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 Booster Dose (50 µg) of Recombinant Ricin Toxin Vaccine (RVEc™) in Previously Vaccinated Healthy Adults (NCT01846104), a na phase 1 study. The primary outcome is Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01846104 |
| Phase | Phase 1 |
| Condition | Ricin Poisoning |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | U.S. Army Medical Research and Development Command |
| Results posted | Yes |
2. Clinical Question
Population
Healthy adults previously vaccinated with RVEc were eligible for this booster study. Participants were recruited from a cohort that had received three 50-μg doses in a prior Phase 1 trial, NCT01317667. The study enrollment was 4.
Intervention
Participants received a single 50-μg booster dose of RVEc, a recombinant ricin toxin A-chain vaccine. The registry record describes administration of one dose and identifies safety and immunogenicity as the study purpose.
Comparator
There was no separate comparator group. The registry describes a single-group study, with allocation listed as not applicable. The study therefore does not provide a randomized, concurrent comparison with an unvaccinated group, another vaccine dose, or placebo.
Primary question
The primary endpoint counted vaccinated participants who experienced adverse events by nature and severity over six months. Secondary outcomes concerned participants reaching specified total ELISA IgG and toxin-neutralizing antibody titer thresholds. The registry record does not report results for those secondary outcomes.
The central statistical question is descriptive: what adverse-event counts were recorded among this small group after a booster, and how much can those counts establish about safety? The posted serious-adverse-event count is zero among 4 participants at risk; the count for other adverse events is 4 among 4 at risk. These are participant counts, not a complete description of event frequency, timing, or clinical detail. The record does not provide a comparison group that could help separate events associated with vaccination from events that would occur in the absence of the booster.
Immunogenicity is part of the stated study purpose, but the available record identifies antibody thresholds rather than reporting the numbers of participants who reached them. Thus, the record supports discussion of the intended questions and the posted safety counts, but not a conclusion about the antibody response or a comparative treatment effect.
3. Trial Design
This was a completed Phase 1, single-group study of a 50-μg RVEc booster in previously vaccinated healthy adults. Enrollment was 4. Participants came from a cohort that had received three 50-μg RVEc doses in an earlier Phase 1 study. The booster study began on 2013-04-30, and primary completion was recorded as 2013-06-30. The sponsor was the U.S. Army Medical Research and Development Command.
The intervention was a single booster dose. The registry lists allocation as not applicable and masking as none. There was no concurrent control arm, so the design is not a randomized comparison. The recorded safety outcome concerns the number of vaccinated participants who experienced adverse events by nature and severity, with a six-month timeframe. The safety description says the analysis used 4 subjects at every time point except Day 180, for which it used 3 subjects.
The study's stated purpose included both safety and immunogenicity. The secondary outcomes were counts of participants who developed total ELISA IgG titers at least 1:500 and TNA anti-ricin toxin-neutralizing antibody titers at least 1:50. The registry record lists 3 outcome measures, but does not report the numerical results for these antibody outcomes. It also lists no analysis records.
These design features determine the scope of interpretation. The study can describe what was observed among the enrolled participants, but it cannot estimate a randomized contrast against a control condition. The small group also means that participant-level counts can change substantially in response to even a small number of additional observations. The registry record does not report the protocol details, the rationale for the enrollment size, or a statistical analysis plan. It is therefore not possible to establish from the record how outcome definitions, follow-up procedures, or analysis choices were prespecified.
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 | 50-μg Booster Dose RVEc |
|---|---|
| STARTED | 4 |
| COMPLETED | 3 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | 50-μg Booster Dose RVEc |
|---|---|
| Withdrawal by Subject | 1 |
Analysis population for the primary outcome, as defined in the registry: All statistical analysis of safety data was conducted using 4 subjects at every time point except Day 180 (for which there were 3 subjects).
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 | 50-μg Booster Dose RVEc |
|---|---|---|
| Participants analysed | 4 | |
| Age, Continuous | years | 39 (SD 10.03) |
| Sex: Female, Male: Female | Participants | 2 |
| Sex: Female, Male: Male | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Vaccinated Participants Who Experienced Adverse Events by Nature and Severity., measured over Six months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts vaccinated participants who experienced adverse events, classified by nature and severity. Its stated timeframe is six months. An endpoint based on the number of participants affected is a participant-level count: it describes how many people had an event, not necessarily how many separate events occurred. A participant may experience more than one event, so an event count and a count of participants with an event answer different questions.
