Safety and Efficacy of CJ-50300 in Healthy Volunteers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of CJ-50300 in Healthy Volunteers (NCT00607243), a randomized phase 2, phase 3 study. The primary outcome is Cutaneous Take Reaction.

2. Clinical Question

This is a comparison of two dose groups of the same cell-culture derived smallpox vaccine, rather than a comparison of vaccination with no vaccine or with a different vaccine. The posted primary outcome is a count of participants meeting the reaction definition. The registry reports 81 participants with the reaction among 82 in the conventional-dose group and 41 among 41 in the low-dose group. Its comparison expresses the low-dose group minus the conventional-dose group as a risk difference of 0.012, with a confidence interval from -0.012 to 0.036.

The registry’s summary describes safety, reactogenicity, and immunogenicity as trial aims. Antibody response and cell-mediated immunity are listed as secondary outcomes, but their numerical findings are not reported in the registry record. The primary comparison therefore addresses the posted cutaneous reaction endpoint, not every stated aim of the trial. The record does not report a question about clinical protection against smallpox.

3. Trial Design

The registry describes a randomized, quadruple-masked, parallel-group Phase II/III trial of CJ-50300 in healthy volunteers. Seoul National University Hospital is listed as sponsor. The recorded start is 2008-01, primary completion is 2008-06, and status is completed. Enrollment is 123. The registry lists smallpox as the condition and CJ-50300 as the biological intervention.

The conventional-dose group received conventional CJ-50300 at 2.5 x 100000 pfu/dose, while the low-dose group received diluted CJ-50300 at 2.5 x 10000pfu/dose. The posted primary outcome is cutaneous take reaction, measured as participants with a qualifying reaction. The registry gives a timeframe of 7-9 day and defines the reaction by vesicular or pustular lesions, definite palpable induration or congestion around a central lesion, or a crust or ulcer at the vaccination site during post-vaccination days 6-8. The site was photographed and measures were taken, according to the outcome description.

Random allocation means assignment is based on a chance process rather than being wholly determined by participant or investigator choice; this is a general design principle, not a statement about the allocation procedure used in this trial. The registry does not report the allocation sequence method or how masking was implemented. It does not identify which roles were included in the quadruple masking. The record also does not report site count, eligibility criteria beyond the healthy-volunteer description, or the timing and details of follow-up beyond the primary endpoint timeframe.

The record lists Antibody Response and Cell-mediate Immunity as secondary outcomes. It reports four outcome measures in total, but only two secondary outcomes are identified in the record. The information about outcome definitions and results is therefore incomplete for assessing all intended measurements. No protocol or statistical analysis plan is reported in the registry record.

4. Participant Flow and Accounting

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

Initial Post-vaccination Period

Telephone Safety Assessment Period

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.

6. Primary Endpoint

The registry lists the primary outcome as Cutaneous Take Reaction, measured over 7-9 day.

The primary endpoint is Cutaneous Take Reaction, counted as participants who experienced a qualifying reaction at the vaccination site. The record defines a take reaction as a vesicular or pustular lesion, an area of definite palpable induration or congestion surrounding a central lesion, or a crust or ulcer. It places the reaction assessment on post-vaccination days 6-8 and gives the endpoint timeframe as 7-9 day. The site was photographed and measures were taken.

This is a binary participant-level outcome: each participant is counted according to whether the defined reaction occurred. In general, a binary endpoint allows a comparison of event proportions between groups. It can be useful for a prespecified observable response when the event itself is considered relevant to the study question. In this record, the outcome is a local skin reaction after vaccination; it should not be read as a direct measure of protection against smallpox or as a complete measure of vaccine safety or immune response.

The registry reports 81 of 82 participants in the conventional-dose group and 41 of 41 in the low-dose group as having a take reaction. It does not report an endpoint population description, a separate adjudication procedure, or details about handling assessments that could not be classified. Those details matter when assessing how consistently the definition was applied and how missing or uncertain observations affected the endpoint.

7. Results Posted in the Registry

• Low-dose Group: 100.0% (41/41) versus 98.8% (81/82) on control; risk difference 1.2 percentage points (95% CI -1.2 to 3.6), risk ratio 1.01 (0.99–1.04); unadjusted two-proportion z-test p = 0.478.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the risk difference represent?

For a binary outcome, the risk in a group is the proportion of participants with the event. The risk difference compares those proportions by subtraction. A value above zero for the stated low-dose relative to conventional-dose comparison indicates a higher observed event proportion in the low-dose group; a value below zero indicates a lower observed proportion. A value of zero corresponds to equal proportions. These are general interpretations of the measure. The registry reports a risk difference of 0.012, with a confidence interval from -0.012 to 0.036.

The estimate describes the observed contrast under the posted group data and the calculation used for the registry result. It does not establish that dose assignment alone caused any difference. Randomization is intended, as a general design principle, to support fair comparisons by making assignment less dependent on participant characteristics, but assessment still depends on the allocation procedure, follow-up, outcome measurement, and analysis. The details of those procedures are not reported in the registry record.

How should the confidence interval be read?

A confidence interval is a statistical range reflecting uncertainty in an estimate under a specified method and its assumptions. In general, wider intervals indicate less precision, while narrower intervals indicate more precision. The risk-difference interval from -0.012 to 0.036 includes zero. Thus, it does not rule out either a lower or higher underlying reaction proportion in the low-dose group relative to the conventional-dose group. The registry does not identify the confidence-interval method, so the exact assumptions behind its limits are not reported.

