Criteria for considering studies for this review

We included all studies that determined the diagnostic accuracy of the index test in comparison with a defined reference standard, including case‐control designs. We only included studies from which we could extract data on true positives (TP), false positives (FP), false negatives (FN), and true negatives (TN). We excluded unpublished studies reported only in abstracts and conference proceedings.

We included patients of any age who had rifampicin‐resistant TB or MDR‐TB or may have had resistance to any of the second‐line TB drugs, irrespective of background burden of drug resistance and patient population.

The index test was MTBDRsl version 1.0 or version 2.0.

We considered the following target conditions.

Fluoroquinolone (FQ) resistance.

Second‐line injectable drug (SLID) resistance.

XDR‐TB.

We included studies that used one or more of the following reference standards.

Culture‐based drug susceptibility testing (DST): solid culture or a liquid culture.

Sequencing of the gyrA or rrs genes (MTBDRsl version 1.0) or additionally the gyrB and eis promoter regions (MTBDRsl version 2.0).

A composite reference standard with two components: culture‐based DST and sequencing of the same samples. If a specimen was resistant according to culture‐based DST or had a mutation, we classified the specimen as having the target condition. If both culture‐based DST and sequencing indicated susceptibility, we classified the specimen as not having the target condition.

Two reference standards used sequentially: culture‐based DST followed by selective testing by sequencing of samples with discrepant results. Discrepant results may be either index test positive/culture‐based DST negative or index test negative/culture‐based DST positive.

There are strengths and limitations to each of the reference standards. Culture‐based DST is the accepted reference standard, but it is considered to be imperfect and is dependent on the drug concentration threshold used to define resistance. Sequencing is considered to be more accurate than culture‐based DST; however, this is only if it targets all known resistance‐determining regions, which are not fully known for the FQs and the SLIDs. Therefore, targeted sequencing may miss mutations that cause drug resistance.

We carried out separate analyses for the different reference standards, which we have described below. In our primary analysis we used culture‐based DST as the reference standard. We expected all or nearly all included studies to report results using this reference standard.