Safety endpoints are used to organize observations about unwanted events after an intervention. Classifying events by nature and severity can distinguish broad types of experience and levels of seriousness, but the registry's primary-endpoint description does not give a detailed list of event categories or grading rules. Those details are not reported in the registry record. The posted group-level figures include counts for serious and other adverse events, but do not provide the full nature-and-severity breakdown described by the endpoint title.
The endpoint is descriptive in this single-group study. It records events among participants who received the booster, without a concurrent group for comparison. Accordingly, the count alone cannot establish whether an event was caused by the booster. Nor does a participant count by itself describe the timing, duration, recurrence, or clinical course of each event. Those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety figures are counts within a very small single group: 0 of 4 participants at risk had a serious adverse event, while 4 of 4 participants at risk had an other adverse event. These are descriptive observations for this study group. They do not establish the rate expected in a broader population, and the absence of a concurrent comparator prevents a direct estimate of how the booster compares with no booster or another intervention.
A zero count is not proof that the underlying risk is zero. With few participants, an event that is uncommon can fail to appear in the observed group. The information is especially limited for estimating rare outcomes. Conversely, the count of other adverse events indicates that each participant at risk was recorded as affected in that category, but the group summary does not state how many events each participant experienced, what those events were, or how severe they were. The detailed descriptions needed to interpret those counts are not reported in the registry record.
The safety endpoint names a six-month timeframe. The registry description says safety analyses used 4 subjects at every time point except Day 180, when 3 subjects were used. That difference in the number analyzed means the available observations were not identical at every time point. The reason for the smaller Day 180 count, the status of the participant not included at that time, and any approach to missing observations are not reported in the registry record. It would be inappropriate to assume why the count changed.
The study also sought immunogenicity information, with secondary outcomes based on total ELISA IgG and toxin-neutralizing antibody thresholds. Although the thresholds are specified, the numbers of participants reaching them are not reported in the registry record. No antibody result should therefore be inferred from the study purpose or from the safety counts.
The registry lists no analysis records. It does not report inferential comparisons, confidence intervals, or a statistical analysis plan. Without those details, the most defensible reading is a descriptive one: the posted safety summary records no serious adverse events among the participants at risk and records other adverse events for the participants at risk. The precision and generalizability of these observations are limited by the small group and single-group design.
9. Statistical Methods Explained
Statistical interpretation begins with the type of outcome. The primary endpoint is a count of participants who experienced adverse events, so the natural summary is a number of affected participants out of those at risk. The registry reports a serious-adverse-event count of 0 among 4 at risk and an other-adverse-event count of 4 among 4 at risk. These summaries describe participants, not individual event episodes. They should not be read as a count of all events unless the registry explicitly defines them that way.
What does a participant count tell the reader?
A participant count is straightforward to understand, but it leaves important information out. It indicates whether a participant had an event within the category, not how many events that person experienced or when they occurred. If the same participant experienced recurring events, a participant-level count would not distinguish that from a single event. Likewise, a group count does not describe the event's duration, severity details, or relationship to dosing. These details are not reported in the registry record.
For a binary outcome, a proportion can be used to describe the observed fraction affected. In general, statistical uncertainty around a proportion reflects how much the observed group may differ from the population value it is intended to estimate. With a very small sample, that uncertainty can be substantial, even when the observed count is at an endpoint such as none affected or all affected. The registry record does not report confidence intervals or an inferential analysis for these adverse-event counts, so no interval estimate should be attributed to the study.
Why does the lack of a control group matter?
In general, a randomized controlled comparison helps distinguish differences associated with an intervention from differences that could arise for other reasons. This study has one group and no comparator. Its adverse-event counts describe what was recorded after the booster in the enrolled participants, but do not quantify a difference relative to an alternative condition. Events observed after vaccination are not, solely because of their timing, proof of causation. A causal comparison would require a suitable design and analysis that are not present in the registry record.
The record lists allocation as not applicable and masking as none. Those design details should not be replaced with assumptions about concealed allocation, blinded assessments, or a control procedure. Whether the study used detailed standardized event ascertainment beyond what is stated is not reported in the registry record.
How should the time-specific analysis population be read?
The primary outcome description says safety data were analyzed using 4 subjects at every time point except Day 180, for which 3 subjects were used. This is a time-specific analysis-population statement. It does not explain why the count differed at Day 180 or whether the same participants contributed observations at every other time point. In general, changes in the number observed over follow-up can affect interpretation because the composition of the analyzed group may change. The record does not report the reason for the Day 180 count, how missing observations were handled, or whether any sensitivity analysis was undertaken.
