Use of the pragmatic-explanatory continuum indicator summary tool in low- and middle-income country settings: systematic review.

Pragmatic Trials and Improving Long-Term Care: Recommendations From a National Institutes of Health Conference.

Clinical trials are sometimes classified as being explanatory or pragmatic, although they are rarely reported in that way. Explanatory trials may seek to investigate the efficacy of new treatments by imposing strict limitations on many aspects of trial design, including, for example, recruiting only those patients who are most likely to respond. In contrast, the objective of pragmatic trials is to assess whether treatments work in conditions more appropriate to routine practice. This dichotomy is, however, over-simplistic; there is usually a continuum, which is a consequence of there being many areas of trial design that can vary between the extremities of the explanatory and pragmatic approaches. The PRECIS (pragmatic-explanatory continuum indicator summary) wheel based on 10 domains, which include inclusion criteria, flexibility of delivery of the intervention and intensity of follow-up, has been proposed as a way of enabling researchers to assess the extent to which the trials they are designing could be considered explanatory or pragmatic. In this article, we consider how the PRECIS tool can be applied to trials of tuberculosis treatment. In view of the well-recognised delay in getting results from well-conducted clinical trials into practice, we would suggest that if more pragmatic trials were to be conducted, physicians would better understand the implications of the results for their own practice and be more ready to adopt new treatments.

Prenatal exposure to ambient air pollution and extreme temperatures are among the major risk factors of adverse birth outcomes and with potential long-term effects during the life course. Although low- and middle-income countries (LMICs) are most vulnerable, there is limited synthesis of evidence in such settings. This document describes a protocol for both an umbrella review (Systematic Review 1) and a focused systematic review and meta-analysis of studies from LMICs (Systematic Review 2). We will search from start date of each database to present, six major academic databases (PubMed, CINAHL, Scopus, MEDLINE/Ovid, EMBASE/Ovid and Web of Science Core Collection), systematic reviews repositories and references of eligible studies. Additional searches in grey literature will also be conducted. Eligibility criteria include studies of pregnant women exposed to ambient air pollutants and/or extreme temperatures during pregnancy with and without adverse birth outcomes. The umbrella review (Systematic Review 1) will include only previous systematic reviews while Systematic Review 2 will include quantitative observational studies in LMICs. Searches will be restricted to English language using comprehensive search terms to consecutively screen the titles, abstracts and full-texts to select eligible studies. Two independent authors will conduct the study screening and selection, risk of bias assessment and data extraction using JBI SUMARI web-based software. Narrative and semi-quantitative syntheses will be employed for the Systematic Review 1. For Systematic Review 2, we will perform meta-analysis with two alternative meta-analytical methods (quality effect and inverse variance heterogeneity) as well as the classic random effect model. If meta-analysis is infeasible, narrative synthesis will be presented. Confidence in cumulative evidence and the strength of the evidence will be assessed. This protocol is registered with PROSPERO (CRD42020200387).

