What is a cause? Dr Brendan Clarke. UCL Department of Science and Technology Studies

Similar documents
Faculty of Medicine. Introduction to Community Medicine Course ( ) Unit 4 Epidemiology. Introduction to Epidemiology.

Can Mechanism plus Statistical Relevance add up to Good Enough Causation?

Mechanisms and the evidence hierarchy

Bradford Hill Criteria for Causal Inference Based on a presentation at the 2015 ANZEA Conference

Introduction to Epidemiology. Introduction to Epidemiology. Introduction to Epidemiology. Introduction to Epidemiology. Introduction to Epidemiology

ASSOCIATION & CAUSATION IN EPIDEMIOLOGICAL STUDIES. Dr. Sireen Alkhaldi Community Medicine, 2016/ 2017 The University of Jordan

Epidemiology. Chapter 2 Causal Concepts

6 December 2012 Last updated at 01:15 GMT. Cancer's global toll

epidemiology: the big picture Madhukar Pai, MD, PhD McGill University

Modelling Experimental Interventions: Results and Challenges

Causal Inference Framework for Considering the Cardiovascular Risks Associated with Ortho Evra

LESSON 1.4 WORKBOOK. How can we identify carcinogens?

What Constitutes Reliable Evidence? Rare Diseases and Clinical Trials

Scientific Method in Vaccine History

Epidemiologic Methods I & II Epidem 201AB Winter & Spring 2002

"Games and the Good" Strategy

Epidemiologic Causation: Jerome Cornfield s Argument for a Causal Connection between Smoking and Lung Cancer

Human Herpes Viruses (HHV) Mazin Barry, MD, FRCPC, FACP, DTM&H Assistant Professor and Consultant Infectious Diseases KSU

VIRUSES AND CANCER Michael Lea

Do Viruses Play a Role in Childhood Leukaemia?

Epidemiology 101. Nutritional Epidemiology Methods and Interpretation Criteria

Causation Assessment and Methodology

SMALL n IMPACT EVALUATION. Howard White and Daniel Phillips 3ie

An Overview. Paediatric Oncology. In Malawi

THE EPISTEMOLOGICAL FUNCTION OF HILL S CRITERIA

Assessing Vaccine Safety Post Licensure. Neal A. Halsey Johns Hopkins University

Loss of early innate immune control leads to severe EBV

Hosts. New Treatments for Cancer

Seeing Versus Doing: Two Modes of Accessing Causal Knowledge

Causality and counterfactual analysis

In Vitro and In Vivo Studies with Epstein-Barr

LESSON 2.4 WORKBOOK. How can we prove infection causes disease?

Disease Detectives. The starred questions can be used as tie breakers. Total Points: 212

Medical Inference: Using Explanatory Coherence to Model Mental Health Assessment and Epidemiological Reasoning Paul Thagard paulthagard.

Clinical Aspect and Application of Laboratory Test in Herpes Virus Infection. Masoud Mardani M.D,FIDSA

Principles of Disease and Epidemiology Chapter 14. Biology 1009 Microbiology Johnson-Summer 2003

Causality in medicine with particular reference to the viral causation of cancers

Determination of the temporal pattern and importance of BALF1 expression in Epstein-Barr viral infection

Complications of Proton Pump Inhibitor Therapy. Gastroenterology 2017; 153:35-48 발표자 ; F1 김선화

Medical Causality and Risk Assessment

Single donator specimens as advantage in external quality control assessments of infectious diseases

Multiple Choice Questions - Paper 1

The Mind-Body Problem: Physicalism

7.342 Chronic infection and inflammation: What are the consequences on your health? Instructors Eva Frickel and Sara Gredmark

Causation and Disease. A Chronological Journey

Lecture II: Difference in Difference. Causality is difficult to Show from cross

Addendum to the 12th Report on Carcinogens

Extrapolation and the Russo Williamson thesis

IN VIVO STUDIES ON VIRAL VIRULENCE

The Primary Prevention of Asthma

Viruses and cancer: Should we be more afraid?

Underlying Theory & Basic Issues

Comments on David Rosenthal s Consciousness, Content, and Metacognitive Judgments

Elevated Immunofluorescence Antibody Titers to Several Herpesviruses in Burkitt's Lymphoma Patients: Are High Titers Unique? 1 ' 2

Probability Factors, Future and Predictions in Project Management:

Concepts of Disease. Dr.P.Selvaraj. Associate Professor of Clinical Medicine. TANUVAS Clinical Medicine Promoting Clinical Excellence Since 1903

Modelling Causation in Evidence-Based Legal Reasoning ICAIL Doctoral Consortium

Viruses. Poxviridae. DNA viruses: 6 families. Herpesviridae Adenoviridae. Hepadnaviridae Papovaviridae Parvoviridae

Neuroscience, Sloppiness, and Ground Truth

Koch s Postulates: An )nterventionist Perspective. Lauren N. Ross and James F. Woodward

Lecture 5 Conducting Interviews and Focus Groups

The gateway theory. Pr Jean-François ETTER PhD (political science) E-cigarette Summit London, November 17, Competing interests: none

Idiopathic Environmental Intolerance (IEI): Toxicogenic and Psychogenic Theories

COURSE: NURSING RESEARCH CHAPTER I: INTRODUCTION

The scope of perceptual content, II: properties

To evaluate a single epidemiological article we need to know and discuss the methods used in the underlying study.

