OpiniãoTwo reviews following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were carried out to look at costs and cost–effectiveness of:
- novel TBST, such as Diaskintest, C-TST and Cy-Tb (primary review); and
- TST and IGRA tests (secondary review).
The articles searched were those presenting economic evaluations of the diagnostic tests (costs and cost–effectiveness) using a health provider perspective and related to TB infection in humans. The articles reviewed were those written in English, Chinese or Russian languages, and published in Medline, OVID, Chinese Biomedical Literature, China National Knowledge Infrastructure and Russian e-library databases. Quality of studies was assessed using Drummond’s checklist.
In addition, a Markov-chain model was developed for the purposes of the GDG meeting, to study the cost–effectiveness of TBSTs versus the currently available tests, the TST and IGRAs. When simulating a cohort of individuals transitioning among different states and steps along the TB cascade of care, the model took into consideration the following parameters:
- prevalence of TB infection in TB-negative individuals, percentage;
- people completing treatment after initiation following a positive TB infection result, percentage;
- people not initiating treatment after testing positive for TB infection, percentage;
- people interrupting treatment after initiation following a positive TB infection test result, percentage;
- progression from TB infection to active TB, probability;
- efficacy of TB infection treatment;
- active TB treatment coverage;
- recovery from active TB (treated + untreated);
- death from active TB (treated + untreated);
- probability of a true positive test result if the patient has TB infection (sensitivity); and
- probability of a true negative test result if the patient does not have TB infection (specificity)
Model parameters, unit costs and estimates of diagnostic test accuracy were sourced from the literature, including from the systematic reviews mentioned above. The manufacturers of novel TBSTs were also contacted to source costs of the new tests. However, only Generium, the manufacturer of Diaskintest, provided estimated test costs, including delivery costs, for different delivery volumes. Consequently, the modelling study focused on Diaskintest as the representative of the TBST class of tests.
The model was parameterized to three countries: Brazil, South Africa and the United Kingdom. Three testing strategies were considered in this analysis: Diaskintest (index); the TST; and QuantiFERON-TB IGRAs, either Gold In-Tube or Gold Plus (comparator tests). Outcomes reported included unit cost (in US dollars)⁵ per patient, incremental cost–effectiveness ratio (ICER) and incremental net benefit per quality-adjusted life year (QALY) gained. Unit costs considered in each country included test kit, staff time, laboratory and disposable costs. Costs were considered from a health system perspective and did not reflect patient or societal costs.
Given that only information on Diaskintest was available, a univariate sensitivity analysis on TBST unit costs and a comparison of the results of the three strategies was performed to identify possible maximum unit costs of new TBSTs, for the strategy to remain cost saving or costeffective, but without specifying a particular type of TBST.
The conclusions were based on the predefined research questions outlined below.
How large are the resource requirements (costs)?
In the eight studies that assessed Diaskintest, most estimated a cost of $1.60 per test. One study evaluated the unit costs considering staff time, consumables and laboratory costs, resulting in a cost of $5.07. This study, using the same costing factors, also estimated the unit cost of C-TST as $9.96. The 29 studies on IGRAs or the TST (or both) estimated an average cost of $37.84 for the TST and $89.33 for IGRAs (accounting for different ingredients). The cost–effectiveness of the tests varied among and within risk groups, with no clear economic consensus around the cost–effectiveness of comparison tests.
What is the certainty of the evidence of resource requirements (costs)?
Based on Drummond’s scores, the quality of studies that have assessed cost–effectiveness of C-TST and Diaskintest in this review was concerning; only one out of eight studies was of high quality. However, the quality of the studies that assessed cost–effectiveness of the TST and IGRAs was generally high.
Does the cost–effectiveness of the intervention favour the intervention or the comparison?
Based on the systematic review results, there was insufficient evidence regarding both the cost and cost–effectiveness of novel TBSTs. The quality of the studies was concerning according to the Drummond’s checklist for economic evaluations. More high-quality studies are needed that consider different health settings and risk populations to estimate the cost–effectiveness and the likely economic impact of these tests.
Results of the Markov-chain model conducted for the purposes of the GDG meeting concluded that, in Brazil, Diaskintest is cost saving compared with the TST and IGRAs. Compared with the
TST, Diaskintest is cost saving at $5.60, with an incremental gain of 0.02 QALYs per patient. Compared with IGRAs, Diaskintest is cost saving at $8.40, with an incremental gain of 0.01 QALYs. In South Africa, Diaskintest is more cost saving than the TST or IGRAs. Compared with the TST, Diaskintest is cost saving at $4.39, with an incremental gain of 0.02 QALYs, and compared with IGRAs, it is cost saving at $64.41, with an incremental gain of 0.01 QALYs. In the United Kingdom, Diaskintest is cost saving compared with the TST but not with IGRAs. Compared with the TST, Diaskintest is cost saving at $73.33, with an incremental gain of 0.04 QALYs; however, compared with IGRAs, Diaskintest showed an increase in cost of $15.80 but still an incremental gain of 0.03 QALYs.
In summary, the modelling and univariate sensitivity analysis results show that, in Brazil and South Africa, use of Diaskintest would potentially save costs per patient and result in greater health gains (QALYs per patient) compared with the TST and IGRAs. In the United Kingdom, Diaskintest results in health gains but is more expensive in terms of expected cost per patient than IGRAs. Our results also show that, in Brazil and South Africa, IGRAs are more costly to implement than the TST but would result in health gains. However, in the United Kingdom, IGRAs are cheaper to implement and are more cost-effective than the TST.
⁵ Throughout this text, “$” signifies US dollars.