Cognitive Effects of Treatment of Interictal Discharges: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cognitive Effects of Treatment of Interictal Discharges (NCT00916149), a non-randomized na study. The primary outcome is Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment.

2. Clinical Question

3. Trial Design

The registry describes a completed, parallel, non-randomized study with no masking. Its stated purpose was to investigate whether levetiracetam, for patients with focal seizures, or lamotrigine, for patients with generalized seizures, reduces interictal discharges, and whether discharge reduction may be related to cognitive performance. The registry lists an enrollment of 31.

The arm descriptions outline treatment groups based on discharge type and frequency. The levetiracetam description refers to 12 people with epilepsy, split between infrequent and frequent focal epileptiform discharges. The lamotrigine description refers to 12 people with epilepsy, split between infrequent and frequent generalized discharges. A no-treatment group is described as 15 healthy subjects. These are descriptions of the planned groups; they should not be treated as the numbers included in every analysis. The preliminary primary analysis instead refers to 11 healthy controls and 6 subjects with partial-onset epilepsy.

EEG and cognitive testing were scheduled before and after treatment. The primary endpoint description gives the timeframe as 1 and 11 weeks. This design permits description of within-person change over time, but non-random allocation and differences between the clinical groups and healthy controls limit direct comparisons between arms. No masking means that participants and study staff were not blinded according to the registry. Further details on allocation procedures, eligibility criteria, adherence, and the statistical plan are not reported in the registry record.

The record lists 32 outcome measures and 60 analyses. This breadth matters when interpreting any individual finding: the registry does not report how outcomes or analyses were prioritized beyond identifying the primary endpoint.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: In a preliminary analysis, data from 11 healthy controls and 6 subjects with partial-onset epilepsy were evaluated.

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: 16 controls enrolled in "no treatment"; 1 subject did not perform tests due to vision loss and difficulty placing EEG leads. Hence, there are 15 subjects in the "no treatment" arm. We were unable to recruit any subjects with generalized epilepsy and frequent discharges, hence we did not complete the analysis of this arm as planned.

6. Primary Endpoint

The registry lists the primary outcome as Mean Change in Focal Interictal Discharges (IEDs) Per Hour, Pre to Post Treatment, measured over 1 and 11 weeks.

The primary endpoint is mean change in focal interictal discharges (IEDs) per hour, measured before and after treatment. An IED is an EEG discharge occurring between clinical seizures. The registry’s primary endpoint description focuses on levetiracetam treatment in subjects with epilepsy and no treatment in healthy controls; it does not describe this endpoint as a comparison involving the lamotrigine group.

Measuring discharge rate per hour gives a rate-based description of EEG activity over the recording period. A pre-to-post change can characterize whether the recorded rate differs after treatment within the people assessed. The registry specifies a mean and standard deviation, and gives the assessment timeframe as 1 and 11 weeks. A mean summarizes the average change in the analyzed group, while the standard deviation describes the spread of individual changes around that average. These are descriptive summaries; without reported values, they do not establish the size or direction of change.

The endpoint is relevant to the study’s stated question about whether treatment affects interictal discharges. The study also investigates a possible relationship between discharge reduction and cognitive performance, but an EEG change alone would not establish that cognitive performance changed in parallel. Numerical means, standard deviations, and other endpoint results are not reported in the registry record. The cognitive outcomes are listed separately as secondary measures.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a continuous measure: change in focal IED rate per hour. The registry identifies the summary as a mean and its dispersion as a standard deviation. It describes an analysis before and after treatment, with the stated timeframe of 1 and 11 weeks. These details identify the kind of quantity intended, but the statistical test, model, and numerical estimates are not reported in the registry record.

What does a mean change describe?

In general, a mean change summarizes the average difference between a participant’s measurement at two assessment times. It can be useful when the scientific question concerns change over time rather than a single measurement. The mean does not show whether all participants changed in a similar way: individual changes may vary, and positive and negative changes can offset one another in the average. The registry’s standard deviation is a measure of that spread, not a measure of uncertainty in the mean.

For repeated measurements, the observations from the same participant are related. General statistical methods for paired measurements account for that relationship when estimating uncertainty or testing a change. The record does not identify whether a paired test, regression model, or another method was used. It also does not report how the hourly rate was calculated from EEG recordings, how recordings were reviewed, or how variability in recording duration and scoring was handled.

How should uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with the data and the method’s assumptions. Its width conveys precision: a narrower interval indicates greater precision than a wider interval. A point estimate without an interval can leave substantial uncertainty about the size and direction of the underlying effect. No confidence interval or other numerical uncertainty estimate for the primary endpoint is reported in the registry record.

A p-value, when used, addresses how compatible the observed data are with a specified statistical model and null hypothesis. It does not measure the probability that a treatment works, and it does not establish the importance of an effect. The primary endpoint entry does not report a p-value or state the hypothesis test. The statistical analysis plan, including any model adjustments, is not reported in the registry record.

