DOCSLIB.ORG

EVIDENCE BASED MEDICINE.Pdf (PDF, 8.01MB)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
EVIDENCE BASED MEDICINE.Pdf (PDF, 8.01MB) RARE BOOKS LIB. &!:bM The University of Sydney Copyright and use of this thesis This thesis must be used in accordance with the provisions of the Copyright Act 1968. Reproduction of material protected by copyright may be an infringement of copyright and copyright owners may be entitled to take legal action against persons who infringe their copyright. Section 51 (2) of the Copyright Act permits an authorized officer of a university library or archives to provide a copy (by communication or otherwise) of an unpublished thesis kept in the library or archives, to a person who satisfies the authorized officer that he or she requires the reproduction for the purposes of research or study. The Copyright Act grants the creator of a work a number of moral rights, specifically the right of attribution, the right against false attribution and the right of integrity. You may infringe the author's moral rights if you: • fail to acknowledge the author of this thesis if you quote sections from the work • attribute this thesis to another author • subject this thesis to derogatory treatment which may prejudice the author's reputation For further information contact the University's Director of Copyright Services Telephone: 02 9351 2991 e-mail: [email protected] Evidence Based Medicine: Evolution, Revolution, or Illusion? A philosophical examination of the foundations of Evidence Based Medicine Adam LaCaze A thesis submitted for the degree of Doctor of Philosophy Department of Philosophy, The University of Sydney, 2009 ii Evidence based medicine: Evolution, Revolution, or Illusion? Preface Declaration of Originality. The content of this thesis represents my own original contribution. Where the work of others is discussed it is clearly referenced. No part of this thesis has been submitted for another de­ gree. Published Papers. The contents of Chapter 2, Evidence based medicine can't be ... , is to be published in Social Epistemology (LaCaze 2008a). iii iv Evidence based medicine: Evolution, Revolution, or Illusion? Abstract Evidence based medicine (EBM) has become the dominant model for inform­ ing and justifying therapeutic decisions. There is increasing philosophical interest in whether the central claims of EBM can be justified. EBM puts forward a methodological hierarchy as a criterion for justifying therapeutic decisions. This hierarchy privileges evidence from randomised interventional studies as a basis for inference over alternative forms of evidence such as observational studies and basic medical science. Proponents of EBM have provided surprisingly little justification for their methodological claims. The early chapters of the thesis examine the justification and interpretation of the hierarchy provided by proponents of EBM. The only sustainable justi­ fication of the hierarchy is as a hierarchy of comparative internal validity. Study dBsigns higher up the hierarchy have the capacity to rule out more sources of systematic error than study designs lower down. While there are good reasons for preferring randomised interventional studies for testing the efficacy of drugs, high internal validity is not sufficient for informing thera­ peutic decisions. In the later sections of the thesis, I turn to the question of external validity. The crucial role that observational studies and basic sci­ ence play in the application of clinical research is demonstrated. In the final chapters, I argue that some of the frequentist methods currently employed to analyse clinical data are ill suited to the task of informing therapeutic deci­ sions. EBM is promoted as a rationalist turn in medicine. If EBM is to fulfil this promise, more attention is needed on the foundations of the approach. This thesis examines the foundational arguments of EBM, and observes the limits of these arguments in informing therapeutic decisions. v vi Evidence based medicine: Evolution, Revolution, or Illusion? Acknowledgements I have been fortunate to receive much support and advice in completing this work. I especially thank my supervisors. From the project's inception to its current status, Mark Colyvan, my principle supervisor, has been an exceptional guide. I have gained much from witnessing Mark's approach to philosophy, both as