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 Effect of Valproic Acid Concentration on Photic Response (NCT00609245), a na phase 4 study. The primary outcome is Difference in SPR During Placebo and VPA Infusions.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00609245 |
| Phase | Phase 4 |
| Condition | Photosensitive Epilepsy |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Vanderbilt University Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with photosensitive epilepsy. The registry record lists 13 participants as enrolled. One participant did not complete the valproic acid infusion because of an adverse event and was not included in the final analysis. Further details about participant characteristics, eligibility criteria, and the analyzed population are not reported in the registry record.
Intervention
The intervention was an intravenous valproic acid infusion. The registry description says participants received placebo on day 1 and valproic acid on day 2. The purpose was to examine whether small changes in the amount of valproate in the blood were associated with changes in the brain's response to flashing lights.
Comparator
The comparator was a placebo infusion. This was not a randomized, masked comparison: allocation is listed as not applicable, masking as none, and the registry says all participants received placebo before valproic acid. The sequence therefore differs from a randomized comparison in which treatment order is assigned without a fixed pattern.
Primary question
The primary outcome was the difference in standard photosensitive range during placebo and valproic acid infusions. The measure reflects how many tested flash frequencies elicited a photosensitive response. The registry specifies monitoring at the start of EEG monitoring and drug infusion, followed by hourly assessments for 12 hours. It does not report the numerical difference, its uncertainty, or a statistical test result.
3. Trial Design
This was a completed phase 4 study sponsored by Vanderbilt University Medical Center. It was registered as a single-group study, with 13 participants enrolled. The registry lists placebo and valproic acid as the drug interventions. Its arm description states that all participants had placebo on day 1 and a valproic acid infusion on day 2. Thus, the recorded treatment order was fixed rather than randomly assigned.
The study was not masked. The registry identifies allocation as not applicable and masking as none. These design features matter when interpreting a change between the two infusion periods: observed differences can reflect the infusion condition, but the record does not establish that other influences on the measured response were controlled through randomization or masking. The record does not describe a separate parallel group receiving only one of the infusions.
The study began in 2007-12, and primary completion was recorded in 2008-12. Its status is completed. These dates describe the registry record and do not provide additional information about the duration of any individual participant's monitoring beyond the stated outcome timeframe.
The primary outcome was the difference in standard photosensitive range during placebo and valproic acid infusions. The registry describes measurement at the start of EEG monitoring and drug infusion and on an hourly basis for 12 hours. It lists the outcome summary as a mean with full range dispersion. A specific statistical model, handling of repeated observations, and method for combining hourly measurements into a treatment-period comparison are not reported in the registry record.
One participant did not complete the valproic acid infusion because of an adverse event and was excluded from the final analysis. The record does not explain how incomplete or otherwise missing measurements were handled, nor does it provide a detailed description of the final analysis population. Numerical primary outcome results are 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.
Overall Study
| Stage | Valproate Infusion |
|---|---|
| STARTED | 13 |
| COMPLETED | 12 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Valproate Infusion |
|---|---|
| Adverse Event | 1 |
Analysis population for the primary outcome, as defined in the registry: 1 patient did not complete infusion of Valproic Acid due to Adverse Event. This patient was not included in final analysis.
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 | Valproate Infusion |
|---|---|---|
| Participants analysed | 13 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 13 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 3 |
| presence of photoparoxysmal response | participants | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Difference in SPR During Placebo and VPA Infusions, measured over At the start of EEG monitoring/drug infusion, and on an hourly basisfor 12 hours.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Full Range |
| Unit | standard photosensitive range (SPR) |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the difference in standard photosensitive range, or SPR, during placebo and valproic acid infusions. The registry describes SPR as a standardized measure derived from intermittent photic stimulation at 14 predetermined frequencies. Each tested flash frequency that elicits a photosensitive response counts as a step; the resulting measure ranges from 0 to 14, with each point representing the number of flash frequencies that elicited such a response.
In general, an endpoint is chosen to represent the outcome a study is designed to assess. SPR provides a structured way to describe responses across the tested flash frequencies, rather than relying only on a narrative description of the EEG response. The study's question was whether small changes in valproate concentration were associated with a change in this response measure. The record does not report the measured concentration values or a concentration-response analysis.
Measurements were scheduled at the start of EEG monitoring and drug infusion and then hourly for 12 hours. Repeated readings can describe how a response changes over the monitoring period, but a meaningful treatment-period summary depends on how those readings are analyzed. The registry identifies the endpoint summary as a mean with full range dispersion; it does not explain how repeated observations were incorporated into the reported comparison.