The causal relation between human papillomavirus and cervical cancer

Introduction. Faculty Highlight: Dr. Mervyn Susser. Causal Inference

COHERENCE: THE PRICE IS RIGHT

Gold and Hohwy, Rationality and Schizophrenic Delusion

21/07/2017. Lymphoproliferations in immunodeficiency. IBD and EBV associated LPD in GIT Han van Krieken. Inflammatory bowel disease and cancer

In Bed With The Devil: Recognizing Human Teratogenic Exposures

Lessons Learned from Adverse Events and Assessment of Causal Relationships. Neal A. Halsey Johns Hopkins University

What is AIDS? AIDS is GRID. (Gay Related Immune Deficiency)

Chapter 2 Epidemiology

Properties of Herpesviruses

Testing for Herpes Simplex Infections Getting it DONE!

- A cancer is an uncontrolled, independent proliferation of robust, healthy cells.

CONTENTS NOTE TO THE READER... 1

USA Product Listing. Serology Diagnostic Products

EXPERIMENTAL RESEARCH DESIGNS

Principles of Molecular Virology STAGE / YEAR: 3 CREDITS: 10. PROGRAMME COMMITTEE: Biomedical Sciences. VERSION: 4th March 2015

What is the relationship between the mind and the brain?

Under the Radar Screen: How Bugs Trick Our Immune Defenses

Case Report Bilateral Breast Masses with a Rare Etiology

Doing After Seeing. Seeing vs. Doing in Causal Bayes Nets

Bacteriology Virology Mycology Parasitology Immunology Pathology Epidemiology. Microbe alternate terms Germs, microorganisms, pathogens, agents, bugs

Persistent Infections

TRANSLATING RESEARCH INTO PRACTICE

Gastric Carcinoma with Lymphoid Stroma: Association with Epstein Virus Genome demonstrated by PCR

Epstein-Barr Virus 1

Human Experimentation

number Done by حسام أبو عوض Lara Abdallat Dr. Maha

Pathogenicity of Infectious Diseases

DISEASE DETECTIVES PRACTICE ACTIVITIES

Book Information Jakob Hohwy, The Predictive Mind, Oxford: Oxford University Press, 2013, ix+288, 60.00,

Purification and Fluorescent Labeling of Exosomes Asuka Nanbo 1*, Eri Kawanishi 2, Ryuji Yoshida 2 and Hironori Yoshiyama 3

11 questions to help you make sense of a case control study

[1] provides a philosophical introduction to the subject. Simon [21] discusses numerous topics in economics; see [2] for a broad economic survey.

Transcription:

What is a cause? Dr Brendan Clarke UCL Department of Science and Technology Studies

Causation is important to medicine

Causation is important to medicine Causal relations imply something beyond mere association Correlation alone does not imply causation

Causation is important to medicine Causal relations imply something beyond mere association Correlation alone does not imply causation Applications

Causation is important to medicine Causal relations imply something beyond mere association Correlation alone does not imply causation Applications Diagnosis and treatment

Causation is important to medicine Causal relations imply something beyond mere association Correlation alone does not imply causation Applications Diagnosis and treatment Discovery and research

Causation is important to medicine Causal relations imply something beyond mere association Correlation alone does not imply causation Applications Diagnosis and treatment Discovery and research Medicolegal applications

Determining cause is difficult

Determining cause is difficult It is difficult to differentiate causal from noncausal processes

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination Medical schemes of cause

Koch-Henle postulates (1840, 1882, 1890) The same organism must be present in every case of the disease. The organism must be isolated from the diseased host and grown in pure culture. The isolate must cause the disease when inoculated into a healthy, susceptible animal. The organism must be reisolated from the inoculated, diseased animal. [Grimes, D.J. 2006. Koch's Postulates Then and Now, Microbe. 1(5): 223 8.]

