Examining current practice for the analysis and reporting of harm outcomes in phase II and III pharmacology trials: exploring methods to facilitate improved detection of adverse drug reactions

Introduction Randomised controlled trials (RCTs) provide data to help establish the harm-profile of drugs but evidence suggests that this data is underutilised and analysis practices are suboptimal. Aims To develop and assess methods for the analysis and presentation of harm outcomes in phase II/III drug trials that can facilitate the detection of adverse drug reactions (ADRs) and enable communication of informative harm-profiles.Methods A systematic review looked at current practice for collection, analysis and reporting of harm outcomes and a scoping review to identify statistical methods proposed for their analysis was undertaken. A survey of clinical trial statisticians measured awareness of methods for the analysis of harm outcomes, barriers to their use and opinions on solutions to improve practice. Alternative strategies for analysis and presentation of harm outcomes were explored. Results The review of current practice confirmed that data on harm outcomes is not being fully utilised, providing evidence of inappropriate and inconsistent practices. The scoping review revealed a broad range of methods for the analysis of both prespecified and emerging harms. The survey confirmed sub-optimal practices and while there was a moderate level of awareness of alternative approaches, use was limited. Guidance and training on more appropriate methods was unanimously supported. Recommendation were devised via consensus to encourage trialists to use visualisations for analysing and reporting harm outcomes. Of the evaluated methods for the analysis of emerging harms none were appropriate in trials ≤5000 participants with some utility in specific scenarios, recommendations for use are provided. Conclusion Clinical trial statisticians agree that there is a need to improve how we analyse and report harm outcomes in RCTs. Efforts to date have focused on prespecified harm outcomes, with little thought given to emerging harms. Several solutions for immediate adoption are proposed but there remains the need for an easy to implement, objective, signal detection approach. Guidelines for best analysis practice that are endorsed by key stakeholders would also enable a more coherent and consistent path for change.Open Acces

Scientific evidence and the toxic tort: A socio-legal study of the issues, expert evidence and judgment in Reay and Hope v. British Nuclear Fuels plc.

Providing a socio-legal analysis of the issues, expert evidence and judgment in Reay and Hope v BNFL plc., the thesis offers an insight into the complexity of the toxic tort. Starting with an overview of the history of Sellafield, the thesis reflects on the scientific and epidemiological concerns surrounding the link between childhood cancer and nuclear installations. Drawing on scientific knowledge and epistemological considerations, the thesis moves on to the difficulties of verifying causation in science and the problems of establishing causation in law. Outlining the role of the expert witness and scientific expert evidence, the thesis proceeds with a case analysis, before broaching the thorny issue of judicial decision making and in particular, the difference between the 'discovery' and 'justification' process. Moving on to the Judgment in Reay and Hope, attention is given to the potential application of probability theory to the judicial decision making process. Lasting just short of one hundred days and including the testimony of numerous scientific experts, Reay and Hope marked new ground in a number of ways; it was the first personal injury claim to test the concept of genetic damage from radiation; the only time that a Queen's Bench Division Judge had been allocated a full-time judicial assistant; and one of the first trials to endorse a satellite video link for examination of international expert witnesses. As far as judicial management is concerned, the case was a forerunner in having Counsels' Opening Statements in writing in advance of the trial, as well as having written daily submissions of key issues from plaintiffs and defendants upon conclusion of oral evidence. The circumstances that led to the trial relate to events in excess of thirty to forty years ago when the fathers of Dorothy Reay and Viven Hope were employed by the Defendants and their predecessors (the United Kingdom Atomic Energy Authority) as fitters for the Sellafield Plant. Intrinsic to the litigation was whether paternal preconception irradiation caused or materially contributed to a predisposition to cancer leading to Dorothy's death from leukaemia and Vivien Hope's non-Hodgkin's lymphoma. As a consequence of the various statutory provisions, the Plaintiffs did not need to prove negligence on the part of the Defendants. In order to succeed the Plaintiffs had to prove on the balance of probabilities that radiation from Sellafield was a material contributory cause of the Plaintiffs' disease. The fundamental issue therefore was causation. In addition to the case analysis, two pieces of empirical research were conducted for the purposes of this thesis. The first, a Social Survey (consisting of thirty four questions) was circulated to 160 members of the Academy of Experts (quantitative research); the second, a letter, involved written communication with sixty five judges from the Queen's Bench Division of the High Court (qualitative research). Underlying this socio-legal case analysis are fundamental questions with regard to existing legal principles, liability and judicial decision making

Bryn Mawr College Annual Report , 1951-52.

