Identification of Herpes Simplex Virus (HSV) Shedding in the Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Routine PCR, and Culture: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Identification of Herpes Simplex Virus (HSV) Shedding in the Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Routine PCR, and Culture (NCT01878383), a registered phase not stated study. The primary outcome is Sensitivity of Detection of HSV DNA by GeneXpert PCR From Specimens Obtained From the Genital Tract of Non-pregnant Women in STI Clinics, as Compared With HSV Culture.

2. Clinical Question

This is a diagnostic-detection question, not a comparison of treatment outcomes. It asks how GeneXpert PCR findings relate to results from a reference method for the stated population. The record says specimens were collected on the day of enrollment and describes the primary endpoint as applying to vaginal swabs collected at the time of an active outbreak. It does not report how many specimens were culture-positive, how many GeneXpert results were positive in that subgroup, or how many observations contributed to the endpoint. Those omissions prevent the sensitivity estimate from being reconstructed from the registry record.

3. Trial Design

The registry identifies NCT01878383 as a completed device trial sponsored by the University of Alabama at Birmingham. The recorded start is 2014-01, and the primary completion date is 2019-12-31. Enrollment is recorded as 12550. The record describes the GeneXpert assay as the intervention and HSV as the condition.

The study summary describes detection of HSV DNA shedding from the female genital tract. It states that GeneXpert was compared with routine PCR in pregnant and nonpregnant women and with HSV culture in nonpregnant women. The primary endpoint is narrower: sensitivity of GeneXpert PCR relative to HSV culture among nonpregnant women with active HSV lesions. Thus, the endpoint should not be read as a single comparison covering every population or every comparator described in the study summary.

The registry record identifies the comparison as not randomized and says allocation was not stated. The listed groups differ in pregnancy status and lesion status: one is described as nonpregnant women with active HSV lesions, and the other as pregnant women without active HSV lesions. They are not a like-for-like control comparison. The record does not describe a randomized allocation process or a matched design, and it does not report enough information to characterize other design features in detail.

The group descriptions say that nonpregnant women were presenting to a local health department and pregnant women were presenting in active labor. These descriptions provide context for recruitment but do not establish that the groups were otherwise comparable. The registry record does not report the number of participants contributing to each primary comparison, the number of specimens collected, or the analysis population used for the endpoint. It also does not report a protocol-level explanation of the enrollment target. Enrollment alone should therefore not be treated as the number analyzed for the primary endpoint.

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

Reasons for not completing this period:

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 Sensitivity of Detection of HSV DNA by GeneXpert PCR From Specimens Obtained From the Genital Tract of Non-pregnant Women in STI Clinics, as Compared With HSV Culture, measured over on day of enrollment.

The primary endpoint is sensitivity of GeneXpert PCR for detecting HSV DNA in genital-tract specimens from nonpregnant women with active HSV lesions, using HSV culture as the comparator. The registry describes the endpoint as the percentage of GeneXpert assessments agreeing with standard HSV culture among subjects who were positive for HSV according to culture. It gives the timeframe as the day of enrollment.

Sensitivity focuses on detection within the reference-positive group. In general, it answers how often the method being evaluated identifies a finding among cases identified as positive by the reference method. It does not, by itself, describe how often a positive GeneXpert result is correct among all GeneXpert-positive results, nor does it describe performance among people whose culture result is negative. Those questions require different summaries.

The endpoint is useful for examining detection relative to the chosen comparator, but its interpretation depends on the population and specimen context. Here, the stated target is nonpregnant women with active lesions and the specimen is a vaginal swab. The endpoint should not automatically be generalized to pregnant women, women without active lesions, other specimen types, or comparisons with routine PCR.

The registry record names a 95% confidence interval as the measure of precision, but it does not report the sensitivity estimate, interval limits, or endpoint denominator. Consequently, the record does not establish the observed level of sensitivity or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is expressed as sensitivity, with a 95% confidence interval. This is a proportion-based diagnostic-performance measure. In general, sensitivity is calculated within a group defined as positive by a reference method, and it describes the share of that group identified as positive by the method under evaluation. In this trial record, HSV culture defines the reference-positive group and GeneXpert PCR is the assay being assessed. The registry record does not report the counts required to reproduce the estimate.

What does the confidence interval communicate?

In general, a confidence interval describes statistical uncertainty around an estimated quantity under the assumptions of the method used to construct it. It is not a guarantee that the estimate is correct, nor does it account automatically for bias, selection, measurement error, or an imperfect reference method. For a diagnostic proportion, the interval's precision depends in part on the amount of relevant information in the reference-positive group. The record names a 95% confidence interval but does not state its limits, the interval procedure, or the endpoint sample size. Its precision therefore cannot be assessed from the registry record.

Why does the reference method matter?

