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Systematic reviews (SR) and meta-analysis (MA) of randomised controlled trials (RCT) are the trustworthy sources of evidence. However, most systematic reviews focus on pair-wise comparisons. Network-meta-analysis (NMA) offers quantitative methods of integrating data from all the available comparisons of many different treatments for each outcome. In a systematic review of interventions, Summary of Findings (SoF) tables present the main findings of a review in a transparent and simple form. However, it is unknown how to present NMA findings in a tabular format. Moreover, systematic reviews and meta-analysis of interventions can summarize bodies of evidence from randomized and non-randomized studies (NRS). Integrating both sources of evidence in a single study can be challenging particularly in the context of assessing the certainty of the evidence, as well as presenting findings of both RCTs and NRS sources of evidence. In our study, we described how 276 NMA were conducted and how authors reported their main findings. We also conducted 32 interviews with users of NMAs and we designed two final NMA-SoF tables. Furthermore, we conducted two systematic reviews that included RCTs and NRS to address methodological challenges. Based on our results, we developed two NMA-SoF table formats to report the main findings of NMAs. The final format was appealing for users and allowed them to better understand NMA findings. Assessment of quality of individual NRS remains challenging and further research is needed to increase its appropriateness in systematic reviews of NRS. We determined that quality assessment of individual NRS was particularly challenging to implement due to the complexity of NRS evaluation tools. Our evaluation revealed that effect estimates of RCTs and NRS were better presented separately. / Thesis / Doctor of Philosophy (PhD) / Systematic reviews (SR) are a summary of studies that address a particular clinical question. Frequently, SRs are complemented with a statistical aggregation of results of individual studies to produce a single estimate. Summary of findings (SoF) tables are designed to present the most relevant information of systematic reviews and meta-analysis. However, it is unknown how to present network meta-analysis (NMA) findings in SoF tables. Another challenge relates to the integration of randomized controlled trials (RCTs) and non-randomized (NRS) studies. Methodological challenges in systematic reviews need to be addressed through careful research. In our study, we appraised how NMA were conducted, and how they presented their main findings. We designed two versions of SoF tables to present NMA findings. Moreover, we conducted two systematic reviews that included RCTs and NRS to address potential challenges in analyzing and presenting their findings.

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.

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Background Selective reporting of outcomes within a published study based on their nature or direction can result in systematic differences between reported and unreported data. Direct evidence of outcome reporting bias is limited to case reports. Objective To study empirically the nature of outcome reporting bias in randomised controlled trials (RCTs). Methods Three cohorts of RCTs were identified: PubMed-indexed RCTs published in December 2000; trial protocols approved by a Danish ethics committee from 1994-95; and trial protocols funded by a government agency in Canada from 1990-98. Data on reported and unreported outcomes were recorded from all trial publications and a survey of authors. An outcome was considered incompletely reported if insufficient data were presented for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial, and then pooled using a random effects meta-analysis. Protocols and publications were also reviewed for discrepancies in primary outcome reporting. Results 519 trials with 10,557 outcomes, 102 trials with 3613 outcomes, and 48 trials with 1390 outcomes were identified for the PubMed, ethics committee, and funding agency cohorts respectively. 22%-35% of outcomes per parallel group study were, on average, incompletely reported for meta-analysis. Fully reported outcomes had a two- to three-fold higher odds of being statistically significant compared to incompletely reported outcomes. The most common reasons given for omitting outcomes included a lack of clinical importance, lack of statistical significance, and space constraints. Major discrepancies between primary outcomes in protocols and publications were found in one half of trials. Discussion and conclusions The reporting of trial outcomes is frequently inadequate for meta-analysis; is biased to favour statistical significance; and is inconsistent with pre-specified protocol outcomes. Unacknowledged modifications to outcomes specified in trial protocols constitute scientific misconduct. Meta-analyses may therefore produce inflated and unreliable estimates of treatment effect.