Includes the President\u27s Annual Reports to the Board of Directors of Bryn Mawr College for the years 1951-1952, 1952-1953, 1953-1954, 1955-1956, and 1956-1957, 1961-1962, and 1962-1963.https://repository.brynmawr.edu/bmc_annualreports/1008/thumbnail.jp

Bryn Mawr College Annual Report , 1951-52.

Includes the President\u27s Annual Reports to the Board of Directors of Bryn Mawr College for the years 1951-1952, 1952-1953, 1953-1954, 1955-1956, and 1956-1957, 1961-1962, and 1962-1963.https://repository.brynmawr.edu/bmc_annualreports/1008/thumbnail.jp

The religious and theological foundations of natural science

This thesis examines the religions and theological foundations of natural science. A mythology has arisen, both popularly and academieally, that locates the historical origins of science in the great humanistic movements of the Renaissance and Eniightenment. Conversely Calvinism and Puritenism are regarded as regressive forces, the enemies of freedom and progress, interested only in rigerons morality and otherwordly piety. Philosophically there is a wide spread divorce between faith and knowledge, religion and science, while sociologically science is seen to advance with the shaking off of the fetters of religious belief. The choice of approach was difficult. I elected for an overview rather than an exhaustive detail of one aspect. This was a choice against specialisation and the abstreative loss of concrete reality. It alse seems more consonant with the topic under consideration. The major divisions are as follows: Part I: An historical section which contextualises the study and indicates origins and motivations of modern science in religious interests - particularly Calvinism. By the nature of such a study there is a degree of ambivalence. Part II: The thesis is established by a review and brief eritique of secular philosophies of sciences. This again is ambivalent though I have scught to plant signposts to the clearer statement presented in Part IV. Part III: A survey of Christian responses to the topic. While remaining within Protestant thought I have tried to do justice to as many divergent positions as is consistent with overall coherence. Part IV: this seeks to establish the religious and theological foundations of natural science on Christian perspectival grounds - viewing religion as the crientation of the heart in a basic commitment to the universe: and seeing in the theology of the sovereignty of God, His law, the dectrines of creation and cultural activity, clear motivations to scientific activity. So this is the crux of my thesis. I also give some practical application in terms of the problems of the environment and technic, and how the fundamental issues pertain therein. I believe the basic contribution to the subject is not, in the first instance, detailed originality but in an original synthesis of materil. Detailed contributions are inter alia: 1. A critical introduction to the thought of 'Cosmonomiem' where that impinges on my topic. The study, based within the parameters of nesyeweerd's 'Cosmonomic Idea', seeks to apply cosmonomism in a more scientific field than that in which most of its proponents work. 2. More specifically I point to my suggested solution of Mackay's complementary model of science and relgions; 3. My causal-perspectival interpretation of the influence of Calvin(ism) which goes further than Merton, Neekyaas or Torrance. 4. My critique of the theological spectrum - liberal and evangelical. I point particularly to my analysis of erangelicals who are largely uncritiqued from within their own perspective and ignored by liberals, despite their vest amount of literature on science and belief; and 5. The exposure of a confusion between 'science' and 'scientia' ; and between 'religion', 'theology' and 'faith'. Inter alia my conclusions include: 1. Religion and natural science (but not theology and natural science) are not separate entities, for the former founds and activates the latter. The whole discussion of science 'and' religion/belief is a false dichotomy and therefore a pseudo-problem. 2. The religious foundation of science does not dictate/coereo scientific scientific theories. While it can give a definite 'no' to some theories, it can only give a conditional 'yes' to theories. 3. There is, strictly speaking, no 'theology of science' but a theological framework within which science can be understood. 4. Unnecessary conceptual problems have been created by seeing laws of nature as antonomous from the law of God. 5. 'The' scientific method is mythological

Bowdoin Orient v.133, no.1-25 (2001-2002)

https://digitalcommons.bowdoin.edu/bowdoinorient-2000s/1002/thumbnail.jp

The Music Sound

A guide for music: compositions, events, forms, genres, groups, history, industry, instruments, language, live music, musicians, songs, musicology, techniques, terminology , theory, music video. Music is a human activity which involves structured and audible sounds, which is used for artistic or aesthetic, entertainment, or ceremonial purposes. The traditional or classical European aspects of music often listed are those elements given primacy in European-influenced classical music: melody, harmony, rhythm, tone color/timbre, and form. A more comprehensive list is given by stating the aspects of sound: pitch, timbre, loudness, and duration. Common terms used to discuss particular pieces include melody, which is a succession of notes heard as some sort of unit; chord, which is a simultaneity of notes heard as some sort of unit; chord progression, which is a succession of chords (simultaneity succession); harmony, which is the relationship between two or more pitches; counterpoint, which is the simultaneity and organization of different melodies; and rhythm, which is the organization of the durational aspects of music