Diagnoses Without Names: Challenges for Medical Care, Research, and Policy

Foreword
References
Preface: Introduction—When A Diagnosis Has No Name
The Definition of Diagnosis
The Purposes of Diagnosis
Can We Quantify and Use Uncertainty?
Lessons from the Workshop
Acknowledgments
Contents
Contributors
Part I: What Is a Diagnosis?
1: Chasing My Cure: Lessons Learned from My Rare Illness
Introduction
My Diagnostic Journey
Defining Castleman Disease and Advancing the Field
Conclusion
References
2: A Pragmatic Approach to Diagnostic Categorization
Introduction
What Are the Goals of Diagnosis?
Consequences of Diagnosis
What Are the Kinds of Diagnostic Categories?
How Does Diagnosis Happen?
What Are the Consequences of Not Having a Suitable Diagnostic Category?
Factors Contributing to Diagnostic Difficulties
General Recommendations for Diagnostic Change
Examples
Conclusions
References
3: How Diagnoses Are Assigned
Classification in Medicine
Disease, Illness and Sickness
Pattern Recognition
Development of Clinical Expertise
The Diagnostic Process
The Manifest Continuum
When the Illness Has No Name
The Problem with Assigning a Label
Recommendations for Management
Conclusions
References
4: Toward Molecular Diagnoses for Autoimmune Rheumatic Diseases
Introduction
Molecular Clustering in Autoimmune Rheumatic Disease
Patients with Symptoms Who Do Not Meet Current Classification Guidelines: Lessons from Incomplete Lupus Erythematosus (ILE) and Undifferentiated Connective Tissue Disease (UCTD)
Uncertain Disease Classification in Understudied Populations
Conclusion
References
Part II: Purposes of Diagnosis
5: Diagnostic Uncertainty in Drug Development
Introduction
Defining Diagnostic Uncertainty in Drug Development
Addressing the Lack of Representativeness in Clinical Trials
Real-World Evidence
Clinical Trial Optimization
Keeping the End in Mind: The Patient at the Center of the Drug Development Process
Conclusions
References
6: Confronting the Inevitability of Diagnostic Uncertainty Across Multiple Legal Domains
Introduction
Preliminary Thoughts Prompted by the Pandemic
Contested Vital Signs, Pre-diseases, and Beyond
Emphasizing Etiology and Prognosis
Demanding Diagnostic Prowess
Expertise and Etiology
Perils in Prognostication
Inadvertent Consequences of Undue Inventiveness
Looking Beyond the Courtroom
Final Musings About Trans-scientific Enterprises
References
7: The FDA and the Drug Development Process
Introduction
Stages of Drug Development and Review
Investigational New Drug Application (IND)
Phase 1
Phase 2
Phase 3
New Drug Application (NDA)
Phase 4: Postmarketing Requirement and Commitment Studies
What Does FDA Approval Mean?
Accelerated Approval
Drug Development Designations
Summary
References
Part III: Assigning
8: Diagnosis of Systemic Lupus Erythematosus in the Age of Precision Medicine
Introduction
SLE
Can Genomics and Transcriptomics Be Used to Diagnose SLE?
Gene Expression Studies and Organ Involvement
Summary and Conclusions
References
9: The Impact of Antinuclear Antibody Testing on the Naming and Misnaming of Disease
The Problems of ANA Determination
Symptomatology
The Issue of Nomenclature
References
10: In the Box or Out of the Box
References
11: Ever-Evolving Disease Classification Criteria for Clinical Trials and Studies: The Case of Systemic Lupus Erythematosus
Introduction
What Is the Difference Between Disease Diagnosis and Classification? And Why Do We Need Classification Criteria for Clinical Research and Trials?
The Evolution of Classification Criteria for Systemic Lupus Erythematosus
Cases Below the Threshold
Summary
References
12: Prognosis: A Framework for Clinical Practice When Patients Have ‘Symptoms with No Diagnosis’
Diagnosis in Clinical Practice
Challenge 1: The Benefits and Hazards of Searching for a Diagnosis
Challenge 2: How to Classify Patients with Symptoms that Do Not Have a Diagnosis?
