STRENGTHS AND LIMITATIONS OF THIS STUDY

A large and diverse study population made up of various sickle cell disease (SCD) stakeholder groups, including parents whose babies have been screened for SCD, healthcare workers and policy-makers, will be recruited from across seven African countries.

The study will provide a broad assessment of the individual, organisational and external factors that may influence the reliability, feasibility, acceptability, adoption and sustainability of using dried blood spots-point of care testing for newborn screening of SCD in African countries.

Given the limited resources, including funding, we were not able to engage more stakeholders, such as primary and community healthcare workers, in the protocol development.

Introduction

Sickle cell disease (SCD) is an inherited blood disorder, affecting approximately 515 000 newborns annually, with roughly 75% occurring in Africa.1 Children with SCD face increased mortality risks, due to infections and other life-threatening complications associated with SCD. Childhood mortality due to SCD can be effectively prevented through early initiation of prophylactic measures, administration of penicillin, pneumococcal immunisations, malaria chemoprophylaxis, and parental education on the importance of seeking early medical attention. Newborn screening (NBS) offers a critical opportunity to enable early start of these interventions, yet its implementation remains rare across Africa.

A few initiatives, such as the Consortium on Newborn Screening in Africa (CONSA), are making efforts to introduce routine NBS for SCD in Africa. CONSA, whhich has presence in Ghana, Nigeria, Liberia, Kenya, Tanzania, Uganda and Zambia, aims to demonstrate the benefits of NBS for SCD in Africa through the introduction of standards-of-care practices for NBS and early intervention therapies such as antibiotic prophylaxis and immunisations.2 At the national level, Angola, Benin, Ghana, Liberia and Tanzania have pilot tested NBS programmes for SCD.3–8 However, sustainability of such programmes is often hindered by high cost and logistical challenges (e.g. shortage of skilled technicians, unstable electricity supply and costly reagents) of traditional SCD diagnostic methods such as isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC).9 10 Also, HPLC, while recognised as the gold standard for SCD diagnosis, may be less reliable in low-resource settings due to logistical difficulties associated with sample storage and processing.11

Point-of-care technologies (POCTs), including HaemoTypeSC and SickleScan, present cost-effective alternatives for SCD screening and allows for rapid results delivery and early diagnosis of SCD.12 13 HemoTypeSC and SickleScan are simple and easy to perform, take less than 15 min, do not require electricity, or specialised equipment, use less blood for testing and can be performed by healthcare workers with little or no medical laboratory experience.13 The diagnostic accuracy and feasibility of POCT using HemoTypeSC and SickleScan have been demonstrated in Angola, Ghana, Nigeria, Tanzania, Uganda and Democratic Republic of Congo.14–20 However, challenges related to interpretation of results and cost-effectiveness of the traditional use of these POCTs have been reported.13 17 Also, while SickleScan was favoured by healthcare workers in Angola,18 it is more expensive than HemoTypeSC, making HemoTypeSC (approximately US$2.5 per test), the preferred POCT for use in resource-limited settings.

Integrating NBS into primary healthcare structures, such as immunisation programmes and antenatal clinics, can be an effective strategy for NBS of SCD in African countries.21 However, the standard HemoTypeSC uses fresh capillary blood, screening must be on the spot. This is a huge barrier to implementation at primary healthcare facilities. Using dried blood spots (DBS), instead of fresh capillary blood on HemoTypeSC, can be a more practical approach.15 Nonetheless, there is limited empirical evidence to guide the implementation and adoption in primary healthcare settings in Africa. The SickleInAfrica consortium22 will be conducting implementation science research on DBS-POCT for NBS of SCD in Africa after a preliminary quantitative validation step. This protocol mainly focuses on the qualitative aspects of the larger SickleInAfrica NBS project on “Clinical and Implementation Research for Newborn Screening for Sickle Cell Disease Using Dried Blood Spots for Point-of-Care Tests.”

Objectives

Previous studies on NBS for SCD in Africa have predominantly focused on the perspectives of SCD programme leaders,9 with limited involvement of mothers and caregivers of babies that have been diagnosed with SCD. When patients and caregivers were involved, it was limited to investigating opportunities and challenges oforr the full integration of NBS into the healthcare system.23 There is need for a comprehensive exploration of factors affecting adoption and long-term sustainability from the perspectives of multiple stakeholders. This SickleInAfrica NBS project aims to address this gap by employing qualitative research methods to explore factors that could influence the adoption of DBS-POCT at primary healthcare centres in comparison to traditional diagnostic approaches such as IEF and HPLC. The overarching aim will be addressed through four specific objectives:

To evaluate the performance characteristics and cost of DBS-POCT against IEF/HPLC.

