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• Cost-effectiveness and tuberculosis elimination: a détente?
  Sean M Cavany, Charlotte Anderson, Helen Maguire, Frank Sandmann, H. Lucy Thomas, Richard G. White and Tom Sumner
  Published on: 20 March 2019
• Cost-effectiveness and tuberculosis elimination: never the twain shall meet
  Tom Wingfield, Peter MacPherson, L Peter Ormerod, S Bertel Squire and Paul Cleary
  Published on: 31 August 2018

• Published on: 20 March 2019

  Cost-effectiveness and tuberculosis elimination: a détente?

  • Sean M Cavany, Postdoctoral Scholar Biological Sciences, University of Notre Dame
  • Other Contributors:
    • Charlotte Anderson, Senior Scientist
    • Helen Maguire, Professor
    • Frank Sandmann, Research Scientist
    • H. Lucy Thomas, Consultant
    • Richard G. White, Professor
    • Tom Sumner, Assistant Professor

  We would like to thank Dr. Wingfield et al. for their thoughtful response on our cost-effectiveness analysis of tuberculosis contact tracing in London(1). The authors provide a number of insights which complement and expand upon our results and highlight the many complexities of TB interventions, both currently and as we head towards elimination.

  Wingfield et al. raise important points regarding heterogeneity on contact tracing yield, something we touched upon in the discussion of our paper. As they mention, such heterogeneity is likely to increase as countries such as the UK near elimination. We found that the yield of active cases around non-pulmonary cases needed to be very high – in our analyses, the incremental cost-effectiveness ratio (ICER) for screening such contacts was below £30,000 per quality-adjusted life year (QALY) when the yield of contacts reached about 0.1 active cases found per index case, i.e. when 4% of contacts screened are positive. However, this ignores synergistic effects caused by those infectious contacts potentially being more infectious and infectious for longer, due to their being part of a high-risk group, and so the actual threshold may be lower.

  We also agree with Wingfield et al. that careful thought must be given to the interpretation of the ICER in the context of TB elimination, as in any context. Rather than treating the willingness-to-pay threshold as a strict and universal cut-off value, the ICER should be considered alo...

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  We would like to thank Dr. Wingfield et al. for their thoughtful response on our cost-effectiveness analysis of tuberculosis contact tracing in London(1). The authors provide a number of insights which complement and expand upon our results and highlight the many complexities of TB interventions, both currently and as we head towards elimination.

  Wingfield et al. raise important points regarding heterogeneity on contact tracing yield, something we touched upon in the discussion of our paper. As they mention, such heterogeneity is likely to increase as countries such as the UK near elimination. We found that the yield of active cases around non-pulmonary cases needed to be very high – in our analyses, the incremental cost-effectiveness ratio (ICER) for screening such contacts was below £30,000 per quality-adjusted life year (QALY) when the yield of contacts reached about 0.1 active cases found per index case, i.e. when 4% of contacts screened are positive. However, this ignores synergistic effects caused by those infectious contacts potentially being more infectious and infectious for longer, due to their being part of a high-risk group, and so the actual threshold may be lower.

  We also agree with Wingfield et al. that careful thought must be given to the interpretation of the ICER in the context of TB elimination, as in any context. Rather than treating the willingness-to-pay threshold as a strict and universal cut-off value, the ICER should be considered alongside the whole suite of available scientific evidence and public-policy objectives, forming one component within a multi-criteria decision analysis framework featuring other considerations such as the value of international recognition of successful disease elimination(2). In this way, combined with more targeted screening programmes, it may be possible to bridge the gap between cost-effectiveness analysis and TB elimination, allowing the twain to meet.

  1. Cavany SM, Vynnycky E, Anderson CS, Maguire H, Sandmann F, Thomas HL, et al. Should NICE reconsider the 2016 UK guidelines on TB contact tracing? A cost-effectiveness analysis of contact investigations in London. Thorax. 2019 Feb 1;74(2):185–93.
  2. Baltussen R, Niessen L. Priority setting of health interventions: the need for multi-criteria decision analysis. Cost Eff Resour Alloc. 2006 Aug 21;4(1):14.

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  Conflict of Interest:
  None declared.

