VALTREX Once Daily For Viral Shedding In Herpes Simplex Virus 2 (HSV-2) Seropositive Subjects. VALTREX® Tablet is a Trademark of GlaxoSmithKline Group of Companies.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VALTREX Once Daily For Viral Shedding In Herpes Simplex Virus 2 (HSV-2) Seropositive Subjects. VALTREX® Tablet is a Trademark of GlaxoSmithKline Group of Companies. (NCT00116844), a randomized phase 4 study. The primary outcome is Mean Percent Days of Subclinical Shedding as Determined by Type-specific Polymerase Chain Reaction (PCR) Assay for HSV-2.

2. Clinical Question

This is a question about a measured virologic outcome during treatment periods, not a direct comparison of symptomatic episodes or long-term clinical outcomes. For each participant, a day was classified as shedding or no shedding based on PCR, and as clinical or subclinical based on whether genital lesions were present. The primary outcome focused on subclinical days with PCR data. The registry also lists secondary outcomes concerning total shedding, viral DNA copy number, absence of shedding, and recognized clinical signs or symptoms.

The two sequences were valacyclovir followed by placebo, or placebo followed by valacyclovir. Because each sequence involved both treatments, the comparison is a crossover rather than a parallel-group treatment assignment. The record does not report further details about how sequence or period effects were handled in the primary analysis.

3. Trial Design

The registry record identifies a completed phase 4, randomized, double-blind, two-way crossover study sponsored by GlaxoSmithKline. Eligible subjects were assigned to one of two treatment sequences: VALTREX 1 g once daily followed by placebo, or placebo followed by VALTREX 1 g once daily. The description specifies 60 days in each treatment period and a washout period of 7 days between periods. The recorded enrollment was 73.

Daily genital and anal-rectal swabs were collected during each 60-day treatment period and the washout period. PCR results classified each study day as shedding or no shedding. Separately, days were classified as clinical when genital lesions were present, or subclinical when they were absent. The primary endpoint used subclinical days with PCR data.

The posted arm summaries report a mean and standard deviation for each treatment, with n=56 for valacyclovir and n=56 for placebo. Those summaries describe treatment-specific outcome data; they do not provide the paired participant-level values or the within-participant covariance needed to reconstruct a crossover contrast from the summary statistics alone.

The record names the intent-to-treat crossover population as participants who received at least one dose and had at least one PCR swabbing result in each treatment period. It also notes that analyses use participants with data available at indicated time points. The registry record does not report the original sample-size justification, a detailed statistical analysis plan, or how sequence, period, or carryover effects were assessed. It also does not report the handling of missing PCR observations beyond the population definition and endpoint denominator description.

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.

Before assignment: Eligible male or female immunocompetent participants in general good health were enrolled. Additionally, participants must be Herpes Simplex Virus Type 2 (HSV-2) seropositive at screening. VALTREX (valacyclovir hydrochloride) is registered trademark of GlaxoSmithKline.

Period 1: Treatment Period 1 (60 Days)

Reasons for not completing this period:

Period 2: Washout Period (7 Days)

Period 1: Treatment Period 2 (60 Days)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat crossover (ITTC) population was defined as consisting of all participants who received at least one dose of investigational product and had at least one PCR swabbing result in each treatment period. Only those participants with data available at the indicated time points were analyzed.

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.

Population: The ITTE population was defined as consisting of all participants who received at least one dose of investigational product and at least one safety and/or efficacy evaluation.

6. Primary Endpoint

The registry lists the primary outcome as Mean Percent Days of Subclinical Shedding as Determined by Type-specific Polymerase Chain Reaction (PCR) Assay for HSV-2, measured over Up to Day 60 of each treatment period (up to 160 days).

The primary endpoint is the mean percentage of subclinical days with HSV-2 shedding detected by a positive type-specific PCR result. For each participant, the percentage was defined using the number of subclinical days with PCR-detected shedding divided by the total number of subclinical days with PCR data, multiplied by 100. A day counted as subclinical when genital lesions were absent. Days with lesions were classified as clinical and were not part of this subclinical-day percentage.

