Using Bayesian statistics in confirmatory clinical trials in the regulatory setting: a tutorial review.

Bayesian statistics plays a pivotal role in advancing medical science by enabling healthcare companies, regulators, and stakeholders to assess the safety and efficacy of new treatments, interventions, and medical procedures. The Bayesian framework offers a unique advantage over the classical framework, especially when incorporating prior information into a new trial with quality external data, such as historical data or another source of co-data. In recent years, there has been a significant increase in regulatory submissions using Bayesian statistics due to its flexibility and ability to provide valuable insights for decision-making, addressing the modern complexity of clinical trials where frequentist trials are inadequate. For regulatory submissions, companies often need to consider the frequentist operating characteristics of the Bayesian analysis strategy, regardless of the design complexity. In particular, the focus is on the frequentist type I error rate and power for all realistic alternatives. This tutorial review aims to provide a comprehensive overview of the use of Bayesian statistics in sample size determination, control of type I error rate, multiplicity adjustments, external data borrowing, etc., in the regulatory environment of clinical trials. Fundamental concepts of Bayesian sample size determination and illustrative examples are provided to serve as a valuable resource for researchers, clinicians, and statisticians seeking to develop more complex and innovative designs.

Best Practices and Recommendations for Research Using Virtual Real-Time Data Collection: Protocol for Virtual Data Collection Studies.

BACKGROUND: The COVID-19 pandemic and the subsequent need for social distancing required the immediate pivoting of research modalities. Research that had previously been conducted in person had to pivot to remote data collection. Researchers had to develop data collection protocols that could be conducted remotely with limited or no evidence to guide the process. Therefore, the use of web-based platforms to conduct real-time research visits surged despite the lack of evidence backing these novel approaches. OBJECTIVE: This paper aims to review the remote or virtual research protocols that have been used in the past 10 years, gather existing best practices, and propose recommendations for continuing to use virtual real-time methods when appropriate. METHODS: Articles (n=22) published from 2013 to June 2023 were reviewed and analyzed to understand how researchers conducted virtual research that implemented real-time protocols. "Real-time" was defined as data collection with a participant through a live medium where a participant and research staff could talk to each other back and forth in the moment. We excluded studies for the following reasons: (1) studies that collected participant or patient measures for the sole purpose of engaging in a clinical encounter; (2) studies that solely conducted qualitative interview data collection; (3) studies that conducted virtual data collection such as surveys or self-report measures that had no interaction with research staff; (4) studies that described research interventions but did not involve the collection of data through a web-based platform; (5) studies that were reviews or not original research; (6) studies that described research protocols and did not include actual data collection; and (7) studies that did not collect data in real time, focused on telehealth or telemedicine, and were exclusively intended for medical and not research purposes. RESULTS: Findings from studies conducted both before and during the COVID-19 pandemic suggest that many types of data can be collected virtually in real time. Results and best practice recommendations from the current protocol review will be used in the design and implementation of a substudy to provide more evidence for virtual real-time data collection over the next year. CONCLUSIONS: Our findings suggest that virtual real-time visits are doable across a range of participant populations and can answer a range of research questions. Recommended best practices for virtual real-time data collection include (1) providing adequate equipment for real-time data collection, (2) creating protocols and materials for research staff to facilitate or guide participants through data collection, (3) piloting data collection, (4) iteratively accepting feedback, and (5) providing instructions in multiple forms. The implementation of these best practices and recommendations for future research are further discussed in the paper. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53790.

Using Qualitative Questionnaires in Medical Education Research.