an enjoyable activity of intrinsic merit and as a profession. I am a grateful beneficiary of Mark's generosity, optimism and wisdom. Jason Grossman, my associate supervisor, has been an tireless source of helpful advice and optimism. I am indebted to Jason for his passionate and patient guidance through the challenging terrain of philosophy of statistics. Jason's expertise has benefited the thesis immensely. Katie Steele has been my unofficial third supervisor and confidant. Katie graciously took me under her wing early in my PhD. Our many conversations on matters of formal and informal philosophy have enlightened me as much as I have enjoyed them. For coffee, conversations, ideas and inspiration I thank Neil Cottrell, Damian Cox, Chris Cutts, Steve Duffull, Fiona Fidler, Christopher Crannell, Paul Griffiths, Margeurite La Caze, Aidan Lyon, Frank May, John Matthew­ son, Hatha McDivitt, Fabien Medvecky, Lisa Nissen, Debra Rowett, Nick Shaw, Sue Tett, Neil Thomason, Scott Tyler, Karl Winckel, Bonnie Wintle, and John Worrall. I have worked with a number of excellent pharmacists and other health professionals who have shaped the questions broached in this thesis. In par­ ticular, I thank Chris Cutts, Neil Cottrell, Ian Coombes, Steve Duffull, Debra Rowett and Frank May. Through previous work I had the opportunity to meet regularly with a group of general practitioners working in rural Queens­ land, I thank them for sharing their insights on the challenges of therapeutic decision making. Fabien Medvecky, Karl Winckel and Scott Tyler kindly read and com- Vll viii Evidence based medicine: Evolution, Revolution, or Illusion? mented on sections of the thesis in its current form. For long-term support, and for supplying all the preconditions that are impossible to list, I thank David, Maureen, Megan, Damien and Sarah. And, for her unconditional and unwavering support, I thank Sanam. Prologue Rofecoxib was a heavily marketed, and widely used, anti-inflammatory agent that was withdrawn from the worldwide market in September 2004. Now, rofecoxib is a well recognised, and widely used, example of the challenges of regulatory and clinical decision making. The rofecoxib story is striking. Rofecoxib was withdrawn following post­ marketing evidence that it increased the risk of heart attacks and strokes. Prior to this, rofecoxib had progressed through the phases of drug develop­ ment without significant hitch. That is, its risks were not uncovered until after it had passed what we accept to be the 'best tests' of a drug's effi­ cacy and safety. But this is not what is especially striking about rofecoxib. Despite the rigours of drug development, some rare, though catastrophic, ad­ verse effects can only be detected once a drug is used by a very large number of people. What is especially striking in this case is that the risks of rofe­ coxib are relatively common, both in terms of presentation and frequency. The cardiovascular effects of rofecoxib are not entirely idiosyncratic. Indeed, the possibility of an increased risk of blood clots (leading to heart attacks or strokes) is foreseeable on pharmacological grounds. And, based on current data, the frequency of heart attacks and strokes caused by rofecoxib is in the range of 30 to 80 additional events per 10,000 patients per year; by con­ trast, a 'rare' adverse effect, say, for example penicillin anaphylaxis, occurs in about one patient in every 10,000. Even more disturbing is that rofecoxib was developed in anticipation of its safety benefits. In many ways rofecoxib, and the class of drugs it belongs to, had all the hallmarks of being a success story for biomedical science. Tra­ ditional anti-inflammatory agents, despite their effectiveness in relieving pain and inflammation, pose significant public health risks due to their propen­ sity to cause gastrointestinal damage. The COX-2 inhibitor class, of which rofecoxib is a member, were developed out of an increased pharmacological IX X Evidence based medicine: Evolution, Revolution, or Illusion? and physiological understanding of how anti-inflammatories work. COX-2 inhibitors are pharmacologically targeted to work just as well as traditional anti-inflammatories while minimising gastrointestinal risks. On this basis, these drugs were eagerly awaited, and once available, heavily prescribed. The anticipated improvements in gastrointestinal safety were