The age at which children enter school represents a transitional period between early childhood and adolescence that involves increasing autonomy, interaction with peers, and exposure to environments outside the home. Although mortality is generally much lower in the 5 to 9 age group compared with infancy and early childhood, there are many preventable causes of mortality, morbidity, and disability that emerge in this age group, including injuries, noncommunicable diseases, and vaccine-preventable and highly treatable infections.1 Partly because of relatively low mortality rates and less frequent contacts with the health system, school-age children and younger adolescents ages 5 to 14 have been referred to as the “missing middle,” in that there is a dearth of robust data on key health indicators, morbidity burden, and cause-specific mortality in this group.2 Many health issues that have a high burden in early childhood can persist in older children, especially in low- and middle-income countries (LMIC), resource-constrained settings, and marginalized communities worldwide. Undernutrition and infections occurring in the context of poverty remain leading causes of morbidity and mortality in school-age children living in LMIC,3 whereas those children in higher-income settings are more likely to die due to injuries or noncommunicable disease (NCD). In addition, the prevalence of overweight and obesity in children and adolescents has increased steadily over the last few decades,4 though the rate of these increases varies widely among countries.5New risk factors relating to diet, lifestyle, mental health, injuries, and NCDs also become more prominent as children approach and enter adolescence, many of which can contribute to the development of chronic NCDs over the life course. Within this period, school-age children begin to establish healthy lifestyle habits (eg, diet, physical activity, avoidance of substance use), and are learning about sexual and reproductive health and rights, as well as the measures they can take to protect themselves and others. This represents a window of opportunity for educational interventions to support good health, optimal development, and well-being. A growing body of evidence suggests that school-based and digital platforms and delivery strategies are promising tools that aid in the delivery of health interventions to older children.The methodology and reviews described herein contributed to the portion of the upcoming 2022 Lancet Optimizing Child and Adolescent Health and Development Series6 related to school-age child and adolescent health interventions. This Lancet Series is the product of an ongoing academic collaboration involving global child health researchers worldwide, including many who are authors on articles within this supplement. The aim of the specific Lancet Series article citing this supplement is to provide a comprehensive overview of systematic reviews describing the most recent evidence for effective interventions to support maternal, newborn, child, and adolescent health and development from preconception through to 20 years of age.Figure 1 provides an overview of the key child health domains, and a breakdown of the intervention review topics addressing key risk factors covered by the articles included in this journal supplement. On the basis of work done in previous comprehensive overviews of interventions for child and adolescent health (eg, Disease Control Priorities, 3rd edition7; Lancet Adolescent Health Commission8), we identified a comprehensive set of key child health domains that represented priority areas for interventions to address modifiable risks for the major causes of child mortality and morbidity. The factors that informed which domains were covered in this supplement included: conditions with a high global burden of disease, conditions with disproportionate impacts on vulnerable and marginalized populations, potential to support improved human capital development across the life course, and pragmatic considerations including whether the topic had recently been covered elsewhere. In cases where the child health domain was deemed too broad in scope for a single review (eg, infectious diseases), the subtopics for individual reviews were also chosen on the basis of these factors. The age group of specific interest for these reviews was older school-age children (ages 5–9.9), though the period of early adolescence (ages 10–14.9) was also recognized as an important area of overlap and transition. The general outcomes of interest aligned with those chosen through consensus by the Lancet Series working group. These included, but were not limited to, mortality, severe morbidity, disability, growth and development, knowledge and behavior, and indicators of improved human capital development such as academic achievement.The methodological approaches taken, and child health domains covered in this supplement of reviews, was informed by a broad initial literature-scoping and evidence-mapping process to identify key health interventions and associated evidence for their effectiveness in the form of systematic reviews. This was done across all domains, from preconception and pregnancy to ages 0 to 20 to inform the 2022 Lancet Optimizing Child and Adolescent Health and Development Series.6 This involved leveraging existing large-scale intervention overviews (eg, Disease Control Priorities 3rd edition, Lancet Series) that had already highlighted existing effective interventions and the most recent systematic reviews detailing the evidence for their effectiveness. Additional targeted searches for newer interventions and systematic reviews in each domain were also conducted. Through this evidence-mapping process, we