To explore the views of healthcare workers and policy-makers regarding the suitability of using DBS-POCT for NBS for SCD compared with IEF and HPLC. This will enable SickleInAfrica to gain insights into factors that may influence the acceptability and feasibility of DBS-POCT at primary healthcare facilities over IEF and HPLC.

To explore the perceptions of mothers and healthcare workers on the implementation of DBS-POCT at primary healthcare facilities including maternity wards, antenatal care facilities and vaccination centres.

To identify factors that may influence the adoption of DBS-POCT at primary healthcare facilities in comparison to IEC and HPLC.

Methodology

The qualitative arm of the SickleInAfrica NBS implementation project is heavily informed by the first two phases of the study. The SickleInAfrica NBS study is made of three phases (figure 1). The first phase is a performance evaluation of the DBS-POCT against the gold standard methods, that is, IEF and HPLC. Specifically, the diagnostic performance of DBS-POCT will be assessed using 100 samples obtained from newborns from each participating country. The protocol involves the collection of DBS samples from babies at immunisation clinics, which will be transported to a clinical laboratory for testing. Positive samples identified through DBS-POCT will be confirmed by either IEF or HPLC. The second phase (quantitative phase) involves the use of a cross-sectional practice capacity survey, administered to healthcare workers and parents of babies screened for SCD, to identify factors that may influence acceptability, adoption and sustainability of DBS-POCT for NBS of SCD compared with IEF and HPLC. The third phase is a qualitative study to gain in-depth understanding of acceptability, barriers and facilitators of Using DBS-POCT for NBS of SCD in Africa.

Figure 1

Overall SickleInAfrica NBS study sites and design. Final numbers of FGD/IDI will be determined by the principle of saturation. CHEWs, community health extension workers; FGD, focus group discussion; IDI, in-depth interview; NBS, newborn screening; PF, performance characteristics; QP, quantitative phase.

Qualitative study design: theoretical and empirical approach

After the performance evaluation and quantitative phase, a theoretically informed phenomenological qualitative study will be done to explore the perspectives of various stakeholders (parents whose babies have been screened for SCD, healthcare workers and policy-makers) regarding the acceptability, barriers, facilitators of using DBS-POCT for NBS of SCD in Africa.

Theoretical approach

The study design is anchored on the Consolidated Framework for Implementation Research (CFIR), a widely used theoretical framework in implementation science.24 The CFIR facilitates the prediction and explanation of contextual factors that act as barriers and facilitators to the effective implementation of an intervention. It comprises five key domains: inner setting, outer setting, intervention characteristics, characteristics of individuals involved and processes of implementation.24 25 Within these domains are 37 specific constructs that may act as barriers and/or enablers to implementation. The strength of the CFIR framework lies in its extensive range of constructs, which not only encompass attributes of the intervention but also the broader environmental and organisational context within which implementation occurs. The use of the CFIR would facilitate a nuanced analysis of the various factors that may influence the successful implementation, adoption and sustainability of DBS-POCT for SCD screening at primary healthcare facilities in Africa (table 1).

Table 1

CFIR domains for the SickleInAfrica NBS implementation science project

In addition to drawing on the CFIR, this study will use the implementation outcome model26 27 to inform data analysis and interpretation. The implementation outcome model complements the CFIR as it offers a comprehensive taxonomy of conceptually distinct implementation outcomes, both anticipated and actual, namely, acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration and sustainability (table 2).

Table 2

Anticipated use of the implementation outcome model for the SickleInAfrica NBS implementation science project

Collection of empirical qualitative data

Qualitative research methods are invaluable tools for obtaining comprehensive insights into the underlying reasons for both the failures and successes in implementing evidence-based innovations.28 In this study, a combination of qualitative data collection methods will be used to explore the perspectives of various stakeholders regarding the acceptability, barriers and facilitators of the use of DBS-POCT for NBS of SCD. Data collection is scheduled to commence in June 2024 and end in August 2024. The qualitative data collection phase will involve:

Semi-structured, one-on-one, in-depth interviews (IDIs) and focus group discussion (FGD) with healthcare workers to gain an understanding of their experiences and expectations of using DBS-POCT for NBS for SCD at primary healthcare centres. This will provide insights into the day-to-day encounters, challenges and opportunities for improvement

Semi-structured IDIs with policy-makers to facilitate discussions around their perspectives and insights regarding the implementation of DBS-POCT for SCD NBS. This will provide insights into broader contextual factors (resources, policies, etc) that may influence the adoption and sustainability of DBS-POCT for universal screening of SCD in the participating countries.

