This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections (NCT00466817), a randomized phase 3 study. The primary outcome is Change in Best Ear Hearing Assessments at 6 Months..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00466817 |
| Phase | Phase 3 |
| Condition | Cytomegalovirus Infection |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 109 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Results posted | Yes |
2. Clinical Question
Population
Infants with symptomatic congenital cytomegalovirus (CMV) infection were the study population. The brief summary describes infants 30 days old or younger. The registry record lists an enrollment of 109, while the brief summary says the study would include 104 infants; the relationship between these figures is not explained in the registry record.
Intervention
The intervention was six months of oral valganciclovir. The brief summary says all infants received valganciclovir for the initial six weeks, after which those assigned to the longer course continued valganciclovir.
Comparator
The comparator was six weeks of oral valganciclovir followed by placebo for the remainder of the six-month period. The comparison therefore concerns continuing active treatment after the shared initial treatment period, rather than starting treatment versus no treatment.
Primary question
The primary outcome was change in best-ear hearing assessment between baseline and six months. The question was whether hearing classifications changed differently between the two assigned groups. The registry record describes the outcome and the participants included in its analysis, but does not report the category counts or a single comparative estimate for this question.
The study also recorded safety outcomes and hearing assessments at later follow-up points. Its brief summary describes study-related safety, hearing, and developmental evaluations for up to two years, followed by telephone contact for an additional three years. Those follow-up plans do not themselves establish that every participant completed every assessment. The comparison should be understood as a trial of treatment duration after an initial six weeks of valganciclovir, in infants with symptomatic congenital CMV infection.
3. Trial Design
This was a phase 3, randomized, placebo-controlled, triple-masked, parallel-group study sponsored by the National Institute of Allergy and Infectious Diseases. The registry lists the study as completed, with an enrollment of 109. The recorded study start was 2008-06, and primary completion was 2011-12. The registry record does not explain whether these dates refer to planned or actual milestones.
The treatment groups shared an initial six-week period of oral valganciclovir. After that period, participants were assigned to continue valganciclovir or to receive placebo, completing a six-month period. Thus, the randomized contrast concerns continued valganciclovir after the shared initial treatment period. The placebo group was not described as receiving placebo from the start.
Randomization supports a comparison between assigned groups by helping balance factors that might otherwise differ between them. The registry identifies the study as triple-masked but does not state which specific roles were masked. The recorded parallel design means participants were assigned to a group for the comparison rather than crossing between treatment groups.
The brief summary describes 104 infants as the intended participants, whereas the enrollment field records 109. The registry record does not reconcile these figures. It also describes participants as 30 days old or younger, but detailed eligibility criteria are not reported in the registry record. The registry lists 24 outcome measures and no analysis entries. The primary endpoint description says that only randomized participants with both baseline and six-month hearing exams were analyzed; it records 43 participants in each group with both exams. The handling of other analysis populations is not reported in the registry record.
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: All 109 subjects started on valganciclovir. At the end of 6 weeks, subjects were randomized to valganciclovir or placebo. of the 109 subject that started, 12 dropped out before randomization and 1 subject was randomized but never received any blinded study drug.
Overall Study
| Stage | Placebo: 6 Wks Valganciclovir Followed by 18 Wks of Placebo | Valganciclovir: 24 Wks of Valganciclovir |
|---|---|---|
| STARTED | 49 | 47 |
| COMPLETED | 44 | 43 |
| NOT COMPLETED | 5 | 4 |
Analysis population for the primary outcome, as defined in the registry: Only subjects randomized and subjects that had both baseline and 6 month hearing exams were analyzed for the primary endpoint. Some subjects failed to have the one or both of the two hearing exams (baseline and/or 6 months). There were 43 subject in each group (placebo and active) that had both hearing results reported
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.
| Characteristic | Unit | Placebo: 6 Wks of Valganciclovir Followed by 18 Wks of Placebo | Valganciclovir: 24 Wks of Valganciclovir | Total |
|---|---|---|---|---|
| Participants analysed | 49 | 47 | 96 | |
| Age, Continuous | weeks | 19 (2 to 30) | 14 (5 to 30) | 15 (2 to 30) |
| Sex: Female, Male: Female | Participants | 20 | 16 | 36 |
| Sex: Female, Male: Male | Participants | 29 | 31 | 60 |
| Region of Enrollment: United States | participants | 49 | 47 | 96 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Best Ear Hearing Assessments at 6 Months., measured over Between baseline and 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was change in best-ear hearing assessment between baseline and six months. Hearing was evaluated by an independent audiologist. Baseline assessment included a brainstem evoked response (BSER) assessment and autoacoustic emissions (OAEs). At six months, BSER and/or visual reinforcement audiometry (VRA) and OAEs were obtained.
