ADDRESSING
SICKLE CELL
DISEASE

A STRATEGIC PLAN
AND BLUEPRINT
FOR ACTION

Committee on Addressing Sickle Cell Disease:
A Strategic Plan and Blueprint for Action

Marie McCormick, Henrietta Awo Osei-Anto, and
Rose Marie Martinez, Editors

Board on Population Health and Public Health Practice

Health and Medicine Division

A Consensus Study Report of

THE NATIONAL ACADEMIES PRESS
Washington, DC
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This activity was supported by Contract/Task Order No. HHSP233201400020B/HHSP23337086 between the National Academy of Sciences and the Office of the Assistant Secretary for Health, an operating agency of the U.S. Department of Health and Human Services. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organizations or agency that provided support for this project.

International Standard Book Number-13: 978-0-309-66960-3
International Standard Book Number-10: 0-309-66960-X
Digital Object Identifier: http://doi.org/10.17226/25632
Library of Congress Control Number: 2020943342

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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2020. Addressing sickle cell disease: A strategic plan and blueprint for action. Washington, DC: The National Academies Press. http://doi.org/10.17226/25632.

COMMITTEE ON ADDRESSING SICKLE CELL DISEASE: A STRATEGIC PLAN AND BLUEPRINT FOR ACTION

MARIE CLARE McCORMICK (Chair), Sumner and Esther Feldberg Professor (Emerita), Department of Social and Behavioral Sciences, Professor of Pediatrics, Harvard University

GILDA BARABINO, Dean and Daniel and Frances Berg Professor, The Grove School of Engineering, The City College of New York

MARY CATHERINE BEACH, Professor, General Internal Medicine and Berman Bioethics Institute, Johns Hopkins University

LORI E. CROSBY, Professor of Pediatrics, Cincinnati Children’s Hospital

AMY DAWSON, Associate Director, Medical Director, Fort Wayne Medical Education Program

DARIUS LAKDAWALLA, Quintiles Chair in Pharmaceutical Development and Regulatory Innovation, Director of Research, University of Southern California

BERNARD (BERNIE) LOPEZ, Professor and Executive Vice Chair, Department of Emergency Medicine, Sidney Kimmel Medical College, Thomas Jefferson University

JONATHAN D. MORENO, David and Lyn Silfen University Professor, Professor of Medical Ethics and Health Policy, Professor of History and Sociology of Science, and Professor of Philosophy, University of Pennsylvania

ENRICO M. NOVELLI, Associate Professor of Medicine, University of Pittsburgh; Director, Adult Sickle Cell Program, and Chief, Section of Benign Hematology, University of Pittsburgh Medical Center

J. ANDREW ORR-SKIRVIN, Associate Clinical Professor, School of Pharmacy, and Interim Department Chair, Department of Pharmacy and Health System Sciences, Northeastern University

IFEYINWA (IFY) OSUNKWO, Hematologist–Oncologist Director, Sickle Cell Program, Atrium Health

SUSAN PAULUKONIS, Program Director, California Rare Disease Surveillance Program, Tracking California

CHARMAINE ROYAL, Associate Professor, Department of African and African American Studies, Duke University

KIM SMITH-WHITLEY, Clinical Director, Division of Hematology, Director, Comprehensive Sickle Cell Center, Children’s Hospital of Philadelphia, University of Pennsylvania

Staff

HENRIETTA AWO OSEI-ANTO, Study Director

KAREN M. ANDERSON, Senior Program Officer

T. CHERI BANKS, Associate Program Officer (September 2018–December 2019)

AHMED MOUER, Research Assistant (July 2019–January 2020)

PAMELA RAMEY-McCRAY, Senior Program Assistant (December 2018–March 2019)

CYNDI TRANG, Research Associate (from June 2019)

HAYAT YUSUF, Senior Program Assistant (March 2019–February 2020)

ROSE MARIE MARTINEZ, Senior Director, Board on Population Health and Public Health Practice

Consultant

ROBERT POOL, Deliberate Practice Consulting

Reviewers

This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.