Why does the comparison structure matter?

In general, random allocation helps balance measured and unmeasured characteristics between treatment groups on average. This study is explicitly non-randomized. Further, the described treatment groups and healthy controls differ in clinical status and in the type of discharges being studied. Consequently, an observed contrast between the groups would not, by itself, isolate a treatment effect. The registry also states that the arms are not a like-for-like control comparison. The record does not report an adjusted analysis that would address these differences.

The pre-to-post format can describe change among those assessed, but a before-and-after comparison is not automatically a causal comparison. In general, changes may reflect influences over time in addition to treatment. A concurrent control may help with interpretation only when the groups are suitably comparable and the analysis supports the intended contrast. The no-treatment group is described as healthy controls, not as an untreated group with the same epilepsy characteristics as the treated participants.

What do the planning illustrations mean?

General sample-size illustrations estimate the number of participants needed under specified assumptions to detect a target effect. The registry’s stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. These are planning assumptions, not a report of how the study was designed or powered. The registry does not report its own sample-size justification. Any such illustration is not observed power and should not be read as evidence that the study had adequate power to detect its actual effect.

The registry notes that time-to-event planning tables use a total number of events, while other planning tables give participants per arm. This primary endpoint is continuous rather than time-to-event. No numerical planning count or fraction is reported in the registry record, so those values cannot be interpreted from the record. More generally, a planning calculation depends on assumptions about the target effect and variability; it does not substitute for observed effect estimates and uncertainty intervals.

The record’s listing of 32 outcome measures and 60 analyses also raises a general methods issue. When many outcomes or analyses are considered, chance findings become more likely unless analysis priorities and multiplicity procedures are addressed. The record does not state a multiplicity strategy or identify which analyses were prespecified beyond naming the primary endpoint. It also does not report the inferential methods used for secondary cognitive outcomes.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("No Treatment", "Levetiracetam")
n   <- c(11, 6)
m   <- c(-28.8, 0.54)
sp  <- c(71.8, 1.44)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  No Treatment  11  -28.800  71.800  -77.036  19.436
CARM  Levetiracetam  6  0.540  1.440  -0.971  2.051

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 32 outcome measures and 60 analyses. It names a primary endpoint and lists secondary cognitive measures, including CVLT learning and recall measures, BVMT-R learning and recall measures, and QOLIE. The record does not explain how the primary endpoint was distinguished from the broader set of outcomes for analysis or reporting, beyond its designation as primary.

When many outcomes or analyses are examined, some results may appear notable by chance. In general, a prespecified analysis hierarchy or multiplicity adjustment can help readers understand how to interpret multiple statistical tests. Whether either approach was used is not reported in the registry record. Numerical results for the secondary cognitive measures are also not reported, so their direction, size, and precision cannot be assessed.

Missing-data procedures are not reported in the registry record. The record does not state how incomplete EEG recordings, missed cognitive assessments, withdrawals, or other unavailable measurements were handled. Nor does it describe imputation, sensitivity analyses, or reasons for missing data. Without this information, the extent to which the analyzed participants represent those enrolled cannot be assessed.

The preliminary primary analysis identifies 11 healthy controls and 6 subjects with partial-onset epilepsy. The registry does not give a general analysis-population definition for each outcome, such as which participants were included in each analysis or how treatment discontinuation was handled. It also does not report a statistical analysis plan. These omissions limit assessment of selective reporting, missing-data bias, and the consistency of analysis populations across outcomes.

12. 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 non-serious adverse event terms

The adverse-event record reports serious adverse events in the at-risk groups as 0 for levetiracetam, 0 for lamotrigine, and 0 for no treatment. Deaths are also reported as 0 in each group. The stated numbers at risk for serious adverse events are 8 for levetiracetam, 5 for lamotrigine, and 12 for no treatment.

For other adverse events, the record reports 0 for levetiracetam, 1 for lamotrigine, and 1 for no treatment. The corresponding numbers at risk are 8, 5, and 12. These are registry counts, not rates; no percentages or comparative risk estimates are reported. The adverse-event numbers at risk do not necessarily describe the analysis populations for the EEG endpoint, and the registry does not explain how they relate to the arm descriptions.

Zero reported serious events does not establish that an intervention is free of risk. The counts are limited to the participants and events represented in this registry record, and the record does not provide event narratives, severity details for the other events, or additional information about ascertainment. These safety figures should be read as reported counts rather than as evidence that the groups had equivalent safety.

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

The record describes a study designed to examine whether treatment is associated with changes in interictal discharges and whether those changes may relate to cognitive performance. It identifies levetiracetam as the treatment in the primary focal-discharge analysis, describes a no-treatment healthy-control group, and names a separate lamotrigine group for generalized discharges. It also specifies the primary measure and assessment timeframe.