This endpoint expresses the frequency of detected shedding among eligible days with PCR data. It is a continuous measure reported as a percentage of days, and the registry summarizes it using a mean and standard deviation. It is used to quantify a virologic outcome across repeated daily swabs, rather than relying on a single test result or only on recognized symptoms. A lower percentage means that a smaller share of the recorded subclinical days had PCR-detected shedding; this describes the endpoint itself and does not establish what happened outside the observed treatment periods.

The endpoint depends on both the classification of days and availability of PCR data. Days without PCR data are not included in the stated denominator. The registry record does not report additional rules for missing swabs, the minimum amount of data required at each time point beyond its population definition, or a sensitivity analysis for missing observations.

7. Results Posted in the Registry

• VALTREX 1 g Once Daily: mean 1.50 versus 5.10 on control; difference -3.60 (95% CI -6.34 to -0.86), standardized effect d = -0.49; z-test p = 0.010.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Mean Percent Days of Total HSV-2 Shedding

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • VALTREX 1 g Once Daily: mean 1.50 versus 5.50 on control; difference -4.00 (95% CI -6.77 to -1.23), standardized effect d = -0.54; z-test p = 0.005.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for VALTREX 1 g Once Daily than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes span total HSV-2 shedding, the presence of any shedding, viral DNA copy numbers on days with subclinical or total shedding, and recognized clinical signs or symptoms of genital herpes. The posted secondary results include a mean comparison for total HSV-2 shedding. Its direction is consistent with the primary endpoint: the treatment summary for valacyclovir is lower than the placebo summary, and the recalculated mean difference is negative. The registry also reports p < 0.001 from a Wilcoxon rank-sum test for that outcome.

This pattern relates to the primary result because both outcomes describe shedding, although the primary endpoint restricts the assessment to subclinical days and the secondary endpoint concerns total shedding. Consistent directions across related measures can add context, but they do not independently establish that every listed outcome changed in the same way. Numerical results for the other listed secondary outcomes are not reported in the registry record.

Secondary analyses generally carry less weight than a prespecified primary analysis when many outcomes are considered. General statistical explanation: testing multiple outcomes creates more opportunities for a small p-value to arise by chance, and a multiplicity plan can address that concern. The registry record does not report whether a multiplicity adjustment or hierarchy was prespecified. The secondary p-value should therefore be treated as supportive descriptive evidence rather than as a standalone confirmatory finding. It does not answer questions about the unreported secondary measures or establish an effect on clinical symptoms.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Mean Percent Days of Total HSV-2 Shedding
• Number of Participants With no Shedding
• Mean Log HSV-2 DNA Copy Number Per Day on Days With Subclinical Shedding
• Mean Log HSV-2 DNA Copy Number Per Day on Days With Total Shedding
• Percent Overall Study Population Who Have Recognized Clinical Signs/Symptoms of Genital Herpes Infection During the Study

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: it is a percentage for each participant, summarized across treatment observations by a mean and standard deviation. A mean describes the average value, while the standard deviation describes how spread out the observed values are around that average. These summaries are descriptive; by themselves, they do not account for the crossover pairing between observations from the same participant.

What the recalculated comparison represents

The recalculated comparison is an unadjusted difference between the posted treatment means. The reported estimate is -3.6 percentage points for valacyclovir minus placebo. Negative values mean that the posted mean was lower in the valacyclovir treatment summary. The confidence interval is calculated from the posted summary statistics, and the recalculated p-value is 0.01. These calculations are not the registry's reported analysis and should not be mistaken for a participant-level crossover model.

In a crossover study, the same participant can contribute measurements under both treatments. A paired analysis can use the within-participant relationship between those observations. The treatment-specific means and standard deviations do not reveal that relationship, so the recalculated unadjusted comparison cannot reproduce a paired contrast. General statistical consideration: accounting for pairing can affect the estimated uncertainty, because the two measurements from a participant may be related.

What the registry reports

The registry reports a nonparametric Wilcoxon rank-sum test with p < 0.001 for the primary comparison. In general, a rank-based test evaluates the ordering of observations rather than comparing means under a normal-distribution model. Its p-value does not directly express the size of a mean difference. The registry does not report the rank-sum statistic, an effect estimate for this analysis, or confidence limits for it. The posted record also does not explain whether or how the rank-sum test was adapted to the crossover design.

