Background: Systematic reviews (SRs) should be kept up-to-date to maintain importance in informing health care policy and practice. However, updating policies and practices of health care organizations (HCOs) that fund or conduct SRs are either unclear or non-existent. Objective: To examine updating policies and practices of relevant HCOs. Primary Research Design: An exploratory Internet survey of 195 HCOs within the international SR community. Results: The completed response rate was 58% (n=114) across 26 countries. Although 57% of organizations reported to have a formal updating policy, 59% reported updating practices as irregular. Moreover, 54% estimated more than half of their respective SRs were likely out dated. Resource constraints were a prominent barrier. Most (70%) supported centralizing updating efforts across institutions or agencies. Significance: This research provides a baseline glimpse of the state of updating among HCOs globally involved in evidence synthesis and therefore adds to a limited body of knowledge.

Background: Systematic reviews (SRs) should be kept up-to-date to maintain importance in informing health care policy and practice. However, updating policies and practices of health care organizations (HCOs) that fund or conduct SRs are either unclear or non-existent. Objective: To examine updating policies and practices of relevant HCOs. Primary Research Design: An exploratory Internet survey of 195 HCOs within the international SR community. Results: The completed response rate was 58% (n=114) across 26 countries. Although 57% of organizations reported to have a formal updating policy, 59% reported updating practices as irregular. Moreover, 54% estimated more than half of their respective SRs were likely out dated. Resource constraints were a prominent barrier. Most (70%) supported centralizing updating efforts across institutions or agencies. Significance: This research provides a baseline glimpse of the state of updating among HCOs globally involved in evidence synthesis and therefore adds to a limited body of knowledge.

‘Rapid review’ is an accelerated evidence synthesis approach that has emerged to meet the needs of knowledge users in healthcare settings who require timely input to support evidence-informed policy and practice questions. Although use of rapid reviews continues to expand, there is a paucity of research on this topic. This thesis addresses three identified knowledge gaps: 1) To address the lack of an established definition for rapid reviews, a modified Delphi process was used to pursue expert consensus on the defining characteristics of rapid reviews and an operational definition; 2) To further our understanding of the prevalent opinions and perceptions towards rapid reviews, a Q methodology was used to characterize the viewpoints of research producers and knowledge users; and, 3) To extend our knowledge on the characteristics, conduct and reporting quality of rapid reviews, compliance with currently accepted checklists (AMSTAR, PRISMA) was explored in a sample of recent rapid reviews.

Rare diseases currently impact over 250 million people worldwide, accounting for over 3.5% of the global population. Clinicians caring for individuals living with rare diseases face difficulties providing accurate diagnosis and effective treatments. The low prevalence of individual rare diseases, and limited data and constrained resources available for research, makes it challenging to develop useful clinical guidelines. The objective of this thesis is to share our experience in conducting evidence synthesis for the guideline development of a rare disease—chronic hypoparathyroidism, and show how we addressed the challenges encountered during the review process. The thesis begins by describing the challenges of evidence synthesis for guideline development in the context of rare diseases. I then present our strategies to overcome these challenges in three systematic reviews prepared for a chronic hypoparathyroidism guideline. The thesis ends by summarizing the challenges and solutions, highlighting strengths and limitations, and describing opportunities and challenges for future research in evidence synthesis for rare diseases. / Thesis / Candidate in Philosophy

The relationship between human health and nutrition is complex and limited widely accepted guidance on proper methods of evidence synthesis is available for nutritional issues. While concepts and methods of evidence synthesis in pharmacological treatments can be mostly applied to nutritional interventions, characteristics unique to the nutrition- and dietetics-related topics can lead to distinct challenges that may not be encountered in evidence synthesis of traditional medical interventions. In addition to traditional methods for pooling the results, state-of-the-art methodologies such as GRADE or network meta-analysis, while being widely used in many medical fields, their use in the field of nutrition and food science is surprisingly rare. This thesis begins with the assessment of methodological quality of available public health guidelines on sugar intake to determine the extent to which nutritional guidelines follow currently available guidance in evidence synthesis and making practice recommendations. Subsequently, we present two examples of proper implementation of evidence synthesis methods in standard pairwise meta-analysis and indirect treatment comparison and handling of relevant challenges including applications of GRADE approach. Further, this thesis presents a network meta-analysis in the field of nutrition and child health in which the challenges of conducting multiple treatment comparison are tackled and a new approach for presenting and making conclusion from network meta-analysis results is proposed. / Thesis / Doctor of Philosophy (PhD)