Most students in Health Profession Education courses are new to the world of qualitative research. Faced with the challenge of designing a research project, they are often drawn towards using the questionnaire as a data collection method, commonly assuming that utilising open-ended questions alone constitutes qualitative research design. Designing questionnaires that meet the standards of rigour is challenging, and this common assumption reflects inexperience with and misunderstandings of qualitative ontology, as well as the lack of methodological literature on designing and developing qualitative questionnaires. This paper is written with research supervisors as well as students in mind, as it is aimed to help elucidate the decision-making process and the justification for using a qualitative questionnaire. Drawing upon examples of research conducted by our students, and the wider literature, we demonstrate how qualitative questionnaires can produce rich and meaningful findings when they (1) prioritise qualitative research values, and (2) follow a rigorous design process when the questionnaire is developed. We conclude by offering a simple framework for developing rigorous qualitative questionnaires to those who may consider using this approach.

Co-creation of a toolkit to assist risk communication and clinical decision-making in severe preeclampsia: SPOT-Impact study design.

Globally, the incidence of hypertensive disorders of pregnancy, especially preeclampsia, remains high, particularly in low- and middle-income countries. The burden of adverse maternal and perinatal outcomes is particularly high for women who develop a hypertensive disorder remote from term (<34 weeks). In parallel, many women have a suboptimal experience of care. To improve the quality of care in terms of provision and experience, there is a need to support the communication of risks and making of treatment decision in ways that promote respectful maternity care. Our study objective is to co-create a tool(kit) to support clinical decision-making, communication of risks and shared decision-making in preeclampsia with relevant stakeholders, incorporating respectful maternity care, justice, and equity principles. This qualitative study detailing the exploratory phase of co-creation takes place over 17 months (Nov 2021-March 2024) in the Greater Accra and Eastern Regions of Ghana. Informed by ethnographic observations of care interactions, in-depth interviews and focus group and group discussions, the tool(kit) will be developed with survivors and women with hypertensive disorders of pregnancy and their families, health professionals, policy makers, and researchers. The tool(kit) will consist of three components: quantitative predicted risk (based on external validated risk models or absolute risk of adverse outcomes), risk communication, and shared decision-making support. We expect to co-create a user-friendly tool(kit) to improve the quality of care for women with preeclampsia remote from term which will contribute to better maternal and perinatal health outcomes as well as better maternity care experience for women in Ghana.

Adverse maternal and perinatal outcomes is high for women who develop preeclampsia remote from term (<34 weeks). To improve the quality of provision and experience of care, there is a need to support communication of risks and treatment decisions that promotes respectful maternity care.This article describes the methodology deployed to cocreate a user-friendly tool(kit) to support risk communication and shared decision-making in the context of severe preeclampsia in a low resource setting.

Approaches and experiences implementing remote, electronic consent at the Leeds Clinical Trials Research Unit.

BACKGROUND: Use of electronic methods to support informed consent ('eConsent') is increasingly popular in clinical research. This commentary reports the approach taken to implement electronic consent methods and subsequent experiences from a range of studies at the Leeds Clinical Trials Research Unit (CTRU), a large clinical trials unit in the UK. MAIN TEXT: We implemented a remote eConsent process using the REDCap platform. The process can be used in trials of investigational medicinal products and other intervention types or research designs. Our standard eConsent system focuses on documenting informed consent, with other aspects of consent (e.g. providing information to potential participants and a recruiter discussing the study with each potential participant) occurring outside the system, though trial teams can use electronic methods for these activities where they have ethical approval. Our overall process includes a verbal consent step prior to confidential information being entered onto REDCap and an identity verification step in line with regulator guidance. We considered the regulatory requirements around the system's generation of source documents, how to ensure data protection standards were upheld and how to monitor informed consent within the system. We present four eConsent case studies from the CTRU: two randomised clinical trials and two other health research studies. These illustrate the ways eConsent can be implemented, and lessons learned, including about differences in uptake. CONCLUSIONS: We successfully implemented a remote eConsent process at the CTRU across multiple studies. Our case studies highlight benefits of study participants being able to give consent without having to be present at the study site. This may better align with patient preferences and trial site needs and therefore improve recruitment and resilience against external shocks (such as pandemics). Variation in uptake of eConsent may be influenced more by site-level factors than patient preferences, which may not align well with the aspiration towards patient-centred research. Our current process has some limitations, including the provision of all consent-related text in more than one language, and scalability of implementing more than one consent form version at a time. We consider how enhancements in CTRU processes, or external developments, might affect our approach.

