Living with Chronic Disease: Measuring Important Patient-Reported Outcomes (eBook)

Dr Paul Kamudoni (PhD MSc.) is a Scientific Associate Director in the Global Evidence and Value Development – R&D department at Merck KgaA in Darmstadt (Germany) where he leads the Centre of Excellence for Patient Reported Outcomes. Dr Kamudoni trained as a Pharmacoeconomist and a Clinical Outcome Measurement Scientist at Cardiff University. In his day to day work, he is involved in the development and validation of PRO measures, and the design and integration of PRO endpoints in clinical trials and other types of studies. He maintains an active research interest in methodological issues in the integration of electronic health records with prospective PRO assessments, and the application of item response theory in PRO measurement among others. Dr Nutjaree Pratheepawanit Johns (PhD PharmD) is an Associate Professor at the Faculty of Pharmaceutical Sciences, and melatonin research group, Khon Kaen University, Thailand. She has held a number of academic positions both in Thailand and abroad, including a fellowship at the Western Institutional Review Board (WIRB) (Olympia, WA, USA). Dr Johns has an expertise in cancer care and quality of life (QoL) research and collaborates with several cancer centres in Northeastern Thailand. She has developed and tested a number of PRO measures including cross-cultural adaptation into the Thai language. Dr Johns is also a principal investigator in many clinical trials investigating the effects of disease or interventions on QoL of cancer patients. She has been a recipient of several prestigious awards including Scholarship for Developing Country, International Society for Quality of Life Research and the Doyle Prize: Postgraduate section, Palliative Medicine Journal. Professor Sam Salek (PhD RPh FFPM FRPS MCMS FESCP) is Professor of Pharmacoepidemiology at the University of Hertfordshire, Hatfield, visiting Professor at the Estate of Hessen, Germany, and Director of the Institute for Medicines Development, Cardiff, UK. Professor Salek’s research focuses mainly on four areas: development and application of PRO measures; drug safety evaluation and pharmacovigilance; pharmacoeconomics and economic evaluation of healthcare; and pharmaceutical regulation & medicines development in the mature and emerging markets. He has published 22 books and 600+ journal articles and abstracts. Professor Salek is a member of five Editorial Boards and an active member of several societies.

Foreword 5
Preface 7
Contents 9
Part I: A New Roadmap for Development of a PRO Measure 13
1: Overview 14
Patient-Reported Outcome as a Concept 15
Scope for the Use of PROs 15
Assessing PROs in Long-Term Conditions 17
Approaches to Measuring PROs 20
Aims and Objectives 21
References 23
2: Approaches to the Development and Use of PRO Measures: A New Roadmap 25
Characteristics of a PROM: Core Measurement Attributes 26
Conceptual Framework 26
Measurement Models and Scoring Algorithms 26
Acceptability and Practicality 27
Validity 27
Content Validity 27
Construct Validity 28
Criterion Validity 29
Reliability 29
Internal Consistency 29
Split-Half Reliability 29
Inter-Rater Reliability 30
Temporal Stability (Test-Retest Reliability) 30
Responsiveness 30
Interpretability 31
Characteristics of a PROM: Additional Attributes 31
Response Scales 31
Frame of Reference 31
Mode of Administration 32
Interview Format 32
Paper-and-Pencil Self-Completion 32
Electronic PRO (ePRO) Self-Completion 33
Interactive Voice Response (IVR) Self-Completion 33
A Roadmap for the Development of a PROM 33
Step 1: Define Objectives of Development of the PROM 35
Step 2: Generate Hypothesis and Conceptualise the PROM: Disease Model/Hypothetical Conceptual Physico-Psychosocial Model 35
Review of Literature and PROMs 35
Disease Burden 35
Appraisal of Relevant PROMs 36
Development of Hypothetical Conceptual Framework 36
Step 3: Gather and Select Item Concepts: Concept Elicitation/Qualitative Research 36
Eliciting Patient Input: Investigating the Experience of Patients Using Qualitative Research Methods 37
Step 4: Design and Build the PROM: Content Definition/Item Generation 38
Step 5: Refine the PROM’s Content: Cognitive Debriefing/Content Validation Panels 39
Cognitive Interviews 39
Expert Panel for Content Validation 39
Step 6: Explore PROM’s Practicality and Applicability 40
Step 7: Fine-Tune the PROM, Evaluate Item Performance and Establish Scoring Algorithms 40
Step 8: Generate Psychometric Evidence and Other Supportive Information 43
Validity 43
Reliability 44
Responsiveness 44
Interpretability 45
Cross-Cutting Emergent Approaches 46
Patient Engagement 46
Use of Social Networking Sites 47
Appendix: Technical Notes 48
Practical Considerations in Study Design During PRO Development 48
Sample Size 48
Missing Data 49
Suggestions for Statistical Analysis in PROM Development 50
Performing Exploratory Factor Analysis 51
Performing Rasch Analysis 52
References 54
Part II: An Illustration of the New PRO measure development Roadmap Using Research in Hyperhidrosis as A Practical Example 60
3: Conceptualisation and Qualitative Development of a PRO Measure 61
Part I: Hyperhidrosis Disease—Disease Background 61
Impact on HRQoL 63
Part II: The Qualitative Development of the Hyperhidrosis Quality of Life Index (HidroQoL) 65
Step 1: Define Objectives of Development of the PROM 65
