a text book on clinical trials in the development and marketing of medical devices and the English version of Regulation 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices.
CONTENT
The combination of different test uses and different stages of development determine the required test characteristics and suitability of study designs. In an earlier stage of test development it may be crucial to know whether a test can differentiate diseased persons from healthy controls, although this tells us little about how a test will perform in practice. Later stages focus on the diagnostic accuracy of a test in a clinically relevant situation. However, a test that perfectly distinguishes between patients with and without a certain condition may still have little effect on patient outcomes. Therefore, randomized controlled trials of testing may be needed, as well as post-marketing monitoring.
IMPLICATIONS
Both researchers and users of tests need to be aware of the limitations of diagnostic test accuracy and realize that accuracy is only indirectly linked to people's health status.
Topics: Clinical Trials as Topic; Diagnostic Techniques and Procedures; Evaluation Studies as Topic; Reagent Kits, Diagnostic; Reproducibility of Results; Research Design
PubMed: 29906592
DOI: 10.1016/j.cmi.2018.06.011 -
Journal of Surgical Oncology Jan 2022Treatment of regional lymph nodes in melanoma has been controversial for more than a century. A series of clinical trials evaluating elective lymph node dissection and... (Review)
Review
Treatment of regional lymph nodes in melanoma has been controversial for more than a century. A series of clinical trials evaluating elective lymph node dissection and then sentinel lymph node biopsy have helped define the current standard of care. These trials resulted in increasingly selective application of surgical intervention for regional lymph nodes in melanoma. First by focusing on optimal candidates for elective lymph node dissection and then by identifying patients through sentinel lymph node biopsy. The current standard of sentinel lymph node biopsy for appropriately selected patients and nodal observation for many patients, even with involved sentinel nodes is both more accurate in staging and much less morbid than what came before.
Topics: Clinical Trials as Topic; Clinical Trials, Phase III as Topic; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Melanoma; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Sentinel Lymph Node Biopsy
PubMed: 34897707
DOI: 10.1002/jso.26744 -
Hormone and Metabolic Research =... Dec 2017Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between... (Review)
Review
Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms. In this clinical scenario, the recently published SPARTACUS trial aimed at answering the question whether AVS in fact is superior for differential diagnosis in comparison to imaging of the adrenal glands. In this multicenter study, patients were randomized to be treated according to AVS results or based on abdominal imaging only. Clinical outcome in both patient groups after one year was reported as not different. While the study results found broad interest, it also stirred considerable controversies. This review provides an overview on the different views regarding the outline of the SPARTACUS trial and the interpretation of its results.
Topics: Adrenal Glands; Aldosterone; Blood Specimen Collection; Clinical Trials as Topic; Diagnosis, Differential; Humans; Hyperaldosteronism; Tomography, X-Ray Computed
PubMed: 29165736
DOI: 10.1055/s-0043-120524 -
Seminars in Liver Disease Nov 2017Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months,... (Review)
Review
Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months, treatment options are limited and ineffective. Recent advances on the understanding of the pathomechanisms of AH have identified numerous potential targets for new therapeutic interventions. Many of those targets are currently under preclinical testing and/or in human clinical trials for nonalcoholic steatohepatitis. Thus, the field of AH should be ready to launch new efforts and targeted clinical trials for this underserved patient population. There are remaining challenges in designing clinical trials in AH that include definition of the severity of disease, common data elements in clinical trial design, and selection of clinically meaningful endpoints. Future efforts and consensus meetings between regulatory agencies, academic and clinical experts, and industry will be instrumental to advance this emerging and greatly needed field of clinical investigations.
Topics: Clinical Trials as Topic; Hepatitis, Alcoholic; Humans; Research Design; Treatment Outcome
PubMed: 29272895
DOI: 10.1055/s-0037-1608788