explored coverage and extent of LMIC-specific evidence across all child health domains to identify areas where school-age evidence was lacking and determined that there were significant gaps in existing evidence for intervention effectiveness in school-age children.We funneled the reviews identified during this initial scoping process that contained studies covering school-age children and adolescents into the individual reviews for each domain of child health covered in this supplement. We elected to conduct targeted overviews of systematic reviews if there was deemed to be a large body of existing evidence syntheses. In cases where there was a lack of evidence syntheses of intervention effectiveness for a given domain of school-age child health, conventional systematic reviews of primary literature (ie, experimental studies) were conducted. The general methodology for these 2 approaches are described below. See Table 1 and Fig 1 for a summary of the review methods used for each child health domain, and Fig 2 for a breakdown of the main methodology followed in each type of review.For those child health domains that encompassed a variety of intervention types addressing a wide range of risk factors and health conditions, and for which the initial scoping process identified a variety of existing systematic reviews of intervention effectiveness, an overview of systematic reviews was undertaken. This approach was taken to ensure comprehensiveness, reduce duplication of review efforts, and make the review process feasible.In addition to incorporating those relevant reviews previously identified in the initial literature-scoping and evidence-mapping exercise, tailored searches were executed in several databases (eg, Medline, Cochrane Database of Systematic Reviews, Campbell Library) to identify literature published up until the end of 2020. Evidence derived from Cochrane reviews and other high-quality systematic reviews that synthesized evidence from randomized controlled trials and quasi-experimental studies examining the effectiveness of interventions was prioritized for inclusion. A first pass of title and abstract screening for relevance was conducted, followed by a full text screening that was done by at least 2 reviewers against inclusion criteria. Two reviewers independently filled a standardized data abstraction form to capture review characteristics, the characteristics of included studies and interventions (eg, age coverage, country representation, delivery platform), and pooled-effect estimates (eg, risk ratios, odds ratios, mean differences, 95% confidence intervals) derived from meta-analyses where they were reported. The main outcomes of interest across the reviews included measures of child morbidity, mortality, development, academic achievement, and mental and physical well-being. The extracted data were then matched among reviewers to check for errors and ensure consistency, and then consolidated into a single table for inclusion in the article. The AMSTAR 2 tool12 was used for review quality assessment, and was also conducted in duplicate, with any disagreements in ratings resolved by consensus or the involvement of a third reviewer.If for a given domain the initial evidence-mapping exercise revealed that the existing evidence-synthesis literature was lacking for the school-age group, we proceeded with a conventional systematic review of primary literature. All systematic reviews were reported in accordance with the reporting guidance provided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria.13Search strategies were developed using the population, intervention, control, and outcomes methodology, relevant medical subject headings terms, and keywords derived from the scoping search. The search terms were adapted for use in other bibliographic databases in combination with database-specific filters for controlled trials, where these were available. Searches for the individual, domain-specific reviews were conducted in a variety of databases, including but not limited to: PubMed, Embase, Medline, PsycINFO, Ovid SP, The Cochrane Library, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register, and the World Health Organization regional databases. Evidence derived from LMIC was prioritized for synthesis, though evidence from high-income countries (HIC) settings was leveraged to highlight whether effective interventions exist in cases where LMIC evidence was sparse. Gray literature searches and additional hand searching were conducted in Google Scholar and reference lists of relevant articles, book chapters, and reviews.After removal of duplicate studies, a multistage screening process was performed to select studies that met the eligibility criteria. Each title and abstract was assessed by at least 1 reviewer, who excluded those that were deemed irrelevant. At the full-text review stage, at least 2 reviewers assessed all full texts. Any disagreements in inclusion decisions were resolved by discussion and, where necessary, by consulting a third reviewer. At this stage, reasons for exclusion were documented. The methods section of each individual review in this supplement describes their selection and eligibility criteria, which differed depending on the child health domain being assessed. Data from included studies were independently extracted and coded by 2 review authors using standardized, previously piloted data extraction forms, which sought general study characteristics, details of the population, intervention, comparison groups, and quantitative outcome data. Data extraction forms were matched and checked, and if necessary, a third review author was consulted in the event of any disagreements to establish consensus.Assessment of risk of bias