eventually es­ tablished. Unfortunately, the cardiovascular risks identified a couple of years later are of a similar magnitude to the gastrointestinal benefits. Rofecoxib was approved, and spent four and a half years on the market, before its propensity for grave side effects was established. Clearly, this is an undesirable state of affairs. A number of questions arise immediately, perhaps the most urgent among these is: what went wrong? The answer is unsettling; in a strong sense, nothing went wrong. Rofecoxib was tested according to the methods we accept to be our 'gold standard'. Specifically, a significant number of reasonably sized randomised controlled trails con­ ducted prior to and soon after market approval failed to demonstrate the cardiovascular risks. The VIGOR study (Bombardier et al. 2000) provided some (disputed) evidence that rofecoxib may increase the risk of heart at­ tacks and strokes, but it
Load more

Recommended publications
  • What Statistics Can and Can't Tell Us About Ourselves | the New Yorker
    What Statistics Can and Canʼt Tell Us About Ourselves | The New Yorker 2019-09-04, 1005 Books September 9, 2019 Issue What Statistics Can and Can’t Tell Us About Ourselves In the era of Big Data, we’ve come to believe that, with enough information, human behavior is predictable. But number crunching can lead us perilously wrong. By Hannah Fry September 2, 2019 https://www.newyorker.com/magazine/2019/09/09/what-statistics…3&utm_medium=email&utm_term=0_c9dfd39373-f791742ba3-42227231 Page 1 of 15 What Statistics Can and Canʼt Tell Us About Ourselves | The New Yorker 2019-09-04, 1005 Making individual predictions from collective characteristics is a risky business. Illustration by Ben Wiseman 0"00 / 23"27 Audio: Listen to this article. To hear more, download Audm for iPhone or Android. arold Eddleston, a seventy-seven-year-old from Greater Manchester, H was still reeling from a cancer diagnosis he had been given that week https://www.newyorker.com/magazine/2019/09/09/what-statistics…3&utm_medium=email&utm_term=0_c9dfd39373-f791742ba3-42227231 Page 2 of 15 What Statistics Can and Canʼt Tell Us About Ourselves | The New Yorker 2019-09-04, 1005 when, on a Saturday morning in February, 1998, he received the worst possible news. He would have to face the future alone: his beloved wife had died unexpectedly, from a heart attack. Eddleston’s daughter, concerned for his health, called their family doctor, a well-respected local man named Harold Shipman. He came to the house, sat with her father, held his hand, and spoke to him tenderly.
    [Show full text]
  • Note for the Record: Consultation on Clinical Trial Design for Ebola Virus Disease (EVD)
    Note for the record: Consultation on Clinical Trial Design for Ebola Virus Disease (EVD) A group of independent scientific experts was convened by the WHO for the purpose of evaluating a proposed clinical trial design for investigational therapeutics for Ebola virus disease (EVD) during the current outbreak, 26 May 2018 Experts Sir Michael Jacobs (Chair), Dr Rick Bright, Dr Marco Cavaleri, Dr Edward Cox, Dr Natalie Dean, Dr William Fischer, Dr Thomas Fleming, Dr Elizabeth Higgs, Dr Peter Horby, Dr Philip Krause, Dr Trudie Lang, Dr Denis Malvy, Sir Richard Peto, Dr Peter Smith, Dr Marianne Van der Sande, Dr Robert Walker, Dr David Wohl, Dr Alan Young. There are many pathogens for which there is no proven specific treatment. For some pathogens, there are treatments that have shown promising safety and activity in the laboratory and in relevant animal models but have not yet been evaluated fully for safety and efficacy in humans. In the context of an outbreak characterized by high mortality rates, the Monitored Emergency Use of Unregistered Interventions (MEURI)1 framework is a means to provide access to promising but unproven investigational therapies, but is not a means to evaluate reliably whether these compounds are actually beneficial to patients or not. In light of the current Ebola Zaire DRC outbreak with a high case fatality rate, the WHO convened an independent expert panel to evaluate investigational therapeutics for MEURI use2, and that panel affirmed the importance of moving to appropriate clinical trials as soon as possible. Against this background, a clinical trial design has been proposed with a view to generating reliable evidence about safety and efficacy.