A blinded study audiologist classified hearing by ear as normal, mild hearing loss, moderate hearing loss, or severe hearing loss, based on hearing thresholds. The audiologist then assigned a best-ear classification for each participant at each visit. This approach represents the participant using the better-classified ear; for example, the endpoint description explains that a participant with mild hearing loss in one ear and severe hearing loss in the other would have a best-ear classification of mild hearing loss.
Using the best ear gives a participant-level summary of hearing status and avoids treating two ears from one participant as independent observations in that particular classification. Assessing change between baseline and six months makes the outcome about a difference over time, rather than only a single follow-up classification. However, the registry record does not report the numbers in each hearing category at baseline or six months, the direction or size of the changes, or a comparative estimate between groups. It therefore describes what the endpoint measures without giving enough outcome information to quantify the treatment-group contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the primary endpoint and gives a limited description of who contributed to its analysis, but it does not report the primary outcome results as a treatment-group comparison. In particular, it does not provide category counts, a change estimate, a confidence interval, or a p-value for the six-month best-ear hearing assessment. The registry record also notes that the outcome has several categories or time points and is not reduced to one comparison. Without those results, the direction, magnitude, and precision of the primary contrast cannot be assessed from the posted results.
The primary analysis population is described as randomized participants with both baseline and six-month hearing exams. There were 43 participants in each group with both exams. This is a description of the available endpoint population, not a report of how hearing changed. The registry notes that some participants did not have one or both exams. It does not report how missing exams were handled beyond specifying that participants without both exams were not included in the primary endpoint analysis.
The safety record gives counts of participants with serious and other adverse events in three groups, including a nonrandomized group. These figures should be read as event-affected participant counts within the listed groups, not as a randomized comparison of the primary hearing outcome. The nonrandomized group is distinct from the two assigned treatment groups, and the registry does not provide a basis for treating it as an equivalent comparison group. Serious adverse event counts do not replace the missing primary hearing results.
The registry lists 24 outcome measures but no analysis entries. This limits what can be concluded about the prespecified statistical approach, comparisons across outcomes, or inferential results. Although the record names later hearing outcomes and safety measures, their existence does not establish the values observed or the conclusions drawn by investigators.
In general, an estimate describes the observed contrast, while a confidence interval describes the range of values compatible with the data under the method used. Neither is reported for the primary endpoint in the registry record. The absence of these statistics does not mean the groups were identical, nor does it establish that a difference occurred. It means the posted record does not allow the primary comparison to be quantified. The appropriate interpretation is therefore limited: the study compared treatment durations and recorded hearing and safety outcomes, but the primary comparative result is not reported in the registry record.
9. Statistical Methods Explained
Randomization, masking, endpoint definition, and the handling of incomplete observations each affect how a clinical trial should be interpreted. The registry record contains some design and endpoint details, but it does not report the full statistical analysis plan or the analysis results. The distinctions below separate information stated in the record from general statistical concepts.
What does randomization contribute?
In general, random assignment is intended to make treatment groups comparable at the start of a trial, including with respect to factors that may affect outcomes. This makes differences in outcomes between assigned groups more interpretable as differences associated with assignment, subject to the trial's conduct and analysis. The record identifies this study as randomized and parallel-group. It does not report details of the randomization sequence, how assignments were concealed, or whether the primary analysis followed an intention-to-treat approach. Those methods are not reported in the registry record.
The treatment contrast also needs to be defined accurately. All infants were described as receiving six weeks of valganciclovir before assignment to continued valganciclovir or placebo. Accordingly, the randomized comparison is about the period after those shared initial six weeks. It is not a comparison of valganciclovir against no prior valganciclovir.
What does masking mean for interpretation?
The registry identifies the study as triple-masked. Masking can reduce the chance that knowledge of treatment assignment affects care, outcome assessment, or reporting. Here, hearing was assessed by an independent audiologist who was blinded to assignment, according to the endpoint description. The registry does not identify all roles covered by triple masking, so it is not possible to say from this record exactly who else was masked.