for included studies was conducted according to criteria and tools outlined in the Cochrane Effective Practice and Organization of Care guidelines14 for randomized trials, nonrandomized trials, controlled before–after, interrupted time series, and the Cochrane Handbook for Systematic Reviews of Interventions.15 Assessments were conducted independently by 2 review authors; scores were compared, and a final risk of bias judgement was reported for the included studies of each systematic review. Randomized trials were assessed using the Cochrane Risk of Bias tool15 across the following domains: randomization process, deviations from the intended interventions (blinding of personnel, participants, and outcome assessment), missing outcome data, outcome measurement, the selection of the reported result, disclosure of funding, and conflicts of interest. Studies were assigned an overall risk of bias judgement accordingly (low risk, high risk, or some concerns/medium risk). Quasi-experimental study designs were assessed using the Risk of Bias Tool for Nonrandomized Studies of Interventions (ROBINS-I) tool.15,16 Studies were assessed according to the following domains: bias because of confounding, bias in selection of study participants, bias in classification of interventions, bias because of deviations from intended interventions, bias because of missing data, bias in measurement of outcomes, and bias in selection of the reported result. Each study was assigned an overall risk of bias judgement (low, moderate, serious, and critical risk).Meta-analyses were conducted where possible using Review Manager 5.4 software.17 Randomized controlled trials and cluster-randomized controlled trials were analyzed separately from quasi-experimental study designs. To mitigate heterogeneity within included studies, a random-effects meta-analysis was used for pooled outcomes. For those situations where meta-analysis was not possible, data on the effect of interventions from individual studies was tabulated and reported, and a narrative synthesis was conducted for each key intervention domain.Where there were a sufficient quantity of comparable studies (in both interventions and outcome), a summary of the intervention effect and a measure of quality for key outcomes were produced using the Grading of Recommendations Assessment, Development and Evaluation approach.18 The Grading of Recommendations Assessment, Development and Evaluation approach considers 5 domains (study limitations, consistency of effect, imprecision, indirectness, and publication bias) to assess the quality of the body of evidence for each outcome. The evidence was downgraded from “high quality” by 1 level for serious (or by 2 levels for very serious) limitations, depending on assessments for risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates, or potential publication bias.The aim of the authors of this supplement of reviews is to comprehensively assess the available evidence for the effectiveness of interventions to improve health and well-being in school-age children and adolescents. The initial literature-scoping and evidence-mapping process, followed by the different review approaches taken, has helped to maximize the scope covered across this set of reviews, and has allowed us to provide the most comprehensive assessment of the state of the published literature covering interventions for school-age children and adolescents. The individual reviews in this supplement have also highlighted child health domain-specific gaps in the evidence for both primary literature in the school-age group, and gaps in existing evidence syntheses.It is important to note that, for the reviews within this supplement, the descriptions of intervention effects are meant to provide an overview of what is currently known in terms of evidence for effectiveness, and do not imply that other interventions were ineffective simply because there was an evidence gap. Given the limited space and large scope, it was only possible to provide the highlights of specific comparisons and outcomes in each of the results sections. Comprehensive tables of study characteristics, outcomes, and effect estimates are provided in both the main articles and appendices.Although we were specifically interested in focusing on LMIC research, this was only feasible for a few review topics (eg, sexual and reproductive health and rights, neglected tropical diseases) because of a dearth of literature. Instead of being used to attempt to generalize their effectiveness to LMIC settings, evidence from intervention effectiveness in HIC settings are included and described to establish that effective interventions do indeed exist and may differ in their impact between settings. This approach has previously been used in the context of adolescent health interventions.19 This evidence from HIC could act as a starting point for future research and implementation in various LMIC settings, with program components tailored to local contexts.In the case of those reviews taking the overview of systematic reviews approach, we were limited to including only those primary studies already included in systematic reviews and could not cover each subdomain in depth. Thus, we were unable to identify and include those primary studies that may not have been included in systematic reviews because of studies not being identified in review authors’ database searches, not meeting their inclusion criteria, or falling out of the time frame of the review. Furthermore, some systematic reviews of primary literature were unable to perform meta-analyses because of high heterogeneity or a lack of high-quality evidence from randomized trials, which makes synthesizing the existing evidence more difficult.

