Evaluation of the 4th Generation QuantiFERON-TB Test (QFT-Plus) for the Detection of Tuberculosis Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the 4th Generation QuantiFERON-TB Test (QFT-Plus) for the Detection of Tuberculosis Infection (NCT02687529), a registered phase not stated study. The primary outcome is Number of Participants With Concordant CST001 Assay Results for All Replicates Across Three Testing Sites.

2. Clinical Question

3. Trial Design

The registry record identifies this as a completed study sponsored by QIAGEN Gaithersburg, Inc. It lists enrollment of 66 and records the study start as 2015-10-27 and primary completion as 2015-11-07. The intervention is a device named CST001. The listed groups are Low Risk and Known Risk; each is described as tested with CST001.

The record’s brief summary states an aim to compare the positivity rate of the investigational assay with the currently approved QuantiFERON-TB Gold In-Tube assay. The primary outcome description, however, focuses on the number of participants with concordant CST001 results for all replicates across three testing sites. It describes reproducibility between three external laboratories, with two operators per site, as the purpose. These are related assay-evaluation themes, but they are not the same statistical question.

The registry record does not describe a randomized allocation. It explicitly notes that the groups are not a like-for-like control comparison. Since both groups are described as tested with CST001, differences between the Low Risk and Known Risk groups should not be interpreted as the effect of assigning one assay rather than another. The registry record does not explain the participant-level use of the approved assay or provide a detailed testing sequence.

Further design details, including eligibility criteria, recruitment procedures, blinding, and the rationale for the group definitions, are not reported in the registry record. The record identifies the study as completed but does not report a narrative account of conduct or deviations from the planned procedures.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Concordant CST001 Assay Results for All Replicates Across Three Testing Sites, measured over 1 day (At time of enrollment).

The primary endpoint is the number of participants whose CST001 assay results were concordant for all replicates across three testing sites. Its unit is participants, and its timeframe is 1 day (At time of enrollment). The endpoint description says it was intended to demonstrate reproducibility between three external laboratories, with two operators per site.

In general, reproducibility concerns whether repeated measurements or assessments yield consistent classifications under different testing conditions or operators. For a binary assay result, concordance means that the specified results agree according to the endpoint definition. Requiring agreement for all replicates makes this a participant-level summary: a participant is counted according to whether the full set of results meets the stated concordance condition. The registry record does not give additional operational details about the replicates or the precise rule for classifying concordance.

This endpoint is useful for assessing consistency across testing settings, but it does not by itself quantify positivity relative to the approved assay. Nor does a count alone describe the pattern of disagreements or indicate which assay result was correct. The primary endpoint’s observed count and any accompanying uncertainty are not reported in the registry record, so its reported reproducibility result cannot be characterized from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is recorded?

The primary outcome is a count of participants meeting a defined condition: concordant CST001 results for all replicates across three testing sites. This is a binary participant-level classification before it is summarized as a count. In general, a binary outcome places each participant into one of two categories, such as meeting or not meeting the endpoint condition. The registry record identifies the measure as a count but does not report the count itself or the number analyzed for this endpoint.

That distinction matters because a count needs a denominator to convey the proportion meeting the condition. The total enrollment is 66, but the registry record does not state that all enrolled participants were included in the primary endpoint analysis. Without a reported analysis denominator, it would be inappropriate to treat enrollment automatically as the endpoint denominator or to derive a rate.

What does concordance capture?

In general, concordance describes agreement among results assessed under specified conditions. Here, those conditions involve CST001 replicates across three testing sites, with the endpoint description also referring to two operators per site. A participant counts as concordant only according to the endpoint’s rule for all replicates. The exact replicate-level arrangements and classification rule are not reported in the registry record.

Concordance is not the same as accuracy. Agreement can describe consistency without establishing that the agreeing result correctly identifies a participant’s infection status. A comparison with another assay can provide information about agreement between assays, but it does not alone establish which assay is correct. The registry record’s brief summary mentions a positivity-rate comparison with QuantiFERON-TB Gold In-Tube, while the primary endpoint describes cross-site reproducibility. The numerical results for either question are not reported in the registry record.

How should uncertainty be understood?

