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

Marco J Haenssgen, Nutcha Charoenboon, Nga T T Do, Thomas Althaus, Yuzana Khine Zaw, Heiman F L Wertheim, Yoel Lubell, Marco J Haenssgen, Nutcha Charoenboon, Nga T T Do, Thomas Althaus, Yuzana Khine Zaw, Heiman F L Wertheim, Yoel Lubell

Abstract

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.

Keywords: Antibiotic prescription; Contextual factors; Intervention implementation; Myanmar; Qualitative research; Thailand; Vietnam.

Conflict of interest statement

Ethics approval and consent to participate

Written informed consent was obtained from all participants. The Thailand and Myanmar research was registered under ClinicalTrials.gov identifier NCT02758821 and approved by the University of Oxford Tropical Research Ethics Committee (ref. 49-15), Mahidol University Faculty of Tropical Medicine Ethics Committee (ref. 16-015), the Chiang Rai Provincial Public Health Office Ethics Committee (ref. CR 0032.002/3516), and the Myanmar Department of Medical Research (ref. Ethics/DMR/2016/137). The Vietnam research was registered at ClinicalTrials.gov Identifier NCT01918579 and approved by the Oxford University Tropical Research Ethics Committee (OxTREC Ref. 176-12), the ethical committee of the National Hospital for Tropical Diseases in Hanoi (39/IRB-NHTD), and by local authorities in Vietnam.

Consent for publication

N/A.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Contextual factors influencing C-reactive protein point-of-care test (CRP POCT). Source: Authors, derived from qualitative analysis. “Health systems” here comprise all formal and informal actors involved in promoting, maintaining, or restoring health according to the World Health Organization [91], which can include for example medicine-selling grocery stores alongside public and private hospitals

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