Quantum dots (QDs) are a class of nanomaterials with unique fluorescent properties that have gained significant attention in the research of Chinese herbal medicines (CHMs). Due to their exceptional optical characteristics, stability, biocompatibility, and other advantages, QDs are increasingly utilized in CHM studies. This review explores the diverse applications of QDs, including their use in detecting active ingredients and common exogenous pollutants in CHMs, as well as in assessing the degradation of such pollutants in both CHMs and their growing environments. Furthermore, the paper discusses the potential of QDs synthesized from CHMs as tools for analyzing other substances and modulating their pharmacological effects. The review also highlights the preparation methods, detection principles, and specific research strategies related to QDs. Integrating QDs into CHM research is poised to drive the modernization and internationalization of the CHM industry.

BackgroundReducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required.MethodsA systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted.Results179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions.ConclusionsEvidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts.

BackgroundWomen in low- and middle-income countries (LMICs) are disproportionally affected by perinatal depression and anxiety and lack access to mental health care. Integrating perinatal mental health care into routine maternal care is recommended to address gaps in access to mental health care in such under-resourced settings. Understanding the effectiveness of interventions that integrate perinatal mental health care into routine maternal care in LMICs is critical to inform ongoing intervention development, implementation, and scale-up. This systematic review aims to assess the effectiveness of interventions that integrate perinatal mental health care into routine maternal care to improve maternal mental health and infant health outcomes in LMICs.MethodIn accordance with the PRISMA guidelines, an electronic database search was conducted seeking publications of controlled trials examining interventions that aimed to integrate perinatal mental health care into routine maternal care in LMICs. s and full text articles were independently reviewed by two authors for inclusion utilizing Covidence Review Software. Data was extracted and narrative synthesis was conducted.FindingsTwenty studies met eligibility criteria from the initial search results of 2,382 unique citations. There was substantial heterogeneity between the study samples, intervention designs, and outcome assessments. Less than half of the studies focused on women with active depression or anxiety. Most studies (85%) implemented single intervention designs involving psychological, psychosocial, psychoeducational, or adjuvant emotion/stress management. There were few interventions utilizing multicomponent approaches, pharmacotherapy, or referral to mental health specialists. Outcome measures and assessment timing were highly variable. Eighteen studies demonstrated significantly greater improvement on depression and/or anxiety measures in the intervention group(s) as compared to control.ConclusionIntegrated interventions can be effective in LMICs. The findings provide a critical understanding of current interventions design gaps. This includes the lack of comprehensive intervention designs that incorporate increasing intensity of treatment for more severe illness, pharmacotherapy, mental health specialist referrals, and non-mental health professional training and supervision. The findings also provide strategies to overcome design and implementation barriers in LMICs. Study findings provide a foundation for future evidence-based adaptation, implementation, and scale-up of interventions that integrate perinatal mental health care into routine maternal care in LMICs.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/display_ record.php?ID=CRD42021259092], identifier [CRD42021259092].

BackgroundFor Comparative Effectiveness Research (CER) there is a need to develop scales for appraisal of available clinical research. Aims were to 1) test the feasibility of applying the pragmatic-explanatory continuum indicator summary tool and the six CER defining characteristics of the Institute of Medicine to RCTs of acupuncture for treatment of low back pain, and 2) evaluate the extent to which the evidence from these RCTs is relevant to clinical and health policy decision making.MethodsWe searched Medline, the AcuTrials™ Database to February 2011 and reference lists and included full-report randomized trials in English that compared needle acupuncture with a conventional treatment in adults with non-specific acute and/or chronic low back pain and restricted to those with ≥30 patients in the acupuncture group. Papers were evaluated by 5 raters.Principal FindingsFrom 119 abstracts, 44 full-text publications were screened and 10 trials (4,901 patients) were evaluated. Due to missing information and initial difficulties in operationalizing the scoring items, the first scoring revealed inter-rater and inter-item variance (intraclass correlations 0.02–0.60), which improved after consensus discussions to 0.20–1.00. The 10 trials were found to cover the efficacy-effectiveness continuum; those with more flexible acupuncture and no placebo control scored closer to effectiveness.ConclusionBoth instruments proved useful, but need further development. In addition, CONSORT guidelines for reporting pragmatic trials should be expanded. Most studies in this review already reflect the movement towards CER and similar approaches can be taken to evaluate comparative effectiveness relevance of RCTs for other treatments.