The endpoint description defines the scale and measurement procedure, but does not provide the observed SPR values, the estimated difference between infusion conditions, or uncertainty around that difference. Those results are not reported in the registry record, so the endpoint definition alone cannot establish the direction or precision of any observed change.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the clinical question and how the primary outcome was intended to be measured, but it does not include the numerical primary outcome result. In particular, the estimated difference in SPR between placebo and valproic acid infusions is not reported in the registry record. The record also does not report a confidence interval, a p-value, or another measure of statistical uncertainty for that difference. Consequently, the direction, size, and precision of the primary comparison cannot be described from the recorded information.
The outcome scale is defined as 0 to 14, based on the number of tested flash frequencies that elicited a photosensitive response. This definition explains what an SPR value represents; it does not show what values participants actually had. Likewise, specifying a mean and full range as the outcome summary does not supply the mean, range, or change in either. It is important to keep the measurement definition distinct from the result.
The fixed sequence is also central to interpretation. All participants received placebo on day 1 and valproic acid on day 2, and the study was not masked. A difference between the periods could be consistent with a change associated with the infusion condition, but the design does not separate that association from possible period, order, or other time-related influences. Random assignment of treatment order and masking are not described; the registry instead records that allocation was not applicable and masking was none.
The final analysis excluded one participant who did not complete the valproic acid infusion because of an adverse event. The remaining analysis population is not described in enough detail to establish how many participants contributed complete outcome data at each assessment or how incomplete measurements were treated. This matters because the available observations may differ across infusion periods, while a paired or repeated-measures interpretation depends on the measurements included and their relationship.
The registry lists one outcome measure and one analysis, but that listing does not provide a full statistical analysis plan. It does not state how the hourly measurements were modeled, what contrast was tested, what assumptions were checked, or whether any adjustments were made. The posted information therefore supports a description of the design and measurement, not a conclusion about the magnitude, statistical uncertainty, or clinical importance of the observed difference. No treatment-effect conclusion should be drawn from the endpoint definition or design description alone.
9. Statistical Methods Explained
Statistical interpretation depends on the relationship between the design, the endpoint, and the analysis. The registry describes a single-group study with a fixed sequence: placebo on day 1, followed by valproic acid on day 2. It specifies a mean and full range for the primary outcome and says measurements were made at the start of EEG monitoring and infusion, then hourly for 12 hours. It does not state the statistical method used to compare these observations.
What does a difference in means represent?
In general, a difference in means describes how far apart the average measured outcomes are under two conditions. For this study, the named outcome is SPR during placebo and valproic acid infusions. Because both conditions were scheduled for the same participants, a within-participant analysis could focus on changes in each participant, but the registry record does not report whether such an analysis was used. A comparison of group averages and an analysis of participant-level changes are not interchangeable in every setting; the chosen method should match the study design and the available observations.
The endpoint is measured repeatedly across the monitoring period. In general, repeated measurements from the same person tend to be related rather than independent. An analysis that treats every hourly reading as unrelated can misrepresent the amount of information in the data. Methods for repeated observations can account for within-person correlation, but the specific method, correlation structure, and time summary are not reported in the registry record. No model should be attributed to the study without that information.
Why does the study sequence matter?
In general, randomization helps prevent treatment assignment from being systematically tied to other factors. Here, the record describes a fixed order for every participant, with placebo first and valproic acid second. A change over time could therefore coincide with the change in infusion condition. Possible period or order effects are general design considerations, not documented findings in this study. The registry does not report an adjustment for period, order, or other time-related influences.
Masking is also relevant in general because awareness of the assigned condition can influence conduct, assessment, or interpretation. The registry lists masking as none. That fact does not demonstrate that bias occurred, but it means the record does not describe masking as a safeguard. The outcome involves an EEG-based response measure; the registry does not explain whether assessors were independent of knowledge about the infusion condition.
How should uncertainty be read?
In general, a confidence interval gives a range of values compatible with the observed data and the assumptions of the analysis. Its width conveys precision: a narrower interval indicates greater precision than a wider one, while the interval's position indicates which effect values are compatible with the data. A p-value, when reported, addresses how unusual the data would be under a stated null hypothesis and analysis assumptions; it is not a direct measure of effect size or clinical importance. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record.
The record also does not report the observed mean SPR values or the full range of observations. It is therefore not possible to describe variability in the measured outcomes or determine whether an estimated difference was precise. The stated scale from 0 to 14 clarifies the possible measure, not the observed distribution.
What do the planning assumptions tell readers?
