Aligning the principles and practice of research integrity and research fairness in global health: a mixed-methods study.

INTRODUCTION: In the past decade, global health research has seen a growing emphasis on research integrity and fairness. The concept of research integrity emerged in response to the reproducibility crisis in science during the late 2000s. Research fairness initiatives aim to enhance ownership and inclusivity in research involving partners with varying powers, decision-making roles and resource capacities, ultimately prioritising local health research needs. Despite extensive academic discussions, empirical data on these aspects, especially in the context of global health, remain limited. METHODS: To address this gap, we conducted a mixed-methods study focusing on research integrity and fairness. The study included an online frequency survey and in-depth key informant interviews with researchers from international research networks. The dual objectives were to quantify the frequency of practices related to research integrity and fairness and explore the determinants influencing these practices in global health. RESULTS: Out of 145 participants in the quantitative survey (8.4% response rate), findings indicate that global health researchers generally adhere to principles of research integrity and fairness, with variations in reported behaviours. The study identified structural, institutional and individual factors influencing these patterns, including donor landscape rigidity, institutional investments in relationship building, guidelines, mentoring and power differentials among researchers. CONCLUSION: This research highlights that, despite some variations, there is a substantial alignment between research integrity and fairness, with both sharing similar determinants and the overarching goal of enhancing research quality and societal benefits. The study emphasises the potential to explicitly recognise and leverage these synergies, aligning both agendas to further advance global health research.

Prevalence of responsible research practices among academics in The Netherlands.

Background: Traditionally, research integrity studies have focused on research misbehaviors and their explanations. Over time, attention has shifted towards preventing questionable research practices and promoting responsible ones. However, data on the prevalence of responsible research practices, especially open methods, open codes and open data and their underlying associative factors, remains scarce. Methods: We conducted a web-based anonymized questionnaire, targeting all academic researchers working at or affiliated to a university or university medical center in The Netherlands, to investigate the prevalence and potential explanatory factors of 11 responsible research practices. Results: A total of 6,813 academics completed the survey, the results of which show that prevalence of responsible practices differs substantially across disciplines and ranks, with 99 percent avoiding plagiarism in their work but less than 50 percent pre-registering a research protocol. Arts and humanities scholars as well as PhD candidates and junior researchers engaged less often in responsible research practices. Publication pressure negatively affected responsible practices, while mentoring, scientific norms subscription and funding pressure stimulated them. Conclusions: Understanding the prevalence of responsible research practices across disciplines and ranks, as well as their associated explanatory factors, can help to systematically address disciplinary- and academic rank-specific obstacles, and thereby facilitate responsible conduct of research.

Promoting trust in research and researchers: How open science and research integrity are intertwined.

Proponents of open science often refer to issues pertaining to research integrity and vice versa. In this commentary, we argue that concepts such as responsible research practices, transparency, and open science are connected to one another, but that they each have a different focus. We argue that responsible research practices focus more on the rigorous conduct of research, transparency focuses predominantly on the complete reporting of research, and open science's core focus is mostly about dissemination of research. Doing justice to these concepts requires action from researchers and research institutions to make research with integrity possible, easy, normative, and rewarding. For each of these levels from the Center for Open Science pyramid of behaviour change, we provide suggestions on what researchers and research institutions can do to promote a culture of research integrity. We close with a brief reflection on initiatives by other research communities and stakeholders and make a call to those working in the fields of research integrity and open science to pay closer attention to one other's work.

Prevalence of questionable research practices, research misconduct and their potential explanatory factors: A survey among academic researchers in The Netherlands.

Prevalence of research misconduct, questionable research practices (QRPs) and their associations with a range of explanatory factors has not been studied sufficiently among academic researchers. The National Survey on Research Integrity targeted all disciplinary fields and academic ranks in the Netherlands. It included questions about engagement in fabrication, falsification and 11 QRPs over the previous three years, and 12 explanatory factor scales. We ensured strict identity protection and used the randomized response method for questions on research misconduct. 6,813 respondents completed the survey. Prevalence of fabrication was 4.3% (95% CI: 2.9, 5.7) and of falsification 4.2% (95% CI: 2.8, 5.6). Prevalence of QRPs ranged from 0.6% (95% CI: 0.5, 0.9) to 17.5% (95% CI: 16.4, 18.7) with 51.3% (95% CI: 50.1, 52.5) of respondents engaging frequently in at least one QRP. Being a PhD candidate or junior researcher increased the odds of frequently engaging in at least one QRP, as did being male. Scientific norm subscription (odds ratio (OR) 0.79; 95% CI: 0.63, 1.00) and perceived likelihood of detection by reviewers (OR 0.62, 95% CI: 0.44, 0.88) were associated with engaging in less research misconduct. Publication pressure was associated with more often engaging in one or more QRPs frequently (OR 1.22, 95% CI: 1.14, 1.30). We found higher prevalence of misconduct than earlier surveys. Our results suggest that greater emphasis on scientific norm subscription, strengthening reviewers in their role as gatekeepers of research quality and curbing the "publish or perish" incentive system promotes research integrity.