In general, a confidence interval expresses the range of estimates reasonably compatible with the observed data under a specified statistical method. Its width reflects uncertainty, which depends on factors including the amount of information and variability in the data. No confidence interval or other measure of uncertainty for the primary outcome is reported in the registry record. As a result, neither the estimated extent of concordance nor its precision can be assessed from the posted outcome information.

In general, a hypothesis test assesses compatibility between data and a specified null hypothesis under a statistical model. A p-value is not a measure of the size or practical importance of an effect. The registry record does not report a hypothesis test or p-value for the primary endpoint or the stated positivity-rate comparison. The statistical test, if any, is not reported in the registry record.

What do the planning illustrations represent?

In general, sample-size planning uses assumptions about the effect to detect, the significance level, allocation, and statistical method to illustrate the number of participants that might be needed. The planning assumptions described for this study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They define the effect to detect as a stated fraction of the observed effect. These calculations are planning illustrations based on the observed effect, not evidence that the study had a particular probability of detecting an effect.

For non-time-to-event outcomes, the stated convention is participants per arm. These planning illustrations do not establish the actual sample-size justification for the trial, and they should not be described as observed power. The trial’s own sample-size justification and design assumptions are not reported in the registry record. The record also does not provide the observed effect needed to interpret particular planning values in relation to the clinical assay question.

What methods are not described?

The registry record does not report a statistical analysis plan, an analysis population for the endpoint, a method for handling missing assay results, or an approach to multiplicity. It lists one primary outcome measure and one analysis, but that does not establish which statistical procedures were used or whether all planned analyses were reported. Details of any adjustment, stratification, or sensitivity analysis are not reported in the registry record.

In general, over-dispersion is a concern when observed variability exceeds what a statistical model assumes; it can make standard errors too small if the model is not appropriate. The posted primary endpoint is a participant count, and the registry record does not describe a model or variance estimate for which over-dispersion could be assessed. There is therefore no basis in the record to claim that an over-dispersion adjustment was needed or used.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Low Risk", "Known Risk")
n      <- c(34, 32)
events <- c(32, 23)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Low Risk  34  32  94.1  80.3  99.3  80.9  98.4  80.8  98.2
ARM  Known Risk  32  23  71.9  53.3  86.3  54.6  84.4  54.5  84.4

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and one analysis. It does not report how multiplicity was handled. A single listed primary outcome may reduce concerns about repeated testing across multiple primary endpoints, but the record does not establish that no additional outcomes or analyses were considered. The stated positivity-rate comparison and the primary reproducibility endpoint also concern distinct questions; their relationship in the analysis plan is not reported in the registry record.

Missing-data handling is not reported in the registry record. The primary endpoint requires results for all replicates across three testing sites, so incomplete testing could affect whether a participant can be classified under the endpoint definition. The record does not say whether incomplete results occurred, how they were treated, or whether any participants were excluded from the primary analysis.

The analysis population is also not reported in the registry record. Although enrollment was 66 and the safety listings identify 34 and 32 participants at risk in the two groups, those details do not establish the primary endpoint denominator. No participant flow, endpoint-specific analysis count, or reasons for missing data are recorded. Accordingly, the extent to which the analyzed participants represent everyone enrolled cannot be assessed from the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The safety listings report 0 participants with serious adverse events in the Low Risk group, with 34 participants at risk, and 0 in the Known Risk group, with 32 participants at risk. They also report 0 participants with other adverse events in each group, using the same group-specific numbers at risk. No serious adverse event terms are listed.

These entries describe the registry’s recorded counts; they do not establish that no events occurred outside the scope or reporting practices represented in the record. The record does not provide further details about adverse-event collection, severity definitions, duration of follow-up, or attribution to CST001. Death counts are not reported in the registry record.

The safety figures should not be treated as a comparison of assay safety between groups. Both groups were tested with CST001, and the record does not describe a randomized safety comparison. The figures are descriptive counts and do not provide a detailed assessment of risk or a basis for estimating rare events.

13. What the Result Does, and Does Not, Mean

The record establishes that the study evaluated CST001 in Low Risk and Known Risk groups and that its primary endpoint concerned participant-level concordance across replicates and testing sites. It also records a broader stated aim of comparing the investigational assay’s positivity rate with the currently approved QuantiFERON-TB Gold In-Tube assay. These details identify the questions the study was designed to address.

