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 Phase I Randomized, Placebo-Controlled, Double-Blind, Dose Ranging Study, Safety, Tolerability and Immunogenicity (NCT00772954), a randomized phase 1 study. The primary outcome is Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With One of Two Formulations of Clostridium Difficile Toxoid Vaccine or a Placebo Vaccine..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00772954 |
| Phase | Phase 1 |
| Condition | Clostridium Difficile Infection, Clostridium Difficile Diarrhea |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 36 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi |
| Results posted | Yes |
2. Clinical Question
Population
Healthy male and female adults aged 18 to 55 years were eligible for the study. Safety assessments were conducted in the safety population. Further eligibility criteria and details about that population are not reported in the registry record.
Intervention
Participants in one vaccine group were scheduled to receive 50 μg of Clostridium difficile toxoid vaccine on Day 0, Day 28, and Day 56. A second vaccine group was scheduled to receive 100 μg on the same days.
Comparator
The placebo group was scheduled to receive vaccine diluent buffer on Day 0, Day 28, and Day 56. The record describes the study as placebo-controlled.
Primary question
The primary outcome asks how many participants reported treatment-emergent adverse events after vaccination with either vaccine formulation or placebo, from Day 0 up to 70 days after the first vaccination. The registry record reports serious and other adverse event counts, but does not provide a detailed statistical comparison between groups.
This is a safety-focused question in a Phase I study. It concerns reported events during a defined follow-up period, rather than whether vaccination prevents Clostridium difficile infection or diarrhea. Although the study title and summary also refer to immunogenicity, the posted primary outcome is the number of participants reporting treatment-emergent adverse events. Immunogenicity results are not reported in the registry record.
3. Trial Design
The registry record describes a randomized, parallel-group, Phase I study with an enrollment of 36. It lists three groups: placebo, 50 μg Clostridium difficile toxoid vaccine, and 100 μg Clostridium difficile toxoid vaccine. Participants were scheduled for three administrations, on Day 0, Day 28, and Day 56. The record identifies the study as terminated. The reason for termination is not reported in the registry record.
The study is described as randomized and placebo-controlled. The registry record identifies masking as triple, while the study title describes the study as double-blind. The record does not explain this difference or specify which people were masked. Allocation procedures, the method used to conceal assignment, and any details about how masking was maintained are not reported in the registry record.
The listed study dates are 2006-03 for study start and 2006-06 for primary completion. The sponsor is Sanofi. The study population was healthy male and female adults aged 18 to 55 years. More detailed eligibility criteria, the number assigned to each group beyond the adverse-event risk counts, and information about participants who did not follow the scheduled vaccination plan are not reported in the registry record.
The record lists one outcome measure and no posted analyses. Its primary safety outcome covers Day 0 up to 70 days after the first vaccination. The registry record does not give a detailed protocol, a statistical analysis plan, or an explanation of the study's termination. Those omissions limit assessment of how the trial was intended to proceed and how its reported counts relate to the original plan.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 36 participants who met the inclusion, but no exclusion criteria were enrolled and vaccinated.
Overall Study
| Stage | Placebo Vaccine Group | Clostridium Difficile Toxoid Vaccine Group 1 | Clostridium Difficile Toxoid Vaccine Group 2 |
|---|---|---|---|
| STARTED | 12 | 12 | 12 |
| COMPLETED | 12 | 12 | 11 |
| NOT COMPLETED | 0 | 0 | 1 |
Reasons for not completing this period:
| Reason | Placebo Vaccine Group | Clostridium Difficile Toxoid Vaccine Group 1 | Clostridium Difficile Toxoid Vaccine Group 2 |
|---|---|---|---|
| Adverse Event | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety assessments were on the safety population.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Placebo Vaccine Group | Clostridium Difficile Toxoid Vaccine Group 1 | Clostridium Difficile Toxoid Vaccine Group 2 | Total |
|---|---|---|---|---|---|
| Participants analysed | 12 | 12 | 12 | 36 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 12 | 12 | 12 | 36 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age Continuous | Years | 38.3 (SD 12.98) | 36.9 (SD 12.67) | 30.0 (SD 8.57) | 35.1 (SD 11.84) |
| Sex: Female, Male: Female | Participants | 7 | 11 | 5 | 23 |
| Sex: Female, Male: Male | Participants | 5 | 1 | 7 | 13 |
| Region of Enrollment: United States | participants | 12 | 12 | 12 | 36 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Reporting Treatment-Emergent Adverse Events Post-vaccination With One of Two Formulations of Clostridium Difficile Toxoid Vaccine or a Placebo Vaccine., measured over Day 0 up to 70 days post first vaccination.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants reporting treatment-emergent adverse events after vaccination with one of the two vaccine formulations or placebo. The stated observation period runs from Day 0 up to 70 days after the first vaccination, and the safety assessments were on the safety population. The registry record gives separate counts for serious adverse events and other adverse events.