The recalculated p-value of 0.01 and the registry's p < 0.001 come from different analyses. They should not be treated as interchangeable estimates of the same test. The mean difference and its confidence interval describe the summary-based calculation, whereas the registry's p-value is attached to its reported rank-sum analysis. The discrepancy flag is false, and the record presents both results without indicating that the calculations conflict.

Why distribution and design matter

General statistical explanation: percentage outcomes can be bounded and may have many observations near the lower limit. Such features can make a symmetric, normal approximation a poor description of individual values. A rank-based method can be useful when the analysis is based on ranks rather than a normal model, but method choice does not remove the need to account for the study design. For crossover data, period, sequence, and within-participant dependence can matter. Whether these issues were evaluated is not reported in the registry record.

Over-dispersion is general statistical terminology for variability greater than a model expects. When a model assumes less variability than is present, uncertainty can be understated and tests can be too optimistic. The registry does not report a model-based analysis of this endpoint, an over-dispersion assessment, or a prespecified distributional assumption. It would therefore be inappropriate to infer that such a model was used or that over-dispersion was formally evaluated.

How to read a confidence interval and p-value

General statistical explanation: a confidence interval gives a range of effect estimates compatible with the data and the calculation's assumptions. It communicates both the estimated direction and the precision of the estimate. It is not a range containing a fixed proportion of individual participant outcomes, and it does not account for design features absent from the calculation. Here, the recalculated confidence interval has negative limits, while the registry's rank-sum result is reported as a p-value without an effect estimate or interval.

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null model and the analysis assumptions. It is not the probability that the null hypothesis is true, and it does not indicate the probability that an observed difference is important to patients. The two reported p-values reflect different analytical approaches, and neither alone resolves questions about crossover handling, missing observations, or multiplicity.

11. Confidence Intervals and Precision

The recalculated primary mean difference is -3.6 percentage points. Its confidence interval has both limits below zero, so the interval is compatible with a negative mean difference under the assumptions used for the unadjusted summary-based calculation. The interval communicates uncertainty as well as direction: it is not a claim that the true difference equals the point estimate exactly.

Precision should be interpreted in light of the calculation. The posted treatment summaries provide means, standard deviations, and n=56 in each treatment summary, but not participant-level paired differences. A crossover analysis can use the relationship between each participant's observations under the two treatments. Because that relationship is not available in the summaries, the recalculated interval cannot incorporate it. It should therefore be read as an unadjusted summary-based interval rather than a fully design-aware interval.

The registry reports p < 0.001 from a Wilcoxon rank-sum test, but does not report an effect estimate or confidence interval for that test. That p-value does not supply the missing precision information about the magnitude of the rank-based comparison. The recalculated p-value of 0.01 accompanies the mean comparison and also does not replace the interval.

General statistical explanation: confidence intervals are conditional on the data and methods used to calculate them. They do not automatically incorporate missing-data uncertainty, multiplicity, or the effects of analysis choices. The registry record does not report a multiplicity adjustment or enough detail to assess sensitivity to missing PCR observations. Thus, the interval is informative for the stated unadjusted calculation, but it does not resolve the broader uncertainty about the full analysis strategy.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrative calculations based on the observed effect, not the original trial's design calculation. The original sample-size assumptions are not reported in the registry record. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect.

For 100% of the observed effect, the planning illustration gives 67 participants per arm for 80% power and 89 participants per arm for 90% power. For 75% of the observed effect, the corresponding figures are 118 and 158 participants per arm. For 50% of the observed effect, they are 265 and 354 participants per arm.

In plain language, the 80% power column describes the planning number per arm under which the calculation would have an 80% chance of detecting the specified effect if the assumptions hold. The 90% power column uses a higher target probability of detection, and therefore requires more participants in these illustrations. Smaller effects need more participants to detect under the same assumptions, which is why the planning figures rise as the effect fraction gets smaller.

This is not observed power. It is a planning illustration based on the observed effect and stated assumptions, not evidence about the probability that this completed study detected an effect. The figures do not account for the crossover structure beyond the stated equal-allocation assumption, and they should not be read as the trial's original design requirements.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -3.600; pooled standard deviation σ = 7.385.
2. n = 2 × (1.96 + 0.842)² × 7.385² / -3.600² = 66.1, rounded up to 67 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -3.6                      # observed difference in means
sigma <- 7.38545868582311                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(116844)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 67 (80% power), 89 (90% power)
 75% of observed effect: n per arm = 118 (80% power), 158 (90% power)
 50% of observed effect: n per arm = 265 (80% power), 354 (90% power)
power.t.test: 67 
Simulated power at n = 67 per arm: 0.795 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports a nonparametric Wilcoxon rank-sum analysis for the primary outcome, with p < 0.001. It does not report that analysis's effect estimate, test statistic, or confidence interval. The sponsor's reported analysis therefore gives a result for its stated test, but the registry record does not provide enough detail to reconstruct the estimate or determine how the test handled the crossover pairing.