Regression discontinuity design for the study of health effects of exposures acting early in life.

Regression discontinuity design (RDD) is a quasi-experimental approach to study the causal effect of an exposure on later outcomes by exploiting the discontinuity in the exposure probability at an assignment variable cut-off. With the intent of facilitating the use of RDD in the Developmental Origins of Health and Disease (DOHaD) research, we describe the main aspects of the study design and review the studies, assignment variables and exposures that have been investigated to identify short- and long-term health effects of early life exposures. We also provide a brief overview of some of the methodological considerations for the RDD identification using an example of a DOHaD study. An increasing number of studies investigating the effects of early life environmental stressors on health outcomes use RDD, mostly in the context of education, social and welfare policies, healthcare organization and insurance, and clinical management. Age and calendar time are the mostly used assignment variables to study the effects of various early life policies and programs, shock events and guidelines. Maternal and newborn characteristics, such as age, birth weight and gestational age are frequently used assignment variables to study the effects of the type of neonatal care, health insurance, and newborn benefits, while socioeconomic measures have been used to study the effects of social and welfare programs. RDD has advantages, including intuitive interpretation, and transparent and simple graphical representation. It provides valid causal estimates if the assumptions, relatively weak compared to other non-experimental study designs, are met. Its use to study health effects of exposures acting early in life has been limited to studies based on registries and administrative databases, while birth cohort data has not been exploited so far using this design. Local causal effect around the cut-off, difficulty in reaching high statistical power compared to other study designs, and the rarity of settings outside of policy and program evaluations hamper the widespread use of RDD in the DOHaD research. Still, the assignment variables' cut-offs for exposures applied in previous studies can be used, if appropriate, in other settings and with additional outcomes to address different research questions.

Replication of null results: Absence of evidence or evidence of absence?

In several large-scale replication projects, statistically non-significant results in both the original and the replication study have been interpreted as a 'replication success.' Here, we discuss the logical problems with this approach: Non-significance in both studies does not ensure that the studies provide evidence for the absence of an effect and 'replication success' can virtually always be achieved if the sample sizes are small enough. In addition, the relevant error rates are not controlled. We show how methods, such as equivalence testing and Bayes factors, can be used to adequately quantify the evidence for the absence of an effect and how they can be applied in the replication setting. Using data from the Reproducibility Project: Cancer Biology, the Experimental Philosophy Replicability Project, and the Reproducibility Project: Psychology we illustrate that many original and replication studies with 'null results' are in fact inconclusive. We conclude that it is important to also replicate studies with statistically non-significant results, but that they should be designed, analyzed, and interpreted appropriately.

Comparative review of novel model-assisted designs for phase I/II clinical trials.

In recent years, both model-based and model-assisted designs have emerged to efficiently determine the optimal biological dose (OBD) in phase I/II trials for immunotherapy and targeted cellular agents. Model-based designs necessitate repeated model fitting and computationally intensive posterior sampling for each dose-assignment decision, limiting their practical application in real trials. On the other hand, model-assisted designs employ simple statistical models and facilitate the precalculation of a decision table for use throughout the trial, eliminating the need for repeated model fitting. Due to their simplicity and transparency, model-assisted designs are often preferred in phase I/II trials. In this paper, we systematically evaluate and compare the operating characteristics of several recent model-assisted phase I/II designs, including TEPI, PRINTE, Joint i3+3, BOIN-ET, STEIN, uTPI, and BOIN12, in addition to the well-known model-based EffTox design, using comprehensive numerical simulations. To ensure an unbiased comparison, we generated 10,000 dosing scenarios using a random scenario generation algorithm for each predetermined OBD location. We thoroughly assess various performance metrics, such as the selection percentages, average patient allocation to OBD, and overdose percentages across the eight designs. Based on these assessments, we offer design recommendations tailored to different objectives, sample sizes, and starting dose locations.

