Patient Centric Blood Sampling and Quantitative Analysis

Neil Spooner, Ph.D., C.Chem., F.R.S.C., is the Founder of Spooner Bioanalytical Solutions and the Patient Centric Sampling Interest Group (PCSIG) where he champions the implementation of patient centric sampling approaches. Dr Spooner is also the Editor In Chief of Bioanalysis Journal and is a Senior Visiting Research Fellow at the University of Hertfordshire, UK. Emily Ehrenfeld is President of New Objective, Inc, an industry leader in high performance nano/microflow technologies. Joe Siple is Director, Corporate Relations for New Objective, Inc., an industry leader in high performance nano/microflow technologies. Mike S. Lee, PhD, is the founder of the Annual Symposium on Clinical and Pharmaceutical Solutions and Analysis (CPSA) and is the CEO of New Objective, Inc, an industry leader in high performance nano/microflow technologies.

• List of Contributors xiiiForeword xviiPreface xix1 Patient Centric Healthcare – What’s Stopping Us? 1Jenny Royle and Rachel Jones1.1 The Evolution of Future Health Systems 11.2 Exploring the Barriers to Home Sampling 31.2.1 Barrier One—The Discord Between Innovation and Practice 41.2.2 Barrier Two—Ethical and Operational Considerations 51.2.3 Barrier Three—Where Does the Liability Sit? 71.2.4 Barrier Four—Addressing the Technology Challenge 81.2.5 Barrier Five—The Human Touch 91.2.6 Barrier Six—Trust in Data Security 101.2.7 Barrier 7—Adherence to Service Change 111.3 Conclusion: The Changing Role of Home Sampling 12References 132 Tips for Successful Quantitative Assay Development Using Mitra Blood Sampling with Volumetric Absorptive Microsampling 17James Rudge2.1 What is Volumetric Absorptive Microsampling? 172.2 Tip 1—Ensure the Use of a Correct Sampling Procedure to Prevent Volume-Related Biases 182.3 Tip 2—Working with Wet Whole Blood 192.3.1 Is Your Choice of Assay Biologically Relevant in Blood? 192.3.2 Working with Blood as a Matrix 202.3.3 Allowing Analytes to Equilibrate Ex Vivo 212.3.4 Bridging Between Venous Capillary Blood and the Role of Anticoagulants 222.4 Tip 3—Working with Dried Whole Blood 242.4.1 Dried Blood Spot Cards 242.4.2 Volumetric Hematocrit Bias—Blood Viscosity 252.4.3 Dried Blood is a Complicated Matrix 262.4.4 Working with “Aged” Blood 262.4.5 Temporal Extraction Bias or Degradation? 272.5 Tip 4—Optimizing Extraction Efficiencies from VAMS 292.5.1 Measuring Percentage Recovery from Mitra Samplers 302.5.2 Extraction Conditions—Where to Start 312.5.2.1 Consulting the Literature and Matching Physicochemical Properties 312.5.2.2 Adapting Published DBS Methods 322.5.2.3 Converting from a Wet (Whole Blood or Plasma) Method 322.5.2.4 Starting from a Blank Canvas—What to Consider? 332.5.2.5 Choice of Matrix 352.5.3 Aqueous Extraction Conditions 362.5.4 Organic Extraction Conditions 372.5.5 Generic Extraction Conditions 392.6 Conclusions 40References 413 Preanalytical Considerations for Implementation of Microsampling Solutions 49Bradley B. Collier, Peyton K. Miesse, and Russell P. Grant3.1 Introduction 493.2 Sample Matrices 503.2.1 Venous Sample 513.2.2 Capillary Blood 543.2.3 Material Selection 623.2.4 Dried Samples 623.2.5 Conclusions 633.3 Alternate Sample Acceptance Criteria 633.4 Collection 653.4.1 Device and Kit Components 663.4.2 Training and Preparation 673.4.3 Wound Generation 683.4.4 Collecting Sample 703.4.5 Post Collection Processing 723.4.6 Conclusions 723.5 Transportation and Sample Stability 733.5.1 Specimen Matrix and Separation 733.5.2 Storage Condition 743.5.3 Measurement Technique 773.5.4 Hematocrit Effects 793.5.5 Conclusions 793.6 Preanalytical Processing 803.6.1 Separation of Plasma and Serum 803.6.2 Sample Dilution 813.6.3 Conclusions 823.7 Overall Conclusions 82References 834 Collection and Bioanalysis of Quantitative Microsamples: Technological Innovations and Practical Implications 93Regina V. Oliveira, Marc Yves Chalom, and