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• Published on: 31 August 2018

  Cost-effectiveness and tuberculosis elimination: never the twain shall meet

  • Tom Wingfield, Clinical Lecturer in Infection LIV-TB Cross Campus Collaboration, University of Liverpool and Liverpool School of Tropical Medicine, Liverpool
  • Other Contributors:
    • Peter MacPherson, Senior Lecturer
    • L Peter Ormerod, Physician and Professor
    • S Bertel Squire, Professor
    • Paul Cleary, Consultant Epidemiologist

  The National Institute for Health and Care Excellence (NICE) 2016 Tuberculosis (TB) guidelines no longer recommend screening contacts of adults with extra-pulmonary TB (ETB). However, no new evidence since the previous published guidelines was provided to support this policy change. Moreover, despite the guidance, some regional TB multidisciplinary teams and services continue to screen ETB contacts.(1)

  In their original article in Thorax, Cavany et al estimated the cost-effectiveness of screening ETB contacts in London.(2) The authors’ findings suggest that screening of such contacts is unlikely to be cost-effective at the threshold of £30,000/QALY - the “willingness to pay” threshold commonly used by NICE.(3) The authors’ findings are tempered by the data being London-specific and not generalizable to the rest of England, and the lack of robust available evidence on either transmission rates or index cases’ pre-diagnosis symptom duration. Nevertheless, the authors recognise these limitations and their sensitivity analysis suggests that, even with assumptions of higher rates of transmission or prolonged symptom duration, their principal findings would not change.

  The findings of this strong, well-designed study are important and provide much needed evidence for national debate around strategies for TB contact screening. Resources for TB services across England, especially those allocated to tracing contacts of TB patients, are becoming increasingly constrain...

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  The National Institute for Health and Care Excellence (NICE) 2016 Tuberculosis (TB) guidelines no longer recommend screening contacts of adults with extra-pulmonary TB (ETB). However, no new evidence since the previous published guidelines was provided to support this policy change. Moreover, despite the guidance, some regional TB multidisciplinary teams and services continue to screen ETB contacts.(1)

  In their original article in Thorax, Cavany et al estimated the cost-effectiveness of screening ETB contacts in London.(2) The authors’ findings suggest that screening of such contacts is unlikely to be cost-effective at the threshold of £30,000/QALY - the “willingness to pay” threshold commonly used by NICE.(3) The authors’ findings are tempered by the data being London-specific and not generalizable to the rest of England, and the lack of robust available evidence on either transmission rates or index cases’ pre-diagnosis symptom duration. Nevertheless, the authors recognise these limitations and their sensitivity analysis suggests that, even with assumptions of higher rates of transmission or prolonged symptom duration, their principal findings would not change.

  The findings of this strong, well-designed study are important and provide much needed evidence for national debate around strategies for TB contact screening. Resources for TB services across England, especially those allocated to tracing contacts of TB patients, are becoming increasingly constrained. Therefore, it is vital that a pragmatic approach is taken to prioritise the most cost-effective, evidence-based strategies for identifying people most at risk of latent TB infection and progression to active TB disease. Cavany et al’s excellent paper raises certain key points relating to the wider policy implications of the cost-effectiveness of TB prevention strategies in low-burden settings.

  First, as set out in the World Health Organization’s “End TB Strategy”(4) and PHE and NHS England’s “Collaborative Tuberculosis Strategy 2015-2020”,(5) the shared aim of the global TB community is to eliminate tuberculosis (defined as less than one case of active TB disease per 100,000 population). This goal is especially pertinent with regards to cost-effectiveness in low burden settings like Western Europe because, as incidence and prevalence of TB continue to decline, the cost per tracing episode will increase, probably non-linearly, and therefore meeting cost-effectiveness thresholds will become increasingly difficult.(6) For example, in North West England, declines in TB incidence have been associated with an increase in the proportion of TB cases who have complex social and clinical risk factors requiring enhanced case management (ECM) and hence greater per patient resource allocation.(7)

  Second, cost-effectiveness estimates often assume homogeneity of clinical and social risk factors of TB patients and contacts when, in practice, such populations are profoundly diverse. We conducted an analysis of our North West England cohort of 2,139 TB cases and their 10,019 contacts. Our research showed that prevalence of active TB disease among contacts of patients with ETB was similar to the London cohort (0.44% versus 0.7% in Cavany et al, respectively) but varies widely according to the index patient’s social and clinical complexity as measured by ECM need.(1) Excluding contacts who would meet other criteria for routine contact tracing and/or active case finding (e.g. migrants, homeless people, or drug users), the rate of active TB disease in contacts of extrapulmonary TB patients with no ECM need versus the highest ECM need were 0.06% versus 1.5%, respectively.(8) Therefore, whilst we agree that contact tracing of all ETB contacts may not be cost-effective, focusing on a small number of high-risk ETB contacts (in whom approximately 1 in 66 will have active TB disease in our North West cohort) may still be an appropriate allocation of resources in the context of aiming towards regional elimination of TB.