Asking those who know their needs best: A framework for active engagement and involvement of childhood cancer survivors and parents in the process of psychosocial research-A workshop report.

BACKGROUND: Patient and public involvement and engagement (PPIE) in healthcare research is crucial for effectively addressing patients' needs and setting appropriate research priorities. However, there is a lack of awareness and adequate methods for practicing PPIE, especially for vulnerable groups like childhood cancer survivors. AIMS: This project aimed to develop and evaluate engagement methods to actively involve pediatric oncological patients, survivors, and their caregivers in developing relevant research questions and practical study designs. METHODS AND RESULTS: An interdisciplinary working group recruited n = 16 childhood cancer survivors and their caregivers to work through the entire process of developing a research question and a practicable study design. A systematic literature review was conducted to gather adequate PPIE methods which were then applied and evaluated in a series of three workshop modules, each lasting 1.5 days. The applied methods were continuously evaluated, while a monitoring group oversaw the project and continuously developed and adapted additional methods. The participants rated the different methods with varying scores. Over the workshop series, the participants successfully developed a research question, devised an intervention, and designed a study to evaluate their project. They also reported increased expertise in PPIE and research knowledge compared to the baseline. The project resulted in a practical toolbox for future research, encompassing the final workshop structure, evaluated methods and materials, guiding principles, and general recommendations. CONCLUSION: These findings demonstrate that with a diverse set of effective methods and flexible support, actively involving patients, survivors, and caregivers can uncover patients' unmet disease-related needs and generate practical solutions apt for scientific evaluation. The resulting toolbox, filled with evaluated and adaptable methods (workbook, Supplement 1 and 2), equips future scientists with the necessary resources to successfully perform PPIE in the development of health care research projects that effectively integrate patients' perspectives and address actual cancer-related needs. This integration of PPIE practices has the potential to enhance the quality and relevance of health research and care, as well as to increase patient empowerment leading to sustainable improvements in patients' quality of life.

Identifying meta-research with researchers as study subjects: Protocol for a scoping review.

BACKGROUND: Meta-research in which researchers are the study subjects can illuminate how to better support researchers and enhance the development of research capacity. Comprehensively compiling the literature in this area can help define best practices for research capacity development and reveal gaps in the literature. However, there are challenges to assessing and synthesizing the breadth of the meta-research literature produced. METHODS: In this article, we discuss the current barriers to conducting literature reviews on meta-research and strategies to address these barriers. We then outline proposed methods for conducting a scoping review on meta-research with researchers as study subjects. DISCUSSION: Due to its interdisciplinary nature, broad scope, and difficult to pinpoint terminology, little is known about the state of meta-research with researchers as the study subjects. For this reason, there is a need for a scoping review that will identify research performed in which researchers were the study subjects.

Evaluation of different landing pages on behavioural engagement with the CARA dashboard: A user research protocol.

BACKGROUND: CARA set out to develop a data-visualisation platform to facilitate general practitioners to develop a deeper understanding of their patient population, disease management and prescribing through dashboards. To support the continued use and sustainability of the CARA dashboards, dashboard performance and user engagement have to be optimised. User research places people at the centre of the design process and aims to evaluate the needs, behaviours and attitudes of users to inform the design, development and impact of a product. OBJECTIVE: To explore how different initial key messages impact the level of behavioural engagement with a CARA dashboard. METHODS: Participating general practices can upload their practice data for analysis and visualisation in CARA dashboards. Practices will be randomised to one of three different initial landing pages: the full dashboard or one of two key messages: a between comparison (their practice prescribing with the average of all other practices) or within comparison (with practice data of the same month the previous year) with subsequent continuation to the full dashboard. Analysis will determine which of the three landing pages encourages user interaction, as measured by the number of 'clicks', 'viewings' and 'sessions'. Dashboard usage data will be collected through Google analytics. DISCUSSION: This study will provide evidence of behavioural engagement and its metrics during the implementation of the CARA dashboards to optimise and sustain interaction. TRIAL REGISTRATION: ISRCTN32783644 (Registration date: 02/01/2024).