    [Show full text]
  • Sir Richard Doll, Epidemiologist – a Personal Reminiscence with a Selected Bibliography
    British Journal of Cancer (2005) 93, 963 – 966 & 2005 Cancer Research UK All rights reserved 0007 – 0920/05 $30.00 www.bjcancer.com Obituary Sir Richard Doll, epidemiologist – a personal reminiscence with a selected bibliography The death of Richard Doll on 24 July 2005 at the age of 92 after a short illness ended an extraordinarily productive life in science for which he received widespread recognition, including Fellowship of The Royal Society (1966), Knighthood (1971), Companionship of Honour (1996), and many honorary degrees and prizes. He is unique, however, in having seen both universal acceptance of his work demonstrating smoking as the main cause of the most common fatal cancer in the world and the relative success of strategies to reduce the prevalence of the habit. In 1950, 80% of the men in Britain smoked but this has now declined to less than 30%. Richard Doll qualified in medicine at St Thomas’ Hospital in 1937, but his epidemiological career began after service in the Second World War when he worked with Francis Avery Jones at the Central Middlesex Hospital on occupational factors in the aetiology of peptic ulceration. The completeness of Doll’s tracing of previously surveyed men so impressed Tony Bradford Hill that he offered him a post in the MRC Statistical Research Unit to investigate the causes of lung cancer. For the representations of Percy Stocks (Chief Medical Officer to the Registrar General) and Sir Ernest Kennaway had prevailed against the then commonly held view that the marked rise in lung cancer deaths in Britain since 1900 was due only to improved diagnosis.
    [Show full text]
  • Whoseжlegacyжwillжreadersж Celebrateжthisжyear?
    BMJ GROUP AWARDS •ЖReviewЖtheЖshortlistsЖforЖallЖcategoriesЖatЖhttp://bit.ly/aUWoE5 Sir George Alleyne •ЖListenЖtoЖtheЖawardsЖlaunchЖpodcastЖatЖbmj.com/podcasts A highly respected figure in global health, George Alleyne has played LIFETIME ACHIEVEMENT AWARD a large part in tackling HIV and non-communicable disease and WhoseЖlegacyЖwillЖreadersЖ is an energetic promoter of health equality across the world. Currently the chancellor of the University celebrateЖthisЖyear? of the West Indies, Sir George is also the former director of the Pan Annabel FerrimanЖintroducesЖthisЖyear’sЖawardЖandЖ American Health Organization. Adrian O’DowdЖrevealsЖtheЖshortlistedЖcandidates Born in Barbados, he graduated in medicine from the University When Belgian senator Marleen Temmerman called on women in Belgium of the West Indies in 1957 and to refuse to have sex with their partners until the country’s politicians continued his postgraduate ended eight months of wrangling and formed a government, few people studies in the United Kingdom and effect on national economies. in the UK had heard of her. But readers of the BMJ were in the know and the United States. During more Sir George has served on various unsurprised. than a decade of original research, committees including the For Professor Temmerman, an obstetrician and gynaecologist, had he produced 144 publications in scientific and technical advisory won the BMJ Group’s Lifetime Achievement Award last April. In that case, scientific journals, which qualified committee of the World Health it was not for suggesting a “crossed leg strike” to end political deadlock him at just 40 years of age to be Organization Tropical Research (a solution advocated by the women of Greece in Aristophanes’ play appointed professor of medicine Programme and the Institute of Lysistrata) but for her services to women’s health in Belgium and Kenya.