Diagnostic performance is always interpreted relative to a comparator or reference definition. Here, the primary endpoint is agreement with HSV culture among subjects who were culture-positive. This operational definition makes the culture-positive group central to the interpretation. In general, if a reference method does not identify every true case, a sensitivity estimate relative to that method describes agreement with the reference classification rather than an error-free account of biological status. The registry record does not provide enough information to evaluate culture procedures or their limitations, so no further conclusion about reference accuracy is warranted.

Why keep the comparisons separate?

The study summary describes GeneXpert comparisons with routine PCR in pregnant and nonpregnant women and with culture in nonpregnant women. The primary outcome specifically concerns the culture comparison in nonpregnant women with active lesions. A method comparison against culture is not interchangeable with a comparison against routine PCR. In general, different comparators can classify specimens differently, and different populations can have different result patterns. The record does not report numerical findings for these comparisons, so their relative performance cannot be assessed.

The group descriptions also require care. The registry record states that the comparison is not randomized and that allocation was not stated. The described groups differ in pregnancy and active-lesion status. In general, a difference between such groups could reflect differences in who was assessed or in the circumstances of specimen collection, not merely a device-related distinction. Because the primary endpoint itself is framed as a diagnostic sensitivity comparison, it should be interpreted on its own terms rather than as a randomized causal contrast.

What do planning calculations mean?

In general, sample-size planning illustrations estimate how much information a future study might need under specified assumptions. They are not observed results and are not evidence that a completed study had a particular probability of detecting an effect. The record's planning description states that its illustrations use the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. It also distinguishes total events for time-to-event calculations from participants per arm for other calculations. These are planning assumptions, not the trial's own design justification. The registry record does not report a design-based sample-size rationale, and no sample-size illustration values are stated in this record.

More generally, a normal approximation simplifies calculations by using a distribution-based approximation to the sampling behavior of an estimate. Such an approximation may be convenient, but its appropriateness depends on the data and design. The registry record does not state the analysis method used for the primary sensitivity estimate, so it would be inappropriate to attribute a particular interval or test procedure to the trial.

The study summary describes a PCR system that performs sample processing and real-time PCR in an integrated cartridge within the GeneXpert instrument. That description explains the device workflow, but it does not establish the analytic validation details, operating procedures, blinding, or handling of indeterminate results. Those details are not reported in the registry record. Statistical interpretation should distinguish the device description from evidence about the accuracy or reproducibility of its results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures and 3 analyses. It does not report how the analyses were related to one another for statistical interpretation, whether any outcomes were designated as secondary or exploratory, or whether a multiplicity adjustment was used. Without that information, the chance of false-positive findings across multiple statistical tests cannot be evaluated from the record. This does not establish that an adjustment was or was not used; the approach is not reported in the registry record.

The record describes the primary endpoint as sensitivity with a 95% confidence interval, but it does not provide the numerical estimate, interval limits, or analysis denominator. It also does not report missing-data handling, the number of invalid or inconclusive tests, or whether specimens lacking a result were excluded or otherwise addressed. These omissions matter because diagnostic analyses can depend on how unavailable results are classified and on which specimens are included.

The registry record does not define the analysis population, such as whether all enrolled participants, all participants with collected specimens, or only participants with paired valid test results contributed to the endpoint. Enrollment should not be substituted for an endpoint-specific denominator. The record also does not report a prespecified statistical analysis plan, interim-analysis procedures, or the handling of protocol deviations. These methods are not reported in the registry record, so readers cannot check whether the reported analysis followed a prespecified approach.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

The registry safety entries list serious adverse events, other adverse events, and deaths for the described groups. The recorded affected counts are 0 for serious adverse events, 0 for other adverse events, and 0 deaths in each listed group. The record gives at-risk counts of 50 for the nonpregnant-women/active-lesions group and 12500 for the pregnant-women/no-active-lesions group.

These entries describe what was recorded in the registry for the listed categories. They should not be read as proof that no adverse event of any kind occurred, or as evidence that the groups had comparable safety experience. The registry record does not provide event definitions, collection procedures, observation duration, or additional detail about safety monitoring. It also does not explain how the at-risk counts relate to the enrollment entry or to the primary endpoint analysis. Safety interpretation should therefore remain confined to the listed counts and categories, without extending them to unreported events or populations.

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

The registry record defines a focused diagnostic-performance question: whether GeneXpert PCR detects HSV DNA in vaginal specimens from nonpregnant women with active lesions when HSV culture is positive. It also describes a broader study program involving routine PCR comparisons in pregnant and nonpregnant women and culture comparisons in nonpregnant women. Keeping these questions separate is essential because the populations and comparators are not the same.

What the record does establish is the intended endpoint, its stated timeframe, the presence of a 95% confidence interval as the precision measure, and the study's completed status. It also describes the device workflow at a general level and records enrollment as 12550. The record does not report the primary sensitivity estimate or its interval. It therefore does not show the observed level of agreement with culture or how precisely that level was estimated.