Repeated observations from the same participants are also not independent in the way observations from different people may be. General methods for repeated data account for within-participant dependence when estimating uncertainty or comparing time points. The registry record does not describe a repeated-measures method, and no particular method should be assumed. Its posted safety summary is best treated as descriptive unless further analysis details are available.
What can be inferred from the immunogenicity outcomes?
The registry identifies antibody outcomes using thresholds: total ELISA IgG titers at least 1:500 and TNA anti-ricin toxin-neutralizing antibody titers at least 1:50. Such threshold outcomes classify participants according to whether their measured titer reaches a prespecified level. A threshold count does not show the full distribution of titers, the distance of each value from the threshold, or how values changed from before to after the booster. The record does not report the counts or continuous titer results, and it does not report the statistical analyses for these outcomes.
How do planning calculations differ from observed evidence?
General sample-size planning asks how many participants might be needed under stated assumptions to detect a chosen effect with a specified statistical procedure. The planning assumptions associated with this record describe 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 the observed effect. Such calculations are hypothetical planning illustrations, not evidence about the study's observed power. They do not change the actual single-group design, and equal allocation between two arms is not a description of the enrolled study.
The registry record does not report the study's own sample-size justification. It does not report a prespecified target effect or a design calculation for the single-group booster study. A planning illustration based on an observed effect cannot establish that the original study had adequate power, particularly when the trial has no randomized comparator. No numerical planning result is stated in this explanation.
What statistical analysis is documented?
The registry lists no analysis records. It does not specify a model, hypothesis test, confidence-interval procedure, adjustment for repeated measurements, or multiplicity strategy. General statistical methods can describe how such analyses might be conducted, but they cannot be attributed to this study without documentation. The available interpretation should remain tied to the reported participant counts and the stated study design.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures: the primary adverse-event measure and secondary outcomes for total ELISA IgG and TNA anti-ricin toxin-neutralizing antibody thresholds. It does not report a multiplicity strategy, such as whether outcomes were prioritized for confirmatory testing or whether statistical error rates were adjusted across outcomes. No analysis records are listed, so the record does not establish which outcomes were formally tested or how any tests were interpreted.
Multiplicity is a general concern when several outcomes or comparisons are examined. The more questions considered, the greater the chance that at least one result may appear notable by chance if each is assessed separately. This general principle does not imply that any such testing occurred in this study. Since the registry does not report inferential analyses, there are no reported p-values or multiplicity adjustments to interpret.
The safety description states that 4 subjects were used at every time point except Day 180, when 3 were used. This establishes a difference in the number included at that time point, but not its cause. The handling of missing observations, the reason for the change, and any imputation or sensitivity analyses are not reported in the registry record. The record also does not describe a broader analysis-population framework, such as intention-to-treat or per-protocol definitions. The only stated population information is the safety analysis count by time point.
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 |
|---|---|---|---|
| 50-μg Booster Dose RVEc | 0 | 4 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 50-μg Booster Dose RVEc | 4 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 50-μg Booster Dose RVEc |
|---|---|---|
| Injection site pain | General disorders | 3 of 4 |
| Hyper-natraemia | Metabolism and nutrition disorders | 3 of 4 |
| Migrain | Nervous system disorders | 1 of 4 |
| Temporo-mandibular joint syndrome | Musculoskeletal and connective tissue disorders | 1 of 4 |
| Haematuria | Renal and urinary disorders | 1 of 4 |
| Blood creatine phosphor-kinase increased | Investigations | 1 of 4 |
| Vessel puncture site haematoma | General disorders | 1 of 4 |
| Blood urea increased | Metabolism and nutrition disorders | 1 of 4 |
The registry reports 0 serious adverse events among 4 participants at risk and 4 other adverse events among 4 participants at risk. These are participant counts within the study group. The serious-adverse-event summary does not list a serious event term, and the record's death count is not reported in the registry record. A blank or unreported death value should not be treated as a numerical finding.
The other-adverse-event count does not identify the event types, number of event episodes, severity distribution, or timing. Although the primary endpoint is described by nature and severity over six months, those details are not present in the group-level figures. The counts therefore provide only a limited view of the safety observations.
In general, a count of zero observed events does not demonstrate that the underlying risk is absent, especially in a very small study. Likewise, an event recorded after a dose is not by itself evidence that the dose caused it. With no comparator group, the figures cannot quantify an excess or reduced risk relative to another condition. The record supports a descriptive reading of the reported counts, not a definitive causal safety conclusion.