The recalculation uses the posted means and standard deviations to estimate an unadjusted mean difference of -3.6 percentage points and a 95% confidence interval with negative limits; its unadjusted p-value is 0.01. This is a simple summary-based calculation, not a replication of the Wilcoxon rank-sum analysis or a paired crossover model. The methods answer related but not identical statistical questions.

The record marks the discrepancy flag as false. The difference between the reported p-value and the recalculated p-value should therefore be read as a difference between analytical methods, not as a recorded conflict in the results. Neither value should be substituted for the other. The registry's reported test is best understood as the sponsor-posted analysis, while the recalculation offers a separate view of the difference in posted means. Details of any fuller sponsor analysis plan, including treatment of period and sequence, are not reported in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is clearly named in the registry, and five secondary outcomes are listed. However, the record does not report whether the sponsor specified a multiplicity strategy, such as a testing hierarchy or adjustment across outcomes. Without that information, the interpretation of secondary p-values is uncertain: multiple outcome tests can increase the chance of at least one apparently notable result even when no underlying effect exists. This is a general statistical concern, not evidence that a particular result is false.

The record does not provide a full statistical analysis plan. It does not report whether interim analyses were planned or conducted, how sequence and period effects were assessed, or whether carryover was tested or handled. Those details should not be inferred from the crossover design alone. The reported Wilcoxon rank-sum method is named, but the registry does not describe how it was applied to paired crossover observations.

The population description says that the intent-to-treat crossover population included participants who received at least one dose and had at least one PCR swabbing result in each treatment period. It also notes that only participants with data available at indicated time points were used. The endpoint definition excludes subclinical days without PCR data from its denominator. The record does not report the amount or pattern of missing swab data, reasons for missingness, imputation methods, or sensitivity analyses addressing missing observations.

These gaps matter because missing PCR results could affect the observed percentage if data availability is related to shedding or treatment period. General statistical explanation: an analysis of available observations relies on assumptions about why data are missing, and different assumptions can lead to different estimates. The registry record does not state which assumptions were made or whether they were examined. It is therefore possible to describe the posted estimates and methods, but not to determine from the record alone how robust the findings are to missing data or analysis choices.

16. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lower limb fracture (1.6%), loss of consciousness (1.6%).

The registry's adverse-event figures list serious adverse events affecting 0 in the VALTREX 1 g once-daily group and 1 in the placebo group. The corresponding at-risk counts are 65 and 63. The record lists lower limb fracture and loss of consciousness as serious-event terms, each at 1.6%; it does not assign those terms to a particular treatment group in the listed terms.

Other adverse events affected 29 of 65 at risk in the valacyclovir group and 42 of 63 at risk in the placebo group. Deaths are listed as 0 in each group. These are registry counts and percentages, not an adjusted comparison. The record does not report event timing, duration, severity beyond the serious-event classification, or a statistical comparison of adverse events. The crossover treatment summaries for the efficacy endpoint should not be treated as the denominators for these safety figures.

These safety data describe recorded events in the registry and should not be interpreted as establishing comparative safety. The small number of serious events and the absence of further event detail limit what can be concluded from the listing.

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

The posted primary summaries show a lower mean percentage of subclinical days with PCR-detected HSV-2 shedding during the valacyclovir treatment period than during the placebo period. The unadjusted recalculated mean difference is -3.6 percentage points, and its confidence interval has negative limits. The registry's reported Wilcoxon rank-sum analysis has p < 0.001. These results describe the observed endpoint and the analyses recorded for the trial.

They do not establish that every participant had less shedding, because group means do not show individual response patterns. They do not establish an effect on recognized genital herpes symptoms, transmission, or outcomes beyond the observed treatment periods. Although the registry lists those as secondary areas of interest, numerical results for most of those secondary outcomes are not reported in the registry record.