We thank the following individuals for their review of this report:

Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report, nor did they see the final draft before its release. The review of this report was overseen by OTIS W. BRAWLEY, Johns Hopkins University, and MAXINE HAYES, University of Washington. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.

Acknowledgments

The study committee and the Health and Medicine Division project staff take this opportunity to recognize and thank the many individuals who shared their time and expertise to support the committee’s work and inform its deliberations.

This study was sponsored by the Office of Minority Health at the Office of the Assistant Secretary for Health at the U.S. Department of Health and Human Services. We thank Admiral Brett Giroir and Captain David Wong for their support and guidance.

The committee benefited greatly from discussions with the individuals who presented at and attended the committee’s open sessions: Lakiea Bailey, Zyekevious (Zye) Barnes, Edward Benz, Jr., Beatrice Bowie, Brynn Bowman, Stephen Cha, Cheryl Damberg, Bernard Dauvergne, Tracie Bullock Dickson, Brian M. Elliott, ADM Brett P. Giroir, Jeffrey Glassberg, Gregory Green, Jonathan Hamilton, Elijah Henry, Tony Ho, Mary Hulihan, Charles Jonassaint, Ronald M. Kline, Ruth Krystopolski, Ted W. Love, Marc Manley, Donna McCurry, Emily Riehm Meier, Shirley Miller, Betsy Myers, Jennifer Nsenkyire, Tosin Ola, Derek Robertson, Kathryn Sabadosa, Carmen Sánchez, Adrienne Bell-Cors Shapiro, Amy Shapiro, Barbara Speller-Brown, James G. Taylor VI, Michael Thomas, Alexis Thompson, Sara van Geertruyden, Mark Walters, Richard P. Weishaupt, Shauna H. Whisenton, Wanda Whitten-Shurney, Celia Witten, Teonna Wolford, and CAPT David Wong. The committee would also like to thank all participants who attended the committee’s open sessions and all others who made or submitted comments or materials for the committee’s consideration. The committee is grateful to these presenters for volunteering to share their

expertise, knowledge, data, and opinions not only with the committee but also with the members of the public who participated in the committee’s open sessions. The committee also appreciates the efforts of numerous individuals who assisted project staff in identifying the presenters. We would like to thank and acknowledge organizations who supported and provided us with invaluable information to consider for this report, including the staff at the American Society of Hematology, the Association of Public Health Laboratories, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration.

Furthermore, we acknowledge the many staff within the Health and Medicine Division who provided support in various ways to this project, including Stephanie Hanson, Aimee Mead, Sophie Yang, Rebecca Chevat, Dionna Ali, and Anne Styka; Nicole Joy and Greta Gorman from the communications office; Lauren Shern and Taryn Young, who provided support during the review process; Misrak Dabi, financial associate for the project; the late Daniel Bearss, senior research librarian, who conducted and compiled all of the literature searches; Jorge Mendoza-Torres, senior research librarian, who assisted with additional searches; Robert Pool, for his editorial assistance provided in preparing the final report; and Andrea Matthews of the Children’s Sickle Cell Foundation, Inc., Pittsburgh, Pennsylvania, for sharing her expertise and personal experience to inform the report. Finally, we want to thank our consultants, Anna Hood, Jenny Park, Shantanu Srivatsa, and Jeffrey Yu, who assisted committee members with identifying information for this report.

Preface

This consensus study report was commissioned by the Office of Minority Health at the Office of the Assistant Secretary for Health at the U.S. Department of Health and Human Services to provide a comprehensive approach to the management and potential interventions for sickle cell disease (SCD), a genetic condition affecting approximately 100,000 people in the United States and millions worldwide.¹ While the molecular basis for the symptoms and complications of SCD and screening techniques to identify newborns with the disease have been known for decades, the development of interventions to improve the quality of life for these individuals, as well as the organization of health care systems to deliver appropriate care, has lagged. There has been substantial success in increasing the survival of children with SCD, but this success had not been translated to similar care as they now become adults. As will be argued in the report, a factor contributing to the slow progress is the fact that SCD is largely a disease of African Americans and as such exists in a context of racial discrimination, mistrust of the health care system, and the effects of poverty. In addition, there is substantial evidence that those with SCD may receive poorer quality of care. Finally, it should be noted that for a condition for which the presenting symptom may be acute and chronic pain, receipt of appropriate treatment is also influenced by the opioid crisis.

