Assessment of risk of bias in the included randomized controlled trials (RCTs) has become an essential step in systematic reviews, which informs the decision of whether to rate down certainty of evidence due to risk of bias applying the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Many instruments exist for rating risk of bias in RCTs; however, even those most commonly used that developed by the Cochrane group, suffer from limitations. In particular, the revised Cochrane instrument, while reflecting methodological advances, sacrificed simplicity and practicability. The objective of this thesis is to use rigorous methodology to develop a simple-structured RCT risk of bias instrument that is easy for systematic review authors to use. The thesis begins with a chapter introducing the background and the structure of the thesis. The thesis subsequently describes a systematic survey of existing RCT risk of bias instruments for their included items, through which we collected potential candidate items for the new instrument. We then present a summary of empirical evidence investigating how the possible risk of bias issues influence the estimates of intervention effects in RCTs, which assisted with the item selection for the new instrument. Then, this thesis describes the detailed process for instrument development and providing the new instrument. This thesis ends with a chapter summarizing key findings, discussing strengths and limitations, and exploring directions for future research. / Thesis / Doctor of Philosophy (PhD)

Thesis (Ph.D.)--University of Alabama at Birmingham, 2008. / Title from PDF title page (viewed on Sept. 17, 2009). Includes bibliographical references (p. 93-97).

Background: Despite the high prevalence of ADHD, results of research on persistence rates remain scattered. Previous studies identify methodological limitations resulting in various developmental trajectories of ADHD symptoms. Methods: The aim of this scoping review is to provide an overview of the litterature on ADHD symptom persistence in young people (<25 years) with a focus on measurement assessment by QUADAS-2 and gender differences. Results: The results confirm heterogeneity both within studies regarding quality of measurements but also between studies regarding methodological choices. While this review indicates some diagnostic stability within the samples, mainly in studies with lower risk of bias, it also demonstrates symptom change with age. However, the confidence in these results is greatly limited by risk of bias. Discussion: It is questionable whether ADHD trajectories would be considered quite so heterogeneous if methods of assessing the condition were more homogeneous. Future research within the field is in great need of standardized methods and reporting standards. / Bakgrund: Trots ADHD:s höga prevalens så pekar forskning avseende symtomens varaktighet på spridda resultat. Tidigare studier föreslår metodologiska begränsningar som resulterat i olika utvecklingsförlopp för ADHD symptom. Metod: Denna översikt syftar till att kartlägga litteraturen gällande varaktigheten av ADHD symptom för unga upp till 25 år, med fokus på bedömning av mätningarna med QUADAS-2 och att undersöka könsskillnader. Resultat: Resultaten bekräftar heterogeniteten både inom studier avseende kvaliteten på mätningarna och mellan studier avseende metodologiska val. Översikten indikerar en viss diagnostisk stabilitet inom urvalen, i huvudsak för studier med lägre risk of bias, men även förändringar i symptom med ålder. Tilliten till dessa resultat är dock i hög grad begränsad av risk för bias. Diskussion: Det kan ifrågasättas om utvecklingsförloppet för ADHD skulle anses vara lika heterogent om metoderna för bedömning skulle vara mer homogena. Framtida forskning inom området är i behov av både standardiserade metoder och förbättrad rapporteringsstandard.

No description available.