A participant count is a straightforward way to describe how many people in each group had at least one event meeting the endpoint definition. It is useful in a safety study because it summarizes the occurrence of reported events during the specified follow-up. The count alone does not describe the event's severity, duration, cause, or clinical importance. The record does not provide the endpoint's detailed event definitions, rules for counting multiple events in one participant, or a separate analysis of event timing.
The study title also names immunogenicity, but the posted primary endpoint is a safety measure. Immunogenicity outcomes and their results are not reported in the registry record. This endpoint therefore cannot answer whether the vaccine prevents infection or diarrhea, or characterize an immune response.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record reports zero participants with serious adverse events in each of the three groups. For other adverse events, the reported counts are 11 in the placebo group, 12 in the 50 μg vaccine group, and 12 in the 100 μg vaccine group. The corresponding risk counts are 12 in each group. These are descriptive counts; the registry record does not post a statistical comparison, confidence intervals, or p-values for them.
The counts describe participants recorded as having events during the stated safety follow-up. They do not establish that an event was caused by the assigned intervention. Nor does the absence of reported serious events in these groups establish that serious events cannot occur. The record gives no detailed event terms for the serious-event outcome and no deaths values; deaths are not reported in the registry record.
The other-event counts are close in the sense that the posted counts are 11, 12, and 12, but these counts alone do not establish that the groups are equivalent. In general, a comparison must account for uncertainty, and a small study can leave substantial uncertainty even when observed counts look similar. No uncertainty estimates or formal between-group tests are posted. It would therefore be inappropriate to infer a precise difference, or a lack of difference, from the counts alone.
The study was randomized, which is intended in general to support fair comparisons by assigning participants to groups without choosing treatment based on their characteristics. However, randomization does not remove uncertainty, and this record does not report enough details to assess allocation procedures or the balance of participant characteristics. The enrollment was 36; the risk counts reported for the adverse-event outcomes are 12 in each group. The record does not explain whether all enrolled participants contributed to these counts or describe any missing observations.
The primary outcome title refers broadly to treatment-emergent adverse events, while the posted summary separates serious events from other events. The registry record notes that the primary outcome has several categories or time points and was not reduced to one comparison. No single combined primary-effect estimate is therefore reported. The findings should be read as safety counts within the registry record, not as a definitive comparative safety analysis or evidence about vaccine efficacy.
9. Statistical Methods Explained
The posted outcome is a participant count, not a continuous measurement such as a laboratory value. For each group, the record gives the number at risk and the number affected for serious events and other events. A count makes the result easy to interpret at face value: it states how many participants were recorded as having an event. It does not, by itself, quantify the uncertainty around a group comparison.
What does randomization contribute?
In general, random allocation is used to reduce systematic differences between groups at the time of assignment. If allocation is implemented as intended, differences in outcomes can be compared without deliberately selecting participants for a particular intervention. Randomization does not guarantee that groups will have identical characteristics, especially in a small study, and it does not replace reporting baseline characteristics or analysis methods. The allocation procedure and baseline group characteristics are not reported in the registry record.
What does masking mean for interpretation?
In general, masking is intended to limit the influence of knowledge about assigned treatment on care, reporting, or assessment. The registry record identifies masking as triple, while the title describes the study as double-blind. It does not explain the terminology or specify who was masked. That missing detail makes it difficult to evaluate how masking may have affected event reporting or assessment. The record does not describe the placebo's appearance or the procedures used to preserve masking.
How should event counts be read?
A count of participants with an event is a simple summary. It differs from a count of all event episodes: one participant may have more than one event, but the posted endpoint is expressed as the number of participants reporting events. The record does not state how repeated events were handled in the summary, how events were classified, or whether the other-event category includes a particular severity range. General statistical practice distinguishes the frequency of participants affected from the total number of event occurrences; the posted participant counts should not be interpreted as event totals.
In general, a confidence interval expresses a range of values compatible with the data under a statistical model and indicates uncertainty in an estimate. A p-value, when used, measures how unusual data at least as extreme as those observed would be under a specified null hypothesis and model. Neither a confidence interval nor a p-value is posted for these event counts. No formal estimate of the difference between groups is reported, so the precision of a comparative effect cannot be assessed from the registry record.