12. What the Result Does, and Does Not, Mean
The study documents a booster-dose safety assessment in previously vaccinated healthy adults and records a limited set of participant-level adverse-event counts. Specifically, the registry reports no serious adverse events among the 4 participants at risk and other adverse events among the 4 participants at risk. These observations describe this study group during the stated follow-up framework; they are not a precise estimate of how often such outcomes would occur in a larger population.
The design limits what can be concluded. There was no concurrent control group, so the study cannot estimate a comparative effect of the booster on adverse events. The small enrollment also means the observed counts provide little information about uncommon outcomes. The absence of a reported serious event is not evidence that serious events cannot occur, while the count for other events does not, without event details, convey their clinical nature or severity.
The study's stated purpose included immunogenicity, and the registry identifies antibody thresholds for secondary outcomes. However, the numbers reaching those thresholds are not reported in the registry record. The record therefore does not support a conclusion about the size, distribution, or change in antibody responses.
More broadly, the registry does not report an inferential statistical analysis or the study's analysis plan. The interpretation should remain descriptive and should not be extended into a claim of efficacy, comparative benefit, or definitive safety. The record also does not report enough information to assess how missing observations were handled or how adverse events were categorized in detail.
13. Why This Trial Matters Statistically
This study illustrates the distinction between a safety count and a comparative safety estimate. A single-group study can record events after an intervention and describe the participants affected, but without a concurrent comparator it cannot estimate how those counts differ from what would have occurred under another condition. That design distinction matters even when a count is easy to interpret.
It also illustrates how sample size constrains precision. With enrollment of 4, a zero count for serious adverse events is a limited observation rather than assurance that the underlying risk is absent. A small study can contribute descriptive information while remaining unable to characterize uncommon outcomes reliably. Statistical interpretation should therefore emphasize the range of questions the design can answer, rather than treating a count as a complete safety profile.
The difference between the stated six-month outcome timeframe and the time-specific analysis population is another important detail. The record says 4 subjects were included at each time point except Day 180, when 3 were included. Without an explanation for that difference, readers cannot determine why the available number changed or whether it affected the interpretation of follow-up.
Finally, the study's immunogenicity purpose and specified antibody thresholds do not substitute for reported antibody results. Clear reporting of outcome values, analysis choices, and missing-data handling is essential for understanding what a clinical study establishes. In this record, the posted adverse-event counts can be described, but the missing analytical and outcome details constrain interpretation.
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 enrollment was 4, limiting the amount of information available about the frequency and range of adverse events. This is particularly important for uncommon outcomes: a small group may not include an event even when it can occur in a broader population. The serious-event count should therefore be read as an observation in this study, not as evidence that serious events are impossible.
The design was single-group, with allocation listed as not applicable and masking as none. There was no randomized comparator to support a relative-risk estimate or help distinguish intervention-associated events from events that could occur for other reasons. The study was Phase 1 and enrolled healthy adults previously vaccinated with RVEc; the findings should not automatically be generalized to populations outside that described group.
The registry's primary endpoint is framed around adverse events by nature and severity, but the posted group summary does not provide detailed event terms, event counts, or severity breakdowns. The death value is not reported in the registry record. The record also does not report the numbers of participants reaching either antibody threshold, despite listing immunogenicity as a study purpose.
Safety analysis counts differed at Day 180, with 3 subjects analyzed there and 4 at other time points. The reason for the difference and the handling of missing observations are not reported. The record does not provide an analysis plan, inferential results, or the study's sample-size justification. These omissions limit assessment of precision, prespecification, and the robustness of the reported summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Booster Dose (50 µg) of Recombinant Ricin Toxin Vaccine (RVEc™) in Previously Vaccinated Healthy Adults — NCT01846104.
- Registry record last updated 2019-12-27; status last verified 2019-12.
- Results first posted 2016-11-21.
- 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
NCT01846104 was a completed Phase 1, single-group study of a 50-μg RVEc booster in previously vaccinated healthy adults. Enrollment was 4, and the sponsor was the U.S. Army Medical Research and Development Command. The primary outcome counted participants with adverse events by nature and severity over six months.
The registry reports 0 serious adverse events among 4 participants at risk and other adverse events among 4 participants at risk. Safety analyses used 4 subjects at each time point except Day 180, when 3 were used. Secondary outcomes specified antibody thresholds, but their numerical results are not reported in the registry record. No analysis records are listed. The single-group design and limited enrollment support descriptive interpretation only.