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Response to comments by Garner et al and Portero and Rubio

Posted by plosmedicine on 31 Mar 2009 at 00:02 GMT

Author: Thelma Tupasi
Position: President
Institution: Tropical Disease Foundation
Additional Authors: This response is written on behalf of all authors of the original article
Submitted Date: November 17, 2006
Published Date: November 20, 2006
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

The comments of Garner et al [1] and Portero and Rubio [2] on our article "Feasibility and Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the Philippines"[3] warrant a response.

Garner et al focus on four issues: 1) lack of independence because of author affiliations and financial support from the Global Fund to fight AIDS, TB and Malaria (GFATM); 2) whether results can be replicated beyond the pilot project that was studied; 3) the need to pay attention to health system capacity; and 4) financial sustainability. Portero and Rubio state that Makati Medical Center (MMC) is a tertiary institution operating under "ideal" conditions not typical of other health facilities, and that lack of attention to building laboratory capacity may hinder service expansion. They also argue that a community-based care approach should have been studied at the pilot stage.

The standard methods used for statistical analysis and economic evaluation in our study [4,5,6], a rigorous peer-review process, and the application of previously-established methods for the evaluation of MDR-TB treatment [7] provide for objectivity in the results that are reported. We strongly disagree with the insinuation that the participation of WHO or funding from the GFATM biased either the analysis or the way in which results were reported.

Pilot projects are often an important first step in implementing and evaluating new interventions. At the same time, it is well recognized that results can be different when services are scaled up. We agree that care is required when interpreting results from pilot projects, and that evaluation of MDR-TB treatment when implemented at a larger scale is necessary. Our article identifies the factors that we believe need to be replicated if results are to be reproduced elsewhere. In the meantime, it is important to highlight that while housed in a tertiary facility, the project was based in an outpatient clinic; that the cost-effectiveness results are consistent with those for a national programme in Peru [7]; and that community-based care is now available. Since 2004, patients have been treated at their local public health centre, which has helped to increase cure rates and reduce default rates compared to those observed during the study period [8].

We agree that health system capacity should be considered when new interventions are implemented. In the Philippines, expansion of MDR-TB treatment has been planned such that treatment sites will typically manage 1 to 3 patients at any given time. Decentralization of services to a larger number of treatment sites is helping to integrate MDR-TB treatment into existing TB treatment services provided at primary health care level, while increasing accessibility for patients. Treatment sites will be overseen by larger treatment centres, selected according to various criteria including their capacity and willingness to take on additional responsibilities. Laboratory and human resource capacity are being enhanced at treatment centres and treatment sites, just as capacity was enhanced at MMC during the pilot phase. Such costs (including infrastructure and training) were included in our cost-effectiveness analysis, and Garner et al are incorrect when they state that they were not. All resources used in the start-up and implementation phases of the project were costed, in line with standard guidelines [4].

It is true that most of the current funding for MDR-TB treatment is from the GFATM. However, the government has provided additional funds for TB control, including MDR-TB treatment, since 2005. Funding for the treatment of new drug-susceptible cases has not been reduced. This demonstrates that MDR-TB treatment can be provided without compromising basic tuberculosis control. Indeed, some of the investments needed for expansion of MDR-TB treatment, such as building laboratory capacity, may strengthen the health system as a whole.

Regarding more specific criticisms [2], the lack of HIV testing and long-term follow-up are acknowledged in our article (though HIV prevalence remains low, at less than 0.1%)[9]. We specifically compared patients that were enrolled with cases who were eligible but not enrolled. The two groups were similar, except that enrolled cases had more, rather than less, severe patterns of drug resistance. Results are referred to in our article and reported in supplementary material. Also as reported in our article, we analyzed the relationship between several variables and treatment outcomes; the only statistically significant result was that women appeared more likely to be cured than men. Contrary to the claim made by Portero and Rubio, Resch et al made no suggestion that our study lacked independence.[10]

In conclusion, the overall goal of our study was to contribute to the evidence base on the management of MDR-TB in low and middle-income countries. We support the development and implementation of evidence-based management strategies for all TB patients.


1. Garner P, Alejandria M, Lansang MA (2006). Is DOTS-Plus a Feasible and Cost-Effective Strategy? PLoS Med 3(9): e350.
2. Portero JL and Rubio M. Multidrug-resistant tuberculosis in the Philippines: totem and taboo. PLoS Med (30 October 2006).
3. Tupasi TE, Gupta R, Quelapio MID, Orillaza RB, Mira NR, Mangubat NV, Belen V, Arnisto N, Macalintal L, Arabit M, Lagahid JY, Espinal M, Floyd K. Feasibility and Cost-Effectiveness,of Treating Multidrug-Resistant Tuberculosis: A Cohort Study in the Philippines. PLoS Medicine Vol. 3, No. 9, e352 DOI: 10.1371/journal.pmed.0030352
4. Drummond MF, O'Brien B, Stoddart GL, Torrance GW (1997). Methods for the Economic Evaluation of Health Care Programmes. 2nd ed. Oxford: Oxford University Press (379 pages).
5. Gold MR, Siegel JE, Russell LB, Weinstein MC, eds. (1996) Cost-effectiveness in Health and Medicine. New York: Oxford University Press (456 pages).
6. Hammersley JM, Handscomb DC. Monte Carlo Methods. London: Methuen; 1964.
7. Suarez PG, Floyd K, Portocarrero J, Alarcon E, Rapiti E, et al. (2002) Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru. Lancet 359: 1980-1989.
8. Mira NR, Quelapio MI, Tupasi TE, Vianzon RG, Lofranco V, et al. (2006). Implementing programmatic MDR-TB management by involving various partners: experiences from Manila, Philippines. Int J Tuberc Lung Dis. 10 (11):S4.
9. (accessed 14 November 2006).
10. Resch SC, Salomon JA, Murray M, Weinstein MC (2006) Cost-effectiveness of treating multidrug-resistant tuberculosis. PLoS Med 3(7): e241. DOI: 10.1371/journal. pmed.0030241

No competing interests declared.