Targeted test evaluation: a framework for designing diagnostic accuracy studies with clear study hypotheses.

Most randomized controlled trials evaluating medical interventions have a pre-specified hypothesis, which is statistically tested against the null hypothesis of no effect. In diagnostic accuracy studies, study hypotheses are rarely pre-defined and sample size calculations are usually not performed, which may jeopardize scientific rigor and can lead to over-interpretation or "spin" of study findings. In this paper, we propose a strategy for defining meaningful hypotheses in diagnostic accuracy studies. Based on the role of the index test in the clinical pathway and the downstream consequences of test results, the consequences of test misclassifications can be weighed, to arrive at minimally acceptable criteria for pre-defined test performance: levels of sensitivity and specificity that would justify the test's intended use. Minimally acceptable criteria for test performance should form the basis for hypothesis formulation and sample size calculations in diagnostic accuracy studies.

Guidance was developed on how to write a plain language summary for diagnostic test accuracy reviews.

OBJECTIVE: To develop guidance for authors of diagnostic test accuracy (DTA) reviews to help them write a plain language summary of the results of their review. STUDY DESIGN AND SETTING: We used a combination of focus groups, user testing, and a web-based survey. Participants included patient representatives, media representatives, and health professionals. RESULTS: We present step-by-step guidance for authors of DTA reviews for writing a plain language summary. This guidance is illustrated with examples of reader-tested sentences, explanations, and a figure. CONCLUSION: We hope this guidance will allow reviewers to present the findings of DTA reviews so that it is easier for readers to understand the results and conclusions. This will increase the accessibility of these reviews for various audiences.

Erratum to: Methods for evaluating medical tests and biomarkers.

[This corrects the article DOI: 10.1186/s41512-016-0001-y.].

Barriers to making recommendations about medical tests: a qualitative study of European guideline developers.

OBJECTIVES: Development of medical test guidelines differs from intervention guideline development. These differences can pose unique challenges in building evidence-based recommendations to guide clinical practice. The aim of our study was to better understand these challenges, explore reasons behind them and identify possible solutions. SETTING AND PARTICIPANTS: In this qualitative study, we conducted in-depth interviews between February 2012 and April 2013 of a convenience sample of 17 European guideline developers experienced in medical test guideline development. OUTCOMES MEASURED: We used framework analysis with deductive and inductive approaches to generate the themes from the interviews. We kept interpretation grounded in the data. RESULTS: Guideline developers acknowledged that inclusion of patient important outcomes in their guideline development was necessary but lacking. This and other challenges raised fell into 3 broad and overlapping domains: methodological issues, resource limitations and a lack of awareness on the need for evidence that links testing to patient outcomes. Education was mentioned as a key solution to increase awareness and address the resources limitations mentioned. CONCLUSIONS: Challenges guideline developers face were interlinked across the domains of methodological issues, resource limitations and a lack of awareness. Solutions that addressed these challenges in parallel are needed. Raising awareness, education and training of relevant stakeholders such as medical doctors, funders and regulators to look beyond test accuracy is key to having a long-term resolution to the issues faced in medical test guideline development.

Circulating antigen tests and urine reagent strips for diagnosis of active schistosomiasis in endemic areas.