Introduction: Oral mucositis is an inflammatory and frequently ulcerative side effect of cancer therapy, which has been identified by patients as the most debilitating side effect of their treatment. Mucositis is a dose limiting toxicity which exerts a substantial clinical and economic impact and negatively affects patient quality of life. The patient experience of mucositis is under-reported in the literature. To date, no interventions have been identified that have proven successful in the prevention of mucositis for patients receiving all types of therapy. Vitamin E has shown conflicting results in clinical trials. This thesis combines appraisal of the literature and empirical research,and uses lessons learned from previous studies together with the results of a feasibility study to identify a best practice model for future trials. Methods: The Cochrane risk of bias (ROB) instrument was used to assess the ROB in the studies included in the Cochrane prevention review. A sensitivity analysis was conducted after studies assessed at unclear or high risk of overall bias were excluded. A systematic review of assessment instruments was conducted which identified 50 instruments. Consideration of the appropriateness of these instruments for the use in a clinical trial for the prevention of mucositis was based on the practicality, comparability, and reproducibility, and the impact of these instruments on patients. Three of these instruments were chosen for use in a clinical trial of adults undergoing stem cell transplant. Finally, a feasibility study was designed, developed and conducted which investigated vitamin E for the prevention of mucositis in patients undergoing conditioning for bone marrow transplantation. Through lessons learned from previous studies, consultations with medical professional, the MHRA, ethics committee and suppliers, a protocol was developed for a double blind RCT. The process of gaining MHRA and ethical approval, and the repackaging of intervention and placebo products to meet MA-IMP requirements are described. Results: 130 articles were assessed for risk of bias. Only ten studies were assessed as being at low overall risk of bias. Blinding of outcome assessors and adequate allocation concealment were identified to be important considerations in the planning of future studies. Although only nine patients were recruited into the feasibility study, a number of issues affecting the design and conduct of future trials were identified. Recruitment in particular was identified to be problematic. Strategies for overcoming this problem in future trials were discussed. The methods of blinding and allocation concealment employed were found to be feasible for use in future trials. Expected adverse events patients undergoing stem cell transplantation were also reported. Conclusion: Further studies are required to investigate interventions for the prevention of mucositis. It is of upmost importance that these trials are rigorous in both their methodology and subsequent reporting in order to elicit the maximum benefit for patients taking part in clinical trials, and future patients undergoing therapy for cancer.

Introduction: Poor mental health in children and adolescents is a growing public health concern. Attention Deficit and Hyperactivity Disorder (ADHD) is a prevalent disorder in youth, impacting their mental well-being. Understanding the link between ADHD and comorbid disorders such as depression is crucial for the treatment of children and adolescents with ADHD. Aim: The aim was to perform a systematic literature review to explore the type of available studies and if there is an increased risk of depression among children and adolescents with ADHD compared to controls. Materials and methods: PubMed and PsycInfo identified 18 relevant articles (January 2014 to October 2023). Inclusion criteria required a diagnosis of ADHD and depression or relevant symptoms. The Newcastle Ottawa Scale evaluated risk of bias and data were extracted for analysis. Results: Out of 1,136,320 participants in the 18 studies, 83% reported a statistically significant higher rate of depression or depressive symptoms in individuals with ADHD. The risk varied, with hazard ratios in two larger studies ranging from 7.16 to 8.64. Risk of bias also varied, emphasizing the need for cautious interpretation. Discussion: The findings highlight the need for thorough assessment of depression symptoms in children and adolescents with ADHD. The study emphasizes the importance of updating guidelines to include specific screening for depression in this population and the potential benefits of early intervention to prevent or alleviate comorbid depression. Conclusion: This study reinforces the significant ADHD-depression association in children and adolescents, urging increased attention and intervention strategies for improved care and treatment.

<p><em>Background:</em> There is a shifting culture toward evidence-based plastic surgery. The use of high-quality evidence in patient decision-making is essential. To help achieve this goal the best evidence in the field needs to be identified, and the validity of this evidence verified.</p> <p><em>Objective:</em> This systematic review was designed to evaluate the plastic surgery literature by focusing on the prevalence of, and examining key components of quality of, Randomized Controlled Trials (RCTs) comparing surgical interventions.</p> <p><em>Methods: </em>An electronic search of the pertinent plastic surgery literature identified all RCTs published from 2000 to 2013 that compared one surgical intervention to another surgical intervention. Working in teams of two investigators independently, and in duplicate, assessed each manuscript for potential relevance and performed data extraction. Descriptive statistics, theory-driven multinomial regression, and independent samples t-test were used for data analysis.</p> <p><em>Results:</em> Of the 1664 hits obtained, 173 RCTs were included. These RCTs demonstrated the following data: 35% of RCTs performed and reported randomization properly, and 12% of RCTs reported proper allocation concealment methods. Outcome assessors were blinded in 48 (34%) RCTs, and patients blinded in 45 (26%) RCTs. Multinomial regression demonstrated that trials reporting an a <em>priori</em> sample size are significantly more likely to have a low risk of bias. One-third of trials did not state a primary outcome. The mean and median sample sizes were 73 and 43 patients respectively. Funding and conflict of interest reporting improved over time.</p> <p><em>Conclusions:</em> This systematic review establishes a baseline of the quality of evidence that currently guides practice for surgical interventions in plastic and reconstructive surgery. For the readers of plastic surgery literature to have confidence in the literature, risks of bias should be minimized and transparently reported. This will encourage plastic surgeons to apply the results and findings from published RCTs in their practice, providing patients them with the best possible treatments.</p> / Master of Science (MSc)

