A Study of V950 in People With Alzheimer Disease (V950-001 AM7): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of V950 in People With Alzheimer Disease (V950-001 AM7) (NCT00464334), a randomized phase 1 study. The primary outcome is Number of Participants Who Experienced at Least One Adverse Event.

2. Clinical Question

The study’s stated purpose was to test the safety, tolerability and immune response to V950, with or without ISCOMATRIX™. The primary outcome posted in the registry addresses adverse events; it does not itself report an immune-response result. The record describes the study as randomized, double-blind, placebo-controlled and dose-escalating. Its listed enrollment is 86 participants.

The clinical question is broader than whether a particular dose or formulation differs from placebo. The registry lists several V950 and ISCOMATRIX™ combinations, alongside two placebo formulations, and reports the number of participants with at least one adverse event in each group. The results therefore describe event counts across these groups. They do not, on their own, establish a comparative effect or explain whether individual events were considered related to study treatment.

3. Trial Design

The registry describes NCT00464334 as a randomized, double-blind, parallel-group Phase 1 study. It is titled “A Study of V950 in People With Alzheimer Disease (V950-001 AM7).” The official title describes evaluation of safety, tolerability and immunogenicity for V950 formulated on aluminum-containing adjuvant, with or without ISCOMATRIX™. The listed sponsor is Merck Sharp & Dohme LLC.

Enrollment is listed as 86. The registry lists 11 groups: two placebo groups and nine V950 groups. The V950 amounts are 0.5 mcg, 5 mcg and 50 mcg; the listed ISCOMATRIX™ amounts vary by group. The two placebo groups are labeled 0 mcg and 16 mcg of IMX. Each group description specifies a 0.5 mL intramuscular injection at Months 0, 2 and 6.

The primary endpoint population consists of participants who received at least one dose of vaccine. The primary outcome counts those participants who experienced at least one adverse event, with a timeframe of up to 4 years after the first dose. The registry defines an adverse event as an unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study-drug use, regardless of whether it was considered related to the product.

The study is marked completed. Its listed start is 2007-03, and primary completion is listed as 2012-01. The randomization method, allocation concealment, detailed masking procedures, dose-escalation rules and the protocol’s statistical plan are not reported in the registry record. The record also does not describe how participants were assigned across the 11 groups or whether group sizes were intended to be equal.

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.

Only the first 6 of 11 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Population consists of all participants who received at least one dose of vaccine.

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.

Only the first 6 of 12 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced at Least One Adverse Event, measured over Up to 4 years after first dose of vaccine.

The primary endpoint is the number of participants who experienced at least one adverse event. It is a participant count: each person is counted according to whether they had one or more qualifying events during the specified follow-up, rather than according to the total number of events they experienced. The timeframe is up to 4 years after the first vaccine dose.

The registry’s adverse-event definition is broad. It covers an unfavorable and unintended change in body structure, function or chemistry that is temporally associated with study-drug use, whether or not it is considered related to the product. Thus, the endpoint does not distinguish by itself between events judged related and events judged unrelated. It also does not characterize event severity, duration or clinical course.

Counting participants with at least one event is useful in safety reporting because it gives a direct account of how many people in each group had an event during the stated follow-up. It is different from counting all events: a participant with multiple events still contributes once to this endpoint. The registry reports the group sizes and participant counts for this outcome, but does not provide confidence intervals or comparative analyses for the endpoint. The primary endpoint should therefore be read as descriptive counts, not as a standalone estimate of a treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is described as randomized, double-blind and parallel-group. Randomization is a design method intended, in general, to reduce systematic differences between treatment groups at the start of a study. Double blinding generally means that treatment assignment is concealed from participants and specified study personnel, although the registry record does not state exactly who was blinded or how masking was maintained. A parallel-group design assigns participants to a group that receives its assigned intervention rather than having each participant receive every intervention in sequence. These general descriptions explain the design labels; the detailed procedures are not reported in the registry record.

What does the primary outcome count?

The primary outcome is binary at the participant level: a participant either experienced at least one adverse event during the stated timeframe or did not. The posted values are counts of participants with an event, alongside the number of participants in each group. The endpoint is not a count of every event. If a participant had more than one adverse event, the endpoint still counts that participant once. The registry’s defined population includes all participants who received at least one vaccine dose.

General statistical explanation: binary outcomes are often described using counts and proportions. A count is easiest to interpret alongside its group denominator, because the same count can have different meanings in groups of different sizes. For this endpoint, the registry posts both quantities, but no confidence intervals or formal comparisons. The results can therefore be read as observed participant counts without treating them as precise estimates of an underlying event probability.

What would a confidence interval add?

General statistical explanation: a confidence interval is a range of values that conveys the uncertainty of an estimate under a specified statistical method. For a comparison between groups, it can show which differences are compatible with the observed data and how imprecise the estimated contrast may be. A point estimate alone does not communicate that uncertainty. The registry record does not report confidence intervals for the primary outcome, so the precision of comparative estimates cannot be assessed from the posted results.

Why does the study have several groups?