Measurement of social capital in relation to health in low and middle income countries (LMIC): A systematic review

Collaborative approaches towards building midwifery capacity in low income countries: A review of experiences

BackgroundMedical device procurement processes for low- and middle-income countries (LMICs) are a poorly understood and researched topic. To support LMIC policy formulation in this area, international public health organizations and research institutions issue a large body of predominantly grey literature including guidelines, manuals and recommendations. We propose to undertake a systematic review to identify and explore the medical device procurement methodologies suggested within this and further literature. Procurement facilitators and barriers will be identified, and methodologies for medical device prioritization under resource constraints will be discussed.Methods/designSearches of both bibliographic and grey literature will be conducted to identify documents relating to the procurement of medical devices in LMICs. Data will be extracted according to protocol on a number of pre-specified issues and variables. First, data relating to the specific settings described within the literature will be noted. Second, information relating to medical device procurement methodologies will be extracted, including prioritization of procurement under resource constraints, the use of evidence (e.g. cost-effectiveness evaluations, burden of disease data) as well as stakeholders participating in procurement processes. Information relating to prioritization methodologies will be extracted in the form of quotes or keywords, and analysis will include qualitative meta-summary. Narrative synthesis will be employed to analyse data otherwise extracted. The PRISMA guidelines for reporting will be followed.DiscussionThe current review will identify recommended medical device procurement methodologies for LMICs. Prioritization methods for medical device acquisition will be explored. Relevant stakeholders, facilitators and barriers will be discussed. The review is aimed at both LMIC decision makers and the international research community and hopes to offer a first holistic conceptualization of this topic.

Background Skilled attendance at birth is considered key to accomplishing Sustainable Development Goal (SDG) 3.1 aimed at reducing maternal mortality. Many maternal deaths can be prevented if a woman receives care by skilled health personnel. Maternal utilization of skilled health delivery services in rural areas in low- and middle-income countries is 70% compared to 90% in urban areas. Previous studies have found community-based interventions may increase rural maternal uptake of skilled health delivery services, but evidence is lacking on which strategies are most effective. Objective To review the effectiveness of community-based strategies to increase rural maternal utilization of skilled health personnel for childbirth delivery in low-and middle-income countries. Methods We conducted a narrative review. PubMed, CINAHL, Cochrane Library, and PsycINFO databases were searched for articles from database inception through 13 November 2019. Key search terms were pre-determined. Information was extracted on studies meeting our inclusion criteria: cluster and randomized trials, rural setting, reproductive aged women, community engagement, low- and middle-income countries. Studies were considered effective if statistically significant (p < 0.05). A narrative synthesis was conducted. Results Ten cluster randomized trials out of 5,895 candidate citations met the inclusion criteria. Strategies included home-based visits, women’s groups, and combined approaches. Out of the ten articles, only three studies were found to significantly increase maternal uptake of skilled health personnel for delivery, and each used a different strategy. The results are inconclusive as to which strategies are most effective. Limitations of this review include heterogeneity and generalizability of studies. Conclusions This research suggests that different strategies may be effective at improving maternal utilization of skilled health personnel for delivery in certain rural settings while ineffective in others. More research is warranted to better understand the context in which strategies may be effective and under what conditions.

Research on media and suicide in low- and middle-income countries: A systematic review, narrative synthesis and meta-analysis.