Identifying Existing Guidelines, Frameworks, Checklists, and Recommendations for Implementing Patient-Reported Outcome Measures: Protocol for a Scoping Review.

BACKGROUND: Implementing patient-reported outcome measures (PROMs) to measure and evaluate health outcomes is increasing worldwide. Along with this emerging trend, it is important to identify which guidelines, frameworks, checklists, and recommendations exist, and if and how they have been used in implementing PROMs, especially in clinical quality registries (CQRs). OBJECTIVE: This review aims to identify existing publications, as well as publications that discuss the application of actual guidelines, frameworks, checklists, and recommendations on PROMs' implementation for various purposes such as clinical trials, clinical practice, and CQRs. In addition, the identified publications will be used to guide the development of a new guideline for PROMs' implementation in CQRs, which is the aim of the broader project. METHODS: A literature search of the databases MEDLINE, Embase, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials will be conducted since the inception of the databases, in addition to using Google Scholar and gray literature to identify literature for the scoping review. Predefined inclusion and exclusion criteria will be used for all phases of screening. Existing publications of guidelines, frameworks, checklists, recommendations, and publications discussing the application of those methodologies for implementing PROMs in clinical trials, clinical practice, and CQRs will be included in the final review. Data relating to bibliographic information, aim, the purpose of PROMs use (clinical trial, practice, or registries), name of guideline, framework, checklist and recommendations, the rationale for development, and their purpose and implications will be extracted. Additionally, for publications of actual methodologies, aspects or domains of PROMs' implementation will be extracted. A narrative synthesis of included publications will be conducted. RESULTS: The electronic database searches were completed in March 2024. Title and abstract screening, full-text screening, and data extraction will be completed in May 2024. The review is expected to be completed by the end of August 2024. CONCLUSIONS: The findings of this scoping review will provide evidence on any existing methodologies and tools for PROMs' implementation in clinical trials, clinical practice, and CQRs. It is anticipated that the publications will help us guide the development of a new guideline for PROMs' implementation in CQRs. TRIAL REGISTRATION: PROSPERO CRD42022366085; https://tinyurl.com/bdesk98x. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52572.

Pragmaticism in Cancer Clinical Trials.

Clinical trials are essential for advancing oncology treatment strategies and have contributed significantly to the decline in cancer mortality rates over the past decades. Traditional explanatory trials, focused on establishing intervention efficacy in ideal settings, often lack generalizability and may not reflect real-world patient care scenarios. Furthermore, increasing complexity in cancer clinical trial design has led to challenges such as protocol deviations, slow enrollment leading to lengthened durations of trial, and escalating costs. By contrast, pragmatic trials aim to assess intervention effectiveness in more representative patient populations under routine clinical conditions. Here, we review the principles, methodologies, challenges, and advantages of incorporating pragmatic features (PFs) into cancer clinical trials. We illustrate the application of pragmatic trial designs in oncology and discuss the QUASAR collaborative, TAPUR study, and the ongoing PRAGMATICA-LUNG trial. Although not all oncology trials may be amenable to adopting fully pragmatic designs, integration of PFs when feasible will enhance trial generalizability and real-world applicability. Project Pragmatica and similar initiatives advocate for the integration of real-world practice with clinical trials, fostering a nuanced approach to oncology research that balances efficacy and effectiveness assessments, ultimately with a goal of improving patient outcomes.

Human-Centered Design and Benefit Realization Management in Digital Health Care Solution Development: Protocol for a Systematic Review.