The registry lists multiple V950 dose and ISCOMATRIX™ combinations, as well as two placebo groups. Such a multi-group structure can describe outcomes across different formulations, but it also creates multiple possible comparisons. The record does not report a prespecified comparison hierarchy, a statistical plan for those comparisons, or a method for controlling the chance of false-positive findings across multiple tests. No analyses are listed for the primary outcome, so the counts should not be mistaken for results of a set of formal statistical tests.

How should sample-size illustrations be understood?

General statistical explanation: a sample-size calculation for a future study depends on assumptions about the effect to detect, the significance level, allocation between groups and the statistical method. A planning illustration is not a measure of the probability that the completed study detected an effect. The stated assumptions for planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect expressed as a fraction of an observed effect. Those are planning assumptions, not evidence that the original trial was designed using them. The trial’s own sample-size justification is not reported in the registry record.

For an event-count outcome, the underlying analysis also needs to specify how the event is defined, which participants are included, and how incomplete observations are handled. The registry supplies a primary population definition based on receipt of at least one dose, but the details of any analysis population beyond that definition are not reported. No statistical model, adjustment variables, missing-data method, or interim-analysis approach is reported in the registry record.

General statistical explanation: over-dispersion is relevant when a model for counts assumes less variability than is present in the data. It can make standard errors too small if the extra variability is ignored. The primary outcome in this record is not a total event count or a rate of repeated events; it is the number of participants with at least one event. No count model or over-dispersion adjustment is reported for this endpoint. Consequently, over-dispersion should not be inferred from the posted participant counts.

The sponsor’s statistical analysis, if any, is not included among the posted primary outcome analyses. The registry’s record gives descriptive outcome data rather than a reported inferential analysis. Statistical methods that might be appropriate for other questions cannot be assumed to have been used in this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Placebo to V950/ IMX 0 mcg", "Placebo to V950/ IMX 16 mcg", "V950 0.5 mcg / IMX 0 mcg", "V950 0.5 mcg / IMX 16 mcg", "V950 0.5 mcg / IMX 47 mcg", "V950 0.5 mcg / IMX 94 mcg")
n      <- c(5, 13, 8, 8, 7, 7)
events <- c(4, 11, 7, 8, 6, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Placebo to V950/ IMX 0 mcg  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Placebo to V950/ IMX 16 mcg  13  11  84.6  54.6  98.1  57.8  95.7  57.2  95.3
ARM  V950 0.5 mcg / IMX 0 mcg  8  7  87.5  47.3  99.7  52.9  97.8  51.8  97.2
ARM  V950 0.5 mcg / IMX 16 mcg  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  V950 0.5 mcg / IMX 47 mcg  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8
ARM  V950 0.5 mcg / IMX 94 mcg  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The study lists many intervention groups and two placebo groups, creating several possible ways to compare outcomes. The registry record does not report which comparisons were planned as primary, whether any comparisons were prioritized, or whether a multiplicity adjustment was used. Multiplicity refers, in general, to the increased chance of at least one false-positive result when many statistical tests are conducted. No primary outcome analyses are listed, so there are no posted hypothesis-test results to interpret or adjust.

The registry defines the primary endpoint population as all participants who received at least one dose of vaccine. It does not report a separate intention-to-treat population, per-protocol population, or other analysis-population definition. Although group sizes and event counts are posted, the record does not explain the handling of participants with incomplete follow-up or missing endpoint assessments. A missing-data method, imputation approach, or sensitivity analysis is not reported in the registry record.

The endpoint timeframe is up to 4 years after the first dose. The record does not provide a schedule of adverse-event ascertainment, the amount of follow-up available for each participant, or details about how events after discontinuation were handled. The registry also does not report interim analyses or stopping rules. These omissions prevent a fuller assessment of how multiplicity and incomplete observation may have been addressed in the trial’s analysis.

General statistical explanation: multiplicity and missing data concern different sources of uncertainty. Multiplicity concerns the interpretation of repeated statistical tests; missing data concern outcomes that are not observed or not included. The available record does not provide enough methodological detail to determine how either issue was handled beyond the endpoint population definition.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: arrhythmia (25.0%), contusion (20.0%), depression (20.0%), orthostatic hypotension (20.0%), cardiac arrest (14.3%).

The registry separately reports participants affected by serious adverse events and participants with other adverse events. For serious adverse events, the affected counts and group sizes are: Placebo to V950/IMX 0 mcg, 1 of 5; Placebo to V950/IMX 16 mcg, 0 of 13; V950 0.5 mcg/IMX 0 mcg, 2 of 8; V950 0.5 mcg/IMX 16 mcg, 2 of 8; V950 0.5 mcg/IMX 47 mcg, 3 of 7; V950 0.5 mcg/IMX 94 mcg, 1 of 7; V950 5 mcg/IMX 0 mcg, 4 of 9; V950 5 mcg/IMX 16 mcg, 1 of 8; V950 5 mcg/IMX 47 mcg, 2 of 8; V950 50 mcg/IMX 0 mcg, 1 of 5; and V950 50 mcg/IMX 16 mcg, 0 of 8.