    [Show full text]
  • A Cancer Control Interview With: Sir Richard Peto
    CANCER CONTROL PLANNING A CANCER CONTROL INTERVIEW WITH: SIR RICHARD PETO Sir Richard Peto is Professor of Medical Statistics & Epidemiology at the University of Oxford, United Kingdom. In 1975, he set up the Clincial Trial Service Unit in the Medical Sciences Division of Oxford University, of which he and Rory Collins are now co-directors. Professor Peto's work has included studies of the causes of cancer in general, and of the effects of smoking in particular, and the establishment of large-scale randomised trials of the treatment of heart disease, stroke, cancer and a variety of other diseases. He has been instrumental in introducing combined "meta-analyses" of results from related trials that achieve uniquely reliable assessment of treatment effects. He was elected a Fellow of the Royal Society of London in 1989, and was knighted (for services to epidemiology and to cancer prevention) in 1999. Cancer Control: How should the global target of a 25% reduction country would die before they were 70; now it is 18%. in premature mortality from non-communicable diseases (NCDs) by 2025 be interpreted? Cancer Control: NCD advocates place great emphasis on the Sir Richard Peto: I would define “premature death” as death relative burden of non-communicable diseases compared with during the middle age range of 35 to 69 years. It’s not that communicable diseases. Are they right to do so? deaths after 70 don’t matter – I’m after 70 myself and I’m Sir Richard Peto: I don’t like these things that say “More still enjoying life – but if you are going to do things to reduce people die from NCDs than from communicable disease and NCDs then it is going to be to reduce NCD mortality in your therefore NCDs are more important”.
    [Show full text]
  • A Kernel Log-Rank Test of Independence for Right-Censored Data
    A kernel log-rank test of independence for right-censored data Tamara Fern´andez∗ Arthur Gretton University College London University College London [email protected] [email protected] David Rindt Dino Sejdinovic University of Oxford University of Oxford [email protected] [email protected] November 18, 2020 Abstract We introduce a general non-parametric independence test between right-censored survival times and covariates, which may be multivariate. Our test statistic has a dual interpretation, first in terms of the supremum of a potentially infinite collection of weight-indexed log-rank tests, with weight functions belonging to a reproducing kernel Hilbert space (RKHS) of functions; and second, as the norm of the difference of embeddings of certain finite measures into the RKHS, similar to the Hilbert-Schmidt Independence Criterion (HSIC) test-statistic. We study the asymptotic properties of the test, finding sufficient conditions to ensure our test correctly rejects the null hypothesis under any alternative. The test statistic can be computed straightforwardly, and the rejection threshold is obtained via an asymptotically consistent Wild Bootstrap procedure. Extensive simulations demonstrate that our testing procedure generally performs better than competing approaches in detecting complex non-linear dependence. 1 Introduction Right-censored data appear in survival analysis and reliability theory, where the time-to-event variable one is interested in modelling may not be observed fully, but only in terms of a lower bound. This is a common occurrence in clinical trials as, usually, the follow-up is restricted to the duration of the study, or patients may decide to withdraw from the study.
    [Show full text]
  • STATISTICAL SCIENCE Volume 31, Number 4 November 2016
    STATISTICAL SCIENCE Volume 31, Number 4 November 2016 ApproximateModelsandRobustDecisions..................James Watson and Chris Holmes 465 ModelUncertaintyFirst,NotAfterwards....................Ingrid Glad and Nils Lid Hjort 490 ContextualityofMisspecificationandData-DependentLosses..............Peter Grünwald 495 SelectionofKLNeighbourhoodinRobustBayesianInference..........Natalia A. Bochkina 499 IssuesinRobustnessAnalysis.............................................Michael Goldstein 503 Nonparametric Bayesian Clay for Robust Decision Bricks ..................................................Christian P. Robert and Judith Rousseau 506 Ambiguity Aversion and Model Misspecification: An Economic Perspective ................................................Lars Peter Hansen and Massimo Marinacci 511 Rejoinder: Approximate Models and Robust Decisions. .James Watson and Chris Holmes 516 Filtering and Tracking Survival Propensity (Reconsidering the Foundations of Reliability) .......................................................................Nozer D. Singpurwalla 521 On Software and System Reliability Growth and Testing. ..............FrankP.A.Coolen 541 HowAboutWearingTwoHats,FirstPopper’sandthendeFinetti’s?..............Elja Arjas 545 WhatDoes“Propensity”Add?...................................................Jane Hutton 549 Reconciling the Subjective and Objective Aspects of Probability ...............Glenn Shafer 552 Rejoinder:ConcertUnlikely,“Jugalbandi”Perhaps..................Nozer D. Singpurwalla 555 ChaosCommunication:ACaseofStatisticalEngineering...............Anthony