The report sets forth a substantial agenda beginning with the important need for information across the life span to characterize the trajectory

___________________

¹ This text has changed since the prepublication release of this report to more accurately reflect the estimates of prevalence of sickle cell disease identified in the literature.

of SCD and the antecedents of later complications. In parallel is the need to organize health care delivery and other services at the local, state, and global levels with a knowledgeable workforce to address the multiple needs of those with SCD, including engaging with the educational system and community-based groups. Although there is evidence of several important therapies in the pipeline, greater investment in research is needed into both more of these therapies and the dissemination of effective care into the affected population, especially in view of historical mistrust. This is not an impossible agenda; examples from other inborn conditions indicate that it can be done. The resilience of individuals living with SCD and the dedication of their families and communities that support them should also be harnessed as part of the solution.

I wish to express my gratitude for the excellent and demanding work done by the committee and staff members. However, special thanks are due to the individuals and organizations who shared often searing accounts of living with SCD, underscoring the urgency of the recommendations in the report.

Marie Clare McCormick, Chair
Committee on Addressing Sickle Cell Disease:
A Strategic Plan and Blueprint for Action

Contents

ACRONYMS AND ABBREVIATIONS

SUMMARY

1 INTRODUCTION

Scope of Work

Study Process and Information Gathering

Overview of SCD and SCT

The Sickle Cell Patient and the Health Care System

Policy Making and Funding for SCD

Key SCD Actors

Organization of the Report

References

2 SOCIETAL AND STRUCTURAL CONTRIBUTORS TO DISEASE IMPACT

Introduction

Societal Factors

Individual Factors

Environmental Factors

The Burden of SCD

Conclusions and Recommendations

References

3 SCREENING, REGISTRIES, AND SURVEILLANCE

Screening for SCD and SCT

Communicating Screening Results

The Use of Screening Data

Patient Registries

Public Health Surveillance

Ethical Implications and Privacy Considerations

Conclusions and Recommendations

References

4 COMPLICATIONS OF SICKLE CELL DISEASE AND CURRENT MANAGEMENT APPROACHES

Introduction

Pain in SCD

Overview of SCD Complications

Management of SCD

SCT

Conclusions and Recommendations

References

5 HEALTH CARE ORGANIZATION AND USE

Introduction

Health Care for Children with SCD

Transition from Pediatric to Adult Care

Health Care for Adults with SCD

Comprehensive SCD Care Delivery Model

Barriers to Comprehensive Care

Services for SCT

Conclusions and Recommendations

References

6 DELIVERING HIGH-QUALITY SICKLE CELL DISEASE CARE WITH A PREPARED WORKFORCE

Guidelines for High-Quality SCD Care

Patient-Centered Dimensions of High-Quality Care

Promoting Uptake of Recommendations for SCD Care

Quality Indicators for SCT and Genetic Counseling for SCD and SCT

Summary

The Availability of a Trained and Prepared Workforce

Training the Next Generation of SCD Care Providers

Conclusions and Recommendations

References

7 DEVELOPING AND DELIVERING THE NEXT GENERATION OF THERAPIES

Patient Perspectives

Therapies Under Development

Clinical Trials and the Drug Approval Process

Health Care Delivery Policy

Reimbursement Policy

Conclusions and Recommendations

References

8 COMMUNITY ENGAGEMENT AND PATIENT ADVOCACY

Historical Perspective

Sickle Cell Community-Based Organizations and Patient Advocacy Groups

Challenges Faced by Sickle Cell Advocates and Groups

Models of Patient Advocacy from Other Rare Diseases

Opportunities to Move from Local to System-Level Change

Summary

Conclusions and Recommendations

References

9 STRATEGIC PLAN AND BLUEPRINT FOR SICKLE CELL DISEASE ACTION

References

APPENDIXES

A Public Meeting Agendas and Submissions to the Committee

B Literature Search Terms and Strategy

C Committee and Staff Biographies

D Newborn Screening Results Reporting Protocols for Sickle Cell Disease and Sickle Cell Trait