BACKGROUND: Earlier research shows that a significant number of resources are wasted on software projects delivering less than the planned benefits. It has, however, been evidenced that adopting a human-centered design approach when designing health devices can be beneficial. This understanding from earlier research has raised our interest in investigating how human-centered design might contribute to realizing the potential benefits of health care software projects. To our current knowledge, this intersection of human-centered design and benefit realization management has not yet comprehensively and consistently been researched within the context of digital health care solutions. Therefore, there is a need for evidence synthesis using systematic reviews to address this potential research gap. OBJECTIVE: The objective of this study is to examine if human-centered design helps benefit realization management processes in the development of digital health care solutions and thereby enables better benefit realization. We explore the evidence of assumed or confirmed benefits of using human-centered design in the health care domain and whether better results have been reported when the benefit realization management process is followed. METHODS: This protocol was developed following the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) guidelines. The proposed review would use a planned and systematic approach to identify, evaluate, and synthesize relevant and recent studies (reported in English) to see if there is evidence that using human-centered design and benefit realization management has a positive effect on realizing set benefits in those projects. We will commence a systematic literature search using human-centered design, benefit realization management, and health care-related search terms within 5 repositories (ACM Digital Library, PubMed Central, Scopus, PubMed, and Web of Science). After removing duplicate results, a preliminary scan for titles and abstracts will be done by at least 2 reviewers. Any incongruities regarding whether to include articles for full-text review will be resolved by a third reviewer based on the predefined criteria. RESULTS: Initial queries of 2086 records have been executed and papers are being prescreened for inclusion. The search was initiated in December 2023 and the results are expected in 2024. We anticipate finding evidence of the use of human-centered design in the development of digital health care solutions. However, we expect evidence of benefitting from both human-centered design and benefit realization management in this context to be scarce. CONCLUSIONS: This protocol will guide the review of existing literature on the use of human-centered design and benefit realization management when developing digital health care solutions. The review will specifically focus on finding evidence of confirmed benefits derived from the use of human-centered design and benefit realization management. There may be an opportunity to gain a broader understanding of the tools or approaches that provide evidence of increased benefit realization within the health care domain. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56125.

Health and well-being needs of Indigenous adolescents: a protocol for a scoping review of qualitative studies.

INTRODUCTION: Improving the health of Indigenous adolescents is central to addressing the health inequities faced by Indigenous peoples. To achieve this, it is critical to understand what is needed from the perspectives of Indigenous adolescents themselves. There have been many qualitative studies that capture the perspectives of Indigenous young people, but synthesis of these has been limited to date. METHODS AND ANALYSIS: This scoping review seeks to understand the specific health needs and priorities of Indigenous adolescents aged 10-24 years captured via qualitative studies conducted across Australia, Aotearoa New Zealand, Canada, the USA, Greenland and Sami populations (Norway and Sweden). A team of Indigenous and non-Indigenous researchers from these nations will systematically search PubMed (including the MEDLINE, PubMed Central and Bookshelf databases), CINAHL, Embase, Scopus, the Informit Indigenous and Health Collections, Google Scholar, Arctic Health, the Circumpolar Health Bibliographic Database, Native Health Database, iPortal and NZresearch.org, as well as specific websites and clearinghouses within each nation for qualitative studies. We will limit our search to articles published in any language during the preceding 5 years given that needs may have changed significantly over time. Two independent reviewers will identify relevant articles using a two-step process, with disagreements resolved by a third reviewer and the wider research group. Data will then be extracted from included articles using a standardised form, with descriptive synthesis focussing on key needs and priorities. This scoping review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. ETHICS AND DISSEMINATION: Ethics approval was not required for this review. Findings will be disseminated via a peer-reviewed journal article and will inform a broader international collaboration for Indigenous adolescent health to develop evidence-based actions and solutions.

Study protocol for a scoping review of Lyme disease prediction methodologies.