The study population was HSV-2 seropositive and had no history of symptomatic genital herpes. The findings should be understood in that population and in the context of the recorded 60-day treatment periods and daily PCR sampling. The record does not establish how the result applies to populations or time periods not described in the trial.

The recalculated result is based on posted group summaries rather than paired participant-level crossover data. The registry's reported test is a different method, and its effect estimate and confidence interval are not reported. Missing-data handling, multiplicity, and detailed crossover analysis procedures are also not reported. These limitations constrain how precisely the results can be interpreted. Statistical evidence about a shedding measure is not, by itself, a conclusion about clinical benefit or an individual treatment decision.

18. Why This Trial Matters Statistically

This trial illustrates how the design and analysis interact. In a crossover study, each participant receives both treatments in different periods, so observations under the two treatments may be related. The registry provides treatment-specific means and standard deviations, but those summaries do not preserve the within-participant relationship. A simple recalculation from group summaries can describe the difference in posted means, but it cannot reproduce every feature of a paired crossover analysis.

The record also illustrates why an effect estimate and a p-value provide different information. The recalculated mean difference gives a direction and scale for the average contrast, while its confidence interval communicates uncertainty under the calculation's assumptions. The registry's rank-sum p-value provides a test result but no estimate or interval for that analysis. Reading the methods alongside the numbers makes clear that the reported and recalculated results are not interchangeable.

Finally, the endpoint depends on daily sampling and on classifying days as clinical or subclinical. The proportion is calculated among subclinical days with PCR data, so the definition of the denominator is central to interpretation. The registry's incomplete reporting of missing-data methods, multiplicity, and crossover details shows why an apparently clear numerical result can still leave important methodological questions unresolved. Statistical interpretation requires attention to what was measured, how the comparison was made, and which uncertainties remain.

19. 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 endpoint is a PCR-based shedding measure, and its denominator includes subclinical days with PCR data. The record does not report the extent or pattern of missing daily swabs, or whether missingness differed by treatment period. If data availability is related to the outcome, the observed percentages may not fully represent all eligible days. The registry does not report imputation or sensitivity analyses for this issue.

The crossover design is described by treatment sequence, but detailed analysis of sequence, period, and carryover effects is not reported. The posted summaries do not include paired differences or the within-participant correlation. As a result, the recalculated unadjusted comparison cannot represent the full information available from a participant-level crossover analysis. The registry's reported Wilcoxon rank-sum method is not accompanied by enough detail to evaluate how it reflects the design.

The record lists multiple secondary outcomes but does not report a multiplicity plan. Numerical results for most listed secondary outcomes are not reported in the registry record, limiting assessment of whether the primary finding aligns with other measures. The outcome descriptions also distinguish total shedding, subclinical shedding, viral DNA copy numbers, and recognized symptoms; results for one measure should not be assumed to apply to the others.

The registry describes the target population as HSV-2-seropositive individuals with no history of symptomatic genital herpes and reports 60-day treatment periods. The record does not establish whether these results generalize to other populations or longer observation periods. The original sample-size assumptions, detailed eligibility criteria, and full statistical analysis plan are not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: VALTREX Once Daily For Viral Shedding In Herpes Simplex Virus 2 (HSV-2) Seropositive Subjects. VALTREX® Tablet is a Trademark of GlaxoSmithKline Group of Companies. — NCT00116844.
• Registry record last updated 2018-02-12; status last verified 2017-08.
• Results first posted 2018-02-12.
• 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.

23. Record Summary

The registry record describes a completed, randomized, double-blind, phase 4 crossover trial sponsored by GlaxoSmithKline. It enrolled 73 and compared VALTREX 1 g once daily with placebo in two treatment sequences, with 60-day treatment periods and a 7-day washout period. The primary outcome was mean percentage of subclinical days with HSV-2 shedding detected by PCR.

The posted primary means were 1.5 for valacyclovir and 5.1 for placebo, with n=56 in each treatment summary. The unadjusted recalculated mean difference was -3.6 percentage points, with a confidence interval whose limits are negative. The registry reports p < 0.001 from a Wilcoxon rank-sum test. The record does not report the full crossover analysis plan, missing-data methods, or multiplicity strategy, and numerical results for most listed secondary outcomes are not reported in the registry record.