This thesis explores the transformations of evidence in health research synthesis studies – studies that bring together evidence from a number of research reports on the same/ similar topic. It argues that health research synthesis is a broad and intriguing field in a state of pre-formation, in spite of the fact that it may appear well established if equated with its exemplar method – the systematic review inclusive of meta-analysis. Transformations of evidence are processes by which pieces of evidence are modified from what they are in the primary study report into what is needed in the synthesis study while, supposedly, having their integrity fully preserved. Such processes have received no focused attention in the literature. Yet they are key to the validity and reliability of synthesis studies. This work begins to describe them and explore their frequency, scope and drivers. A ‘meta-scientific’ perspective is taken, where ‘meta-scientific’ is understood to include primarily ideas from the philosophy of science and methodological texts in health research, and, to a lesser extent, social studies of science and psychology of science thinking. A range of meta-scientific ideas on evidence and factors that shape it guide the analysis of processes of “data extraction” and “coding” during which much evidence is transformed. The core of the analysis involves the application of an extensive Analysis Framework to 17 highly heterogeneous research papers on cancer. Five non-standard ‘injunctions’ complement the Analysis Framework – for comprehensiveness, extensive multiple coding, extreme transparency, combination of critical appraisal and critique, and for first coding as close as possible to the original and then extending towards larger transformations. Findings suggest even lower credibility of the current overall model of health research synthesis than initially expected. Implications are discussed and a radical vision for the future proposed.

Vitamin K has a negligible effect on bone mineral density (BMD) and a large but uncertain effect on fractures. The three studies in the thesis explored uncertainty about the effect of vitamin K on fractures using the methods of economic evaluation and Bayesian meta-analysis. In study 1, a Markov probabilistic microsimulation model was developed for a hypothetical cohort of 50-year-old postmenopausal women without osteoporosis. This was a fracture incidence-based model, populated with data from the literature. It was used to examine the cost-effectiveness of two supplementation strategies over a lifetime horizon. We compared vitamin K2 (or vitamin K1) concurrent with vitamin D3 and calcium versus vitamin D3 and calcium alone. Study 2 included a systematic review, and classical and Bayesian univariate meta-analyses to determine the efficacies of the K vitamins on BMD or fractures in current and future trials. Study 3 used Bayesian bivariate random-effects meta-analysis to jointly model the treatment effects on two correlated bone outcomes. We compared the estimates from the univariate and bivariate meta-analyses and explored how these results would change the conclusions of the cost-effectiveness analysis. The strategies including vitamin K were highly cost-effective at willingness-to-pay of $50,000/QALY (quality-adjusted life year); however, the results were most sensitive to changes in the efficacy of vitamin K. The univariate meta-analyses showed large uncertainties in the anti-fracture effects of vitamin K2 in current and future trials. The bivariate 95% credible intervals were considerably narrower than those from the univariate meta-analyses. Using future odds ratios from the bivariate meta-analyses, vitamin K2 cost more than $100,000/QALY while vitamin K1 was cost-saving. Our analyses found substantial uncertainty around the estimates of the vitamin K effect on fractures. We recommend against routine use of vitamin K for fracture prevention. Bayesian bivariate meta-analysis accounts for all available information and should be considered when the treatment effects are measured on two correlated outcomes.

Vitamin K has a negligible effect on bone mineral density (BMD) and a large but uncertain effect on fractures. The three studies in the thesis explored uncertainty about the effect of vitamin K on fractures using the methods of economic evaluation and Bayesian meta-analysis. In study 1, a Markov probabilistic microsimulation model was developed for a hypothetical cohort of 50-year-old postmenopausal women without osteoporosis. This was a fracture incidence-based model, populated with data from the literature. It was used to examine the cost-effectiveness of two supplementation strategies over a lifetime horizon. We compared vitamin K2 (or vitamin K1) concurrent with vitamin D3 and calcium versus vitamin D3 and calcium alone. Study 2 included a systematic review, and classical and Bayesian univariate meta-analyses to determine the efficacies of the K vitamins on BMD or fractures in current and future trials. Study 3 used Bayesian bivariate random-effects meta-analysis to jointly model the treatment effects on two correlated bone outcomes. We compared the estimates from the univariate and bivariate meta-analyses and explored how these results would change the conclusions of the cost-effectiveness analysis. The strategies including vitamin K were highly cost-effective at willingness-to-pay of $50,000/QALY (quality-adjusted life year); however, the results were most sensitive to changes in the efficacy of vitamin K. The univariate meta-analyses showed large uncertainties in the anti-fracture effects of vitamin K2 in current and future trials. The bivariate 95% credible intervals were considerably narrower than those from the univariate meta-analyses. Using future odds ratios from the bivariate meta-analyses, vitamin K2 cost more than $100,000/QALY while vitamin K1 was cost-saving. Our analyses found substantial uncertainty around the estimates of the vitamin K effect on fractures. We recommend against routine use of vitamin K for fracture prevention. Bayesian bivariate meta-analysis accounts for all available information and should be considered when the treatment effects are measured on two correlated outcomes.