Independent, blinded assessment is relevant because hearing classification involves assessment of test results and assignment to severity categories. Blinding can help limit the influence of expectations on that process. It does not by itself resolve missing assessments, differences in follow-up, or limitations in the reported analysis.
How is the primary outcome constructed?
The endpoint uses a best-ear classification at baseline and six months, with hearing classified as normal, mild, moderate, or severe. In general, a categorical endpoint summarizes participants into defined groups rather than measuring a single continuous quantity. A change outcome compares the participant's status at two visits. Statistical analysis may compare category distributions, transitions between categories, or another prespecified summary. The registry record does not report which comparative method was used, nor does it report the category counts needed to describe transitions.
The best-ear measure summarizes each participant by the better of the two ear classifications. That makes the outcome a participant-level summary for this endpoint, although other listed outcomes consider ears separately. Results based on ears require care because two ears from the same participant may be related; in general, treating related observations as independent can understate uncertainty. The registry does not report the statistical method used for the ear-level outcomes.
What can the analysis population tell us?
The primary endpoint description says that only randomized participants with both baseline and six-month hearing exams were analyzed. It reports 43 participants in each group with both exams and notes that some participants lacked one or both exams. This is a complete-assessment subset for the primary endpoint. In general, restricting analysis to participants with observed assessments can affect interpretation if the availability of exams is related to treatment assignment, hearing status, or other characteristics. The record does not report reasons for missing exams or a sensitivity analysis addressing their impact.
The registry record does not state whether other analysis populations were used, whether participants were analyzed as assigned, or how deviations from assigned treatment were handled. These details are not reported in the registry record and should not be inferred from the outcome description alone.
What is the role of planning assumptions?
In general, sample-size planning uses assumptions about the outcome, the effect the study aims to detect, the significance level, allocation, and the statistical method. The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. These are planning assumptions, not a report of the trial's original design justification. The fraction and resulting sample-size values are not reported in the registry record, and the record does not report the trial's own sample-size justification.
Planning calculations should not be confused with observed power. A planning illustration addresses what sample size might be needed under assumptions; it does not establish the probability that the completed trial detected an effect. No calculated sample-size values or observed-effect estimate are reported in the registry record. In general, confidence intervals are useful for showing the precision of an estimated contrast, while p-values address compatibility with a specified null hypothesis under a model. Neither can be reconstructed from the endpoint description alone.
Why do multiple outcomes matter?
The registry lists 24 outcome measures, including hearing assessments at different follow-up points and safety measures. In general, testing many outcomes or time points can increase the chance of finding a nominally notable result by chance if multiplicity is not addressed. Methods such as adjustment, a hierarchy of outcomes, or prespecified emphasis can help manage that issue, but the registry record does not report whether any such strategy was planned or applied. The listed outcome measures alone do not establish that all were analyzed or statistically compared.
The record contains no analysis entries and does not provide the primary comparison. As a result, the statistical methods used to estimate treatment differences, quantify uncertainty, address multiple outcomes, or assess sensitivity to missing data are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 24 outcome measures, including multiple hearing assessments and safety outcomes. Considering several outcomes or time points raises a general multiplicity issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. In general, trial protocols may address this through a prespecified hierarchy, an adjustment, or a clearly designated primary outcome. The registry identifies a primary endpoint but does not report a multiplicity strategy, whether secondary outcomes were adjusted, or which comparisons were considered confirmatory. Those details are not reported in the registry record.
The primary endpoint population is described as randomized participants who had both baseline and six-month hearing exams. The record reports 43 participants in each group meeting this condition and says that some participants did not have one or both exams. The number and reasons for missing exams, and the approach to missing data beyond excluding participants without both exams from the primary endpoint analysis, are not reported in the registry record.
In general, missing data can affect interpretation when the chance of having an observed outcome is related to treatment or outcome status. A complete-assessment analysis may be informative, but its interpretation depends on why assessments are missing and on the assumptions used. The record does not describe sensitivity analyses or other methods for evaluating the impact of missing hearing assessments.