Those design details do not provide the result. The primary mean change and its standard deviation are not reported in the registry record, nor are numerical estimates of uncertainty or a test result. The record therefore does not establish the direction, magnitude, or precision of a change in focal IED rate. It also does not report numerical cognitive outcomes or a result for the proposed relationship between EEG change and cognition.

Even if numerical group differences were available, the non-randomized design and unlike comparison groups would limit causal interpretation. The people receiving treatment had epilepsy and were grouped according to discharge characteristics, whereas the no-treatment controls are described as healthy subjects. An observed difference could reflect group composition or other factors, as well as treatment. The record does not report an analysis that resolves those concerns.

The listed adverse-event counts describe events recorded among the stated at-risk groups. They do not establish comparative safety, particularly without fuller event details and uncertainty estimates. Likewise, a planning illustration based on an observed effect would not be a finding about treatment efficacy, and would not represent observed power.

The most defensible conclusion is about the registry record itself: it documents the study question, design, endpoint, and some safety counts, but does not report the numerical efficacy results needed to judge the primary endpoint or cognitive outcomes. It cannot support a conclusion that treatment does or does not reduce discharges, or that discharge changes do or do not correspond to cognitive changes.

14. Why This Trial Matters Statistically

This study raises a useful statistical question: how should repeated EEG measurements and cognitive assessments be interpreted when treatment groups are selected by clinical characteristics and compared with healthy controls? Its endpoint is a pre-to-post change in a continuous rate, and its stated aim includes a possible association between EEG change and cognitive performance. Those questions require more than identifying an outcome; they depend on how change, uncertainty, and group differences are analyzed.

The non-randomized design makes the distinction between descriptive change and causal effect especially important. A mean change can describe what happened among assessed participants, but it does not automatically answer what would have happened without treatment in comparable people. The control group’s healthy status and the treatment groups’ differing discharge types further complicate direct contrasts. The registry itself cautions that the arms are not a like-for-like comparison.

The record also illustrates why outcome planning and transparent reporting matter. It lists 32 outcome measures and 60 analyses, while reporting no numerical primary endpoint results or secondary cognitive results. Without estimates and uncertainty, readers cannot judge precision, direction, or consistency. Without a stated multiplicity approach and analysis plan, readers cannot assess how multiple analyses were handled.

Finally, the stated planning assumptions clarify that sample-size illustrations are conditional planning exercises, not evidence of study power or findings. Their interpretation depends on the target effect and other assumptions. This distinction is broadly important in clinical research: an analysis can be informative about measurement and design even when the record does not provide enough numerical results to answer the treatment question.

15. Limitations

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

The main limitation for interpreting efficacy is that numerical results for the primary endpoint are not reported in the registry record. The record gives no mean change, standard deviation, confidence interval, or test result. Numerical results for the listed cognitive measures are also not reported. As a result, neither the size nor the precision of any EEG or cognitive change can be assessed.

The non-randomized allocation limits causal interpretation. The registry describes treatment groups with epilepsy and a no-treatment group of healthy controls, and explicitly says the arms are not a like-for-like comparison. The focal-discharge primary analysis is described separately from the generalized-discharge lamotrigine group. These features mean that comparisons across groups may reflect differences in participants or discharge characteristics in addition to treatment.

The preliminary analysis population is stated as 11 healthy controls and 6 subjects with partial-onset epilepsy, while the arm descriptions and adverse-event summaries refer to other group counts. The registry does not explain the relationship among these populations or identify the analysis population for each outcome. This makes it difficult to determine how broadly each analysis applies.

The record does not report details of the statistical analysis plan, missing-data handling, multiplicity procedures, or the methods used to analyze repeated measurements. It also does not report details about EEG scoring, adherence, or the handling of incomplete recordings. The absence of these details prevents assessment of important sources of uncertainty and potential bias. The safety record provides counts but no event descriptions or comparative estimates. These limitations apply to interpretation of the registry record; they do not establish what unreported analyses may have found.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cognitive Effects of Treatment of Interictal Discharges — NCT00916149.
• Registry record last updated 2018-10-03; status last verified 2018-09.
• Results first posted 2018-08-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00916149, titled Cognitive Effects of Treatment of Interictal Discharges, is listed as completed. The registry gives a start date of 2007-01, primary completion of 2012-10, and enrollment of 31. Massachusetts General Hospital is identified as the sponsor. The study is described as non-randomized, parallel, and unmasked, with epilepsy among its conditions.

The interventions are levetiracetam and lamotrigine, alongside a no-treatment healthy-control group. The primary endpoint is mean change in focal IEDs per hour before and after treatment, with the timeframe stated as 1 and 11 weeks. The primary endpoint description refers to a preliminary analysis of 11 healthy controls and 6 subjects with partial-onset epilepsy. The record lists 32 outcome measures and 60 analyses, but numerical primary and cognitive outcome findings are not reported in the registry record.