These are participants affected, not necessarily the total number of serious events. The registry also lists serious-event terms and percentages: Arrhythmia, 25.0%; Contusion, 20.0%; Depression, 20.0%; Orthostatic hypotension, 20.0%; Cardiac arrest, 14.3%; and Dysphagia, 14.3%. The denominator and further context for these percentages are not reported in the registry record, so they should not be used as group-specific risks. Death counts are not reported in the registry record.

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

The posted results establish that the registry recorded participants with at least one adverse event in each listed group, and it gives the corresponding group counts. They also give separate counts of participants affected by serious adverse events. These are descriptive findings for a Phase 1 study with multiple listed formulations and small group sizes.

The counts do not establish that any formulation caused or prevented an adverse event. The primary definition includes events whether or not they were considered related to the product, and the registry does not provide a treatment-related breakdown for the primary endpoint. Nor do the counts show the severity, duration, recurrence or clinical course of all events. The separate serious-event counts give one additional dimension of safety reporting, but do not replace event-level descriptions or an analysis of comparative risk.

The results also do not establish that groups are alike. A lack of reported statistical comparisons is not evidence of equivalence, and the registry does not report confidence intervals to show the precision of possible comparisons. With group sizes ranging from 5 to 13, the descriptive counts alone provide limited information about how well the results would generalize beyond the participants enrolled.

The study’s stated aims included immune response, but no secondary outcomes are posted in the registry record. The primary adverse-event endpoint therefore cannot answer questions about immune response. It likewise does not provide evidence about clinical benefit or disease progression. No conclusion about those outcomes can be drawn from the posted primary safety counts.

In general, a clinical trial result is interpreted in light of its outcome definition, comparison plan, uncertainty, follow-up and analysis population. For this record, the endpoint definition and eligible primary population are stated, but several details of analysis and follow-up are not. The appropriate reading is consequently narrow: these are the recorded participant counts for the specified adverse-event outcomes, not a definitive comparative safety estimate or a complete account of every study objective.

14. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a binary safety endpoint with a multi-group dose and formulation structure. The primary result counts participants who experienced at least one adverse event, rather than counting every event. That distinction matters: a participant-level endpoint answers how many people were affected, while total event counts would answer a different question about recurrence or event burden.

It also illustrates why denominators and uncertainty matter when reading small-group results. The registry reports group sizes and affected-participant counts, but no confidence intervals or comparative analyses. A count can be stated exactly as observed while still leaving substantial uncertainty about the underlying event frequency or differences between groups. Statistical interpretation should not turn the visible counts into an unsupported ranking of formulations.

The design includes two placebo groups and several combinations of V950 dose and ISCOMATRIX™ amount. Multiple groups create multiple possible comparisons, which makes the planned comparison strategy important. That strategy and any multiplicity approach are not reported in the registry record. Without them, the descriptive endpoint results should not be mistaken for confirmatory evidence from a declared set of tests.

Finally, the study’s stated aims are broader than its posted primary endpoint. The record identifies safety, tolerability and immunogenicity as objectives, while the posted primary outcome counts adverse events and no secondary outcomes are posted. This makes a useful distinction between the question an endpoint can answer and the broader aims of a trial. Statistical claims should stay within the outcome and analysis information actually recorded.

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 primary endpoint is broad and counts participants with at least one adverse event regardless of whether the event was considered related to study treatment. The posted result does not distinguish related from unrelated events, and it does not show the number of events per participant, their duration, severity or course. This limits how much can be inferred from the primary count about the nature of the safety experience.

The group sizes are small, ranging from 5 to 13 participants, and the study has 11 listed groups. The registry reports no confidence intervals or primary outcome analyses. As a result, the precision of comparisons cannot be evaluated from the posted results, and the counts should not be interpreted as definitive evidence of differences or similarity between formulations.

The record does not report the randomization sequence, allocation concealment, detailed masking procedures, planned comparisons, statistical model, sample-size justification, interim analyses or stopping rules. It also does not explain how missing endpoint data or incomplete follow-up were handled. These omissions limit assessment of the trial’s analysis methods and the completeness of the safety information.

The primary outcome timeframe extends up to 4 years after the first dose, but the registry does not report participant-level follow-up duration or the timing and frequency of adverse-event assessments. Death counts are not reported in the registry record. Although the study’s stated purpose includes immune response, no secondary outcomes are posted, so the registry results do not characterize that objective.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of V950 in People With Alzheimer Disease (V950-001 AM7) — NCT00464334.
• Registry record last updated 2015-09-25; status last verified 2015-09.
• Results first posted 2012-12-18.
• 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

NCT00464334 is a completed, randomized, double-blind, parallel-group Phase 1 study of V950 in people with Alzheimer disease. The listed enrollment is 86. It includes two placebo groups and nine groups receiving V950 at different doses, with different amounts of ISCOMATRIX™. The registry describes 0.5 mL intramuscular injections at Months 0, 2 and 6.

The primary endpoint counts participants who experienced at least one adverse event up to 4 years after their first dose; the defined population includes participants who received at least one dose. Group-specific counts are posted, along with separate serious adverse-event counts. The record lists no primary outcome analyses and no secondary outcomes. Comparative estimates, confidence intervals, statistical methods for missing data, and the study’s sample-size justification are not reported in the registry record.