Universal Newborn Screening For Sickle Cell Disease In Mozambique

Overview

The overarching goal of this study is to evaluate the feasibility of a new methodology that combines three multi-level implementation strategies to optimize the population-level uptake of essential evidence-based, standard of care treatments for infants with sickle cell disease (SCD) in low-resource settings. The study will be done in Mozambique.

Detailed description

This prospective mixed-methods hybrid effectiveness-implementation feasibility study will evaluate the feasibility and effectiveness of an implementation strategy package designed to improve early diagnosis and care entry for children born with sickle cell disease (SCD) in rural, low-resource settings. The implementation strategy package includes three components: 1) integration of essential products into national supply chain systems, 2) integration of systematic newborn screening using point-of-care-testing into clinical site workflows and 3) linkage of children who screen positive to a PEN-Plus Non-Communicable Disease (NCD) clinic for longitudinal care. Participants will be tracked longitudinally to evaluate protocol adoption over time and clinical outcomes among participating children at 2 years of age.

Primary Objective

* To test if combining three multi-level implementation strategies can facilitate systematic birth diagnosis and timely linkage to evidence-based care interventions for infants with SCD in under-resourced settings.

Secondary Objectives (Micro level):

* To test the clinical effectiveness of implementing the BB-SCD through the three combined implementation strategies to prevent excess mortality of children with SCD under the age of 2 years. * To evaluate the effectiveness of combining the three implementation strategies to promote care retention among infants with SCD by 2 years of age.

Secondary Objectives (Meso level)

* To evaluate the institutional coverage and health facility staff adoption of the treatment for infants through the combined implementation strategies. * To evaluate the need for a confirmatory test among positive and negative screening results using POCT. * To conduct a cost-effectiveness analysis of the combined implementation strategies.

Secondary Objective (Macro level)

* To evaluate the operational effectiveness of integrating the procurement of SCD consumables into national supply chain systems to achieve sustainable availability, effective last mile delivery to relevant clinics and stockout avoidance.

Interventions

• Other Point-of-care testing (POCT) -Patient participants
  Infants will be screened for Sickle Cell Disease using with point-of-care testing (POCT).
• Other Point-of-care testing (POCT) - Healthy control participants
  Infants will be screened for Sickle Cell Disease using with point-of-care testing (POCT) and prospectively monitored for survival.
• Other Context Assessment for Community Health (COACH) survey
  The COACH survey will collect quantitative data on eight contextual factors that impact a site's ability to implement evidence-based interventions.
• Other Semi-structured interview
  Interview questions will revolve primarily around the current process for SCD screening and care referrals, factors impacting newborn care delivery and screening, and challenges to integrating SCD newborn screening and care referral into standard care delivery.

Primary outcome measures

• Percentage of eligible population screened for Sickle Cell Disease [Time frame: 3 years]
• Percentage of new SCD cases linked to care [Time frame: 3 years]

Secondary outcome measures (9)

• Comparison of under-2 mortality between participants with SCD whom received longitudinal care and participants who screened negative for SCD [Time frame: 2 years post-screening and therapy]
• Percentage of SCD cases retained in care by 2 years of age [Time frame: 2 years post-screening and therapy]
• Percentage of eligible secondary-level clinical wards implementing systematic screening and linkage to longitudinal care for new SCD cases [Time frame: 3 years]
• Percentage of eligible health facility staff participants in secondary-level clinical wards implementing systematic screening and linkage to longitudinal care for new SCD cases [Time frame: 3 years]
• Comparison of SCD Screening Performance Results from Initial point-of-care (POCT), Gazelle, and Hemoglobin Fractionation [Time frame: 3 years]
• Cost-Effectiveness of Integrating SCD Consumables into National Supply Chains [Time frame: 2 to 5 years]
• Cost-Effectiveness of POCT for Early SCD Diagnosis [Time frame: 2 to 5 years]
• Cost-Effectiveness of Decentralized PEN-Plus SCD Management [Time frame: 2 to 5 years]
• Frequency of SCD Supply Stockouts at Study Sites [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Children participants: All infants between birth and 6.0 months of age who are born or receive care at secondary-level facilities involved in the UNIQUE study.
• Children participants will fall into one of two categories:

• Patient participants: All infants between birth and 6.0 months of age who were screened through the UNIQUE study and tested positive for SCD (HbSS, HbSC, or other form of SCD) or had indeterminate results.
• Healthy control participants: Infants between birth and 6.0 months of age who screen negative for SCD (HbAA) through the UNIQUE study or tested positive for sickle cell trait (HbAS).
• Health facility staff participants: Healthcare staff ages ≥18 years working at secondary-level facilities involved in the UNIQUE study.
• Supply chain expert participants: Administrative professionals with experience working in or around the national supply chain systems in Mozambique to support procurement, importation, customs clearance, storage, and in-country distribution of medical products.
• National public health system expert participants: Administrative professionals with experience working in the national public health system (e.g., Ministry of Health, MISAU) who oversee the delivery of health services to infants in-country, such as neonatal testing and vaccination programs.

Exclusion criteria

• Children participants:

• Stillbirths.
• Children who received an erythrocyte (blood) transfusion within 3 months of testing. Exogenous (transfused) HbA could artificially lower the sickle hemoglobin concentration, thus causing false-negative results.
• Patient participants: none
• Healthy control participants:

• Stillbirths.
• Children who received an erythrocyte (blood) transfusion within 3 months of testing. Exogenous (transfused) HbA could artificially lower the sickle hemoglobin concentration, thus causing false-negative results.
• Health facility staff participants: none.
• Supply chain expert participants: none.
• National public health system expert participants: none.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07719972 · UNIQUE · U1111-1335-3817

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