Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial

Alistair Story, Robert W. Aldridge, Catherine M. Smith, Elizabeth Garber, Joe Hall, Gloria Ferenando, Lucia Possas, Sara Hemming, Fatima Wurie, Serena Luchenski, Ibrahim Abubakar, Timothy D. McHugh, Peter J. White, John M. Watson, Marc Lipman, Richard Garfein, Andrew C. Hayward*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Citations (Scopus)

Abstract

Background: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. Methods: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN26184967. Findings: Between Sept 1, 2014, and Oct 1, 2016, we randomly assigned 226 patients; 112 to VOT and 114 to DOT. Overall, 131 (58%) patients had a history of homelessness, imprisonment, drug use, alcohol problems or mental health problems. In the ITT analysis, 78 (70%) of 112 patients on VOT achieved ≥80% scheduled observations successfully completed during the first 2 months compared with 35 (31%) of 114 on DOT (adjusted odds ratio [OR] 5·48, 95% CI 3·10–9·68; p<0·0001). In the restricted analysis, 78 (77%) of 101 patients on VOT achieved the primary outcome compared with 35 (63%) of 56 on DOT (adjusted OR 2·52; 95% CI 1·17–5·54; p=0·017). Stomach pain, nausea, and vomiting were the most common adverse events reported (in 16 [14%] of 112 on VOT and nine [8%] of 114 on DOT). Interpretation: VOT was a more effective approach to observation of tuberculosis treatment than DOT. VOT is likely to be preferable to DOT for many patients across a broad range of settings, providing a more acceptable, effective, and cheaper option for supervision of daily and multiple daily doses than DOT. Funding: National Institute for Health Research.

Original languageEnglish
Pages (from-to)1216-1224
Number of pages9
JournalThe Lancet
Volume393
Issue number10177
DOIs
Publication statusPublished - 23 Mar 2019

Bibliographical note

Funding Information:
AS is clinical lead for the Find and Treat service that manages Video-observed therapy. PJW has received research funding from Otsuka for a retrospective study of multidrug-resistant tuberculosis treatment in several eastern European countries. RG reports involvement with SureAdhere Mobile Technology (but no funding was received from the company for work on this study). All other authors declare no competing interests.

Funding Information:
The study was funded by the National Institute of Health Research (NIHR) Programme Grants for Applied Research scheme ( RP-PG-0407-10340 ). PJW was also funded by the UK Medical Research Council ( MR/K010174/1 ) and NIHR Health Protection Research Unit in Modelling Methodology ( Imperial College London) in partnership with Public Health England ( HPRU-2012-10080 ). The views expressed are those of the authors and not necessarily those of the UK Department of Health, MRC, NHS, NIHR or Public Health England. We would like to thank the principal investigators and services in the following UK tuberculosis clinics for taking part in the study: Central Middlesex Hospital, Charing Cross Hospital, Chelsea and Westminster Hospital, Birmingham City Hospital, Coventry George Eliot Hospital, Croydon Hospital, Edgware Community Hospital, Find and Treat, Guy's and St Thomas' Hospital, Hammersmith Hospital, Heart of England NHS Foundation Trust Birmingham Chest Clinic, Hillingdon Hospital, Leicester Glenfield Hospital, Mile End Hospital, Newham General Hospital, North Middlesex Hospital, Northwick Park Hospital, Royal Free Hospital, Birmingham Sandwell Hospital, St Mary's Hospital, Whipps Cross Hospital, and Whittington Hospital. We also thank Patrick Phillips (University of California, San Francisco, CA, USA) for independently reviewing the statistical analysis plan when based at the Medical Research Council Clinical Trials Unit (London, UK).

Funding Information:
The study was funded by the National Institute of Health Research (NIHR) Programme Grants for Applied Research scheme (RP-PG-0407-10340). PJW was also funded by the UK Medical Research Council (MR/K010174/1) and NIHR Health Protection Research Unit in Modelling Methodology (Imperial College London) in partnership with Public Health England (HPRU-2012-10080). The views expressed are those of the authors and not necessarily those of the UK Department of Health, MRC, NHS, NIHR or Public Health England. We would like to thank the principal investigators and services in the following UK tuberculosis clinics for taking part in the study: Central Middlesex Hospital, Charing Cross Hospital, Chelsea and Westminster Hospital, Birmingham City Hospital, Coventry George Eliot Hospital, Croydon Hospital, Edgware Community Hospital, Find and Treat, Guy's and St Thomas' Hospital, Hammersmith Hospital, Heart of England NHS Foundation Trust Birmingham Chest Clinic, Hillingdon Hospital, Leicester Glenfield Hospital, Mile End Hospital, Newham General Hospital, North Middlesex Hospital, Northwick Park Hospital, Royal Free Hospital, Birmingham Sandwell Hospital, St Mary's Hospital, Whipps Cross Hospital, and Whittington Hospital. We also thank Patrick Phillips (University of California, San Francisco, CA, USA) for independently reviewing the statistical analysis plan when based at the Medical Research Council Clinical Trials Unit (London, UK).

Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Fingerprint

Dive into the research topics of 'Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial'. Together they form a unique fingerprint.

Cite this