The registry record does not report the primary endpoint result or the positivity-rate comparison. It therefore cannot establish from the posted results how many participants met the concordance condition, how similar the assays’ positivity rates were, or the precision of either finding. The endpoint title and description are not themselves evidence of a positive or negative result.

Even if concordance results were available, agreement would describe consistency under the tested conditions, not necessarily accuracy against an independent reference. Likewise, positivity-rate comparisons would not by themselves establish the correctness of either assay. The registry record does not report enough information to evaluate the reference standard, participant-level assay agreement, or clinical classification performance.

The study is not recorded as a randomized comparison, and its groups are not described as like-for-like controls. A difference between the Low Risk and Known Risk groups, if reported, would not automatically be attributable to assay assignment. The registry record also does not report the analysis population, missing-data procedures, or a detailed statistical plan.

Accordingly, the posted information supports a careful account of the study’s stated objectives, endpoint, group descriptions, and safety counts. It does not support a conclusion about assay performance or a recommendation about testing.

14. Why This Trial Matters Statistically

Assay evaluations can involve more than one statistical question. This record illustrates the distinction between comparing positivity rates and assessing reproducibility across laboratories, operators, and replicates. Positivity-rate comparison concerns how often an assay classifies participants as positive; reproducibility concerns consistency when the assay is repeated under specified testing conditions. Each question requires its own clearly defined outcome and results.

The primary endpoint is a participant count based on concordance across all replicates at three testing sites. That definition makes the unit of interpretation explicit, but the count and analysis denominator are not reported in the registry record. Without both, readers cannot assess the observed extent of concordance or its precision. This highlights why endpoint definitions and endpoint results need to be considered together.

The group labels also matter. Low Risk and Known Risk are participant-group descriptions, not randomized assay assignments. Both groups were tested with CST001, and the record says they are not a like-for-like control comparison. Recognizing that structure prevents a group contrast from being mistaken for a controlled estimate of assay effect.

Finally, the record separates what can be described from what cannot be inferred. It documents study status, enrollment, the assay under evaluation, the endpoint concept, and adverse-event counts. It does not report the central efficacy or reproducibility results, or key analysis details. Such distinctions are important when interpreting registry information without filling gaps with assumptions.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most important limitation for interpreting the registry record is that the primary endpoint result is not reported. The stated comparison of positivity rates with QuantiFERON-TB Gold In-Tube is also not reported numerically. There are no posted estimates or uncertainty measures in the record with which to judge the size or precision of either result.

The record does not explain how the approved assay was incorporated into the study, including whether participants received both assays or how results were paired. Although the brief summary describes a comparison, the listed intervention and group descriptions identify CST001 testing in both groups. The relationship between the primary reproducibility endpoint and the stated positivity-rate comparison is not described in detail.

The registry record does not report participant eligibility criteria, the basis for Low Risk and Known Risk classification, the primary analysis population, the endpoint denominator, or missing-data handling. It does not provide the detailed replicate structure or the rule used to classify concordance. These omissions limit assessment of how the endpoint was implemented and who contributed to its analysis.

Allocation is not stated, and the registry record notes that this is not a randomized comparison and that the groups are not a like-for-like control comparison. The statistical analysis plan and the trial’s own sample-size justification are not reported. Safety information is limited to group-level counts and does not include further event descriptions or follow-up details. These constraints call for a descriptive reading rather than conclusions about comparative assay performance.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of the 4th Generation QuantiFERON-TB Test (QFT-Plus) for the Detection of Tuberculosis Infection — NCT02687529.
• Registry record last updated 2019-06-19; status last verified 2019-06.
• Results first posted 2019-06-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT02687529 is recorded as a completed evaluation of CST001, a device for tuberculosis infection testing, sponsored by QIAGEN Gaithersburg, Inc. Enrollment was 66. The listed groups are Low Risk and Known Risk, both tested with CST001.

The brief summary states an aim to compare positivity rates with the currently approved QuantiFERON-TB Gold In-Tube assay. The primary endpoint is the number of participants with concordant CST001 results for all replicates across three testing sites, with a stated reproducibility purpose involving three external laboratories and two operators per site. The endpoint result and comparative positivity results are not reported in the registry record.

The safety listings report 0 serious adverse events and 0 other adverse events in each group. The record does not report deaths, the primary analysis population, missing-data handling, or a detailed statistical plan.