PURPOSE Cancer disproportionately affects people living in low- and middle-income countries (LMICs), partly because of delayed medical help-seeking behavior (HSB). Our mixed-methods systematic review synthesized existing studies in LMICs to understand psychosocial influences on cancer-related medical HSB to inform the development of effective interventions to promote earlier HSB for cancer. METHODS We searched peer-reviewed literature databases for quantitative, qualitative, and mixed-methods studies exploring barriers/facilitators to medical HSB for cancer symptoms in adults living in LMICs. Study exclusion criteria were low methodologic quality, non-English language publication, non–peer-reviewed publication, and studies conducted in high-income countries. Study findings were synthesized using meta-analysis, meta-ethnography, and narrative synthesis methods, according to individual study design. RESULTS Fifty studies were included. Many studies used nonstandardized measures/designs, which increased the difficulty integrating findings. Preliminary findings indicate that the use of traditional healers is a key barrier to prompt medical HSB in LMICs. Use of traditional healers for cancer symptoms/treatment was influenced by causal beliefs about symptoms, familial pressure, ease of access, affordability, and a preference to avoid biomedical treatment, which was perceived as invasive, ineffective, and expensive. Additional psychosocial barriers included shame and stigma associated with cancer, such as fear of marital rejection/divorce; limited knowledge of cancer and associated symptoms; financial and access barriers associated with travel and appointments; and cultural barriers, such as women needing permission from the family network. CONCLUSION Such barriers as low symptom knowledge and negative beliefs about cancer are universal barriers to cancer HSB in high-income countries and LMICs, whereas the use of traditional healers and women needing permission to seek medical help seem to be unique to LMICs. Intervention developers should work with local communities to appropriately tailor cancer awareness interventions in LMICs, taking into account cultural influences on HSB. Future evaluations would benefit from using validated measures and robust study designs.

BackgroundClinical trials are the cornerstone for generating high-quality evidence to improve patient outcomes. In metastatic renal cell carcinoma (RCC), research over the past two decades has resulted in a fourfold increase in median overall survival (Lancet, 2024). However, most clinical trials are conducted in high-income countries (HICs), limiting the inclusion of diverse patient populations (JCO CCI, 2020). We aimed to assess the global distribution of RCC clinical trials and identify disparities by country income level.MethodsWe queried the National Clinical Trials database for all trials enrolling patients with RCC between June 1, 2019, and June 1, 2024. We excluded non-interventional studies, pediatric trials, and trials for non-RCC malignancies. Participating countries were categorized using the World Bank Ranking (WBR): high-income (HICs), upper-middle-­income (UMICs), lower-middle-income (LMICs), and low-income countries (LICs). For each eligible trial, we documented RCC subtype, sponsor, trial phase, disease stage, and multinational status. Descriptive statistics were used to summarize trial characteristics. We assessed the association between country income level and trial availability using the Kruskal-Wallis test and Poisson regression to evaluate associations with RCC incidence, mortality, WBR, health expenditure, and gross national income (GNI).ResultsA total of 357 eligible trials were identified. Most (N = 273; 76%) were conducted exclusively in HICs, while only 84 trials (24%) included participation from UMICs, LMICs, or LICs. There were no significant differences in RCC subtype or disease stage across income groups. Pharmaceutical-sponsored trials were more common in non-HICs compared to HICs (64.3% vs. 39.6%, P < .001), whereas government and academic-sponsored trials were more frequent in HICs (60.4% vs. 35.7%, P < .001). Although early-phase trials predominated in all regions, late-phase trials were more common in non-HICs (25% vs. 8.1%, P < .001). Multinational trials were significantly more prevalent in non-HICs (45.2% vs. 15.8%, P < .001). The odds of having an RCC trial available significantly decreased with lower income classification (OR: UMICs 0.20; LMICs 0.05; LICs 0.013 vs. HICs). Poisson regression showed that GNI, health expenditure, and mortality were significantly associated with the number of clinical trials per country.ConclusionsRCC clinical trials are largely concentrated in high-income countries, with limited inclusion of UMICs, LMICs, and LICs. Countries outside the HIC group are more reliant on pharmaceutical industry funding and international collaborations to access clinical research. Addressing these disparities by expanding clinical trial access in non-HICs is essential to promote global equity in RCC care and ensure the generalizability of trial findings across diverse populations.