The use of propensity score methods to examine comparative effectiveness of treatments provided to children  in Kenyan hospitals

Malla, L

Abstract:: Background: Although randomised controlled trials are the best means of measuring efficacy of interventions and inferring causality challenges of limited generalisability to real life populations, cost and applicability for some types of intervention have prompted efforts to develop alternative approaches using observational data. Such approaches are very rarely used in low income settings. This research utilised a large dataset of well characterised admission events to paediatric w...
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APA Style

Malla, L. (2018). The use of propensity score methods to examine comparative effectiveness of treatments provided to children in Kenyan hospitals [PhD thesis]. University of Oxford.

MLA Style

Malla, L. The Use of Propensity Score Methods to Examine Comparative Effectiveness of Treatments Provided to Children in Kenyan Hospitals. 2018. University of Oxford, PhD thesis.

Chicago Style

Malla, L. 2018. “The Use of Propensity Score Methods to Examine Comparative Effectiveness of Treatments Provided to Children in Kenyan Hospitals.” PhD thesis, University of Oxford.
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+ Malla, L More by this author

Division:: MSD
Role:: Author

Contributors

+ English, M

Role:: Supervisor

+ Perera, R

Role:: Supervisor

+ McFadden, E

Role:: Supervisor

+ Clarendon Scholarship More from this funder

+ Nuffield Department of Medicine Studentship More from this funder

DOI:: 10.5287/ora-wrwnokape
Type of award:: DPhil
Level of award:: Doctoral
Awarding institution:: University of Oxford

UUID:: uuid:adb81edf-c445-4f7c-a301-0e0de0b439cb
Deposit date:: 2018-08-30
ARK identifier:: ark:/29072/ora_adb81edfc4454f7ca3010e0de0b439cb

Related item:: Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: protocol for an observational study
Description:: INTRODUCTION: WHO treatment guidelines are widely recommended for guiding treatment for millions of children with pneumonia every year across multiple low-income and middle-income countries. Guidelines are based on synthesis of available evidence that provides moderate certainty in evidence of effects for forms of pneumonia that can result in hospitalisation. However, trials have included fewer children from Africa than other settings, and it is suggested that African children with pneumonia have higher mortality. Thus, despite improving access to recommended treatments and deployment with high coverage of childhood vaccines, pneumonia remains one of the top causes of mortality for children in Kenya. Establishing whether there are benefits of alternative treatment regimens to help reduce mortality would require pragmatic clinical trials. However, these remain relatively expensive and time consuming. This protocol describes an approach to using secondary analysis of a new, large observational dataset as a potentially cheaper and quicker way to examine the comparative effectiveness of penicillin versus penicillin plus gentamicin in treatment of indrawing pneumonia. Addressing this question is important, as although it is now recommended that this form of pneumonia is treated with oral medication as an outpatient, it remains associated with non-trivial mortality that may be higher outside trial populations. METHODS AND ANALYSIS: We will use a large observational dataset that captures data on all admissions to 13 Kenyan county hospitals. These data represent the findings of clinicians in practice and, because the system was developed for large observational research, pose challenges of non-random treatment allocation and missing data. To overcome these challenges, this analysis will use a rigorous approach to study design, propensity score methods and multiple imputation to minimise bias. ETHICS AND DISSEMINATION: The primary data are held by hospitals participating in the Kenyan Clinical Information Network project with de-identifed data shared with the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Research Programme for agreed analyses. The use of data for the analysis described received ethical clearance from the KEMRI scientific and ethical review committee. The findings of this analysis will be published.
Related item:: Comparative effectiveness of injectable penicillin versus a combination of penicillin and gentamicin in children with pneumonia characterised by indrawing in Kenya: a retrospective observational study
Description:: Objectives Kenyan guidelines for antibiotic treatment of pneumonia recommended treatment of pneumonia characterised by indrawing with injectable penicillin alone in inpatient settings until early 2016. At this point, they were revised becoming consistent with WHO guidance after results of a Kenyan trial provided further evidence of equivalence of oral amoxicillin and injectable penicillin. This change also made possible use of oral amoxicillin for outpatient treatment in this patient group. However, given non-trivial mortality in Kenyan children with indrawing pneumonia, it remained possible they would benefit from a broader spectrum antibiotic regimen. Therefore, we compared the effectiveness of injectable penicillin monotherapy with a regimen combining penicillin with gentamicin. Setting We used a large routine observational dataset that captures data on all admissions to 13 Kenyan county hospitals. Participants and measures The analyses included children aged 2–59 months. Selection of study population was based on inclusion criteria typical of a prospective trial, primary analysis (experiment 1, n=4002), but we also explored more pragmatic inclusion criteria (experiment 2, n=6420) as part of a secondary analysis. To overcome the challenges associated with the non-random allocation of treatments and missing data, we used propensity score (PS) methods and multiple imputation to minimise bias. Further, we estimated mortality risk ratios using log binomial regression and conducted sensitivity analyses using an instrumental variable and PS trimming. Results The estimated risk of dying, in experiment 1, in those receiving penicillin plus gentamicin was 1.46 (0.85 to 2.43) compared with the penicillin monotherapy group. In experiment 2, the estimated risk was 1.04(0.76 to 1.40). Conclusion There is no statistical difference in the treatment of indrawing pneumonia with either penicillin or penicillin plus gentamicin. By extension, it is unlikely that treatment with penicillin plus gentamicin would offer an advantage to treatment with oral amoxicillin.
Related item:: Handling missing data in propensity score estimation in comparative effectiveness evaluations: a systematic review
Description:: AIM: Even though systematic reviews have examined how aspects of propensity score methods are used, none has reviewed how the challenge of missing data is addressed with these methods. This review therefore describes how missing data are addressed with propensity score methods in observational comparative effectiveness studies. METHODS: Published articles on observational comparative effectiveness studies were extracted from MEDLINE and EMBASE databases. RESULTS: Our search yielded 167 eligible articles. Majority of these studies (114; 68%) conducted complete case analysis with only 53 of them stating this in the methods. Only 16 articles reported use of multiple imputation. CONCLUSION: Few researchers use correct methods for handling missing data or reported missing data methodology which may lead to reporting biased findings.

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Copyright holder:: Malla, L

Licence:: Terms and Conditions of Use for Oxford University Research Archive

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The use of propensity score methods to examine comparative effectiveness of treatments provided to children in Kenyan hospitals

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The use of propensity score methods to examine comparative effectiveness of treatments provided to children in Kenyan hospitals

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