Critical Path for Sickle Cell Disease

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The Problem

Sickle Cell is a hereditary disease that affects as many as 100,000 people in the United States. It is caused by a single mutation in the b-globin gene, causing the malfunction of hemoglobin, the component of the blood responsible for delivering oxygen to internal organs. The abnormal hemoglobin causes cell deformation, or “sickling,” of red blood cells, a disease hallmark.  These sickle cells can block blood vessels, causing recurrent pain, and damaging the liver, heart and kidneys, which may lead to premature death.

Since the severe form of Sickle Cell Disease (SCD) can decrease the quality of life and shorten patients’ lives, developing novel therapeutics to treat the disease is a clear unmet medical need. However, the heterogeneity of the SCD manifestations and outcomes makes clinical trials very challenging and the success rate low.

The Solution

The CP-SCD’s goal is to create a regulatory science strategy and de-risk medical developments to benefit individuals living with this disease. The CP-SCD consortium aims to bring together a wide range of SCD stakeholders, including partners from pharmaceutical industry companies, academic institutions, regulatory agencies and patient-advocacy organizations to accelerate treatments and therapies for SCD.

The consortium collaborates with C-Path’s Rare Disease Cures Accelerator-Data and Analytics Platform, the Quantitative Medicine Program, the Patient-Reported Outcome Consortium, the Regulatory Science group, and others to accomplish its mission. We analyze clinical trial data, create mathematical models that predict disease development, identify novel biomarkers and provide regulatory solutions for the pharmaceutical industry that could make clinical trials more rapid, less expensive and increase the success rate, thereby making new therapies available to patients with SCD sooner.

The Impact

CP-SCD collects, curates, and analyzes clinical datasets. To date, CP-SCD has accumulated six datasets of clinical data from over 6,000 patients. Data analysis and disease progression modeling are underway to provide model-informed drug development tools for pharmaceutical companies. That enables them to provide better treatments and improve the quality of life for SCD patients. Together, we save lives.

Current CP-SCD Initiatives

Unmet Clinical Needs In Sickle Cell Disease FAQ Icon
  • Despite the mortality rate decreasing by 18.2% for adults from 1979 to 20051 and by 68% for children aged 0 to 3 years from 1983 to 20022, improvements in SCD management and disease modification have lagged.
  • The introduction of pneumococcal vaccination and prophylactic antibiotic treatment have reduced SCD mortality, but a paucity of approved pharmaceutical agents have incompletely addressed the chronic and progressive symptoms and premature causes of death later in life.
  • Stem cell therapy has shown incredible promise, but due to expense and the technology required may remain unavailable to large segments of the population with sickle cell disease.



  • Lanzkron S, Carroll CP, Haywood C. Mortality Rates and Age at Death from Sickle Cell Disease: U.S., 1979–2005. Public Health Rep. 2013;128(2):110–6.
  • Yanni E, Grosse SD, Yang Q, Olney RS. Trends in Pediatric Sickle Cell Disease-Related Mortality in the United States, 1983-2002. The Journal of Pediatrics. 2009 Apr 1;154(4):541–5.
Opportunities In Medical Device Development For Sickle Cell Disease FAQ Icon
  • A more complete understanding of SCD natural history and clinical heterogeneity amongst patients could facilitate smaller, shorter trials that more effectively evaluate treatment efficacy.
  • Better measure harmonization and regulatory acceptance or endorsement of actionable endpoints can ensure incorporation of patient-voice into clinical trials and label claims.
  • More consistent endpoint measures and biomarkers across trials could allow comparison between studies
  • Trial enrollment is challenged by the historical neglect of SCD investigation, inattention to patient needs and failures to implement standard care, and resultant distrust of the medical system.
Solutions To Accelerate Medical Product Development FAQ Icon

In its first year, CP-SCD has begun the process of creating medical product development solutions for the SCD field.

CP-SCD Work To Date FAQ Icon

FDA Liaison appointed from Office of Cardiology, Hematology, Endocrinology and Nephrology – Division of Non-Malignant Hematology (DNH) to enable iterative regulator engagement and ensure alignment of consortium activities with Agency perspectives.

MAY 2021:
Data Working Group launched to enable data sharing collaborations, including prioritization of epidemiological and interventional studies, dataset acquisition and aggregation from multiple data custodians, including NHLBI.

JULY 2021:
Vasoocclusive (VOC) Clinical Outcomes Assessment Working Group launched to evaluate the current landscape of PRO measures relevant to the VOC assessment and identify possible regulatory science solutions.

Preparation to launch a Quantitative Working Group to facilitate regulatory endorsement of biomarkers or COAs that evaluate critical aspects of SCD in clinical trials.

Data Collaboration FAQ Icon

Integration of patient-level data from individual clinical trials and other sources to create an aggregated database to support regulatory endorsement submissions.

CP-SCD works closely with C-Path’s Rare Disease Accelerator– Data and Analytics Platform (RDCA-DAP®), which will eventually host and integrate CP-SCD data efforts. Standardization of key patient-level datasets from individual clinical trials and other data sources will support creation of an aggregated database to support regulatory endorsement submissions.


CP-SCD has so far acquired patient-level data representing nearly 7,000 individuals across six datasets.


Hematopoietic Cell Transplant for Sickle Cell Disease HCT for SCD
Treatment of Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy walk-PHaSST
Optimizing Primary Stroke Prevention in Children with Sickle Cell Anemia STOP II
Hydroxyurea to Prevent Organ Damage in Children with Sickle Cell Anemia (BABY HUG) Phase III Clinical Trial and Follow-Up Observational Studies I and II BABY HUG
Multicenter Study of Hydroxyurea MSH
Cooperative Study of Sickle Cell Disease CSSCD



Aggregation and modeling of these datasets with others to be acquired will allow synergistic insight into natural disease progression and correlation of short-term trial endpoints with long-term disease outcomes.


1. This publication was prepared using BABY_HUG, CSSCD, MSH, STOP_II, WALK_PHASST, and HCT for SCD Research Materials obtained from the NHLBI.

Vaso-Occlusive Crisis (VOC) Clinical Outcome Assessment (COA) Project FAQ Icon

Working group aim 3.3 from CP-SCD Stage 1 Research Plan

  • Review existing COA measures developed for VOC detection and assessment
  • Identify gaps in measurements of VOCs
  • Identify potential existing COAs or domains to fill gaps and be used in standardized manner across clinical trials
  • Define precess and assess regulatory readiness for advancement of COAs, with the goal of future regulatory acceptance


  • Priority: COAs that define VOC event
  • Secondary: COAs that assess VOC impact
  • Rationale: VOC event and/or components (e.g., duration) are going to be primary endpoint(s) of clinical trial. Need an endpoint that can indicate clinical benefitt from the patient perspective – evidence that treatment has a positive impact on how a patient feels, functions, or survives.



Internal C-Path Collaborators FAQ Icon

Rebecca (Becks) Speck, PhD, MPH, Clinical Outcome Assessment (COA) Scientist, COA Program, C-Path

Industry Co-Director FAQ Icon

David Readett, MD, Global Clinical Lead, Pfizer

Government and Regulatory Agencies FAQ Icon