E Sickle Cell Data Collection Program

F Georgia Comprehensive Sickle Cell Center: A Case Study

G Emory Adult Cystic Fibrosis Program

H Health Resources and Services Administration Sickle Cell Disease Programs

I Select Treatments Currently Under Development for Sickle Cell Disease

J Other Training Models for Hematologists

K Sickle Cell Community-Based Organizations and Patient Groups in the United States

L Summary Table of Strategic Plan and Blueprint for Sickle Cell Disease Action

M Summary Table of Sickle Cell Trait Discussion in Report

N Glossary

Boxes, Figures, and Tables

BOXES

S-1 Committee’s Statement of Task

1-1 Committee’s Statement of Task

3-1 A Patient’s Voice: A Changing Perspective

4-1 American Pain Society Pain Taxonomy Diagnostic Criteria for Chronic Pain Associated with SCD (Chronic SCD Pain)

5-1 Key Elements for an Ideal Care Model

6-1 Highlights of the National Heart, Lung, and Blood Institute Expert Panel Recommendations for SCD, 2014

8-1 A Caregiver’s Story

FIGURES

S-1 A life-span approach to understanding and addressing the needs of the SCD population

S-2 Model of person-centric care for SCD

S-3 Strategic plan for improving SCD care and outcomes in the United States

1-1 A life-span approach to understanding and addressing the needs of the SCD population

1-2 Model of person-centric care for SCD

1-3 How sickle cell trait and sickle cell disease are inherited

1-4 Geographic distribution of SCD by state using data derived from the National Newborn Screening Information System

1-5 Mean disease burden in the United States among individuals with certain diseases

1-6 Timeline of key SCD-related milestones

1-7 Timeline of SCD drug approvals

1-8 National Institutes of Health funding for SCD versus cystic fibrosis

1-9 Foundation funding for SCD versus cystic fibrosis

2-1 Estimated number of individuals with SCD across the United States and Medicaid non-expansion states

6-1 Guiding framework for the transformation of care delivery

6-2 Core measure sets for SCD care

6-3 Elements of improving the emergency department experience

7-1 Schematic diagram of the mechanisms of action of pathophysiology-based new therapeutic options for treatment of SCD and sickle cell vasculopathy

8-1 Federal agencies involved in SCD and SCT activities stemming from the Sickle Cell Treatment Act

8-2 Multiple barriers can be addressed by community health workers for SCD

8-3 Funding sources for SCD patient organizations

9-1 Strategic plan for improving SCD care and outcomes in the United States

H-1 HRSA Sickle Cell Treatment Demonstration Program and Sickle Cell Disease Newborn Screening Follow-Up Program

TABLES

1-1 Common SCD Genotypes, Nomenclature, and Mutational Products

1-2 Description of SCD Key Actors

3-1 Stakeholders Informed by Newborn Screening Programs

4-1 Summary of SCD Complications by Affected Organ or System

4-2 Summary of Non-Organ-Specific SCD Complications

5-1 The ABCs for Managing Acute Sickle Cell Pain

5-2 Simple Rules for the 21st-Century Health Care System

6-1 Multidisciplinary Team of Medical Providers and Specialists Necessary to Provide Comprehensive SCD Care

8-1 Community-Based Organization Services Supporting the Needs of Children and Adults with SCD and SCT, Not Including Advocacy

8-2 Proposed Classification System for Stratification of Services Provided by an SCD Community-Based Organization

H-1 Programs at a Glance

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Acronyms and Abbreviations

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