Table 9GRADE Evidence Profile: IGRAs for tuberculosis screening of healthcare workers in low- and middle-income countries

No of Participants
(studies)
Study designLimitationsIndirectnessInconsistencyImprecisionPublication biasQuality of evidence
(GRADE)1
Importance
A. Efficacy of preventive therapy based on IGRA test results
No studiesCritical
(7-9)
B. Predictive value of IGRA for active TB
No studiesCritical
(7-9)
C. Outcome: Correlation of IGRA results with occupational TB exposure
991 (2) A1Cross- sectionalNo serious limitations A2No serious IndirectnessA3Serious A4
(-1)
Serious A5
(-1)
Likely A6Low
⊕⊕○○
Critical
(7-9)
D. Outcome: Correlation between IGRA conversions and occupational TB exposure
No studiesCritical
(7-9)
E. Outcome: Sensitivity for active TB (as a surrogate reference standard for LTBI)
No StudiesImportant
(4-6)
F. Outcome: Concordance between IGRAs and TST (cross-sectional)
1,357 (4)B1Cross-sectionalNo serious limitationsB2SeriousB3
(-1)
SeriousB4
(-1)
SeriousB5
(-1)
LikelyB6Very Low
⊕○○○
Important
(4-6)
G. Outcome: concordance between IGRA and TST conversions (longitudinal)
216 (1) C1LongitudinalNo serious limitations C2Serious C3
(-1)
No serious inconsistency C4Very SeriousC5
(-2)
Likely C6Very Low
⊕○○○
Important
(4-6)

Footnotes:

1

Quality of evidence was rated as high (no points subtracted), moderate (1 point subtracted), low (2 points subtracted), or very low (>2 points subtracted) based on five criteria: imitations, indirectness, inconsistency, imprecision, and publication bias. For each outcome, the quality of evidence started at high when there were randomized controlled trials or high quality observational studies (cross-sectional or cohort studies with diagnostic uncertainty and direct comparison of test results with culture) and at moderate when these types of studies were absent. One point was subtracted when there was a serious issue identified or two points when there was a very serious issue identified in any of the criteria used to judge the quality of evidence.

A1

2 studies were identified evaluating an association between test positivity and occupational exposure to TB. These studies compared only QFT and the TST.

A2

Study limitations were assessed using select quality indicators. Studies satisfied majority of selected quality indicators.

A3

Some indirectness in the choice of reference standard was recognised although the studies were not downgraded for indirectness.

A4

Two studies evaluated the association between 5 variables of occupational exposure to TB and test positivity, estimates ranged from OR=1.28-5.09.

A5

Only 50% of estimates of association of test positivity and exposure reached statistical significance, 95% confidence intervals ranged from: 0.68-9.33. With only two studies, imprecision may be a concern.

A6

Data included in this review did not allow for formal assessment of publication bias using methods such as funnel plots or regression tests. Therefore, publication bias could not be ruled out. Although no points were deducted, some degree of publication bias was considered likely because: 1) literature on IGRAs is rapidly exploding and currently unpublished studies may come out in future (despite an attempt to be comprehensive and include unpublished studies); 2) there are anecdotal examples of unpublished negative studies on IGRAs; 3) because a sizeable proportion of IGRA studies have some level of industry involvement or support, the risk of unpublished negative studies (or delayed publication of negative studies) is not trivial.

B1

4 cross-sectional studies were identified: 3 evaluated a previous version of the QFT, 1 study evaluated only the T-SPOT.TB.

B2

Study limitations were assessed using select quality indicators as the QUADAS scale was not appropriate for concordance studies. Majority of studies satisfied selected quality indicators.

B3

Concordance between IGRAs and the TST is a poor surrogate for patient important outcomes.

B4

Among studies conducted in low- and middle-income countries, there was moderate heterogeneity in estimates of percent agreement between TST and IGRAs (Range: 50-81%).

B5

Due to heterogeneity in effect estimates we could not pool concordance. However, confidence intervals for estimates of concordance for individual studies were wide, and with only 4 studies, imprecision may be a concern

B6

Data included in the review did not allow for formal assessment of publication bias using methods such as funnel plots or regression tests. Therefore, publication bias could not be ruled out. Although no points were deducted, some degree of publication bias was considered likely because: 1) literature on IGRAs is rapidly exploding and currently unpublished studies may come out in future (despite an attempt to be comprehensive and include unpublished studies); 2) there are anecdotal examples of unpublished negative studies on IGRAs; 3) because a sizeable proportion of IGRA studies have some level of industry involvement or support, the risk of unpublished negative studies (or delayed publication of negative studies) is not trivial.

C1

1 longitudinal study was included which assessed concordance between TST and IGRA conversions, using the QFT test.

C2

Study limitations were assessed using select quality indicators as the QUADAS scale was not appropriate for concordance studies. Both studies satisfied the majority of selected quality indicators.

C3

This study was conducted in a low middle income country. Concordance between IGRA and the TST conversions is a poor surrogate for patient important outcomes, and may not be an appropriate reference standard.

C4

This study estimated fair concordance between QFT and TST conversions (96%).

C5

Only 1 study was identified with a small number of participants (n=216).

C6

Data included in this review did not allow for formal assessment of publication bias using methods such as funnel plots or regression tests. Therefore, publication bias could not be ruled out. Although no points were deducted, some degree of publication bias was considered likely because: 1) literature on IGRAs is rapidly exploding and currently unpublished studies may come out in future (despite an attempt to be comprehensive and include unpublished studies); 2) there are anecdotal examples of unpublished negative studies on IGRAs; 3) because a sizeable proportion of IGRA studies have some level of industry involvement or support, the risk of unpublished negative studies (or delayed publication of negative studies) is not trivial.

From: 7, GRADE tables

Cover of Use of Tuberculosis Interferon-Gamma Release Assays (IGRAs) in Low- and Middle- Income Countries
Use of Tuberculosis Interferon-Gamma Release Assays (IGRAs) in Low- and Middle- Income Countries: Policy Statement.
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