Why does the analysis population matter?
The endpoint states that safety assessments were on the safety population. In general, an analysis population specifies which participants contribute to a particular result and can affect how the result is interpreted. The record does not define the safety population or state how participants were included in it. Although the adverse-event groups report 12 participants at risk per group, the registry record does not explain how these denominators relate to enrollment, assignment, vaccination received, or follow-up completion.
The statistical analysis plan is not reported in the registry record. It does not describe planned hypothesis tests, adjustment for baseline variables, handling of missing outcome data, or rules for summarizing multiple event categories or time points. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. As a result, there is no posted single primary effect estimate to interpret. The results are best understood as the listed descriptive counts, without assuming an unreported model or test.
General sample-size calculations can illustrate how many participants per arm a future study might need under stated assumptions. Such planning depends on an effect to detect and choices about significance level, power, allocation, and statistical method. The registry record includes a description of planning assumptions but does not report a numerical planning result or the trial's own sample-size justification. Any planning illustration based on an observed effect would not be observed power and would not establish that this trial was designed to detect a particular difference. The planned statistical methods and rationale for enrollment are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record notes that the primary outcome has several categories or time points and was not reduced to one comparison. It does not report a single combined primary comparison or a set of individual hypothesis tests. This matters because, in general, testing multiple outcomes or time points can increase the chance of finding an apparently notable result by chance. Statistical plans sometimes address this issue by defining a primary comparison in advance or adjusting how results are interpreted. Whether any such approach was planned or used is not reported in the registry record.
No posted analyses are listed. The registry record does not report p-values, confidence intervals, a statistical analysis plan, or a method for addressing multiplicity. It is therefore not possible to determine whether comparisons were planned, exploratory, adjusted, or omitted from the posted results. The absence of a posted test should not be read as evidence that a formal analysis found no difference.
The safety assessments were on the safety population, but the record does not define that population or give missing-data rules. It does not state how participants with incomplete follow-up, missed vaccinations, or unavailable event information were handled. The adverse-event risk counts are reported, but the disposition of participants outside those counts is not explained. Missing-data assumptions and their potential effects on the results 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 |
|---|---|---|---|
| Placebo Vaccine Group | 0 | 12 | 0.0% |
| Clostridium Difficile Toxoid Vaccine Group 1 | 0 | 12 | 0.0% |
| Clostridium Difficile Toxoid Vaccine Group 2 | 0 | 12 | 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 |
|---|---|
| Placebo Vaccine Group | 11 of 12 |
| Clostridium Difficile Toxoid Vaccine Group 1 | 12 of 12 |
| Clostridium Difficile Toxoid Vaccine Group 2 | 12 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Vaccine Group | Clostridium Difficile Toxoid Vaccine Group 1 | Clostridium Difficile Toxoid Vaccine Group 2 |
|---|---|---|---|---|
| Injection site pain | General disorders | 7 of 12 | 12 of 12 | 9 of 12 |
| Headache | Nervous system disorders | 5 of 12 | 4 of 12 | 5 of 12 |
| Diarrhoea | Gastrointestinal disorders | 3 of 12 | 3 of 12 | 2 of 12 |
| Fatigue | General disorders | 3 of 12 | 3 of 12 | 2 of 12 |
| Blood potassium decreased | Investigations | 1 of 12 | 4 of 12 | 3 of 12 |
| Protein urine present | Investigations | 1 of 12 | 4 of 12 | 3 of 12 |
| White blood cell count increased | Investigations | 1 of 12 | 4 of 12 | 3 of 12 |
| White blood cells urine positive | Investigations | 2 of 12 | 2 of 12 | 3 of 12 |
| Eosinophil count increased | Investigations | 3 of 12 | 1 of 12 | 3 of 12 |
| Myalgia | Musculoskeletal and connective tissue disorders | 1 of 12 | 5 of 12 | 1 of 12 |
For serious adverse events, the registry record reports zero affected participants in the placebo group, zero in the 50 μg vaccine group, and zero in the 100 μg vaccine group. Each group has 12 participants at risk for this outcome. The record does not provide serious-event terms, further details about the events assessed, or a statistical comparison. Death counts are not reported in the registry record.
For other adverse events, the record reports 11 affected participants in the placebo group, 12 in the 50 μg group, and 12 in the 100 μg group; the reported risk count is 12 in each group. These are participant counts, not a tally of every event episode. The record does not provide event descriptions or a breakdown by type, severity, or timing.