INTRODUCTION: In the temperate world, Lyme disease (LD) is the most common vector-borne disease affecting humans. In North America, LD surveillance and research have revealed an increasing territorial expansion of hosts, bacteria and vectors that has accompanied an increasing incidence of the disease in humans. To better understand the factors driving disease spread, predictive models can use current and historical data to predict disease occurrence in populations across time and space. Various prediction methods have been used, including approaches to evaluate prediction accuracy and/or performance and a range of predictors in LD risk prediction research. With this scoping review, we aim to document the different modelling approaches including types of forecasting and/or prediction methods, predictors and approaches to evaluating model performance (eg, accuracy). METHODS AND ANALYSIS: This scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines. Electronic databases will be searched via keywords and subject headings (eg, Medical Subject Heading terms). The search will be performed in the following databases: PubMed/MEDLINE, EMBASE, CAB Abstracts, Global Health and SCOPUS. Studies reported in English or French investigating the risk of LD in humans through spatial prediction and temporal forecasting methodologies will be identified and screened. Eligibility criteria will be applied to the list of articles to identify which to retain. Two reviewers will screen titles and abstracts, followed by a full-text screening of the articles' content. Data will be extracted and charted into a standard form, synthesised and interpreted. ETHICS AND DISSEMINATION: This scoping review is based on published literature and does not require ethics approval. Findings will be published in peer-reviewed journals and presented at scientific conferences.

Effect of HIV and substance use disorder comorbidity on the placenta, fetal and maternal health outcomes: systematic review and meta-analysis protocol.

BACKGROUND: Substance use disorders and HIV infection have a bidirectional relationship. People who use illicit drugs are at increased risk of contracting HIV/AIDS, and people living with HIV/AIDS are at increased risk of using substances due to disease-related complications like depression and HIV-associated dementia. There is no adequate evidence on the effect of HIV/AIDS and substance use disorder comorbidity-related effects on placental, fetal, maternal and neonatal outcomes globally. METHODS AND ANALYSIS: We will search articles written in the English language until 30 January 2024, from PubMed/Medline, Cochrane Library, Embase, Scopus, Web of Sciences, SUMsearch2, Turning Research Into Practice database and Google Scholar. A systematic search strategy involving AND/OR Boolean Operators will retrieve information from these databases and search engines. Qualitative and quantitative analysis methods will be used to report the effect of HIV/AIDS and substance use disorders on placental, fetal and maternal composite outcomes. Descriptive statistics like pooled prevalence mean and SD will be used for qualitative analysis. However, quantitative analysis outcomes will be done by using Comprehensive Meta-Analysis Software for studies that are combinable. The individual study effects and the weighted mean difference will be reported in a forest plot. In addition to this, the presence of multiple morbidities like diabetes, chronic kidney disease and maternal haemoglobin level could affect placental growth, fetal growth and development, abortion, stillbirth, HIV transmission and composite maternal outcomes. Therefore, subgroup analysis will be done for pregnant women with multiple morbidities. ETHICS AND DISSEMINATION: Since systematic review and meta-analysis will be conducted by using published literature, ethical approval is not required. The results will be presented in conferences and published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023478360.

Identifying globally relevant learnings from Africa's challenges and solutions to climate change and air pollution-related health impacts: a data science scoping review protocol.

INTRODUCTION: Leveraging data science could significantly advance the understanding of the health impacts of climate change and air pollution to meet health systems' needs and improve public health in Africa. This scoping review will aim to identify and synthesise evidence on the use of data science as an intervention to address climate change and air pollution-related health challenges in Africa. METHODS AND ANALYSIS: The search strategy will be developed, and the search will be conducted in the Web of Science, Scopus, CAB Abstracts, MEDLINE and EMBASE electronic databases. We will also search the reference lists of eligible articles for additional records. We will screen titles, technical reports, abstracts and full texts and select studies reporting the use of data science in relation to the health effects and interventions associated with climate change and air pollution in Africa. ETHICS AND DISSEMINATION: There are no formal ethics requirements as we are not collecting primary data. Results, once published, will be disseminated via conferences and shared with policy-makers and public health, air pollution and climate change key stakeholders in Africa.