How context can impact clinical trials: a multi-country qualitative case study comparison of diagnostic biomarker test interventions.

BACKGROUND: Context matters for the successful implementation of medical interventions, but its role remains surprisingly understudied. Against the backdrop of antimicrobial resistance, a global health priority, we investigated the introduction of a rapid diagnostic biomarker test (C-reactive protein, or CRP) to guide antibiotic prescriptions in outpatient settings and asked, "Which factors account for cross-country variations in the effectiveness of CRP biomarker test interventions?" METHODS: We conducted a cross-case comparison of CRP point-of-care test trials across Yangon (Myanmar), Chiang Rai (Thailand), and Hanoi (Vietnam). Cross-sectional qualitative data were originally collected as part of each clinical trial to broaden their evidence base and help explain their respective results. We synthesised these data and developed a large qualitative data set comprising 130 interview and focus group participants (healthcare workers and patients) and nearly one million words worth of transcripts and interview notes. Inductive thematic analysis was used to identify contextual factors and compare them across the three case studies. As clinical trial outcomes, we considered patients' and healthcare workers' adherence to the biomarker test results, and patient exclusion to gauge the potential "impact" of CRP point-of-care testing on the population level. RESULTS: We identified three principal domains of contextual influences on intervention effectiveness. First, perceived risks from infectious diseases influenced the adherence of the clinical users (nurses, doctors). Second, the health system context related to all three intervention outcomes (via the health policy and antibiotic policy environment, and via health system structures and the ensuing utilisation patterns). Third, the demand-side context influenced the patient adherence to CRP point-of-care tests and exclusion from the intervention through variations in local healthcare-seeking behaviours, popular conceptions of illness and medicine, and the resulting utilisation of the health system. CONCLUSIONS: Our study underscored the importance of contextual variation for the interpretation of clinical trial findings. Further research should investigate the range and magnitude of contextual effects on trial outcomes through meta-analyses of large sets of clinical trials. For this to be possible, clinical trials should collect qualitative and quantitative contextual information for instance on their disease, health system, and demand-side environment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02758821 registered on 3 May 2016 and NCT01918579 registered on 7 August 2013.

The 'Drug Bag' method: lessons from anthropological studies of antibiotic use in Africa and South-East Asia.

Understanding the prevalence and types of antibiotics used in a given human and/or animal population is important for informing stewardship strategies. Methods used to capture such data often rely on verbal elicitation of reported use that tend to assume shared medical terminology. Studies have shown the category 'antibiotic' does not translate well linguistically or conceptually, which limits the accuracy of these reports. This article presents a 'Drug Bag' method to study antibiotic use (ABU) in households and on farms, which involves using physical samples of all the antibiotics available within a given study site. We present the conceptual underpinnings of the method, and our experiences of using this method to produce data about antibiotic recognition, use and accessibility in the context of anthropological research in Africa and South-East Asia. We illustrate the kinds of qualitative and quantitative data the method can produce, comparing and contrasting our experiences in different settings. The Drug Bag method produce accurate antibiotic use data as well as provide a talking point for participants to discuss antibiotic experiences. We propose it can help improve our understanding of antibiotic use in peoples' everyday lives across different contexts, and our reflections add to a growing conversation around methods to study ABU beyond prescriber settings, where data gaps are currently substantial.

Antibiotic knowledge, attitudes and practices: new insights from cross-sectional rural health behaviour surveys in low-income and middle-income South-East Asia.

INTRODUCTION: Low-income and middle-income countries (LMICs) are crucial in the global response to antimicrobial resistance (AMR), but diverse health systems, healthcare practices and cultural conceptions of medicine can complicate global education and awareness-raising campaigns. Social research can help understand LMIC contexts but remains under-represented in AMR research. OBJECTIVE: To (1) Describe antibiotic-related knowledge, attitudes and practices of the general population in two LMICs. (2) Assess the role of antibiotic-related knowledge and attitudes on antibiotic access from different types of healthcare providers. DESIGN: Observational study: cross-sectional rural health behaviour survey, representative of the population level. SETTING: General rural population in Chiang Rai (Thailand) and Salavan (Lao PDR), surveyed between November 2017 and May 2018. PARTICIPANTS: 2141 adult members (≥18 years) of the general rural population, representing 712 000 villagers. OUTCOME MEASURES: Antibiotic-related knowledge, attitudes and practices across sites and healthcare access channels. FINDINGS: Villagers were aware of antibiotics (Chiang Rai: 95.7%; Salavan: 86.4%; p<0.001) and drug resistance (Chiang Rai: 74.8%; Salavan: 62.5%; p<0.001), but the usage of technical concepts for antibiotics was dwarfed by local expressions like 'anti-inflammatory medicine' in Chiang Rai (87.6%; 95% CI 84.9% to 90.0%) and 'ampi' in Salavan (75.6%; 95% CI 71.4% to 79.4%). Multivariate linear regression suggested that attitudes against over-the-counter antibiotics were linked to 0.12 additional antibiotic use episodes from public healthcare providers in Chiang Rai (95% CI 0.01 to 0.23) and 0.53 in Salavan (95% CI 0.16 to 0.90). CONCLUSIONS: Locally specific conceptions and counterintuitive practices around antimicrobials can complicate AMR communication efforts and entail unforeseen consequences. Overcoming 'knowledge deficits' alone will therefore be insufficient for global AMR behaviour change. We call for an expansion of behavioural AMR strategies towards 'AMR-sensitive interventions' that address context-specific upstream drivers of antimicrobial use (eg, unemployment insurance) and complement education and awareness campaigns. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier NCT03241316.

