The Evolution and Reform of Summary Trials in Canadian Military Justice

There is a place where a Canadian citizen can be sent to 30 days detention, by someone who is not a judge, without being represented by counsel, and without having a meaningful right to appeal. It is the summary trial system of the Canadian Armed Forces. This thesis analyses that system and suggests reforms. It is aimed at those who have an interest in improving the administration of military justice at the unit level but want to sufficiently understand the issues before doing so. Through a classic legal approach with elements of legal history and comparative law, this study begins by setting military justice in the Canadian legal firmament. The introductory chapter also explains fundamental concepts, first and foremost the broader notion of discipline, for which summary trial is one of the last maintaining tools. Chapter II describes the current system. An overview of its historical background is first given. Then, each procedural step is demystified, from investigation until review. Chapter III identifies potential breaches of the Charter, highlighting those that put the system at greater constitutional risk: the lack of judicial independence, the absence of hearing transcript, the lack of legal representation and the disparity of treatment between ranks. Alternatives adopted in the Canadian Armed Forces and in foreign jurisdictions, from both common law and civil law traditions, in addressing similar challenges are reviewed in Chapter IV. Chapter V analyses whether the breaches could nevertheless be justified in a free and democratic society. Its conclusion is that, considering the availability of reasonable alternatives, it would be hard to convince a court that the current system is a legitimate impairment of the individual’s legal rights. The conclusion Chapter presents options to address current challenges. First, the approach of ‘depenalization’ taken by the Government in recent Bill C-71 is analysed and criticised. The ‘judicialization’ approach is advocated through a series of 16 recommendations designed not only to strengthen the constitutionality of the system but also to improve the administration of military justice in furtherance of service members’ legal rights.

Respecting and fulfilling the right of post-primary pupils to consent to participate in trials and evaluative research: A discussion paper

This paper provides an introduction to issues surrounding the participation rights of young people in research and the implications of their growing involvement in research as well as providing a discourse on the ethical implications related to consent. The unique contribution of this paper is that it considers children’s rights in respect to the increasing opportunities for young people to take part in evaluation research. The aim of this paper, therefore, is to acknowledge the growing involvement for young people in research and the implications of ensuring that their rights of participation are respected. Secondly we will consider the children’s rights legislation and our obligations as researchers to implement this. Finally we will explore consent as an issue in its own right as well as the practicalities of accessing participants. This paper will postulate that any research about young people should involve and prioritise at all stages of the research process; including participation in decision-making. We conclude by identifying five key principles, which we believe can help to facilitate the fulfilment of post-primary pupils’ ability to consent to participate in trials and evaluative research.

Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials.

BACKGROUND: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. PATIENTS AND METHODS: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. RESULTS: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. CONCLUSIONS: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.

Systematic evaluation of patient-reported outcome (PRO) protocol content and reporting in UK cancer clinical trials: the EPiC study protocol

Introduction Emerging evidence suggests that patient-reported outcome (PRO)-specific information may be omitted in trial protocols and that PRO results are poorly reported, limiting the use of PRO data to inform cancer care. This study aims to evaluate the standards of PRO-specific content in UK cancer trial protocols and their arising publications and to highlight examples of best-practice PRO protocol content and reporting where they occur. The objective of this study is to determine if these early findings are generalisable to UK cancer trials, and if so, how best we can bring about future improvements in clinical trials methodology to enhance the way PROs are assessed, managed and reported. Hypothesis: Trials in which the primary end point is based on a PRO will have more complete PRO protocol and publication components than trials in which PROs are secondary end points.

Methods and analysis Completed National Institute for Health Research (NIHR) Portfolio Cancer clinical trials (all cancer specialities/age-groups) will be included if they contain a primary/secondary PRO end point. The NIHR portfolio includes cancer trials, supported by a range of funders, adjudged as high-quality clinical research studies. The sample will be drawn from studies completed between 31 December 2000 and 1 March 2014 (n=1141) to allow sufficient time for completion of the final trial report and publication. Two reviewers will then review the protocols and arising publications of included trials to: (1) determine the completeness of their PRO-specific protocol content; (2) determine the proportion and completeness of PRO reporting in UK Cancer trials and (3) model factors associated with PRO protocol and reporting completeness and with PRO reporting proportion.

Ethics and dissemination The study was approved by the ethics committee at University of Birmingham (ERN_15-0311). Trial findings will be disseminated via presentations at local, national and international conferences, peer-reviewed journals and social media including the CPROR twitter account and UOB departmental website (http://www.birmingham.ac.uk/cpro0r).