The registry includes assumptions for a planning illustration based on the observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes planning for specified fractions of the observed effect. These are planning assumptions, not results from the trial's enrollment or evidence about the reliability of the observed effect. The actual observed effect and planning counts are not reported in the registry record, so no planning quantity can be interpreted from the listed assumptions alone.
In general, a sample-size calculation estimates how many observations a future design might require under stated assumptions. It is not observed power, and it does not establish whether a study has answered its question. The planning illustration's equal-allocation assumption also differs from the recorded single-group, fixed-sequence design; it should not be mistaken for the way participants were assigned in this trial. No trial-specific sample-size justification or design calculation is reported in the registry record.
What remains unspecified?
The record does not report a detailed model, the exact analysis contrast, handling of incomplete repeated measurements, or checks of statistical assumptions. These details are needed to evaluate whether the method appropriately reflects the paired treatment periods and repeated outcome measurements. Without numerical results and analytic details, statistical interpretation must remain focused on what the registry documents: a prespecified outcome concept, a fixed infusion order, repeated monitoring, and an excluded participant.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure and one analysis. This describes the number of registered outcome and analysis entries, but it does not establish whether the study considered additional outcomes, time points, subgroups, or alternative analytic approaches. A multiplicity adjustment plan, or a statement that no adjustment was needed, is not reported in the registry record.
In general, multiplicity arises when several statistical questions are examined. The more comparisons made, the greater the chance that at least one may appear notable by chance if each is interpreted without regard to the others. A planned hierarchy, adjustment, or clearly defined primary contrast can help readers understand how results were selected and interpreted. The registry does not describe such procedures for this study. The repeated hourly assessment schedule makes the analysis plan particularly relevant, because the record does not say whether the primary comparison used a selected time point, a summary across time, or a model incorporating all readings.
One participant did not complete the valproic acid infusion because of an adverse event and was excluded from the final analysis. The registry does not report how incomplete outcome measurements from this or any other participant were handled, whether measurements from that participant during the placebo period were retained for any analysis, or whether other missing observations occurred. It also does not describe an imputation method or a sensitivity analysis for missing data.
The record therefore does not fully define the analysis population beyond noting this exclusion. It does not state whether the analysis included all participants who began the study, only those completing both infusion periods, or another population definition. These omissions limit assessment of how missingness and the exclusion may affect the primary comparison. The numeric outcome results and a detailed analysis plan are not reported in the registry record.
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 |
|---|---|---|---|
| Valproic Acid | 1 | 13 | 7.7% |
| Placebo | 0 | 13 | 0.0% |
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 |
|---|---|
| Valproic Acid | 0 of 13 |
| Placebo | 0 of 13 |
Most frequent serious adverse event terms
| Event term | Organ system | Valproic Acid | Placebo |
|---|---|---|---|
| rash | Skin and subcutaneous tissue disorders | 1 of 13 | 0 of 13 |
Serious events with the highest arm-level rate: rash (7.7%).
The registry lists 13 participants at risk for serious adverse events in each intervention group. It records one serious adverse event in the valproic acid group and none in the placebo group. Rash is listed among the serious adverse event terms, with 7.7% shown. The record does not describe the event's timing, outcome, or relationship to the infusion in the information available for this summary.
The registry reports no other adverse events in either group. Deaths are not reported in the registry record. These counts describe the recorded safety entries; they do not establish whether an event was caused by an infusion or how the risk compares across treatments. In particular, the fixed sequence and lack of masking mean the groups should not be read as independent, randomized, like-for-like control groups. The one participant who did not complete the valproic acid infusion because of an adverse event was excluded from the final efficacy analysis, according to the record.
In general, safety counts should be read alongside their denominators and the way participants were assigned to conditions. The registry gives the at-risk counts, but does not provide additional detail about event definitions, severity grading beyond the serious-event classification, or adjudication procedures. The recorded counts are descriptive and should not be treated as a precise estimate of comparative safety.
12. What the Result Does, and Does Not, Mean
The record describes a study designed to assess whether SPR changed between placebo and valproic acid infusion periods. It defines how SPR was derived from responses to intermittent photic stimulation and specifies repeated monitoring during the infusion period. These details explain the study question and measurement procedure, but they do not report what happened to the measured outcome.
The numerical primary result is not reported in the registry record. There is no reported mean difference, confidence interval, or p-value for the comparison. As a result, readers cannot determine from this record whether the observed SPR values were higher or lower under either condition, how large any difference was, or how precisely it was estimated. The outcome scale alone cannot fill in those missing results.
