Introduction

Sickle cell disease (SCD) is a chronic disorder characterized by varied clinical outcomes, multi-organ involvement, reduced life expectancy, and low health-related quality of life (HRQOL).

In recent years, numerous clinical trials have failed in late stages due to inadequately defined clinical endpoints, p.e. relying solely on vaso-occlusive events requiring hospitalization to assess treatment efficacy. In this context, patient-reported outcomes measures (PROMs) have emerged as tools to enhance endpoint evaluation, providing a more comprehensive assessment of clinical outcomes and treatment efficacy. They are being incorporated into clinical practice to improve shared decision-making and healthcare quality evaluation, fostering strong engagement from clinicians and patients.

Numerous validated questionnaires exist addressing different aspects of health and wellbeing; however, many are lengthy or lack specificity for SCD.

Here we outline the process to develop a customized PROMs form focused on assessing HRQOL in SCD patients following a patient-centered approach.

The final aim is to integrate PROMs into routine clinical practice for patients with SCD, and to incorporate this new dataset into the RADeep Registry.

Methods and results

In April 2025, under the frame of ERDERA Alliance, a task force was launched within the RADeep network including clinical and PROMs experts from France, Italy, Spain, The Netherlands and UK.

The study population includes all SCD genotypes and exclude individuals who have undergone hematopoietic stem cell transplantation or gene therapy. Three cohorts are defined: adults (≥18 yo), pediatric (6-18yo), and caregivers for pediatric patients. A target of 150-200 patients per country has been set, with PROMs administered once per year during a follow-up visit in steady state.

PROMIS® was selected for this exercise based on the availability of pre-validated domains in SCD, broad accessibility, multiple language translations, adaptability for customization and capacity to enable comparisons across various chronic diseases.

Pain is the most common acute and chronic complication in adult and pediatric patients, and it negatively affects HRQOL and physical functioning. Moreover, pain and fatigue are important predictors of poor HRQOL in SCD. Based on literature review and clinician expertise, three domains were selected: fatigue, pain interference and physical function.

The form tailoring process will be conducted in two phases: first, content validation and assessment of subdomain relevance through the Delphi method; second, item selection using a constrained mathematical programming algorithm, restricted to items that achieved consensus for inclusion in phase 1.

A multinational expert Delphi panel was designed including a total of 37 members: 9 pediatricians, 9 hematologists, 11 patients/caregivers, 5 nurses and 3 psychologists. Each panelist will independently rate the relevance of each item from the selected domain banks using a 5-point Likert scale. Consensus will be determined using the median rating and interquartile range (IQR) based on pre-defined criteria: consensus for inclusion (median of 4 or 5 and IQR ≤ 1), consensus for exclusion (median of 1 or 2 and IQR ≤ 1) and no consensus (median of 3, or IQR > 1). Two rounds of rating are expected.

The final output of this two-phase process will be a set of two fixed-length PROMIS® short forms (adults and pediatric) tailored to SCD population and optimized regarding content validity (relevance and comprehensiveness), reliability (psychometric precision), and feasibility (readability and length).

The short forms will be self-administered, with trained personnel available to support participants while avoiding interview-based formats. Translations will be available in Arabic, Spanish, English, French, Italian, and Dutch. The short forms will be finalized by October 2025 and data collection will start by the end of 2025.

Conclusions

The incorporation of PRO data into routine clinical practice will contribute to a more patient-centered management, allowing clinicians to better monitor disease burden and treatment impact over time.

Furthermore, the integration of dataset into the RADeep Registry, alongside existing clinical and laboratory data, will significantly enhance the registry's relevance and enable multidimensional analyses and generation of regulatory-grade real-world evidence valuable for clinical trials.

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2025
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