Virtual Clinical Trials in PET Imaging for Improved Diagnosis of and Evaluation of Therapies for Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

A critical appraisal of clinical trials conducted and subsequent drug approvals in India and South Africa

Objectives: To assess the relation between the number of clinical trials conducted and respective new drug approvals in India and South Africa. Design: Construction and analysis of a comprehensive database of completed randomised controlled clinical trials based on clinicaltrials.gov from 1 January 2005 to 31 December 2010 and drug approval data from 2006 until 2013 for India and South Africa. Setting: USA, the EU, India and South Africa. Main outcome measures: Percentage of completed randomised clinical trials for an Investigational Medicinal Product (IMP) leading to new drug approval in India and South Africa. Results: A total of 622 eligible randomised controlled trials were identified as per search criteria for India and South Africa. Clustering them for the same sponsor and the same Investigational New Drug (IND) resulted in 453 eligible trials, that is, 224 for India and 229 for South Africa. The distribution of the market application approvals between the EU/USA as well as India and South Africa revealed that out of clinical trials with the participation of test centres in India and/or South Africa, 39.6% (India) clinical trials and 60.1% (South Africa) clinical trials led to market authorisation in the EU/USA without a New Drug Application (NDA) approval in India or South Africa. Conclusions: Despite an increase in clinical trial activities, there is a clear gap between the number of trials conducted and market availability of these new drugs in India and South Africa. Drug regulatory authorities, investigators, institutional review boards and patient groups should direct their efforts to ensuring availability of new drugs in the market that have been tested and researched on their population.

Women’s involvement in clinical trials: historical perspective and future implications

The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women’s response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women’s inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue.

Effectiveness of inulin intake on indicators of chronic constipation; a meta-analysis of controlled randomized clinical trials

Background: Constipation is an intestinal dysfunction. Prebiotics, such as inulin, can improve bowel function by positively influencing intestinal biota. Aim: To analyze the scientific evidence for the role of inulin in improving bowel function in patients with chronic constipation. Methods: A meta-analysis of randomized controlled clinical trials was conducted, grounded on a literature search for the period 1995-2013 (descriptors: inulin & constipation) on PubMed, ScieLo and Central Trials Register Cochrane databases. A total of 24 articles were found, 5 of them were selected for this meta-analysis, involving 252 subjects (experimental group: n = 144, control group: n = 108). The quality of the studies was assessed using the Jadad scale. Results: We found a significant overall effect of inulin on stool frequency (DEM = 0.69, 95%CI: 0.04, 1.34), stool consistency (Bristol scale) (DEM = 1.07, 95% CI: 0.70, 1.45), transit time (DEM = -0.57, 95% CI: -0.99, -0.15) and hardness of stool (RR = 0.42, 95% CI: 0.26, 0.70). Pain and bloating do not improve with inulin intake. Conclusions: inulin intake has a positive effect on bowel function.

Low efficacy of Mebendazole Against Hookworm in Vietman: Two Randomized Controlled Trials

Abstract. Vietnam is participating in a global de-worming effort that aims to treat 650 million school children regularly by 2010. The treatment used in Vietnam is single dose oral mebendazole (Phardazone®) 500 mg. We tested the efficacy of single dose mebendazole 500 mg in the therapy of hookworm infection in a randomized double-blind placebo-controlled trial among 271 Vietnamese schoolchildren. The treatment efficacy of single dose mebendazole in children did not differ significantly from placebo, with a reduction in mean eggs per gram of feces relative to placebo of 31% (95% CI - �9 to 56%, P = 0.1). In light of these findings we then carried out a similar randomized trial comparing triple dose mebendazole, single dose albendazole, and triple dose albendazole against placebo in 209 adults in the same area. The estimated reduction in mean post-treatment eggs per gram of feces relative to placebo was 63% (95% CI 30 - 81%) for triple mebendazole, 75% (47 - 88%) for single albendazole, and 88% (58Ã - 97%) for triple albendazole. Our results suggest that single dose oral mebendazole has low efficacy against hookworm infection in Vietnam, and that it should be replaced by albendazole. These findings are of major public health relevance given the opportunity costs of treating entire populations with ineffective therapies. We recommend that efficacy of anti-helminth therapies is pilot tested before implementation of national gut worm control programs.

The Virtual International Stroke Trials Archive

Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

A series of trials in the UK as part of the Ofcom TV white spaces pilot

“Copyright © [2014] IEEE. Reprinted from 1st International Workshop on Cognitive Cellular Systems 2014 . ISBN: 978-1-4799-4139-1 .This material is posted here with permission of the IEEE. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.”

Some initial results and observations from a series of trials within the Ofcom TV white spaces pilot

“Copyright © [2015] IEEE. Reprinted from Vehicular Technology Conference (VTC Spring), 2015 IEEE 81st. ISBN: 978-1-4799-8088-8. This material is posted here with permission of the IEEE. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to pubs-permissions@ieee.org. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.”