Carlos Roberto V. Kiffer4.1 Introduction 934.2 Practical Implications in Clinical Settings 944.2.1 Clinical Development 954.2.2 Clinical Analyses 964.3 Microsampling Devices—A Patient-Centered Approach 994.3.1 Collection Devices for Microsampling Analysis 994.3.1.1 Blood Sampling Techniques 1024.3.1.2 Other Biological Matrices 1244.4 New Development Areas 1244.4.1 Automated Sample Collectors 1244.4.2 Microfluidic Point-of-Care Devices 1274.5 Summary of Currently Available Patient Centric Sampling Technologies 1274.6 Microsampling Analysis by LC-MS—Analytical Considerations 1274.6.1 Basic Principles of Liquid Chromatography (LC) and Mass Spectrometry (MS) for Bioanalysis of Microsamples 1284.6.1.1 Microspray Ionization Sources 1294.6.1.2 Microflow Liquid Chromatography 1314.6.1.3 Microchip-Based LC 1384.7 Conclusions 138References 1405 Automation in Microsampling: At Your Fingertips? 153Sigrid Deprez, Liesl Heughebaert, Nick Verougstraete, Veronique Stove, Alain G. Verstraete, and Christophe P. Stove5.1 Introduction 1535.1.1 Identifying the Current Bottlenecks for Routine Implementation of Microsampling in Clinical Practice 1535.1.2 The Importance of Analytical Automation for Different Application Fields 1575.2 Automation of Dried Blood Microsampling Analysis Coupled to (LC-) MS/MS: What’s Available? 1595.2.1 Amenability of DBS Samples for Automation 1595.2.2 Commercially Available Automated DBS Extraction Instruments 1625.2.2.1 Automated Extraction of DBS: Workflow 1625.2.2.2 Extraction Process 1635.2.2.3 Extract Processing Strategy 1645.2.2.4 Internal Standard Application 1655.2.3 Points of Attention During Method Validation 1665.2.3.1 Matrix Effects and Recovery 1665.2.3.2 The Hct Effect 1685.2.3.3 Calibration Curve and Dilution Integrity 1695.2.4 Cross-Validation of Automated DBS Procedures 1705.2.5 Current Applications of Automated Online DBS Extraction 1735.2.6 Approaches for Automating Analysis with Other Microsampling Devices 1815.2.7 Alternative Approaches for the Analysis of DBS Samples 1835.2.7.1 Direct Analysis of DBS 1835.2.7.2 Coupling DBS Analysis to Automated Immuno-Analyzers 1845.3 Integration Into a Clinical Laboratory 1855.3.1 Requirements, Challenges, and Advantages of Implementation 1855.3.2 Cost-Effectiveness of Implementation of (Automated) DBS Analysis 1875.4 Conclusions and Future Perspectives 192Acknowledgments 192References 1936 Over 50 Years of Population-Based Dried Blood Spot Sampling of Newborns; Assuring Quality Testing and Lessons Learned 205Amy M. Gaviglio, Kristina Mercer, Konstantinos Petritis, Carla D. Cuthbert, and Suzanne K. Cordovado6.1 Overview of Population-Based Newborn Screening 2056.2 Public Perceptions of NBS 2086.3 Characteristics of the DBS Matrix and Its Utility in NBS 2096.3.1 Recovery of Biochemical and Molecular Analytes from DBS for NBS 2106.3.2 Evaluation of Lot-to-Lot Variability in NBS Collection Devices 2116.3.3 Effect of Hematocrit on DBS Homogeneity, Data Analysis, and Results 2126.3.4 DBS Specimen Collection Transport and Safe Handling 2136.3.5 DBS Analyte Stability and Storage 2166.3.6 Known Interferences with DBS use for NBS 2216.3.7 History of NSQAP—40 Years of Quality Assurance 2226.4 Methods Used in NBS 2326.4.1 Origins of NBS and Expansion of Biochemical Testing 2326.4.2 Origins of Molecular DBS Testing and Expansion in NBS 2386.4.3 How the Expansion of Genomics may Impact NBS 2416.4.4 Expansion of DBS Utility, Including Direct Patient Use 2446.5 Conclusion 245Acknowledgments 246Conflicts of Interest 246References 2467 Considerations for Implementation of Microsampling in Pediatric Clinical Research and Patient Care 263Ganesh S. Moorthy, Christina Vedar, and Athena F. Zuppa7.1 Introduction 2637.2 Considerations for Implementation 2647.2.1 Benefits 2647.2.1.1 Clinical Research 2667.2.1.2 Clinical Care 2677.2.2 Challenges 2687.2.2.1 Clinical Research 2697.2.2.2 Clinical Care 2707.2.3 Laboratory