Semi-structured IDIs and FGDs with parents whose babies have recently undergone testing for SCD using DBS-POCT as part of the study. These will enable an in-depth exploration of their experiences, expectations and factors that may contribute to, or limit, the success and adoption of DBS-POCT for NBS of SCD at PHC in Africa.

Study setting

This study will be conducted in seven African countries namely, Ghana, Mali, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe. These countries are part of SickleInAfrica, a multinational research consortium dedicated both to facilitating SCD research and translating the findings into practical interventions that will improve the quality of life for persons living with SCD in Africa.22 The study will be implemented at the SickleInAfrica clinical networks in each country, including primary sites, satellite sites and affiliated primary healthcare centres. In all the countries, paediatric care for SCD is provided at primary healthcare facilities, and babies diagnosed with SCD have access to folic acid and prophylaxis for infections (e.g, oral penicillin and vaccines).

Participant selection

The study population will consist of the following stakeholders: parents whose babies have been diagnosed with SCD, policy-makers and healthcare workers (eg, physicians, nurses, midwives, community health extension workers, health counsellors and laboratory scientists).

Sampling

Purposive sampling29 will be used to identify potential participants for the IDIs and FGDs. Participants will be selected based on the following criteria:

Able to communicate in English (all sites); French (Mali); Swahili (Tanzania) and other local languages that may be used to a limited extent at the different sites, such as Pidgin in Nigeria, Shona in Zimbabwe, Bambara in Mali and Bemba in Zambia.

Adults (≥18 years) who give informed consent.

Mothers whose babies have just been screened for SCD through the project.

Healthcare workers involved in the NBS screening pilot programme at the study sites.

Policy-makers at hospital level or national SCD programmes.

Sample size

About 10 IDIs will be conducted with each stakeholder group (mothers, healthcare workers and policy-makers) per country, resulting in 30 interviews per country; and an overall total of 210 IDIs across all 7 countries. Additionally, approximately 35 FGDs (5 per country) will be done with parents, with group sizes ranging from 5 to 6. The final sample size will be guided by the principle of data saturation.30 31

Design of IDI and FGD guides

Semistructured topic guides will be used for all IDIs and FGDs. The guides have been developed based on the CFIR and implementation outcome model (tables 1 and 2) and are tailored to each stakeholder group. Specific questions for healthcare workers and policy-makers will focus on (1) their perceptions of implementing NBS for SCD at primary healthcare centres, such as maternity wards, antenatal clinics and vaccination centres in their respective countries and (2) factors that may affect the adoption of NBS for SCD in PHCs, including cost, workforce and sustainability. The IDIs and FGDs with mothers will primarily explore their knowledge and beliefs about NBS for SCD, their opinions on screening at PHCs and suggestions for improving the process for both mothers and their newborns. We are currently piloting the semistructured FGD/IDI guides to improve clarity.

Data analysis data interpretation

All IDIs and FGDs will be audio recorded and transcribed verbatim. The transcripts will then be imported into NVivo V.14, a qualitative data management software,32 to support thematic analysis.33 The analysis process will begin with data familiarisation, where researchers involved in the analysis will repeatedly read the transcripts and field notes to gain a comprehensive understanding of the data. Two transcripts from each participating site will be selected for thematic analysis to develop a coding framework.34 The thematic analysis will adopt a hybrid (inductive and deductive coding) approach.35

Initially, an open (inductive) approach will be employed, with researchers conducting line-by-line open coding of data from the selected transcripts and field notes. This process will enable the identification of interesting codes and insights emerging from the data. Subsequently, analysis will transition to a deductive approach, where codes will be informed by the research questions and the implementation outcome model. This iterative process will result in the development of a preliminary coding framework that will be applied to the entire dataset. The coding framework will be continually reviewed, adapted and refined as new themes emerge throughout the study. The analysis team will convene biweekly to resolve any discrepancies in coding and ensure consistency in the interpretation of data. Data analysis will also highlight instances unique to specific contextual factors, such as social, cultural and political influences.