In general, diagnostic sensitivity addresses identification among reference-positive cases; it is not a complete description of overall test performance. It does not alone characterize results among reference-negative specimens, the probability that a positive test is correct, or performance in populations outside the endpoint's stated scope. The registry record does not provide the information needed to answer those additional questions.

The record also does not establish a randomized comparison between the described groups. Their pregnancy and lesion-status descriptions differ, and allocation is not stated. Accordingly, group contrasts should not be interpreted as causal effects of a device or as evidence that the groups are exchangeable. The endpoint is best understood as a method-comparison question, with important details of the analysis and numerical result absent from the registry record.

Completion and enrollment do not substitute for an outcome estimate. The record's limitations leave uncertainty about the number of evaluable specimens, the handling of missing or invalid results, and the statistical methods applied. Those unknowns constrain what can be concluded from the registry entry and prevent independent verification of the primary result.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it frames a device evaluation as a diagnostic comparison rather than a treatment-effect study. The primary endpoint is sensitivity relative to HSV culture, defined among culture-positive subjects. That framing determines what the endpoint can answer and which observations contribute to it. It also highlights why the comparator and the endpoint population must be stated alongside any estimate.

The record describes more than one testing context: GeneXpert versus routine PCR in pregnant and nonpregnant women, and GeneXpert versus culture in nonpregnant women. These are not interchangeable comparisons. A diagnostic-performance estimate is tied to its reference method, specimen, and population; broad claims that merge the comparisons would obscure those distinctions. The record's specific primary endpoint makes the culture-based question identifiable even though its numerical result is not reported.

The design description also illustrates the importance of distinguishing enrollment from analyzable information. The registry records enrollment as 12550, but does not report the endpoint denominator or the number of valid paired results. For a sensitivity estimate, the relevant information is specifically linked to the culture-positive group and the GeneXpert assessments within that group. Without those details, precision and reproducibility cannot be judged.

Finally, the record states that the comparison was not randomized and that allocation was not stated. The groups described differ in pregnancy and lesion status. Statistical interpretation therefore depends on respecting the limits of the design and avoiding causal language. The record identifies a meaningful diagnostic question, but its missing estimate and analysis details restrict what can be concluded from the registry entry.

14. 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 primary limitation for interpretation is that the registry record does not report the primary sensitivity estimate or the limits of its 95% confidence interval. It also does not state the endpoint denominator, the number of culture-positive specimens, or the number of GeneXpert-positive results among them. The primary result cannot be independently reconstructed from the registry record.

The endpoint is specific to nonpregnant women with active HSV lesions and uses culture as its comparator. The study summary describes other comparisons, including routine PCR in pregnant and nonpregnant women, but numerical results for those comparisons are not reported in the registry record. Findings from the stated primary endpoint would not automatically answer questions about those other populations or comparators.

The registry describes the comparison as not randomized and says allocation was not stated. The listed groups differ in pregnancy and lesion status. The record does not report additional design details that would establish comparability or explain how participants entered the groups. The endpoint should therefore not be interpreted as a randomized causal contrast.

Important analysis details are not reported in the registry record, including the statistical method for estimating sensitivity, the analysis population, handling of missing or invalid test results, and the multiplicity approach. The record also does not report blinding, specimen-handling procedures, or enough detail to assess the reference method's implementation. These are specific information gaps, not evidence that a particular procedure was or was not used.

Although enrollment is recorded as 12550, that figure does not establish how many observations contributed to the primary analysis. The registry record also does not report a design-based sample-size justification. Together, these limitations prevent assessment of the primary result's precision, robustness, and generalizability from the registry entry alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Identification of Herpes Simplex Virus (HSV) Shedding in the Female Genital Tract of Pregnant and Nonpregnant Women by GeneXpert PCR, Routine PCR, and Culture — NCT01878383.
• Registry record last updated 2020-09-09; status last verified 2020-08.
• Results first posted 2020-09-09.
• 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.

18. Record Summary

NCT01878383 is a completed device trial sponsored by the University of Alabama at Birmingham, with enrollment recorded as 12550. Its stated focus is identification of HSV shedding in the female genital tract using GeneXpert PCR, routine PCR, and culture. The primary endpoint concerns sensitivity of GeneXpert PCR relative to HSV culture among nonpregnant women with active HSV lesions, with specimens collected on the day of enrollment.

The record describes comparisons with routine PCR in pregnant and nonpregnant women and with culture in nonpregnant women. It characterizes the comparison as not randomized and says allocation was not stated. The listed groups differ in pregnancy and active-lesion status.

The registry record names a 95% confidence interval for the primary endpoint but does not report the estimate, interval limits, endpoint denominator, or analysis population. It lists 3 outcome measures and 3 analyses, without reporting multiplicity or missing-data methods. Recorded affected counts for serious adverse events, other adverse events, and deaths are 0 in the listed groups.