The design also limits what a difference could establish. All participants received placebo on day 1 and valproic acid on day 2, with no masking. An observed change could be associated with the different infusion condition, but the fixed order means that condition and period occur together. The registry does not report a method that separates these influences. This is a design consideration, not evidence that a particular bias occurred.
The study enrolled 13 participants, and one participant did not complete the valproic acid infusion because of an adverse event and was excluded from the final analysis. The record does not describe all missing-data handling or the exact analysis population. Those details are important for understanding which observations contributed to any comparison, especially when the endpoint is measured repeatedly.
Accordingly, the registry record supports a careful account of the study design, the endpoint definition, and the reported safety counts. It does not support a conclusion about the direction, magnitude, precision, or clinical importance of the primary outcome. Such conclusions require numerical results and sufficient analysis detail, neither of which is reported for the primary endpoint in the registry record.
13. Why This Trial Matters Statistically
This study raises a useful statistical issue: a design can collect repeated measurements under two conditions in the same participants, yet still leave important interpretive questions when treatment order is fixed. The registry states that placebo was given on day 1 and valproic acid on day 2. That structure makes it important to distinguish change associated with the infusion condition from change associated with the passage of time or the order of measurement. The record does not describe an analysis that separates those possibilities.
The endpoint also illustrates why measurement definitions and outcome results serve different purposes. SPR is defined through responses to 14 predetermined flash frequencies and ranges from 0 to 14. This makes the intended outcome understandable, but the scale description does not reveal participants' measured values. Without the estimated difference and an uncertainty measure, readers cannot evaluate either the size or precision of the result.
Repeated hourly assessments create another general methods question: how should measurements from the same person over time be summarized and analyzed? In general, those readings are correlated, and an appropriate analysis should account for the structure of the observations. The registry provides the measurement schedule but does not specify a statistical model or a method for combining readings. This illustrates why a transparent analysis plan is important for interpreting a repeated-measures endpoint.
Finally, the record notes an adverse-event-related infusion discontinuation and exclusion from the final analysis. That detail connects safety and efficacy interpretation: an exclusion can affect which observations contribute to an outcome comparison, while the registry does not explain the missing-data approach. The study is therefore informative as an example of the questions analysts should ask about treatment order, repeated observations, analysis populations, and reporting completeness, without allowing a result to be inferred where the numerical outcome is not reported.
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 main limitation for interpreting the primary outcome is that its numerical result is not reported in the registry record. The record does not give the mean SPR in either infusion condition, the estimated difference, a measure of uncertainty, or a statistical test result. The clinical direction and precision of the outcome therefore cannot be assessed.
The treatment sequence was fixed for all participants, with placebo on day 1 and valproic acid on day 2. Allocation is listed as not applicable, and masking as none. These features make treatment condition coincide with order and period. The record does not describe randomization, counterbalancing, or an analysis addressing possible order or period effects. Such effects are general interpretive concerns; the record does not report that they occurred.
The endpoint involved repeated assessment at the start of monitoring and hourly for 12 hours, yet the statistical method used for those observations is not reported. The record does not state whether the comparison used each participant's change, selected time points, a summary measure, or a repeated-measures model. It also does not report the assumptions underlying the analysis or how within-participant correlation was handled.
One participant did not complete the valproic acid infusion because of an adverse event and was excluded from the final analysis. The record does not explain the handling of incomplete measurements, define the full analysis population, or report sensitivity analyses for missing data. Participant characteristics and additional details about eligibility are also not reported in the registry record.
Finally, the registry does not report a detailed multiplicity plan or a trial-specific sample-size justification. The planning assumptions listed for an illustration do not give a numerical planning result in the record and do not change the actual single-group, fixed-sequence design. These gaps limit evaluation of the analysis and the strength of any inference from the study.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effect of Valproic Acid Concentration on Photic Response — NCT00609245.
- Registry record last updated 2017-06-14; status last verified 2017-05.
- Results first posted 2017-06-14.
- 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
NCT00609245 is a completed phase 4, single-group study sponsored by Vanderbilt University Medical Center. It enrolled 13 participants with photosensitive epilepsy. The record describes placebo on day 1 followed by valproic acid infusion on day 2, with no masking and no randomized allocation.
The primary outcome was the difference in standard photosensitive range during the two infusion conditions. SPR was based on responses to 14 predetermined flash frequencies and ranged from 0 to 14. Measurements were planned at the start of monitoring and hourly for 12 hours. One participant did not complete the valproic acid infusion because of an adverse event and was excluded from the final analysis.
The registry records one serious adverse event in the valproic acid group and none in the placebo group; rash is listed at 7.7%. Numerical primary outcome results and detailed analysis methods are not reported in the registry record.