The existing unit cost estimates for smear, culture, and combined smear and culture tests are very limited, especially in low or lower-middle income countries. Nevertheless, a wide range of published unit cost estimates was observed. For smear alone, the estimated unit cost is between $0.26 and $10.5. For culture alone, the estimated unit cost is between $1.63 and $62.01. For combined smear and culture testing, the estimated unit cost is between $2.27 and $48.23. Adjustment for purchasing power parity does not fully explain the wide range of unit cost estimates we observed.
The wide variability of unit costs is partly due to using different materials and methods in testing, or conducting the study in different years or regions, partly due to non-standardized practice in unit cost defining, data collecting, and reporting. For example, for those with cost components available, the reported components vary greatly across studies, from only including material and overhead cost to covering the costs of building, equipment, and even the spending of patients. Cost data were obtained from different sources, including citing figures from a price list, collecting data from a single health facility in a specific area of a country, and aggregating data from all regions in a country. Non-standardized cost estimates make it very difficult for cross-setting comparison and making meaningful inference.
The quality of the estimates is a concern. About one fifth of the selected studies did not even report the year in which cost data were collected. Half of the selected studies did not specify test methods (Migliori, or Kamolratanakul, or Qunfei, for example) used in reported smear or culture tests. Almost half of the studies did not report what components were included in cost estimation. Since we know these factors have a significant bearing on cost estimates, the lack of standardization–and low quality overall–in cost data collecting and reporting present major challenges for improving our knowledge of unit costs of various MDR-TB monitoring strategies.
The calculated unit cost ratio for culture tests to smear tests from existing studies is greater than the 1.6, a number which was previously generated from cost data collected from a government laboratory in South Africa 
. The extent to which this ratio varies between countries will likely depend on the relative weight of non-traded inputs in the cost of each test. The cost of non-traded inputs such a labour is more sensitive than the cost of traded inputs to the income level of a given country. Therefore, if the share of non-traded inputs in total cost is smaller for cultures than it is for smears, we would expect the ratio to be higher in the lowest income countries and lower in the highest income countries.
The new recommended strategy of monthly–rather than minimum of quarterly–culture test after culture conversion, would cost more. If smear and culture were done quarterly, only 6 combined tests would be required (in addition to 14 monthly smears). According to the current recommendations of monthly smear and culture, 20 combined tests would be required. Smear and culture both have limited ability to predict poor treatment response 
. Culture, however, is much more accurate than smear in detecting the presence of viable mycobacteria. Smear microscopy sensitivity estimates range from 40 to 76%, with lower sensitivity in children and HIV-coinfected patients 
. As the Guidelines note, “high value was placed on outcomes such as preventing death, decreasing the transmission of MDR-TB that could result from its delayed diagnosis, and avoiding increased use of resources. 
” Consequently, increased costs associated with more frequent culture test may be justified because of the importance of early detection of risk for these negative outcomes and the possibility of implementing interventions to avert them. While it remains important for patients on treatment for MDR-TB to have access to good quality culture for their proper monitoring, our findings highlight a high cost difference between culture and smear testing. It is noteworthy that one factor contributing to this difference in low-resource setting may be the relatively infrequent use of culture compared to smear at the time of data collection or publication. These prices may be expected to decline once the initial outlay associated with expanding culture laboratories has been discounted.
Even within the same monitoring method, certain methodological differences may result in cost differences, but also in sensitivity and timing. For example, culture performed in liquid medium, using the MGIT system is known to increase the detection of viable mycobacteria over culture performed in solid LJ or Ogawa medium, while decreasing from 8 weeks to 6 weeks the time required to confirm a culture as negative. Although there was additional cost associated with MGIT in at least 3 studies that compared cost of culture in liquid and solid medium (
, and 
), these cost differences may be justified since they accelerate the time to detection and intervention and increase the sensitivity of the test. There are similar differences among the cost and sensitivity of smear microscopy methods 
Lastly, three studies (
, and 
) reported variation in unit cost of culture depending on whether the result was negative or positive. This highlights another possible source of variability in estimates that was not explicitly reported in the other studies.
This study is the first systematic review of cost estimates for tests commonly used to monitor MDR-TB treatment. We reviewed the relevant literature in Chinese. China has the highest prevalence of TB after India and the availability of Chinese cost data provides critical information for scaling up the monitoring tests for this large at-risk population. Using existing cost data, we also projected the unit cost of combined tests which could serve as useful reference to policy makers.
We propose a framework for evaluating the quality of unit cost data for TB monitoring tests. The five categories included in the quality score are crucial for determining the generalizability and validity of the cost data. They, may not, however, cover all important aspects. For instance, we only distinguished between the availability and absence of cost components, but did not consider the comprehensiveness of cost components. We assigned each category with the same weight and this may oversimplify the evaluation.
The paucity and low quality of unit cost estimates for TB monitoring in developing countries impose technical challenges in predicting the resource needed for strengthening microbiologic monitoring. As new molecular tests are being rapidly introduced globally to diagnose patients with presumptive TB and drug-resistant TB in one step, evaluation of the costs associated with the change in diagnostic practices – which was not the object of this paper - will be necessary. High quality cost data is especially important for the regions with high incidence of tuberculosis and MDR-TB, where scarce resources must be allocated efficiently. We strongly advocate that more data are collected from these regions, and that cost data collection, estimation, and reporting should follow the protocols proposed by the WHO 
to improve the validity and comparability.