The record also does not state whether the primary analysis used an intention-to-treat population, how treatment discontinuations were handled, or how participants were treated in analyses of later outcomes. No analysis entries are listed. These omissions prevent a detailed assessment of the analysis populations and the statistical handling of incomplete follow-up.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Non Randomized | 1 | 13 | 7.7% |
| Active | 11 | 47 | 23.4% |
| Placebo After 6 Weeks of Valganciclovir | 19 | 49 | 38.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Non Randomized | 3 of 13 |
| Active | 45 of 47 |
| Placebo After 6 Weeks of Valganciclovir | 47 of 49 |
Most frequent serious adverse event terms
| Event term | Organ system | Non Randomized | Active | Placebo After 6 Weeks of Valganciclovir |
|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 0 of 13 | 3 of 47 | 8 of 49 |
| Respiratory syncytial virus infection | Infections and infestations | 0 of 13 | 1 of 47 | 3 of 49 |
| Anaemia | Blood and lymphatic system disorders | 0 of 13 | 1 of 47 | 2 of 49 |
| Bronchiolitis | Infections and infestations | 0 of 13 | 2 of 47 | 1 of 49 |
| Otitis medial | Infections and infestations | 0 of 13 | 1 of 47 | 1 of 49 |
| Respiratory tract infection viral | Infections and infestations | 0 of 13 | 1 of 47 | 1 of 49 |
| Dehydration | Metabolism and nutrition disorders | 0 of 13 | 1 of 47 | 1 of 49 |
| Ankyloglossia congenital | Congenital, familial and genetic disorders | 0 of 13 | 1 of 47 | 0 of 49 |
| Diarrhoea haemorrhagic | Gastrointestinal disorders | 0 of 13 | 1 of 47 | 0 of 49 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 0 of 13 | 1 of 47 | 0 of 49 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Non Randomized | Active | Placebo After 6 Weeks of Valganciclovir |
|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 0 of 13 | 15 of 47 | 14 of 49 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 13 | 11 of 47 | 14 of 49 |
| Otitis media | Infections and infestations | 0 of 13 | 11 of 47 | 12 of 49 |
| Diarrhoea | Gastrointestinal disorders | 0 of 13 | 9 of 47 | 13 of 49 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 13 | 6 of 47 | 11 of 49 |
| Anaemia | Blood and lymphatic system disorders | 2 of 13 | 5 of 47 | 9 of 49 |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | 1 of 13 | 5 of 47 | 10 of 49 |
| Vomiting | Gastrointestinal disorders | 1 of 13 | 9 of 47 | 6 of 49 |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | 0 of 13 | 11 of 47 | 4 of 49 |
| Flatulence | Gastrointestinal disorders | 0 of 13 | 5 of 47 | 8 of 49 |
Serious events with the highest arm-level rate: neutropenia (16.3%), respiratory distress (7.7%), respiratory syncytial virus infection (6.1%), bronchiolitis (4.3%), anaemia (4.1%).
The safety record lists serious adverse events and other adverse events for three groups: nonrandomized, active, and placebo after six weeks of valganciclovir. For serious events, the listed group sizes at risk are 13, 47, and 49, with 1, 11, and 19 participants affected, respectively. For other adverse events, the corresponding group sizes at risk are 13, 47, and 49, with 3, 45, and 47 participants affected. These are counts of participants reported as affected, not counts of every individual event occurrence.
The nonrandomized group is not one of the two randomized treatment groups. Its figures should not be combined with, or interpreted as directly comparable to, the randomized groups without additional information. The record does not report the reasons for nonrandomization or provide an adjusted safety comparison. It also does not report deaths in the listed safety information; this should not be interpreted as evidence that no deaths occurred.
The record lists neutropenia at 16.3%, respiratory distress at 7.7%, respiratory syncytial virus infection at 6.1%, bronchiolitis at 4.3%, anaemia at 4.1%, and congenital ankyloglossia at 2.1% among the top serious adverse event terms. These listed percentages are descriptive; the record does not specify their denominator in this summary. They do not by themselves establish comparative risk between treatment groups or whether an event was caused by treatment. The registry also identifies an outcome concerning adverse events leading to permanent discontinuation or an irreversible outcome, but does not report its results in the information.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized comparison of two treatment durations and specifies a primary hearing outcome at six months. It also provides a partial description of the primary analysis population and group-level safety counts. These registry entries describe the study's design and some recorded outcomes, but they do not supply the central comparative result for the primary hearing endpoint.
Without the category counts or a treatment-group estimate for change in best-ear hearing, the posted results do not show how hearing classifications changed in either group, how the groups compared, or how precise any difference was. The record does not report a confidence interval or p-value for this endpoint. It is therefore not possible to use the registry record to quantify the primary treatment contrast or to determine whether the observed data favored either assigned duration.
