Multi-Stakeholder Panel Develops Core Set of Outcomes for Future Research in Sickle Cell Disease

Treatment options for patients with sickle cell disease (SCD) have increased quickly over the past several years. The landscape has expanded from the long-established options of hydroxyurea, repeat blood transfusions, and bone marrow or stem cell transplantation to recently include l-glutamine, voxelotor, and crizanlizumab. Additional agents are currently being studied in clinical trials.

To standardize future research efforts, a group of experts from multiple stakeholder groups has developed a consensus on the outcomes that should be studied at minimum in future clinical trials. Their recommendations were recently published in BMC Medical Research Methodology.

“With this long overdue increase in the pipeline for SCD therapies, the time is ripe to ensure a robust body of evidence on the safety, efficacy, and effectiveness of these new interventions is available for regulatory approval, health technology assessment, market access (coverage and reimbursement), and individual treatment decisions,” wrote the authors, led by Ellen Tambor of the Center for Medical Technology Policy in Baltimore, Maryland. “It is critical to ensure that selected outcomes reflect meaningful benefits of therapy for patients and are useful for decisions faced by regulators, payers, and other stakeholders.”

The article outlines the core outcome set (COS), coreSCD, which is a standard set of outcomes developed by a panel of experts that should be measured and reported, at a minimum, across clinical trials in this specific disease area. They hope the consensus and guidance will help researchers everywhere work toward a consistent, harmonized body of evidence that helps regulators, payers, providers, and patients make informed decisions for effective, value-based treatment.

Development included a research phase and surveys. Subsequently, a multi-stakeholder panel and committee discussed and voted. The group included clinicians, researchers, patients, caregivers, patient advocates, payer representatives, industry representatives, and governmental regulatory representatives.

The final coreSCD is divided into two categories: disease-modifying therapies that seek to improve long-term outcomes and acute interventions that are typically shorter in duration and may seek only to address symptoms.

The COS for clinical trials of disease-modifying therapies is:

  • acute sickle cell pain frequency
  • acute chest syndrome
  • ctroke or cerebrovascular accident
  • neurocognitive function
  • health-related quality of life
  • frequency of hospitalization
  • emergency department/acute care visit
  • need for blood transfusion
  • cause-specific survival/mortality
  • event-free survival

The COS for clinical trials of acute interventions is:

  • acute sickle cell pain frequency
  • acute chest syndrome
  • ability to return to usual activities
  • frequency of hospitalization
  • emergency department/acute care visit
  • cause-specific survival/mortality

The authors specified that the COS is applicable across age groups, although the way each factor is measured may differ between subpopulations (e.g., pain in adult versus pediatric populations). They also noted that the COS does not include side effects and adverse events, because those are already required by regulatory policies.