    [Show full text]
  • Asymptotically Efficient Rank Invariant Test Procedures Author(S): Richard Peto and Julian Peto Source: Journal of the Royal Statistical Society
    Asymptotically Efficient Rank Invariant Test Procedures Author(s): Richard Peto and Julian Peto Source: Journal of the Royal Statistical Society. Series A (General), Vol. 135, No. 2 (1972), pp. 185-207 Published by: Wiley for the Royal Statistical Society Stable URL: http://www.jstor.org/stable/2344317 Accessed: 21-04-2017 17:23 UTC JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at http://about.jstor.org/terms Royal Statistical Society, Wiley are collaborating with JSTOR to digitize, preserve and extend access to Journal of the Royal Statistical Society. Series A (General) This content downloaded from 171.65.37.237 on Fri, 21 Apr 2017 17:23:40 UTC All use subject to http://about.jstor.org/terms J. R. Statist. Soc. A, 185 (1972), 135, Part 2, p. 185 Asymptotically Efficient Rank Invariant Test Procedures By RICHARD PETO AND JULIAN PETO Radcliffe Infirmary, Institute of Psychiatry Oxford University University of London [Read before the ROYAL STATISTICAL SOCIETY on Wednesday, January 19th, 1972, the President Professor G. A. BARNARD in the Chair] SUMMARY Asymptotically efficient rank invariant test procedures for detecting differences between two groups of independent observations are derived. These are generalized to test between two groups of independent censored observations, to test between many groups of observations, and to test between groups after allowance for the effects of concomitant variables.
    [Show full text]
  • Design and Analysis Issues in Family-Based Association
    Emerging Challenges in Statistical Genetics Duncan Thomas University of Southern California Human Genetics in the Big Science Era • “Big Data” – large n and large p and complexity e.g., NIH Biomedical Big Data Initiative (RFA-HG-14-020) • Large n: challenge for computation and data storage, but not conceptual • Large p: many data mining approaches, few grounded in statistical principles • Sparse penalized regression & hierarchical modeling from Bayesian and frequentist perspectives • Emerging –omics challenges Genetics: from Fisher to GWAS • Population genetics & heritability – Mendel / Fisher / Haldane / Wright • Segregation analysis – Likelihoods on complex pedigrees by peeling: Elston & Stewart • Linkage analysis (PCR / microsats / SNPs) – Multipoint: Lander & Green – MCMC: Thompson • Association – TDT, FBATs, etc: Spielman, Laird – GWAS: Risch & Merikangas – Post-GWAS: pathway mining, next-gen sequencing Association: From hypothesis-driven to agnostic research Candidate pathways Candidate Hierarchical GWAS genes models (ht-SNPs) Ontologies Pathway mining MRC BSU SGX Plans Objectives: – Integrating structural and prior information for sparse regression analysis of high dimensional data – Clustering models for exposure-disease associations – Integrating network information – Penalised regression and Bayesian variable selection – Mechanistic models of cellular processes – Statistical computing for large scale genomics data Targeted areas of impact : – gene regulation and immunological response – biomarker based signatures – targeting
    [Show full text]
  • Read the 2019 Issue of Observatory
    GREEN TEMPLETON COLLEGE, UNIVERSITY OF OXFORD 2019 GREEN TEMPLETON LECTURES Mapping 2,000 years of approaches to leadership RESEARCH Avoiding premature death, FinTech and the global commons GLOBAL ENGAGEMENT New faces, relaunched website and revitalised social media THIS YEAR AT GREEN TEMPLETON Welcome to Observatory, a new magazine providing a flavour of life in college over the past year. High among our list of values is our diversity. With close to 80 countries represented in our student body, we have enjoyed celebrations of the Chinese New Year and the US thanksgiving, a South American Living and barbecue, an evening of Indian music, and working in the performances of our African choir this college is always stir the emotions. Our ethos of care applies not only to people but also a source This year for to the environment. Mondays in Green Templeton are the first time, the now meat-free; a decision taken by fellows, students of great University has and staff determined to emphasise the Green in Green recruited more Templeton! This aim includes reducing single-use plastics, pride female than male buying more locally produced food and addressing fuel students. Green consumption in our properties. Templeton was Living and working in this college is a source of already ahead of the curve with 56% of our students being great pride as is evident from the pages that follow. We female. As a graduate college, some of our students arrive are ready to embrace the opportunity provided as the having already had work experience and, with an average Radcliffe Observatory Quarter is being established as entry age of 29, some come with partners and children.