In general, a trial's result is more than a statement that an outcome was measured. Interpretation needs the observed data, an appropriate comparison, and information about uncertainty and analysis choices. Even a reported difference would need to be considered alongside the endpoint definition, missing assessments, safety outcomes, and other relevant outcomes. Here, those considerations cannot fill the gap in the unreported primary comparison.
The safety counts indicate that participants in each listed group were reported as having serious and other adverse events. They should be read descriptively and in the context of the differing group structure, including a nonrandomized group. The figures do not establish a causal relationship between an event and treatment, and they do not replace a comparative assessment of hearing.
The record also lists later hearing and safety outcomes, but outcome titles are not results. The proper conclusion is limited to what is posted: the trial was designed to compare six months of valganciclovir with six weeks followed by placebo, and the primary endpoint concerned six-month hearing change. The comparative primary outcome result is not reported in the registry record. No conclusion about treatment benefit or lack of benefit should be drawn from that absence.
13. Why This Trial Matters Statistically
This study illustrates why a clinical trial's design and its reported results need to be distinguished. The record gives a clear treatment-duration contrast, a defined hearing endpoint, and some information on the assessment process. It also identifies the primary analysis subset. These details help readers understand what the investigators intended to compare and how hearing was classified.
At the same time, a defined endpoint is not enough to evaluate a treatment comparison. For a categorical outcome, readers need the observed classifications or a suitable summary of changes, as well as a comparative estimate and information about its precision. The registry record does not report those primary endpoint results. This makes the absence of outcome reporting statistically important, not merely a missing detail about presentation.
The endpoint also highlights the effect of analysis choices. A participant-level best-ear classification differs from an analysis of left and right ears separately. The primary population excludes participants without both baseline and six-month exams, and the record notes that some assessments were missing. In general, the unit of analysis and the handling of missing observations influence what an estimate means and how much uncertainty it carries.
Finally, the record lists many outcome measures and safety information, but does not provide analysis entries or describe the strategy for multiplicity. This underscores the value of reporting which comparisons were prespecified, how incomplete data were handled, and how estimates were quantified. Without those details and the primary results, readers can assess the trial's broad design but cannot make a statistical appraisal of the main treatment contrast from the registry record alone.
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 most consequential limitation for interpreting this trial record is that it does not report the primary outcome comparison. The endpoint is defined as change in best-ear hearing assessment between baseline and six months, but the registry gives no category counts, change estimate, confidence interval, or p-value. The primary outcome description indicates that it was not reduced to a single comparison because it involves several categories or time points. As a result, the main comparative finding cannot be evaluated from the registry record.
The primary analysis included randomized participants with both baseline and six-month hearing exams, with 43 participants in each group meeting that description. Some participants lacked one or both exams. The number of missing assessments, reasons for missingness, and any sensitivity analyses are not reported in the registry record. This limits assessment of whether the complete-assessment subset adequately represents the randomized groups.
The record lists an enrollment of 109, while the brief summary describes 104 intended participants. It does not explain the relationship between these figures. It also lists a nonrandomized group in the safety information, but does not explain why those participants were not randomized. These details warrant caution when relating the safety counts to the randomized treatment comparison.
Although the registry lists 24 outcome measures, it contains no analysis entries. The methods used for comparative estimates, uncertainty, multiplicity, treatment discontinuation, and later follow-up are not reported in the registry record. The record also does not state the original sample-size justification. A planning illustration is described, but its detailed values are not reported. These limitations restrict interpretation to the study design and the descriptive information that is recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Short-Term vs. Long-Term Valganciclovir Therapy for Symptomatic Congenital CMV Infections — NCT00466817.
- Registry record last updated 2015-08-26; status last verified 2015-07.
- Results first posted 2013-11-13.
- 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.
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18. Record Summary
NCT00466817 is a completed phase 3, randomized, placebo-controlled, triple-masked, parallel-group study of treatment duration in infants with symptomatic congenital CMV infection. Participants were described as receiving six weeks of oral valganciclovir before assignment to continue valganciclovir or receive placebo for the rest of a six-month period. The registry lists enrollment of 109 and records the study start as 2008-06 and primary completion as 2011-12.
The primary endpoint was change in best-ear hearing assessment from baseline to six months. The record describes hearing classification and says that 43 participants in each group had both exams and were analyzed for this endpoint. It does not report a single comparative result, category counts, or inferential statistics for that outcome. Safety counts are listed for nonrandomized and randomized groups, and 24 outcome measures are recorded, but no analysis entries are listed. The primary comparative result and several details of the statistical plan are not reported in the registry record.