scholarly journals Dosing Cariprazine Within and Beyond Clinical Trials: Recommendations for the Treatment of Schizophrenia

2022 ◽  
Vol 12 ◽  
Author(s):  
Elmars Rancans ◽  
Zsófia Borbála Dombi ◽  
Ágota Barabássy
Keyword(s):  
Clinical Trials ◽  
Real Life ◽  
Double Blind ◽  
Optimal Dosing ◽  
Real World Evidence ◽  
Novel Drugs ◽  
Dosing Strategies ◽  
Concomitant Medications ◽  
Dosing Strategy ◽  
The Right

Although the optimal dosing of an antipsychotic medication is known to be essential in the long-term management of schizophrenia, in case of novel drugs such as cariprazine, determining the right dosing strategy is not that simple. Without decades of experience with a particular compound, evidence regarding dosing and titration comes primarily from double-blind, placebo controlled clinical trials that are not necessarily mirroring the real-life experiences of doctors. Via summarizing data from both clinical data (n = 3275) and real-world evidence (observational study n = 116, case studies n = 29), this perspective paper aims to shed a light on the appropriate dosing strategies of cariprazine from treatment initiation through switching strategies to concomitant medications.

Dealing with Ethical Issues in Clinical Trials: The ussr in the Global Context

2021 ◽  
pp. 1-15
Author(s):  
Pavel Vasilyev ◽  
Alexander Petrenko ◽  
Veronika Tayukina
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Drug Development ◽  
Ethical Issues ◽  
Free Market ◽  
Real Life ◽  
Scientific Research ◽  
Experimental Conditions ◽  
Double Blind ◽  
Soviet Model

Abstract This paper discusses several ethical issues related to clinical trials within the Soviet system of drug development and testing, which reflected larger ideological principles of healthcare organization in the ussr, with its focus on eradicating market elements from drug development. The centralized state-controlled system was thought to combat such drawbacks of free-market drug development as high prices and aggressive advertising; also to discourage the duplication of research by numerous independent actors that was perceived to be common in capitalist countries. Another significant ethical issue was the Soviet emphasis on the unity of scientific research and clinical treatment. Their strict separation, introduced to support normative standards defined by the U.S. pharmaceutical drug testing system, was rejected in the ussr where knowledge of new treatment options came from treatment practice, not laboratory-like experimental conditions of randomized controlled double-blind trials. The Soviet design was closer to so-called ‘pragmatic trials’ that focus on solving ‘real-life’ problems in clinical practice. Not all ethical problems were successfully addressed in the Soviet model, where there were always significant gaps between neatly postulated theory and messy clinical practice. The unity of scientific research and clinical practice was difficult to achieve. Archival research shows potential ethical issues related to geographic disparities in carrying out clinical trials, and the importance of personal and informal connections in the Soviet model.

Important issues in the justification of a control treatment in paediatric drug trials

2016 ◽  
Vol 101 (10) ◽  
pp. 962-967 ◽  
Author(s):  
Lauren E Kelly ◽  
Elin Haf Davies ◽  
Agnes Saint-Raymond ◽  
Paolo Tomasi ◽  
Martin Offringa
Keyword(s):  
Decision Making ◽  
Clinical Trials ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Control Treatment ◽  
European Medicines Agency ◽  
Drug Dosing ◽  
Optimal Dosing ◽  
Dosing Strategy ◽  
Selection Of

ObjectiveThe value of comparative effectiveness trials in informing clinical and policy decisions depends heavily on the choice of control arm (comparator). Our objective is to identify challenges in comparator reasoning and to determine justification criteria for selecting a control arm in paediatric clinical trials.DesignA literature search was completed to identify existing sources of guidance on comparator selection. Subsequently, we reviewed a randomly selected sample of comparators selected for paediatric investigation plans (PIPs) adopted by the Paediatric Committee of the European Medicines Agency in 2013. We gathered descriptive information and evaluated their review process to identify challenges and compromises between regulators and sponsors with regard to the selection of the comparator. A tool to help investigators justify the selection of active controls and placebo arms was developed using the existing literature and empirical data.ResultsJustifying comparator selection was a challenge in 28% of PIPs. The following challenging paediatric issues in the decision-making process were identified: use of off-label medications as comparators, ethical and safe use of placebo, duration of placebo use, an undefined optimal dosing strategy, lack of age-appropriate safety and efficacy data, and drug dosing not supported by extrapolation of safety/efficacy evidence from other populations.ConclusionsIn order to generate trials that will inform clinical decision-making and support marketing authorisations, researchers must systemically and transparently justify their selection of the comparator arm for their study. This report highlights key areas for justification in the choice of comparator in paediatric clinical trials.