  Third, robust cost-effectiveness analyses such as Cavany et al’s should motivate the TB community in England to evaluate the predominant drivers of the costs of their TB detection and prevention services. If existing contact tracing strategies are, as in Cavany et al’s research, shown to lack cost-effectiveness, TB multi-disciplinary teams and service providers should consider designing and implementing innovative approaches that are more efficient and better value for money. Identification and characterisation of patients’ risk of an adverse treatment outcome and contacts’ risk of a positive screening event using ECM is one simple strategy,(7,8) but there are many other potential options including: electronic or virtual screening; community engagement and outreach clinics; patient and peer-led active case finding; and socioeconomic support, incentives and enablers. It is essential that future research designing and implementing such novel strategies follows Cavany et al’s lead and includes rigorous cost-effectiveness analysis in order to best inform and guide policy makers and public health commissioners.(9)

  Cavany et al’s research highlights the importance of high-quality cost-effectiveness analysis to guide TB policy. In order to provide optimal TB detection, prevention, and care services tailored to individuals, especially those in underserved groups, future TB policy decisions should take into account heterogeneity within TB populations and the inevitable decrease in cost-effectiveness of interventions in line with declining TB rates. Without such considerations, we will be unlikely to meet the goal of eliminating TB in England.

  References

  1) Wingfield T, MacPherson P, Cleary P, Ormerod LP. High prevalence of TB disease in contacts of adults with extrapulmonary TB. Thorax. 2018 Aug;73(8):785-787. doi: 10.1136/thoraxjnl-2017-210202. Epub 2017 Nov 16.

  2) Cavany SM, Sumner T, Vynnycky E, Flach C, White RG, Thomas HL, Maguire H, Anderson C. An evaluation of tuberculosis contact investigations against national standards. Thorax. 2017 Aug;72(8):736-745. doi: 10.1136/thoraxjnl-2016-209677. Epub 2017 Apr 7.

  3) McCabe C, Claxton K, Culyer AJ. The NICE cost-effectiveness threshold: what it is and what that means. Pharmacoeconomics. 2008;26(9):733-44.

  4) World Health Organisation’s End Tuberculosis Strategy, 2015.
  http://www.who.int/tb/strategy/End_TB_Strategy.pdf?ua=1 WHO, Geneva. Last accessed 29th August 2018.

  5) Collaborative Tuberculosis Strategy for England 2015 to 2020. NHS and Public Health England. https://assets.publishing.service.gov.uk/government/uploads/system/uploa... Last accessed 29th August 2018

  6) Smit GS, Apers L, Arrazola de Onate W, Beutels P, Dorny P, Forier AM, Janssens K, Macq J, Mak R, Schol S, Wildemeersch D, Speybroeck N, Devleesschauwer B. Cost-effectiveness of screening for active cases of tuberculosis in Flanders, Belgium. Bull World Health Organ. 2017 Jan 1;95(1):27-35. doi: 10.2471/BLT.16.169383. Epub 2016 Nov 3.

  7) Tucker A, Mithoo J, Cleary P, Woodhead M, MacPherson P, Wingfield T, Davies S, Wake C, McMaster P, Bertel Squire S. Quantifying the need for enhanced case management for TB patients as part of TB cohort audit in the North West of England: a descriptive study. BMC Public Health. 2017 Nov 15;17(1):881. doi: 10.1186/s12889-017-4892-5.

  8) Wingfield T, MacPherson P, Sodha P, Tucker A, Mithoo J, Squire S B, Cleary P. The association of TB patients’ social risk factors and ethnicity with prevalence of TB infection and disease among their contacts: a cohort study in North West England. Under review with International Journal of Tuberculosis and Lung Disease, August 2018.

  9) Lönnroth K, Migliori GB, Abubakar I, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J. 2015 Apr;45(4):928-52. doi: 10.1183/09031936.00214014

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  Conflict of Interest:
  None declared.

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