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

Abstract

BackgroundContext 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?”MethodsWe 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.ResultsWe 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.ConclusionsOur 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 registrationClinicalTrials.gov, NCT02758821 registered on 3 May 2016 and NCT01918579 registered on 7 August 2013.Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3215-9) contains supplementary material, which is available to authorized users.

Introducing new point-of-care tests for common infections in publicly funded clinics in South Africa: a qualitative study with primary care clinicians

“…Our findings are also similar to findings in qualitative studies set in other LMICs, in particular southeast Asia, that highlight an overall enthusiasm among healthcare workers with the introduction of POCTs,26 but also echo concerns about the impact on workload and constraints of available alternatives to antibiotic treatment 28. Clinicians in southeast Asia reported using a CRP POCT to support their negotiations with patients for a non-antibiotic strategy, helping to manage perceived patient expectations for antibiotics.…”

“…However, it is encouraging to see an increasing number of studies from LMICs (in particular southeast Asia) that have evaluated the use of POCTs for common infection syndromes (beyond HIV, sexually transmitted diseases, TB and malaria). These studies included randomised trials using C reactive protein (CRP) POCTs to guide prescribing decisions 26–30. However, findings from these studies do not necessarily apply to other LMICs where disease spectra and the social and cultural determinants of health and healthcare systems differ 28 31.…”

“…These studies included randomised trials using C reactive protein (CRP) POCTs to guide prescribing decisions 26–30. However, findings from these studies do not necessarily apply to other LMICs where disease spectra and the social and cultural determinants of health and healthcare systems differ 28 31. Developing and implementing interventions to improve the quality of antibiotic prescribing for common infection syndromes are more likely to be effective if sensitive to understanding prescribers’ perceptions of their current practice and their perceptions about context-specific opportunities and challenges for the uptake of new POCTs.…”

In-vitro diagnostic point-of-care tests in paediatric ambulatory care: A systematic review and meta-analysis

“…There are also likely to be important social determinants of prescribing that may override POCT-driven prescribing e.g. parental concern, the potential of rapid deterioration, and especially in LMICs, access to care [31,68,69]. Our data were not able to evaluate if and how parents or carers of children might influence prescribing decisions despite a 'normal' POC result.…”

New impulses from international development for more comprehensive and balanced public engagement evaluation

“…The aforementioned public engagement workshops took place in between these two rounds (depicted in Figure 1 together with the survey activities and the collection of photo narratives). The surveys used a 45-minute health behaviour questionnaire that was developed based on prior qualitative research on treatment seeking and antibiotic use in Southeast Asia [46], comprising modules on sociodemographic background, knowledge and attitudes towards antibiotics and drug resistance, and the stepby-step process of seeking care for an acute illness or discomfort experienced by the respondent or a child under their supervision. Situating the workshops in between the survey rounds enabled a short-term assessment of knowledge, attitude, and behaviour changes among participants and non-participants in the five census survey villages.…”