    [Show full text]
  • CTSU Clinical Trial Service Unit & Epidemiological Studies Unit
    Clinical Trial Service Unit & Epidemiological Studies Unit CTSU University of Oxford Nuffield Department of Clinical Medicine 30 November 2012 CTSU, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK Tel: +44-(0)-1865-743743 Fax: +44-(0)-1865-743985 Website: www.ctsu.ox.ac.uk Dear WHO Expert Committee: I am writing to support the inclusion of fixed dose combination therapy (also known as “polypill” therapy) for secondary prevention of cardiovascular disease in the World Health Organization’s (WHO) Model List of Essential Medicines. I have over the past 30 years been a co-principal investigator in many large-scale trials and meta-analyses of drugs that reduce recurrence rates after occlusive stroke or a myocardial infarct. All these drugs are now off-patent, and together they offer substantial benefits to those who have already suffered such an event, but they are not widely enough used in low and middle-income countries, partly because affordable co-formulations are not conveniently and affordably available To achieve maximum effect, treatments to reduce the global burden of cardiovascular disease must be strategically deployed to reach a diverse population. The availability and use of fixed dose combination therapy for secondary prevention of cardiovascular disease will overcome many of the barriers that currently prevent sufficient treatment, including poor adherence, unaffordable cost and inadequate prescription of medication. Different expert panels, including the WHO and the Combination Pharmacotherapy and Public Health Research Working Group, have recognized the potential value of fixed dose combination therapy for secondary prevention of cardiovascular disease. I agree with and support the recommendation to add fixed dose combination therapy to the WHO Model List of Essential Medicines for secondary prevention of cardiovascular disease based on its relative affordability, availability, and effectiveness.
    [Show full text]
  • Papers BMJ: First Published As 10.1136/Bmj.321.7257.323 on 5 August 2000
    Papers BMJ: first published as 10.1136/bmj.321.7257.323 on 5 August 2000. Downloaded from Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of national statistics with two case-control studies Richard Peto, Sarah Darby, Harz Deo, Paul Silcocks, Elise Whitley, Richard Doll Abstract Introduction Clinical Trial Service Unit and Objective and design To relate UK national trends Medical evidence of the harm done by smoking has Epidemiological Studies Unit since 1950 in smoking, in smoking cessation, and in been accumulating for 200 years, at first in relation to (CTSU), Radcliffe lung cancer to the contrasting results from two large cancers of the lip and mouth, and then in relation to Infirmary, Oxford OX2 6HE case-control studies centred around 1950 and 1990. 1 vascular disease and lung cancer. The evidence was Richard Peto Setting United Kingdom. generally ignored until five case-control studies professor of medical Participants Hospital patients under 75 years of age relating smoking, particularly of cigarettes, to the statistics and with and without lung cancer in 1950 and 1990, plus, epidemiology development of lung cancer were published in 1950, Sarah Darby 2 in 1990, a matched sample of the local population: one in the United Kingdom and four in the United professor of medical 1465 case-control pairs in the 1950 study, and 982 States.3–6 Cigarette smoking had become common in statistics Richard Doll cases plus 3185 controls in the 1990 study. the United Kingdom, firstly among men and then Main outcome measures Smoking prevalence and emeritus professor of among women, during the first half of the 20th century.
    [Show full text]