The Consequences of AMR Education and Awareness Raising: Outputs, Outcomes, and Behavioural Impacts of an Antibiotic-Related Educational Activity in Lao PDR.

Education and awareness raising are the primary tools of global health policy to change public behaviour and tackle antimicrobial resistance. Considering the limitations of an awareness agenda, and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages and also to learn about people's conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity's outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the educational activity influenced the awareness and understanding of "drug resistance", whereas the effects on attitudes were minor. The evidence on the behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance.

A Comparison of Patients' Local Conceptions of Illness and Medicines in the Context of C-Reactive Protein Biomarker Testing in Chiang Rai and Yangon.

Antibiotic resistance is not solely a medical but also a social problem, influenced partly by patients' treatment-seeking behavior and their conceptions of illness and medicines. Situated within the context of a clinical trial of C-reactive protein (CRP) biomarker testing to reduce antibiotic over-prescription at the primary care level, our study explores and compares the narratives of 58 fever patients in Chiang Rai (Thailand) and Yangon (Myanmar). Our objectives are to 1) compare local conceptions of illness and medicines in relation to health-care seeking and antibiotic demand; and to 2) understand how these conceptions could influence CRP point-of-care testing (POCT) at the primary care level in low- and middle-income country settings. We thereby go beyond the current knowledge about antimicrobial resistance and CRP POCT, which consists primarily of clinical research and quantitative data. We find that CRP POCT in Chiang Rai and Yangon interacted with fever patients' preexisting conceptions of illness and medicines, their treatment-seeking behavior, and their health-care experiences, which has led to new interpretations of the test, potentially unforeseen exclusion patterns, implications for patients' self-assessed illness severity, and an increase in the status of the formal health-care facilities that provide the test. Although we expected that local conceptions of illness diverge from inbuilt assumptions of clinical interventions, we conclude that this mismatch can undermine the intervention and potentially reproduce problematic equity patterns among CRP POCT users and nonusers. As a partial solution, implementers may consider applying the test after clinical examination to validate rather than direct prescription processes.

Antibiotics and activity spaces: protocol of an exploratory study of behaviour, marginalisation and knowledge diffusion.

BACKGROUND: Antimicrobial resistance (AMR) is a global health priority. Leading UK and global strategy papers to fight AMR recognise its social and behavioural dimensions, but current policy responses to improve the popular use of antimicrobials (eg, antibiotics) are limited to education and awareness-raising campaigns. In response to conceptual, methodological and empirical weaknesses of this approach, we study people's antibiotic-related health behaviour through three research questions.RQ1: What are the manifestations and determinants of problematic antibiotic use in patients' healthcare-seeking pathways?RQ2: Will people's exposure to antibiotic awareness activities entail changed behaviours that diffuse or dissipate within a network of competing healthcare practices?RQ3: Which proxy indicators facilitate the detection of problematic antibiotic behaviours across and within communities? METHODS: We apply an interdisciplinary analytical framework that draws on the public health, medical anthropology, sociology and development economics literature. Our research involves social surveys of treatment-seeking behaviour among rural dwellers in northern Thailand (Chiang Rai) and southern Lao PDR (Salavan). We sample approximately 4800 adults to produce district-level representative and social network data. Additional 60 cognitive interviews facilitate survey instrument development and data interpretation. Our survey data analysis techniques include event sequence analysis (RQ1), multilevel regression (RQ1-3), social network analysis (RQ2) and latent class analysis (RQ3). DISCUSSION: Social research in AMR is nascent, but our unprecedentedly detailed data on microlevel treatment-seeking behaviour can contribute an understanding of behaviour beyond awareness and free choice, highlighting, for example, decision-making constraints, problems of marginalisation and lacking access to healthcare and competing ideas about desirable behaviour. TRIAL REGISTRATION NUMBER: NCT03241316; Pre-results.