When using evidence from non-randomized studies (NRS) to answer questions about the effects of environmental exposures on health, it is important to assess risk of bias (RoB) of individual studies as part of determining the certainty in the body of evidence. The recently released RoB in Non-randomized Studies of Interventions (ROBINS-I) instrument has undergone careful development and piloting on NRS of health interventions. A key feature of ROBINS-I is evaluating the RoB of studies against an ideal target trial, therefore establishing a structured comparison of RoB against a reference standard. While several instruments exist to evaluate the RoB of NRS of exposure, none of them use such a structured comparison of RoB. Using the fundamental design of ROBINS-I, we explored development of a version of the instrument to evaluate RoB in studies of environmental exposure. We identified important modifications necessitating a distinct instrument: The RoB instrument for NRS of exposures. This work highlights the importance of standardized methods for environmental health decision making, proposes a modified instrument to evaluate the RoB of NRS of exposures, provides guidance for the implementation of the instrument and integration into structured evidence-synthesis frameworks (such as GRADE [Grading of Recommendations Assessment, Development and Evaluation]), and presents evidence on the reliability and validity of the instrument. The RoB instrument for NRS of exposures delivers a standardized instrument that systematic review authors and guideline developers can use to evaluate RoB in NRS of exposures. The nature of these methodological changes allow better integration of RoB assessment in the environmental health field with GRADE. / Thesis / Doctor of Philosophy (PhD) / When making a decision about interventions to reduce or remove an environmental exposure, evidence is needed to weigh the desirable and undesirable consequences of the decision. No research study is perfect. Most of the studies documenting environmental exposures cannot control for the fact that people who might be highly exposed may have different characteristics compared to those who have low levels of exposure other than just the exposure itself. For example, people exposed to more environmental air pollution living in inner cities may also be more likely to smoke or have occupational exposures that could predispose them to lung cancer than those exposed to lower levels of air pollution. Understanding limitations in studies that address those questions informs our certainty that the data represents the truth. The greater the confidence we have in the data, the more likely we are to be certain that removing or reducing exposure will lead to a desirable outcome. A tool can be used to walk people through the evaluation of limitations within each study. However, it is important that the tool evaluates the correct limitations within the study. It is also important that people using the tool can apply it reliably. Without a reliable or valid tool to evaluate the limitations of the studies, it can be difficult to inform decisions on whether or not to implement specific policies. In our study, we tested the ability of a new and well-developed tool (ROBINS for interventions) to identify the limitations in studies linking environmental exposures to health outcomes. Based on the findings from our evaluation, we modified our protocol to see if we could improve our ability to evaluate these studies of environmental exposures. We asked people with an understanding of scientific methods to independently evaluate 35 studies with our modified tool (ROBINS for exposures). We compared those responses to see whether all the reviewers came up with similar decisions and if their decision was similar or different than the conclusion they made using more commonly used tools. Based on our results, we determined that our modified tool does provide a consistent evaluation of study limitations and accurately measures the limitations present in studies of exposure. This tool can be used to inform decisions about removing or reducing one’s exposure to environmental hazards.