Safety and Efficacy of Sub-Antimicrobial-Dose Doxycycline Therapy in Patients with Adult Periodontitis

1998 ◽  
Vol 12 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Sebastian Ciancio ◽  
Robert Ashley
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Dosing Regimen ◽  
Periodontal Health ◽  
Efficacy Data ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Double Blind Placebo ◽  
Optimal Dosing

The objectives of the studies presented here were to assess the safety and efficacy of the adjunctive administration of sub-antimicrobial-dose doxycycline (SDD) for the treatment of adult periodontitis and to confirm the optimal dosing regimen. The studies summarized included four double-blind, placebo-controlled, randomized clinical trials, conducted over a period of 9 to 12 months. Analysis of efficacy data demonstrated that adjunctive SDD treatment resulted in: (1) increases in clinical attachment levels; (2) decreases in probing pocket depths; and (3) reductions in bleeding on probing in patients with adult periodontitis. There were no significant adverse events or unwanted long-term antimicrobial effects associated with orally administered SDD. The results of these clinical trials indicate that the adjunctive use of SDD 20 mg BID is an effective and well-tolerated regimen which can significantly improve several indices of periodontal health.

Novel Therapeutic Approaches and Targets for Treatment of Chronic Urticaria: New Insights and Promising Targets for a Challenging Disease

2020 ◽  
Vol 22 (1) ◽  
pp. 32-45
Author(s):  
Emanuela Martina ◽  
Federico Diotallevi ◽  
Tommaso Bianchelli ◽  
Matteo Paolinelli ◽  
Annamaria Offidani
Keyword(s):  
English Language ◽  
Life Experience ◽  
Case Reports ◽  
Immunosuppressive Agents ◽  
Real Life ◽  
Chronic Spontaneous Urticaria ◽  
New Targets ◽  
Current State ◽  
Pubmed Database ◽  
Novel Drugs

Background: Chronic Spontaneous Urticaria (CSU) is a disease characterized by the onset of wheals and/or angioedema over 6 weeks. The pathophysiology for CSU is very complex, involving mast cells and basophils with a multitude of inflammatory mediators. For many years the treatment of CSU has been based on the use of antihistamines, steroids and immunosuppressive agents with inconstant and frustrating results. The introduction of omalizumab, the only licensed biologic for antihistamine- refractory CSU, has changed the management of the disease. Objective: The aim of this article is to review the current state of the art of CSU, the real-life experience with omalizumab and the promising drugs that are under development. Methods:: An electronic search was performed to identify studies, case reports, guidelines and reviews focused on the new targets for the treatment of chronic spontaneous urticaria, both approved or under investigation. The search was limited to articles published in peer-reviewed journals in the English Language in the PubMed database and trials registered in Clinicaltrials.gov. Results:: Since the advent of omalizumab, the search for new therapies for chronic spontaneous urticaria has had a new impulse. Anti-IgE drugs will probably still be the cornerstone of therapy, but new targets may prove effective in syndromic urticaria or refractory cases. Conclusion:: Although omalizumab has been a breakthrough in the treatment of CSU, many patients do not completely get benefit and even require more effective treatments. Novel drugs are under investigation with promising results.