Background: Dialysis is an intervention that involves the use of fairly advanced technology and is fairly expensive. Patients and health care funders are increasingly demanding evidence for the effectiveness for such high technology high cost interventions. While dialysis therapy has improved immediate prognosis in patients with kidney failure, the long-term survival of patients on chronic renal replacement therapy (dialysis or renal transplantation) is much lower than that of the general population and the mortality rates remain high for patients with acute renal failure needing dialysis. There are considerable variations between different countries and even between the dialysis centres within the same country with regards to the selection of the primary type of dialysis (haemodialysis or peritoneal dialysis) and in the different methods or equipment used to perform the various components of these various modalities. It is possible that variations in clinical practice are associated with variations in clinical outcomes such as mortality and morbidity. It is then important to identify the best practices from the various variations in current use and implementing these best practices may reduce morbidity and mortality of these patients. Methods: Systematic reviews, identifying and including only randomised trials, focusing on key clinical policy decision points in the dialysis process were undertaken. The review of literature was done in a systematic way according to a detailed scientific methodology. For all of the systematic reviews, a detailed protocol was written and agreed to by the authors of the review. The protocol detailed the clinical question, the types of studies, participants, interventions and outcomes to be included, search strategy and the statistical methods to be employed. Relevant randomised studies were then identified by systematically searching the electronic medical databases and reference lists of published studies; data relevant to predetermined outcome measures were extracted and where appropriate summary statistics were derived from meta-analysis. Recommendations and implications for clinical practice and future research studies were made following each review. The areas of dialysis policy reviewed were (1) Comparison of high-flux versus low-flux haemodialysis (HD) membranes for patients with end-stage renal disease (ESRD), (2) Comparison of extracorporeal renal replacement therapy technologies for patients with ESRD, (3) Comparison of intermittent (IRRT) and continuous renal replacement therapy (CRRT) for acute renal failure (ARF) in adults, (4) Comparison of antimicrobial interventions for the prevention of HD catheter related infections, (5) Comparison of continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) for patients with ESRD, and (6) Comparison of treatment measures for depression in dialysis patients. Conclusions: As the currently available evidence has not demonstrated superiority with high-flux membranes with respect to important clinical outcomes such as mortality, quality of life and hospitalisation, it is not possible to recommend the use of these membranes in preference to low-flux membranes. It has not been possible at present to demonstrate with the current evidence available that convective modalities (HF, HDF or AFB) have significant advantages over HD with regard to clinically important outcomes of mortality, dialysis-related hypotension and hospitalisation. It is not therefore possible to recommend the use of one modality in preference to the other. In ARF patients who are haemodynamically stable, the RRT modality does not appear to influence important patient outcomes, and therefore the preference for CRRT over IRRT in such patients does not appear justified in the light of available evidence. CRRT was shown to achieve better haemodynamic parameters such as MAP. APD appears to be more beneficial than CAPD, in terms of reducing peritonitis rates and with respect to certain social issues that impact on patients' quality of life. Further, adequately powered trials are required to confirm the benefits for APD found in this review and detect differences with respect to other clinically important outcomes that may have been missed by the trials included in this review due to their small size and short follow-up periods. APD may however be considered advantageous in select group of patients such as in the younger PD population and those in employment or education due to its psychosocial advantages. Firm conclusions on the efficacy of treatment measures for depression in chronic dialysis patients cannot be made as we identified only one small RCT that was of short duration. Current screening tools for depression are recognised to have poor specificity in the medically ill due to overlap of somatic symptoms of the medical illness. The development of a valid diagnostic tool would be helpful. The systematic reviews in general highlighted the paucity of large-scale randomised trials in nephrology even on topics of great practical relevance such as depression in dialysis. In many of the areas assessed adequate conclusions could not be reached as there was a lack of large-scale well designed randomised controlled trials raising the possibility that important clinical differences between the interventions assessed may have been missed due to Type 2 statistical error. We identified numerous RCTs which were small in size looking at surrogate end-points such as molecular markers of inflammation, especially in the areas of membrane flux and extracorporeal RRT technologies. Unfortunately benefits with surrogate end-points do not necessarily translate to better clinical outcomes. The urgent need of the hour is to conduct well-designed large scale RCTs in major areas of clinical importance such as the use of extracorporeal renal replacement therapy technologies looking at hard clinical end-points such as mortality, hospitalisation and quality of life.

Source: Masters Abstracts International, Volume: 47-06, page: 3373. Advisers: Kelly Volcik; Sarah Baraniuk. Includes bibliographical references.

Thesis (M.N.(Clinical))--Victoria University of Wellington, 2009. / Includes bibliographical references.

Thesis (M.Sc.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Master of Science in Clinical Epidemiology, Department of Public Health Sciences. Title from pdf file main screen (viewed on February 23, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0972. Adviser: Benjamn C. Amick, III. Includes bibliographical references.