La méthode qualitative est en plein essor en médecine et particulièrement en psychiatrie, où la place du sujet, et ses représentations de la maladie et du soin sont centrales dans la prise en charge. Dans le champ de la santé de l'adolescent, de grands travaux permettent des avancées importantes dans la compréhension de la souffrance et les propositions de soins. Les méthodes qualitatives sont pourtant souvent critiquées de par leur contextualité et leur manque de pouvoir de généralisation. Une façon d'améliorer ces deux aspects consiste à appareiller les études traitant la même problématique de manière à en synthétiser les principaux résultats. Cet exercice de synthèse, notablement différent de celui de méta-analyse propre à la recherche quantitative, est réalisé depuis longtemps dans le champ des sciences humaines. Il s'agit de la métasynthèse, ou meta-ethnography. L'exercice de synthèse de la littérature est aujourd'hui de plus en plus codifié en recherche scientifique. Pourtant, certains points sont toujours en discussion - critères d'inclusion des études, critères de qualité des études-. De plus, aucune équipe psychiatrique ne s'est approprié l'outil de la métasynthèse pour l'adapter à la discipline. Ce travail décrit les étapes de la construction et de l'adaptation, à partir du corpus existant, d'une méthode rigoureuse, effective, simple à transposer et enseigner, permettant la métasynthèse de données de la littérature dans le domaine du soin psychique de l'adolescent. Il s'agit d'une part d'une réflexion théorique, épistémologique et méthodologique sur les métasynthèses et leur adaptation au champ de la clinique psychiatrique. Il s'agit d'autre part d'une construction pratique, réalisée à partir de métasynthèses effectuées sur des thématiques du soin psychique de l'adolescent. Les deux premiers articles sont deux travaux de métasynthèse. Le premier concerne l'obésité de l'adolescent. Les résultats obtenus mettent en lumière les limites de la méthode utilisée. Le deuxième article s'intéresse à la question des comportements suicidaires à l'adolescence. Les enseignements méthodologiques du premier article ont permis de perfectionner la méthode de métasynthèse. Enfin, le troisième article propose une description détaillée des étapes de la méthode construite. En discussion, nous proposons de resituer la méthode de la métasynthèse dans le contexte historique du niveau de preuve scientifique. Nous illustrons avec les articles les plus récents les liens toujours plus forts qui se construisent entre la méthode de la métasynthèse, aujourd'hui appelée Qualitative Evidence Synthesis, et la médecine fondée sur les preuves. La métasynthèse est une méthode moderne, qui montre tout son intérêt dans la recherche médicale. Notre méthode appliquée à la psychiatrie de l'adolescent est rigoureuse et fiable, et permet d'accroître la connaissance scientifique et d'améliorer la prise en charge des patients. / Qualitative research is expanding fast in medicine and especially in psychiatry, where the patient and his representations of illness and care are central to treatment. In the field of adolescent health, great work provides important advances in the understanding of suffering and care. Qualitative methods are however often criticized because of their contextuality and their lack of generalization power. One way to improve these aspects is to match studies addressing the same issue so as to synthesize the main results. From a long time, human sciences have taken hold of this exercise of synthesis, which is significantly different from meta-analysis of quantitative research. They have called this work metasynthesis or meta-ethnography. The literature synthesis exercise is now increasingly codified in scientific research. However, some points are still under discussion - For example, inclusion criteria for studies, study quality criteria -. Moreover, no metasynthesis exist in the field of psychiatric research. This work describes the stages of construction and adaptation of a simple, rigorous, efficient, easy to share and teach method, which enables to do qualitative data synthesis in the field of psychological care to adolescents. On the one hand, we propose a theoretical, epistemological and methodological reflection on metasyntheses and their adaptation to the field of psychiatric care. On the other hand, we describe a practical progression: our method is built from metasyntheses conducted on two themes of adolescent psychological care. The first two papers are both metasyntheses. The first one is about adolescent obesity. The results highlight the limitations of the method we used. The second article focuses on the issue of suicidal behavior in adolescence. The methodological lessons of the first article helped us to improve the meta-synthesis method. The third article provides a detailed description of each steps of the method. In discussion, we propose to situate the method of metasynthesis in the historical context of the scientific evidence. We illustrate with recent papers the increasingly strong links that exist between metasynthesis, now called Qualitative Evidence Synthesis, and Evidence-Based Medicine. The metasynthesis is a modern method. It shows its interest in medical research. Our method applied to adolescent psychiatry is rigorous and reliable, and can increase scientific knowledge and improve the care of patients.

Yes / Automated tools to speed up the process of evidence synthesis are increasingly apparent within health behaviour research, however, frameworks to evaluate the development and implementation of such tools are not routinely used. This commentary explores the potential of the Non-adoption, Abandonment, Scale-up, Spread and Sustainability framework (NASSS; Greenhalgh et al., 2017) for supporting automated evidence synthesis in health behaviour change by applying it to the ongoing Human Behaviour-Change Project, which aims to revolutionise evidence synthesis within behaviour change intervention research. To increase the relevance of NASSS for health behaviour change, we recommend i) terminology changes (‘condition’ to ‘behaviour’ and ‘patient’ to ‘end user’) and ii) a that it is used prospectively so that complexities can be addressed iteratively. We draw three conclusions about i) the need to specify the organisations that will use the technology, ii) identifying what to do if interdependencies fail and iii) even though we have focused on automated evidence synthesis, NASSS would arguably be beneficial for technology developments in health behaviour change more generally, particularly for invention development (e.g. for a behaviour change app).