Prerequisites to support high-quality clinical trials in children and young people

2020 ◽  
pp. archdischild-2019-318677
Author(s):  
Steven Hirschfeld ◽  
Florian B Lagler ◽  
Jenny M Kindblom
Keyword(s):  
Clinical Trials ◽  
Healthcare Delivery ◽  
Paediatric Population ◽  
Ecosystem Functions ◽  
Healthcare Delivery System ◽  
High Quality ◽  
Children And Young People ◽  
The Right ◽  
Support Decision Making

Children have the right to treatment based on the same quality of information that guides treatment in adults. Without the proper evaluation of medicinal products and devices in paediatric clinical trials that are designed to meet the rigorous standards of the competent authorities, children are discriminated from advances in medicine. There are regulatory, scientific and ethical incentives to address the knowledge gap regarding efficacy and safety of medicines in the paediatric population. High-quality clinical trials involving children of all ages can generate data that will ultimately close the knowledge gaps and support decision making.For clinical trials that enrol children, the needs are specialised and often resource intensive. Prerequisites for successful paediatric clinical trials are personnel with training in both paediatrics and neonatology and expertise in clinical trials in these populations. Moreover, national and international networks for efficient collaboration, dissemination of information, and sharing of resources and expertise are also needed, together with competent, efficient and high-quality local infrastructure with effective processes. Monitoring and oversight bodies with the relevant competence, including expertise in paediatrics, is also an important prerequisite for paediatric clinical trials. Compromise in any of these components will compromise the downstream results.This paper discusses the structures and competences needed in order to perform effective, high-quality paediatric clinical trials with the ultimate goal of better medicines and treatments for children. We propose a model of examining the process as a series of components that each has to be optimised, then all the components are actively optimised to function together as an ecosystem, and the resulting ecosystem functions well with the general research system and the healthcare delivery system.

scholarly journals Neural alignment predicts learning outcomes in students taking an introduction to computer science course

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meir Meshulam ◽  
Liat Hasenfratz ◽  
Hanna Hillman ◽  
Yun-Fei Liu ◽  
Mai Nguyen ◽  
...  
Keyword(s):  
Computer Science ◽  
Learning Outcomes ◽  
Brain Activity ◽  
Activity Patterns ◽  
Real Life ◽  
Final Exam ◽  
Neural Representations ◽  
Real Life Setting ◽  
The Right ◽  
Mri Study

AbstractDespite major advances in measuring human brain activity during and after educational experiences, it is unclear how learners internalize new content, especially in real-life and online settings. In this work, we introduce a neural approach to predicting and assessing learning outcomes in a real-life setting. Our approach hinges on the idea that successful learning involves forming the right set of neural representations, which are captured in canonical activity patterns shared across individuals. Specifically, we hypothesized that learning is mirrored in neural alignment: the degree to which an individual learner’s neural representations match those of experts, as well as those of other learners. We tested this hypothesis in a longitudinal functional MRI study that regularly scanned college students enrolled in an introduction to computer science course. We additionally scanned graduate student experts in computer science. We show that alignment among students successfully predicts overall performance in a final exam. Furthermore, within individual students, we find better learning outcomes for concepts that evoke better alignment with experts and with other students, revealing neural patterns associated with specific learned concepts in individuals.

scholarly journals Non-Steroidal Anti-Inflammatory Drugs in Colorectal Cancer Chemoprevention

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 594
Author(s):  
Jadwiga Maniewska ◽  
Dagmara Jeżewska
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Clinical Trials ◽  
Cancer Chemoprevention ◽  
Tumor Cell Proliferation ◽  
Double Blind ◽  
New Approach ◽  
Randomized Controlled ◽  
Inflammatory Drugs ◽  
Chemopreventive Effect

Since colorectal cancer is one of the world’s most common cancers, studies on its prevention and early diagnosis are an emerging area of clinical oncology these days. For this study, a review of randomized controlled, double-blind clinical trials of selected NSAIDs (aspirin, sulindac and celecoxib) in chemoprevention of colorectal cancer was conducted. The main molecular anticancer activity of NSAIDs is thought to be a suppression of prostaglandin E2 synthesis via cyclooxygenase-2 inhibition, which causes a decrease in tumor cell proliferation, angiogenesis, and increases apoptosis. The lower incidence of colorectal cancer in the NSAID patients suggests the long-lasting chemopreventive effect of drugs studied. This new approach to therapy of colorectal cancer may transform the disease from a terminal to a chronic one that can be taken under control.

scholarly journals Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Peter Witters ◽  
Andrew C. Edmondson ◽  
Christina Lam ◽  
Christin Johnsen ◽  
Marc C. Patterson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Randomized Study ◽  
Short Term ◽  
Double Blind ◽  
Natural History Study ◽  
Natural History Studies ◽  
Carbohydrate Deficient Transferrin ◽  
Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

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