Zero reported serious events in the posted counts is a description of this study's record, not proof that serious events are impossible or that groups have identical risks. Similarly, the other-event counts do not establish a causal relationship or a comparative effect. Formal uncertainty estimates and analyses are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results show the recorded participant counts for serious and other adverse events during the safety follow-up. They provide a basic description of what was reported in the three study groups. The serious-event count is zero in every group; the other-event counts are 11 for placebo, 12 for the 50 μg vaccine, and 12 for the 100 μg vaccine. The registry record does not post a formal comparison or uncertainty interval for these counts.
These findings do not establish that the vaccine caused or prevented an adverse event. A randomized design can support comparisons in general, but interpretation still depends on the complete results, analysis plan, data quality, follow-up, and uncertainty. Those details are not all reported in the registry record. Without a comparative estimate and its precision, the observed counts cannot demonstrate equivalence or rule out meaningful differences.
The outcome is limited to reported treatment-emergent adverse events over the stated period. It does not answer whether the vaccine prevents Clostridium difficile infection or Clostridium difficile diarrhea. It also does not provide an immunogenicity result, despite immunogenicity being named in the study title and summary. Those outcomes are not reported in the registry record.
The study status is terminated, but the reason is not reported in the registry record. The status alone does not explain whether termination affected recruitment, follow-up, analysis, or reporting. The record should therefore be read as a limited set of safety summaries, not as a complete account of the study's conduct or all outcomes of interest. No medical conclusion should be drawn from these counts alone.
13. Why This Trial Matters Statistically
This study illustrates a basic distinction in clinical-trial interpretation: a descriptive count is not the same as a comparative estimate. The adverse-event counts show how many participants were recorded as affected in each group, while a formal comparison would also require a defined analysis and an account of uncertainty. The registry record does not post that comparison, so readers should avoid treating small differences in counts as established treatment effects.
It also illustrates why endpoint definitions and analysis populations matter. The primary outcome is phrased as a participant count over a stated follow-up period, and the safety population is named. But the registry record does not define the event categories in detail or specify the safety population. Without those elements, readers cannot fully assess what was counted or exactly which participants contributed to each summary.
The record's note that the primary outcome includes several categories or time points is relevant to multiplicity. In general, a study with multiple outcomes or times can raise questions about which comparison was primary and how results were interpreted. No single comparison or multiplicity approach is reported. That limitation is especially important when the posted results are descriptive rather than accompanied by prespecified analyses.
Finally, the record demonstrates that a study's stated scope and its posted results may not align completely: immunogenicity appears in the title and summary, while the available primary result concerns safety. Recognizing what a result does and does not measure is essential for avoiding claims beyond the recorded evidence.
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 registry record offers limited detail about trial conduct and analysis. It does not explain why the study was terminated, whether termination changed the planned enrollment or follow-up, or whether all intended outcomes were collected. It lists 36 enrolled participants, but does not give a participant flow account or explain whether the risk counts represent everyone enrolled, everyone assigned, or those with available safety data.
There is no detailed statistical analysis plan, no posted formal analysis, and no confidence interval or p-value for a comparison. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. The treatment-emergent event definitions, event-level details, handling of repeat events, and missing-data procedures are not reported in the registry record.
The record identifies the study as triple-masked, while the title describes it as double-blind; it does not clarify the difference or say who was masked. It also does not report allocation procedures or baseline characteristics. These omissions restrict assessment of potential bias and group comparability. Finally, the posted outcome is limited to adverse-event counts. Immunogenicity results and evidence about prevention of infection or diarrhea are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase I Randomized, Placebo-Controlled, Double-Blind, Dose Ranging Study, Safety, Tolerability and Immunogenicity — NCT00772954.
- Registry record last updated 2012-05-21; status last verified 2012-04.
- Results first posted 2012-05-21.
- 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
This Phase I study randomized healthy adults aged 18 to 55 years to placebo, 50 μg Clostridium difficile toxoid vaccine, or 100 μg Clostridium difficile toxoid vaccine. Each group was scheduled for vaccination on Day 0, Day 28, and Day 56. The registry record reports an enrollment of 36, a study start of 2006-03, primary completion in 2006-06, and terminated status.
The primary safety outcome concerns treatment-emergent adverse events from Day 0 up to 70 days after the first vaccination. The reported serious-event count is zero in each group; other-event counts are 11 in the placebo group and 12 in each vaccine group. No formal comparative analysis is posted. The reason for termination, detailed event information, immunogenicity results, and statistical analysis plan are not reported in the registry record.