Challenge 3: Explaining Symptoms When There Is No Diagnosis – The Example of Chronic Pain
Challenge 4: How Do We Care for the Sick Individual in a Measured World?
Planning the Future
References
13: When the Illness Has No Name: Focus on Clinical Trials in Systemic Lupus Erythematosus
Chapter
Do All Subjects Enrolled in SLE Clinical Trials Have SLE?
Do Classification Criteria Ensure the Purity of the Study Enrollment?
Do SLE Study Subjects Actually Have Their Stated Disease Activity?
Are Study Subjects Taking Their Medications?
What Steps Can Be Taken to Promote Certainty in SLE Clinical Trials?
Ensure Patients Have SLE
Enrich the Study Population with Informative Patients
Promote Compliance and Adherence
Conclusions
References
14: The Epidemiology of Systemic Lupus Erythematosus
Epidemiology
Identifying Individuals Who May Have SLE
Defining Individuals with SLE
Real-World Experiences
How Many Have SLE? It Depends
Future Directions
Back to John Snow
References
Part IV: Diagnoses
15: Managing and Tolerating Diagnostic Uncertainty
Introduction
Conceptualizing Diagnostic Uncertainty
Managing Diagnostic Uncertainty
Managing Uncertainty: The Meaning and Necessity of Tolerance
References
16: Is There a Textbook for Non-textbook Patients?
Is There a Textbook for Non-textbook Patients?
Theme: Delays in Diagnosis
Theme: Not Believed by Doctors
Theme: Not Believed by Family Members/Family in Denial
Theme: Women Symptoms Are Not Taken Seriously
Theme: Symptoms
Theme: Power Struggle with Doctors
Theme: Treatments Don’t Work
Theme: Mental Health
Theme: Advice to Doctors
Theme: Advice to Patients
17: The Changing Role of Uncertainty in Physician-Patient Relationships
Concepts
The Evolution of Physician-Patient Relationship
The Role of Uncertainty in the Physician-Patient Relationship
Looking to the Future
References
18: Syndromes in Search of a Name: Disorders of Consciousness, Neuroethics, and Nosological Humility
Introduction: Terry’s Story
The Origins of the Vegetative State
From Phenotype to Mechanism
Naming Wisely
The Place of Time
What’s in a Name?
New Nosologies, Pragmatism, and Disability Rights
Coda
References
19: Reflections on the Conference by a Physician-Patient
My Interest in this Conference
Thinking as a Physician
Thinking as a Patient
The Key Lessons
References
20: Clinical Ambiguity in the Intelligent Machine Era (Treats Breaks and Discharges)
Introduction
Healthcare Megatrends
Democratizing Technologies
Ambiguity and Common Sense
Probability Science
Knowledge and Decision-Making
Data Science
Knowledge Representation
Deconvoluting Data Complexity
Computing Science
Making Machines Intelligent
Reasoning and Abstraction
Reliability and Transparency
The Digital Image Advantage
Cognitive Human-Intelligent Machine Parallels
Confidence
Information Processing
Learning
Bias
Context
Intuition and Expertise
Limitations of Current Healthcare AI Applications
Intelligibility
Reproducibility
Data Quality
Lessons Humans Can Learn
From Autonomous Driving Vehicles
From Natural Languages and Semantics
From Resolving Lexical Ambiguity
From Common Sense Challenges
Difficult Questions and Answers
Conclusions
References
21: Shame, Name, Give Up the Game? Three Approaches to Uncertainty
Chapter
Uncertainty as Threat
Uncertainty as Classification Problem
Uncertainty as Part of Process
Research Agenda
Conclusion
References
Others Who Spoke
Others Who Spoke at the Workshop Concurred with and/or Added New Thoughts on Several Topics
Reference
Index