BACKGROUND: Point-of-care (POC) tests for diagnosing schistosomiasis include tests based on circulating antigen detection and urine reagent strip tests. If they had sufficient diagnostic accuracy they could replace conventional microscopy as they provide a quicker answer and are easier to use. OBJECTIVES: To summarise the diagnostic accuracy of: a) urine reagent strip tests in detecting active Schistosoma haematobium infection, with microscopy as the reference standard; and b) circulating antigen tests for detecting active Schistosoma infection in geographical regions endemic for Schistosoma mansoni or S. haematobium or both, with microscopy as the reference standard. SEARCH METHODS: We searched the electronic databases MEDLINE, EMBASE, BIOSIS, MEDION, and Health Technology Assessment (HTA) without language restriction up to 30 June 2014. SELECTION CRITERIA: We included studies that used microscopy as the reference standard: for S. haematobium, microscopy of urine prepared by filtration, centrifugation, or sedimentation methods; and for S. mansoni, microscopy of stool by Kato-Katz thick smear. We included studies on participants residing in endemic areas only. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, assessed quality of the data using QUADAS-2, and performed meta-analysis where appropriate. Using the variability of test thresholds, we used the hierarchical summary receiver operating characteristic (HSROC) model for all eligible tests (except the circulating cathodic antigen (CCA) POC for S. mansoni, where the bivariate random-effects model was more appropriate). We investigated heterogeneity, and carried out indirect comparisons where data were sufficient. Results for sensitivity and specificity are presented as percentages with 95% confidence intervals (CI). MAIN RESULTS: We included 90 studies; 88 from field settings in Africa. The median S. haematobium infection prevalence was 41% (range 1% to 89%) and 36% for S. mansoni (range 8% to 95%). Study design and conduct were poorly reported against current standards. Tests for S. haematobium Urine reagent test strips versus microscopyCompared to microscopy, the detection of microhaematuria on test strips had the highest sensitivity and specificity (sensitivity 75%, 95% CI 71% to 79%; specificity 87%, 95% CI 84% to 90%; 74 studies, 102,447 participants). For proteinuria, sensitivity was 61% and specificity was 82% (82,113 participants); and for leukocyturia, sensitivity was 58% and specificity 61% (1532 participants). However, the difference in overall test accuracy between the urine reagent strips for microhaematuria and proteinuria was not found to be different when we compared separate populations (P = 0.25), or when direct comparisons within the same individuals were performed (paired studies; P = 0.21).When tests were evaluated against the higher quality reference standard (when multiple samples were analysed), sensitivity was marginally lower for microhaematuria (71% vs 75%) and for proteinuria (49% vs 61%). The specificity of these tests was comparable. Antigen assayCompared to microscopy, the CCA test showed considerable heterogeneity; meta-analytic sensitivity estimate was 39%, 95% CI 6% to 73%; specificity 78%, 95% CI 55% to 100% (four studies, 901 participants). Tests for S. mansoni Compared to microscopy, the CCA test meta-analytic estimates for detecting S. mansoni at a single threshold of trace positive were: sensitivity 89% (95% CI 86% to 92%); and specificity 55% (95% CI 46% to 65%; 15 studies, 6091 participants) Against a higher quality reference standard, the sensitivity results were comparable (89% vs 88%) but specificity was higher (66% vs 55%). For the CAA test, sensitivity ranged from 47% to 94%, and specificity from 8% to 100% (4 studies, 1583 participants). AUTHORS' CONCLUSIONS: Among the evaluated tests for S. haematobium infection, microhaematuria correctly detected the largest proportions of infections and non-infections identified by microscopy.The CCA POC test for S. mansoni detects a very large proportion of infections identified by microscopy, but it misclassifies a large proportion of microscopy negatives as positives in endemic areas with a moderate to high prevalence of infection, possibly because the test is potentially more sensitive than microscopy.

Applying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to diagnostic tests was challenging but doable.

OBJECTIVES: The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group developed an approach to assess the quality of evidence of diagnostic tests. Its use in Cochrane diagnostic test accuracy reviews is new. We applied this approach to three Cochrane reviews with the aim of better understanding the application of the GRADE criteria to such reviews. STUDY DESIGN AND SETTING: We selected reviews to achieve clinical and methodological diversities. At least three assessors independently assessed each review according to the GRADE criteria of risk of bias, indirectness, imprecision, inconsistency, and publication bias. Two teleconferences were held to share experiences. RESULTS: For the interpretation of the GRADE criteria, it made a difference whether assessors looked at the evidence from a patient-important outcome perspective or from a test accuracy standpoint. GRADE criteria such as inconsistency, imprecision, and publication bias were challenging to apply as was the assessment of comparative test accuracy reviews. CONCLUSION: The perspective from which evidence is graded can influence judgments about quality. Guidance on application of GRADE to comparative test reviews and on the GRADE criteria of inconsistency, imprecision, and publication bias will facilitate the operationalization of GRADE for diagnostics.

