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Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB
  1. Anne Aspler1,2,
  2. Richard Long2,
  3. Anete Trajman3,
  4. Marie-Josée Dion1,
  5. Kamran Khan4,
  6. Kevin Schwartzman1,
  7. Dick Menzies1
  1. 1Respiratory Epidemiology and Clinical Research Unit, Montreal Chest Institute, McGill University, Canada
  2. 2Faculty of Medicine, University of Alberta, Canada
  3. 3Department of Medicine, Pró-Reitoria de Saúde, Gama Filho University, Brazil
  4. 4Department of Medicine, St Michael's Hospital, University of Toronto, Canada
  1. Correspondence to Dr Dick Menzies, Montreal Chest Institute, 3650 St-Urbain, Room K1.24, Montreal, Quebec, Canada H2X 2P4; dick.menzies{at}


Rationale Treatment for latent tuberculosis infection with isoniazid for 9 months (9INH) has poor completion and serious adverse events, while treatment for 4 months with daily rifampin (4RIF) has significantly higher completion and fewer adverse events.

Objectives To compare the health system costs of 4RIF and 9INH.

Methods In a randomised trial conducted in five Canadian centres, one Brazilian and one Saudi Arabian centre, consenting subjects were randomised to receive 4RIF or 9INH. Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits, investigations and drugs. All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute. Costs were expressed in Canadian dollars.

Results Total health system cost per patient allocated to 4RIF was $854 compared with $970 for 9INH (p<0.0001). The average cost per patient for the 328 of 420 (78%) who completed 4RIF therapy was $1094 compared with $1625 for the 254 of 427 (60%) completing 9INH (p<0.0001). Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events. Total costs related to management of adverse events with 9INH were $48 142 compared with $25 684 for 4RIF (p=0.008). Using these data, incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74%, and cost saving if efficacy exceeded 65%.

Conclusions The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.

RCT registration number NCT00170209.

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  • Funding This study was funded by a grant from the Canadian Institutes of Health Research (CIHR Grant Number MCT#44154). DM currently holds a Chercheur National salary award, KS holds a Chercheur Boursier Clinicien Award from the Fonds de Recherche en Sante de Quebec (FRSQ), AT receives salary support from ICOHRTA AIDS/TB FIC/NIH # 5U2 R TW006883-03 and from FAPERJ (E-26/102.712/2008). None of these funding agencies had any role in the design, conduct, analysis or reporting of the results.

  • Competing interest None.

  • Ethics approval This study was conducted with the approval of the ethics committee of McGill University Health Centre and approved by institutional review boards in each participating institution.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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