Background: Objectives: To produce and synthesize reliable data, systematic reviews need to adhere to rigorous methodological standards. This living meta-review aims to investigate risk of bias and open science practices in systematic reviews from the educational field published between 2022-2023. The aim of this meta-review is to get a better understanding of the current state of educational research regarding the aforementioned topics.  Methods: Eligibility criteria: We included all systematic reviews of educational interventions, instructions, and methods for all K-12 student populations with experimental or quasi-experimental designs where the outcome variables were academic performance of any kind.  Information sources: We searched through the Education Resources Information Centre (ERIC) for systematic reviews published between 2022-2023. In addition, we also hand searched four scholarly databases. Risk of Bias and FAIR principles: To assess systematic reviews risk of bias and open science practices in systematic reviews two tools were used, ROBIS - Risk of bias in systematic reviews, as well as a FAIR assessment tool.  Results: 44 studies that matched our PICOS were included in this meta-review. Out of these studies four (9%) were deemed as having a low risk of bias. The remaining 40 studies were deemed as either having high risk of bias (89%) or unclear risk of bias (2%).  Among the 44 studies included, only four studies (9%) had their data available, and none of them adhered to all of the items regarding the FAIR principles.  Discussion: This meta-review shows that only a small part of systematic reviews in education can be considered low risk of bias, and an even smaller part can be considered adhering to open science principles. Therefore, much needs to change to adapt to new scientific guidelines.

L’Afrique sub-saharienne (SSA) se caractérise par une croissance démographique rapide et une pauvreté notoire. Cette région du monde fait face à une charge de morbidité causée à la fois par les maladies infectieuses traditionnelles et par l’émergence des maladies chroniques. Les essais contrôlés randomisés (ECR) prenant en compte le contexte local sont nécessaires pour renforcer les politiques de santé publique et améliorer l’état de santé des populations. Toutefois à cause des capacités limitées de recherche, les ECR conduits en ASS doivent répondre à des questions prioritaires, les biais (erreurs systématiques) doivent être évités dans les méthodes, et les interventions de santé évaluées doivent être décrites de manière pour faciliter leur implémentation dans la pratique clinique courante. Ces mesures permettent d’éviter le « gâchis de la recherche ». Nos objectifs étaient de décrire l’épidémiologie des ECR conduits en ASS, et d’évaluer la qualité méthodologique (risque de biais) ainsi que le « reporting » des interventions évaluées. Nos travaux ont montré d’une part qu’en ASS, les ECR portent fréquemment sur les maladies à forte morbi-mortalité dans cette région ; mais que les financements des recherches effectuées proviennent surtout des pays à haut revenu (Europe occidentale et Amérique du Nord), et que les auteurs correspondants sont majoritairement affiliés aux institutions des pays à haut revenu. D’autre part, nous avons montré que les méthodes à haut risque de biais peuvent être évitées au moyen d’ajustements méthodologiques simples au coût mineur. L’amélioration de la qualité méthodologique des ECR conduits en ASS implique une large diffusion des méthodes à faible risque de biais ainsi que celle des recommandations pour la description complète des interventions. En outre, une compréhension des barrières et des facilitateurs à l’adhérence à ces méthodes et à ces recommandations est également nécessaire. / Sub-saharan Africa (SSA) is characterized by a high population growth and a significant poverty. In addition, this area deals with a burden of disease due to both traditional infection diseases and the emerging chronic diseases. Randomised controlled trials (RCTs) taking into account the local context are needed to strength health policy and to improve the population health. However, because of constraint research capacities, RCTs performed in SSA must investigate relevant research questions, biases must be avoided in methods, and health interventions evaluated must be reported completely for easing implementation in current clinical practice. Such efforts help to avoid waste of research. Our objectives were to describe the epidemiology of SSA RCTs, and then to evaluate the methodological quality as well as the reporting of evaluated interventions. On the one hand, our works highlighted that SSA RCTs mainly focused on diseases of the highest burden in that area, although they were frequently funded by high-income countries, and most of the corresponding authors were affiliated to those countries. In the other hand, we have shown that methods at high risk of bias can be avoided through simple methodological adjustments of minor cost. Improving the methodological quality of SSA RCTs implies a large dissemination of available methods at low risk of bias and guidelines on the complete reporting of interventions. Furthermore, understanding barriers and facilitators to the uptake of those methods and guidelines is equally required.