Once coding is complete, the framework method described by Gale et al 34 will be used to analyse the data by different dimensions, commonalities of themes, patterns and linkages, as well as by participant characteristics. This will facilitate the comparison of facilitators, enablers and barriers across the domains of the CFIR, both within and between stakeholder categories.

The Standards for Reporting Qualitative Research (SRQR) checklist36 will be used to guide the reporting of the study results. The checklist provides guidelines for transparent and comprehensive reporting of qualitative research findings, enhancing the rigour and trustworthiness of the study’s reporting. Direct quotes from IDIs/FGDs will be used to support the analytical findings. Interpretation of the findings will be validated with a subset of study participants, in line with SRQR requirements, to enhance trustworthiness of the results.

Patient and public involvement

Three stakeholder groups were actively engaged in the development of this protocol. These included representatives from SCD patient support groups, policy-makers responsible for national programmes for SCD or non-communicable diseases, and members of research ethics committees.

SCD patient support group representatives

Representatives from SCD patient support groups provided input into the protocol development. Their contributions focused on general perceptions about NBS for SCD, key social and ethical considerations and recommendations for genetic and psychosocial counselling sessions for mothers. They also emphasised the importance of providing educational information to mothers on how to care for a child with SCD.

Policy-makers

Engagement with policy-makers focused on strategies for facilitating the uptake of DBS-POCT for NBS of SCD at primary healthcare facilities. Policy-makers provided insights into potential policy implications, regulatory considerations and strategies for scaling up DBS NBS programmes. Their input reinforced the need to consider the outer setting, including broader contextual and political factors, that may influence the implementation and adoption of DBS-POCT for SCD.

Research ethics committee members

Members of research ethics committees (RECs) were engaged to identify potential ethical and social issues that may arise in the conduct of the study. Their input helped to ensure that ethical considerations were adequately considered and addressed in the study design.

Ethics and dissemination

Research ethics approvals have been obtained from RECS at all participating countries: Nigeria (NHREC/01/01/2007-13/02/2023); Mali (2021/106/CE/USTBB); Ghana (CHRPE/AP659/23); Uganda (Mak-SOMREC-2022–526); Tanzania (NIMR/HQ/R.8a/Vol IX/4494); Zambia (ERES-2023-Jun-008 and NHRA-002/27/07/2023) and Zimbabwe (MRCZ/A/3055). The protocol was reviewed by a data safety and monitoring board (DSMB) constituted by the funders (NIH).

Written informed consent will be obtained from all participants before their participation in the study. The IDIs and FGDs will be scheduled at a time and place convenient for participants. Participants will be informed of their right to withdraw from the study at any time without consequence.

To ensure participant confidentiality, all identifying information will be removed from transcripts and replaced with pseudonyms or unique identification numbers known only to a limited number of qualitative researchers at each site. Study-related materials containing personal information, such as informed consent forms and recordings, will be stored securely in locked filing cabinets with restricted access. Any digital information stored on computer databases will be password protected and accessible only to authorised personnel.

Preliminary findings will be shared with the SickleInAfrica steering committee to inform project progress and obtain feedback. For academic dissemination, the study findings will be published in peer-reviewed journals and presented at scientific conferences. Authorship will be determined according to the statement of the International Committee of Medical Journal Editors and the SickleInAfrica authorship policy.

For public dissemination, findings will be shared at meetings and webinars organised by SickleInAfrica and will target a broader audience including healthcare professionals, policy-makers SCD patient support groups and the general public. This will be done through policy briefs, accessible reports or presentations tailored to each group. For mothers who participated in the study, we will offer an easy-to-understand summary of the key findings in their preferred language (English, French or Swahili). We anticipate that we may not be able to reach all the mothers due to changes in address or contact details. However, the study results will be shared with the patient support groups that have been part of the design and implementation of this study. This is because they are likely to be in contact with the mothers as part of their peer-to-peer support programme. For policy-makers, we hope that the summary of the study findings will be used to inform policy development regarding NBS for SCD.

Limitations of the study design

Given the limited resources for the study, including funding, we were not able to engage more stakeholders, such as primary and community healthcare workers, in the protocol development. However, we acknowledge that wider stakeholder engagement may have helped to improve the scientific quality of the protocol.

Ethics statementsPatient consent for publication

Not applicable.

Acknowledgments

We thank all the stakeholder groups that participated in the protocol development. We acknowledge the feedback and contributions to the protocol from various SickleInAfrica Consortium members/collaborators and the Data Safety and Monitoring Board for the study