Challenges and Considerations 2717.2.4 Survey Results on Feasibility 2737.3 Conclusion 274References 2748 Simplification of Home Urine Sampling for Measurement of 2,8-Dihydroxyadenine in Patients with Adenine Phosphoribosyltransferase Deficiency 277Unnur A. Thorsteinsdottir, Hrafnhildur L. Runolfsdottir, Vidar O. Edvardsson, Runolfur Palsson, and Margret Thorsteinsdottir8.1 Introduction 2778.1.1 Adenine Phosphoribosyltransferase Deficiency 2788.1.2 Diagnosis of Adenine Phosphoribosyltransferase Deficiency 2808.2 Methods 2818.2.1 Sample Collection 2818.2.2 Preparation of Urine Samples for Analysis 2818.2.3 The UPLC-MS/MS Urinary 2,8-Dihydroxyadenine Assay 2828.3 Results 2838.3.1 Assay Development and Optimization 2838.3.2 Comparison of First-Morning Void Urine Specimens and 24-hr Urine Collections for Assessment of 2,8-Dihydroxyadenine Excretion 2888.4 Discussion 2908.5 Conclusions and Future Directions 291References 2929 Utilization of Patient Centric Sampling in Clinical Blood Sample Collection and Protein Biomarker Analysis 297Jinming Xing, Joseph Loureiro, Dmitri Mikhailov, and Arkady I. Gusev9.1 Introduction 2979.1.1 Challenges with the Current Clinical Trial Model 2979.1.2 Clinical Trial Conduct Faced Unprecedented Challenges Brought by Covid-19 2989.2 Current Patient Centric Sampling Landscape 2999.3 Clinical Proteome Profiling Technologies for Testing Patient Centric Microsampling Devices 3009.3.1 Biomarker and Profiling Can Be Used to Benchmark Patient Centric Sampling Technologies 3009.3.2 Orthogonal Analysis Cultivates Confidence for Biomarker Test with Patient Centric Sampling 3029.4 Clinical Sample Collection with Tap Device: A Clinical Case Study 3039.4.1 Clinical Study with TAP Device 3039.4.2 User Experience, TAP Device Performance, and Sample Hemolysis 3069.4.3 SomaScan Blood Proteome Profiling Landscape 3089.4.4 Orthogonal Confirmation Provided by Quantitative Immunoassay 3139.4.5 Extending Protein Biomarkers Tested by Quantitative Immunoassay Beyond the Zone of Highest Concordance (Negative Controls) 3149.5 Discussion 3189.5.1 Utility of Patient Centric Sampling for Clinical Proteome Sample Collection 3189.5.2 Considerations for Patient Centric Sampling Implementation in Clinical Trials 3209.5.3 Future Outlook for Patient Centric Sampling 322Acknowledgements 323References 32310 Enabling Patient Centric Sampling Through Partnership: A Case Study 327Christopher Bailey, Cecilia Arfvidsson, Stephanie Cape, Paul Severin, Silvia Alonso Rodriguez, Robert Nelson, and Catherine E. Albrecht10.1 Introduction 32710.1.1 The Partnership 32710.1.2 AstraZeneca’s Evolving PCS Approach 32810.1.3 Why Change? 32810.1.4 Patient Choice 32910.1.5 The Challenges—Why Isn’t PCS Already the Norm? 32910.2 Pre-Study Considerations 33110.2.1 Early Engagement 33110.2.2 Feasibility Assessment 33210.3 The Case Study 33210.3.1 Background 33210.3.2 Scientific Considerations 33510.3.3 Regulatory Agency Expectations Bridging 33810.3.4 Study Operations Considerations 33810.3.5 Route of Drug Administration and Potential for Sample Contamination 34010.3.6 Sample Handling 34110.3.7 Training and Patient Recruitment Challenges 34210.3.8 Other Logistical, Data Protection, and Compliance Considerations 34210.3.9 Study Participant Engagement 34310.4 Summary 344References 34711 Perspectives on Adopting Patient Centric Sampling for Pediatric Trials 351Enaksha Wickremsinhe11.1 Overview and Why 35111.1.1 Regulations and Legislation 35111.1.2 Who are Pediatric Patients? 35211.2 Challenges and Current Status 35311.2.1 Conducting Pediatric Studies 35311.2.2 Ethics, Consent, and Assent 35311.2.3 Patient/Parent Burden 35411.2.4 Blood Sampling 35411.2.5 Blood Volume Limits 35511.3 Solutions: How Do We Get This Done 35611.3.1 Microsampling 35611.3.2 Patient Centric Sampling 35711.3.3 Pediatric PCS Devices/Techniques 35811.3.4 COVID-19 Era 35911.3.5 Training 35911.4 Summary 359References 360Index 363