Broad Aim 65
Secondary Objectives 65
Step 2: Hypothesis Generation and Conceptualisation 66
Methods 66
Literature Review to Uncover the Impacts of Hyperhidrosis on Patients’ HRQoL 66
Critical Appraisal of the Instruments Used in HRQoL Measurement in Hyperhidrosis 66
Results 67
Impacts of Hyperhidrosis on Patients’ HRQoL 67
Tools Used in HRQoL Measurement in Hyperhidrosis Patients 67
Step 3: Qualitative Method to Understand Patient’s Experience 70
Methods 70
Findings 71
Qualitative Method to Understand Patient’s Experience 71
Insights into Themes 71
Step 4: Design and Build PRO Measure 72
Generating the Initial Items for the New PRO Measure 72
Choosing a Response Format 73
Choosing a Frame of Reference 73
Choosing a Mode of Administration 74
Choosing a Structure and Format 74
Concluding Remarks 75
Appendix 76
References 79
4: Content Validation by Patients and Experts: Is the PRO Measure Fit for Purpose? 82
Step 5: Refining the Content of the PRO Measure 82
Case Study: Evaluating the Content of the HidroQoL 83
Methods 84
Part I: Performing Expert Panels for Content Validation 84
Part II: Working with Patients During Content Validation 84
Part III: A Review Panel 85
Findings 85
Part I: Expert Panels 85
Qualitative Feedback 85
Ratings by Experts 86
Suggestions for Improving Items 86
Part II: Patient Panels 87
Ratings by Patients 87
Suggestions for Improving Items 88
Part III: Review Panel 88
Integrating the Results 88
Naming the New PRO Instrument 89
Step 6: Explore practicality and applicability 89
Case Study: Pretesting of the HidroQoL 90
Concluding Remarks 90
Appendix 92
Content verification of the 47-item prototype HidroQoL by patients and Experts 92
Practicality Questions 96
References 96
5: Applying Modern Test Theory in PRO Measure Development: Rasch modelling 98
Part I: Fine-Tuning of the HidroQoL Using Rasch Analysis 99
Methods 99
Findings 100
Distribution of Responses 100
Calibrating Item and Person Estimates 100
Item Reduction and Refinement 101
Revising Item Response Scaling 101
Removal of Misfitting Items 102
Testing for Unidimensionality 102
Analysis of Differential Item Functioning (DIF) 102
Testing for Local Independence 105
Part II: Integrating and Using Different Types of Data During the Item Reduction Process—Dealing with Friction 105
Concluding Remarks 107
Appendix 109
Responses to the HidroQoL Items 109
Iterative Steps in the Item Reduction Process of the HidroQoL and Rasch Model Fit Statistics 111
Evaluation of Differential Item Functioning 115
Analysis of DIF Impact at Scale Level: Comparison of Test Characteristic Curves (TCCs) of the HidroQoL-18 Across Patient Subgroups 117
Local Dependence 119
References 120
6: Assessing the Performance of PRO Measures Against Expectations: Psychometric Evaluation 121
Part I: Assessing the Construct Validity of the HidroQoL 122
Methods 123
Study Design 123
Analysis 123
Findings 124
Score Distribution, Correlation Analysis and Factor Analysis 124
Exploratory Factor Analysis (EFA) of the HidroQoL 125
Revised HidroQoL: 21-Item Set 126
Known Group Validity 129
Convergence Validity 130
Part II: Assessing How Well a PRO Measure can Be Used without Errors—Reliability 132
Methods 133
Findings 134
Internal Consistency 134
Inter-Temporal Stability of the HidroQoL Scores 135
Part III: Evaluating Ability to Capture Changes in Patients’ Condition—Responsiveness 137
Methods 137
Findings 138
Part IV: Establishing Criteria for Interpreting Scores of Patient-Reported Outcomes 138
Methods 139
Findings 140
Anchor-Based Approach 140
Integrated Approach 140
Distribution-Based Approach 140
Concluding Remarks 141
Appendix 142
Sample Size Considerations 142
Evaluating the Psychometric Properties of the HidroQoL 143
References 145
Part III: Practical Considerations When Applying PRO Measures 147
7: Integrating PRO Assessment in Clinical Trials, Routine Clinical Practice and Medicines Development Programmes 148
Part I: Integrating PRO Measurements in Clinical Research 148
Steps in Integrating PROs into Clinical Research 149
Clinical Trial Design and Planning Stage 149
Trial Implementation and Practical Stage 150
Data Management and Analysis Stage 150
Results Reporting Stage 152
Part II: PRO Measurement in Routine Clinical Practice – Issues and Considerations 152
Design and Configuration of Routine PRO Assessment 153
Issues and Special Considerations 155
Patients 155
Clinicians 156
Resources and Infrastructure 156
An Illustration of PRO Assessments in Clinical Practice 156
Implementation Process 156
Health-Related Quality of Life Instrument 157
Findings 157
Key Learnings from Case Study 158
Part III: Applying PROs in Regulatory and Patient Access Pathways 159
Use of PROs in Market Authorisation Processes at the FDA and EMA 159
Perspectives from Industry Executives and Regulators 160
Common PRO-Related Issues Encountered in Regulatory Processes 161
Issues in PRO Interpretation and Application 162
Opportunities for Improving the Generation and Use of PRO Data in Regulatory Processes 162
Use of PROs in HTA: An Example of IQWIG and G-BA 163
Part IV: Current Developments in the Field 164
The Role of PROs in Facilitating Flexible Regulatory and Access Pathways 164
Regulatory and HTA Scientific Advice 165
Regulatory Qualification of Drug Development Tools 165
Multi-Stakeholder Approach to PROs 166
Technology and Communication Revolution 167
References 167