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Informing patient-centered care through quantitative benefit-harm assessment in latent tuberculosis

English title Informing patient-centered care through quantitative benefit-harm assessment in latent tuberculosis
Applicant Aschmann Hélène
Number 191414
Funding scheme Early Postdoc.Mobility
Research institution Division of Clinical Epidemiology Department of Epidemiology and Biostatistics University of California, San Francisco
Institution of higher education Institution abroad - IACH
Main discipline Methods of Epidemiology and Preventive Medicine
Start/End 01.04.2021 - 30.09.2022
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All Disciplines (2)

Discipline
Methods of Epidemiology and Preventive Medicine
Infectious Diseases

Keywords (17)

Guideline development; Benefit-harm balance; Benefit-harm assessment; Latent tuberculosis; Patient-centered care; Benefit-risk assessment; Isoniazid preventive therapy; Global health; Prevention; Shared decision-making; Precision medicine; Personalized medicine; Evidence-based medicine; Preference-sensitive ; end TB; stop TB; Public health

Lay Summary (German)

Lead
Personen mit einer latenten Tuberkuloseinfektion (LTBI) sind per Definition gesund und nicht ansteckend. Allerdings könnte eine aktive Tuberkulose-Erkrankung ausbrechen, die ansteckend und potentiell tödlich ist. Um die Tuberkulose-Epidemie zu stoppen, will die Weltgesundheitsorganisation (WHO) vermehrt LTBI präventiv behandeln. Es ist unklar, wer genau von einer solchen präventiven Behandlung profitiert.
Lay summary

Inhalt und Ziele des Forschungsprojekts

Wir werden Nutzen und Schaden der LTBI-Behandlung modellieren und abwägen, um zu bestimmen, wer von einer präventiven Behandlung profitiert. Dies hängt von verschiedenen Faktoren ab. Erstens variiert das Risiko, dass eine Tuberkulose ausbricht je nach Geschlecht, Alter und Vorhandensein einer HIV-Infektion. Zweitens kann ein LTBI-Test eine Infektion verpassen, was besonders wahrscheinlich ist, wenn LTBI verbreitet ist und die getestete Person HIV hat. Drittens führt die präventive, mehrmonatige Antibiotika-Behandlung häufig zu leichten Nebenwirkungen und selten zu schweren Nebenwirkungen, u.a. lebensbedrohlichen Leberschäden. Da die Risikoreduktion eines Tuberkuloseausbruchs durch die präventive Behandlung klein sein kann (z.B. von 5% auf 3%), ist es wichtig zu berücksichtigen, wie belastend die Behandlung und deren Nebenwirkungen für die Person wären. Ziel dieses Projekts ist es, auszuwerten, welche Personen von der präventiven Behandlung profitieren würden. Hierbei berücksichtigen wir die Charakteristika und individuellen Präferenzen der Personen und ihrer Umgebung (z.B. hohe oder tiefe Prävalenz von LTBI und HIV). Wir untersuchen zwei Regionen: die USA und das subsaharische Afrika.

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Unsere Resultate werden wichtige Informationen liefern, um eine Patienten-zentrierte Behandlung der LTBI zu erlauben. Ausserdem werden unsere Resultate eine solide Evidenzbasis bilden, um Patienten dabei zu unterstützen, mit ihrem Arzt zusammen eine informierte, individuelle Entscheidung zu treffen.

Direct link to Lay Summary Last update: 22.09.2021

Responsible applicant and co-applicants

Abstract

People who have latent tuberculosis infection (LTBI) are by definition healthy and not infectious. However, they may develop active tuberculosis (TB), which is contagious and potentially deadly. To break the TB epidemic, the World Health organization aims to scale up LTBI preventive treatment. Because risk for LTBI progressing to TB is difficult to predict and depends on many factors (e.g., sex, age, human immunodeficiency virus (HIV) status), and because diagnostic tests have low sensitivity, managing LTBI is challenging. While patient-centered TB care is one of the aspired pillars of the “end TB” strategy, public health authorities, guideline developers and clinicians lack comprehensive evidence assessments to guide such care.While LTBI treatments can reduce the risk of developing active TB, these risk reductions can be small and uncertain. LTBI treatment consists of several months of antibiotics, causes frequent mild side effects and sometimes serious side effects (including severe hepatotoxicity). Whether the benefits of LTBI treatments outweigh the harms depends on the individual patients’ characteristics, preferences and on the setting (i.e. low or high burden). A stratified quantitative benefit-harm assessment (BHA) systematically puts the evidence on all key determinants into context and can inform guideline development and policy making. BHAs are useful to provide transparent, evidence-based guidance for patient-centered care (i.e. care that considers patient characteristics and preferences).BHAs providing guidance on how to manage LTBI are lacking, in both high and low LTBI burden settings. The work proposed here fills these gaps through two comprehensive BHAs for LTBI treatment, one in a low burden setting (the US) and a second in a high burden setting (sub-Saharan Africa).In low burden settings, emerging evidence suggests novel treatment options may have a better benefit-harm balance compared to standard therapy (6 months of daily isoniazid). Emerging evidence also demonstrates genetic differences may influence the efficacy and adverse effects of isoniazid. It is likely that patients’ individual preferences and perceptions of treatment burden and risks have a large impact on which treatment strategy is optimal and whether screening and treatment is appropriate for them.In high burden settings, such as sub-Saharan Africa, there is a potential conflict between pragmatic public health strategies (with the ultimate goal to eliminate TB) and patient-centered approaches (which consider risk factors and preferences) to manage LTBI. The WHO recommends preventive LTBI treatment for people living with HIV without requiring a prior diagnosis of LTBI. While intuitively, people without LTBI would not seemingly benefit from LTBI treatment, there is both an epidemiologic rationale as well as emerging clinical evidence that they might indeed benefit from treatment. It is essential to clarify optimal screening and treatment strategies.The proposed project uses stratified quantitative BHA based on the most applicable, valid and precise evidence to clarify who should be screened and receive treatment. Thereby it will provide crucial information for guideline developers and policy makers around the world to make LTBI management more patient-centered, and an evidence base for tools to support shared decision-making. Since most of the research in patient-centered care has focused on chronic diseases, this project also aims to initiate a larger movement towards giving patients a voice in research, guidelines and policies around infectious disease. Thus, it will also lead to important advances in the methodology of BHAs and set a new standard in guideline development.This project will be performed at University of California, San Francisco.
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