Guidelines for guideline developers: a systematic review of grading systems for medical tests.

BACKGROUND: A variety of systems have been developed to grade evidence and develop recommendations based on the available evidence. However, development of guidelines for medical tests is especially challenging given the typical indirectness of the evidence; direct evidence of the effects of testing on patient important outcomes is usually absent. We compared grading systems for medical tests on how they use evidence in guideline development. METHODS: We used a systematic strategy to look for grading systems specific to medical tests in PubMed, professional guideline websites, via personal correspondence, and handsearching back references of key articles. Using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument as a starting point, we defined two sets of characteristics to describe these systems: methodological and process ones. Methodological characteristics are features relating to how evidence is gathered, appraised, and used in recommendations. Process characteristics are those relating to the guideline development process. Data were extracted in duplicate and differences resolved through discussion. RESULTS: Twelve grading systems could be included. All varied in the degree to which methodological and process characteristics were addressed. Having a clinical scenario, identifying the care pathway and/or developing an analytical framework, having explicit criteria for appraising and linking indirect evidence, and having explicit methodologies for translating evidence into recommendations were least frequently addressed. Five systems at most addressed these, to varying degrees of explicitness and completeness. Process wise, features most frequently addressed included involvement of relevant professional groups (8/12), external peer review of completed guidelines (9/12), and recommendations on methods for dissemination (8/12). Characteristics least often addressed were whether the system was piloted (3/12) and funder information (3/12). CONCLUSIONS: Five systems for grading evidence about medical tests in guideline development addressed to differing degrees of explicitness the need for and appraisal of different bodies of evidence, the linking of such evidence, and its translation into recommendations. At present, no one system addressed the full complexity of gathering, assessing and linking different bodies of evidence.

The role of Chlamydia pneumoniae in acute respiratory tract infections in young children in The Gambia, West Africa.

BACKGROUND: Little is known about the role of Chlamydia pneumoniae in the aetiology of acute respiratory tract infections (ARI) in children in developing countries. AIMS: To obtain better information, we studied the presence of C. pneumoniae and its association with clinical signs and symptoms of ARI in children under 5 years of age in The Gambia. METHODS: C. pneumoniae was sought by polymerase chain reaction in nasopharyngeal secretions and/or lung puncture aspirates from 324 infants under 3 months of age and 325 children between 3 months and 5 years of age with malnutrition, with or without pneumonia, and in control children. Clinical signs and symptoms for ARI and the spectrum of other viral and bacterial organisms were compared between those positive for C. pneumoniae and those negative. RESULTS: Of 324 young infants, ten (3.1%) showed the presence of C. pneumoniae whereas in the older children 50 of 325 (15%) were positive for C. pneumoniae. There was no significant association between clinical signs and symptoms of ARI and C. pneumoniae positivity in the young infants. Among older infants and children, there was a trend to more frequent lobar alveolar changes in those positive for C. pneumoniae. No bacterial pathogens were found to be significantly associated with C. pneumoniae infection. However, there was an association with measles in the malnutrition group and with RSV in the young infants group. CONCLUSIONS: In this study, C. pneumoniae was not associated with any particular clinical syndrome. We found no evidence that the organism plays a major role in ARI in young children in developing countries such as The Gambia.

SARS transmission and hospital containment.

An outbreak of severe acute respiratory syndrome (SARS) was detected in Singapore at the beginning of March 2003. The outbreak, initiated by a traveler to Hong Kong in late February 2003, led to sequential spread of SARS to three major acute care hospitals in Singapore. The critical factor in containing this outbreak was early detection and complete assessment of movements and follow-up of patients, healthcare workers, and visitors who were contacts. Visitor records were important in helping identify exposed persons who could carry the infection into the community. In the three hospital outbreaks, three different containment strategies were used to contain spread of infection: closing an entire hospital, removing all potentially infected persons to a dedicated SARS hospital, and managing exposed persons in place. On the basis of this experience, if a nosocomial outbreak is detected late, a hospital may need to be closed in order to contain spread of the disease. Outbreaks detected early can be managed by either removing all exposed persons to a designated location or isolating and managing them in place.

Transmission dynamics and control of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic.