Title: Treatment delay in tuberculosis
Funder: Department of Health and Social Care

Abstract: Background Worldwide tuberculosis (TB) is the leading cause of death due to a single infectious agent. Incidence in the United Kingdom is higher than most western European countries. Approximately one-third of pulmonary cases experience treatment delay and this proportion is increasing. Those aged over 65 years are particularly affected by delays and little is known about their experiences of TB. Duration of delay is difficult to measure due to recall bias and insufficient knowledge about the sequence of symptom development. Treatment delay is associated with increased morbidity, mortality, transmission and poor patient experiences. However, the duration after which these consequences occur has not been quantified. Primary care stage of delay is an important contributor and may increase as incidence decreases. Aim and research questions The aim of this project is to address existing gaps in the evidence about TB treatment delay by answering the following questions, using a mixed methods approach: What is the epidemiology of the primary care stage of treatment delay? What is the experience of patients aged over 65 years with TB? What is the optimum diagnostic model to facilitate early referral of patients with TB from primary care? Methods Phase one: Notification data from Public Health England will be linked to the Royal College of General Practitioners Research and Surveillance Centre (RSC) database, Hospital Episode Statistics and mortality data using encrypted NHS numbers. A self-controlled case series approach will be used to evaluate the relative likelihood of developing alert symptoms in the lead up to diagnosis. The first appearance of alert symptoms will be used to re-define the start of treatment delay. Regression techniques will be used to investigate the association of delay with outcomes (death, transmission, duration of treatment and health system use). Phase two: A narrative qualitative study will recruit twelve English and twelve Urdu or Punjabi speaking patients, aged over 65, with TB at any site. After transcribing, a problem-solution approach and levels of narrative approach will be taken to re-story the data and create meta-narratives, respectively. A triangulation protocol will be used to integrate the post-analysis findings from phases one and two. Phase three: I will use logistic regression models to develop a diagnostic prediction tool informing referral of patients from primary care. The tool will be derived from the RSC database and externally validated in The Health Improvement Network database. I will carry out internal validation and calculate performance measures, calibration and discrimination. A decision analysis approach will be used to measure costs and consequences. Patient, public and stakeholder involvement Patients partners have been consulted about the project, the approach for the qualitative work and the development of the plain English summary. Three patient partners will be part of the steering group and will be involved in key decisions in each phase. Impact and dissemination Findings will be disseminated through academic, clinical and public networks and will impact on public and professional facing health messaging. The diagnostic tool will provide a springboard to discussions about improving referral pathways.

Lay abstract: Background and aims of research The aim of this project is to understand and improve treatment delay in tuberculosis (TB). In 2017 people with TB in their lungs waited on average 79 days between their symptoms developing and their treatment starting. One in three people waited for four months or longer. Those aged 65 years and over are more likely to experience this delay than those under 65 years. People with TB infections in parts of the body other than the lungs have even longer delays. Treatment delay is difficult to measure because the symptoms can be vague and may have started a long time ago. Treatment delays can lead to more severe illness, poor experiences with health care, increased spread of the disease to others and sometimes death. It is unclear how much of a delay leads to these effects. Delays in treatment of TB in England are mainly due to patients not seeing a doctor promptly when ill with TB, and GPs not referring quickly enough. TB is associated with stigma in some communities. Even those who know about TB in their communities often feel that they themselves will not be affected. These factors can delay visiting a doctor as can lack of awareness of TB. Most GPs will not see TB very often in their working lives so they are less likely to think of this diagnosis. As TB becomes less common, delays in treatment may get longer. Design and methods Phase one - Timing of TB symptoms I will match information from Public Health England's records of TB notifications to GP electronic medical records. I will search the GP records for TB symptoms in the five years before diagnosis. I will analyse these data to see how long before diagnosis the symptoms start and which symptoms become more common approaching diagnosis. I will look for spread of the disease to others, length of treatment, health system use (both hospital and primary care) and death and see how these vary as treatment delay increases. Phase two - the experience of those aged over 65 I will recruit 24 people (12 English and 12 Urdu or Punjabi speakers) aged over 65 who have been diagnosed with TB and are receiving treatment in the West Midlands. This age group was chosen since there is very little research about their experience of TB. The most commonly used non-English languages were chosen to make sure that a range of views are heard. I will interview each person to ask about their experience and find out what made them decide to see a doctor. The information from phases 1 and 2 will be combined to give a detailed picture of the journey from symptoms to outcome. Phase three - a tool to help early referral I will build on information from phases 1 and 2 and compare symptoms in people with and without TB to develop a tool which will help GPs to identify which patients should be referred for further investigations. I will test how accurate the tool is and if it offers good value for money. Patient and public involvement. There will be three patient partners advising about key decisions. These will include their views on which symptoms are important, the recruitment process, patient information sheets, interview guides and threshold for referral. DisseminationThe results from all three questions will be published in peer-reviewed academic journals and presented at conferences and TB meetings. I will work with TB Alert and patient partners to develop innovative ways to spread information to the general public, people with TB and health care professionals.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: INFECTION