Bradford Hill (1965) What in an association should we consider when determining causation? Strength of association Consistency Specificity Temporal sequence Biological gradient (dose-response) Plausibility and coherence Experimental or interventional evidence Analogy

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination Medical schemes of cause These are, to some extent, successful

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination Medical schemes of cause These are, to some extent, successful But they don t take account of the philosophical literature on cause

Cause in philosophy 300 years of philosophy on cause Lots of different schemes of causation Humean / regularity view of causation Counterfactual conditional causation Cause and linking mechanism Probabilistic / indeterminate cause including Bayesian Action-related causation

Cause in philosophy No dominant view either between schemes or within schemes Extensive, difficult literature Very often written to account for theoretical rather than actual examples

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination Medical schemes of cause These are, to some extent, successful But they don t take account of the philosophical literature on cause

Determining cause is difficult It is difficult to differentiate causal from noncausal processes Attempts have been made to formulate schemes to assist this discrimination Medical schemes of cause These are, to some extent, successful But they don t take account of the philosophical literature on cause This might be a route to improvements...

What should an ideal system of cause do?

What should an ideal system of cause do? Should allow us to reliably discriminate causal from non-causal processes

What should an ideal system of cause do? Should allow us to reliably discriminate causal from non-causal processes Should be amenable to application in practice, providing useful causal judgements

What should an ideal system of cause do? Should allow us to reliably discriminate causal from non-causal processes Should be amenable to application in practice, providing useful causal judgements Should take account of many types of evidence for cause

Koch-Henle postulates (1840, 1882, 1890) The same organism must be present in every case of the disease. The organism must be isolated from the diseased host and grown in pure culture. The isolate must cause the disease when inoculated into a healthy, susceptible animal. The organism must be reisolated from the inoculated, diseased animal. [Grimes, D.J. 2006. Koch's Postulates Then and Now, Microbe. 1(5): 223 8.]

What should an ideal system of cause do? Should allow us to reliably discriminate causal from non-causal processes Should be amenable to application in practice, providing useful causal judgements Should take account of many types of evidence for cause Should be terminologically robust, yet with sufficient flexibility to account for technological development etc

Bradford Hill (1965) What in an association should we consider when determining causation? Strength of association Consistency Specificity Temporal sequence Biological gradient (dose-response) Plausibility and coherence Experimental or interventional evidence Analogy

What should an ideal system of cause do? Should allow us to reliably discriminate causal from non-causal processes Should be amenable to application in practice, providing useful causal judgements Should take account of many types of evidence for cause Should be terminologically robust, yet with sufficient flexibility to account for technological development etc Should incorporate elements from the philosophy of causation

Example of causation in disease discovery

Burkitt's Lymphoma B-cell nonfollicular lymphoma Highly malignant Common in tropical Africa Jaw and abdominal tumours Caused by the Epstein-Barr virus and related to chronic malaria First described 1958 by Denis Burkitt

But Epstein-Barr was not the only virus found in Burkitt's Lymphoma cells... Arbovirus Echo 11 HSV Reovirus 3 Multiple other filterable agents

Summary

Summary The early evidence for the causal roles of both EBV and malaria in Burkitt's lymphoma was equivocal

Summary The early evidence for the causal roles of both EBV and malaria in Burkitt's lymphoma was equivocal Later arguments for causation depended on the interaction of many different domains of evidence

Summary The early evidence for the causal roles of both EBV and malaria in Burkitt's lymphoma was equivocal Later arguments for causation depended on the interaction of many different domains of evidence Evidence of viral detection (EM, ISH, fluorescence, PCR)

Summary The early evidence for the causal roles of both EBV and malaria in Burkitt's lymphoma was equivocal Later arguments for causation depended on the interaction of many different domains of evidence Evidence of viral detection (EM, ISH, fluorescence, PCR) Serological evidence

Summary The early evidence for the causal roles of both EBV and malaria in Burkitt's lymphoma was equivocal Later arguments for causation depended on the interaction of many different domains of evidence Evidence of viral detection (EM, ISH, fluorescence, PCR) Serological evidence Epidemiological and seroepidemiological evidence, especially prospective studies

Conclusions

Conclusions 1. Cause does something that association alone does not

Conclusions 1. Cause does something that association alone does not 2. Determining cause in practice and in theory is difficult

Conclusions 1. Cause does something that association alone does not 2. Determining cause in practice and in theory is difficult 3. There is room for improvement in existing schemes of cause in both medicine and philosophy

Conclusions 1. Cause does something that association alone does not 2. Determining cause in practice and in theory is difficult 3. There is room for improvement in existing schemes of cause in both medicine and philosophy 4. Cause seems to require evidence from multiple domains

Conclusions 1. Cause does something that association alone does not 2. Determining cause in practice and in theory is difficult 3. There is room for improvement in existing schemes of cause in both medicine and philosophy 4. Cause seems to require evidence from multiple domains 5. New schemes of cause must take account of the needs of biomedicine, the demands of philosophy and the manner in which medicine actually happens