The record also lists arm-level intervals: 0.93 to 0.99 for the conventional-dose group and 0.9 to 1.0 for the low-dose group. Their method is not specified. These should not be substituted for the interval on the between-group contrast: uncertainty about each group’s event proportion is different from uncertainty about their difference. The comparison interval is the directly relevant interval for the primary group contrast.

What does the p-value add?

The registry reports an unadjusted p-value of 0.478. In general, a p-value describes how unusual data at least as inconsistent with a null model would be if that null model and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the probability that the result arose by chance in a broad, assumption-free sense. The unadjusted label indicates that the value is not described as adjusted for multiple comparisons. The exact test and its assumptions are not reported in the registry record.

The p-value and confidence interval address related but different aspects of the comparison. The p-value summarizes evidence against a specified null under a test; the interval communicates a range of effect estimates compatible with the data under an interval method. Neither alone determines whether a difference is scientifically important. No threshold for a meaningful difference is reported, and the registry record does not state that the study was designed as an equivalence or non-inferiority trial.

How do the group counts relate to the outcome?

The outcome is recorded as a participant count. The conventional-dose group has 81 participants with a take reaction among 82, and the low-dose group has 41 among 41. These counts give the basis for the posted binary-outcome comparison. In general, binary-outcome methods compare event proportions and account for the amount of information available in each group. Here, the low-dose group has no participant without a recorded take reaction in the posted endpoint count, which can make estimates near the boundary of the possible range. The registry does not report the particular computational approach used to handle that feature.

For event-count data, over-dispersion means the observed variability exceeds what a chosen model expects. As a general statistical concern, over-dispersion can make model-based uncertainty too small if the model does not account for it. The registry does not describe a model for the primary outcome or report a dispersion assessment. No conclusion about whether over-dispersion was relevant to this analysis can therefore be made from the record.

What can be inferred from the reported risk ratio?

The registry also lists a risk ratio of 1.012 with an interval from 0.988 to 1.037. A risk ratio compares group event proportions as a ratio rather than as a difference. In general, a ratio of 1 corresponds to equal proportions, values above 1 indicate a higher proportion in the numerator group, and values below 1 indicate a lower proportion. The posted interval includes 1, and its broad interpretation is consistent with uncertainty about the direction of the contrast. The record does not report whether the risk ratio was prespecified or how it was calculated.

Different effect measures answer the comparison question on different scales. A risk difference gives an absolute contrast in proportions; a risk ratio gives a relative contrast. They should not be treated as interchangeable, and no conversion or additional estimate is needed to interpret the figures posted by the registry. The primary endpoint’s clinical importance cannot be determined from a statistical measure alone.

What information is missing about the analysis?

The registry lists zero analysis records. This describes what is entered in the registry and does not establish that no statistical analysis was conducted. A protocol-level analysis plan, handling of missing outcomes, analysis population, adjustment variables, and method for the primary comparison are not reported in the registry record. It is also not reported whether any interim analyses occurred or how multiplicity was addressed across outcomes. Those omissions limit the ability to reproduce the result or assess whether the posted comparison follows a prespecified plan.

Planning sample-size illustrations based on an observed effect are not evidence of the trial’s original design justification or its observed power. The registry’s planning assumptions describe illustrations using a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects stated as fractions of the observed effect. The trial’s own sample-size justification is not reported in the registry record. Any planning values should be interpreted as hypothetical design calculations, not as outcomes measured in the trial.

10. Confidence Intervals and Precision

The primary comparison has a reported risk difference of 0.012, with a confidence interval from -0.012 to 0.036. The lower limit is below zero and the upper limit is above zero. Thus the interval includes both a possible lower reaction proportion in the low-dose group and a possible higher proportion, as well as values close to no difference. The point estimate alone should not be used to imply that the underlying difference is known with precision.

In general, a confidence interval conveys statistical uncertainty under the method used to construct it. Its width is informative: a relatively broad interval leaves more uncertainty about the effect size, while a narrow interval constrains the range more closely. Whether this interval is sufficiently precise for a practical decision cannot be judged without a prespecified threshold for a meaningful difference. No such threshold is reported in the registry record, and the record does not identify the interval method.

The registry gives arm-level values with intervals of 0.93 to 0.99 for the conventional-dose group and 0.9 to 1.0 for the low-dose group. The interval type is not reported. These limits describe uncertainty around the group values, but the interval for the risk difference is the more direct expression of uncertainty in the contrast between doses. The risk-ratio estimate of 1.012, with interval 0.988 to 1.037, also includes its null value of 1.

The group endpoint counts are 81 of 82 and 41 of 41. The group sizes and the concentration of events are relevant to precision, but the registry does not provide enough methodological detail to assess the calculation beyond the posted estimates. A confidence interval should not be read as a range containing every plausible value with certainty, nor as a probability statement about a particular effect. It is a measure of uncertainty conditional on a statistical method and assumptions.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists Antibody Response and Cell-mediate Immunity as secondary outcomes, as well as the primary Cutaneous Take Reaction endpoint. Four outcome measures are reported in total, but the registry identifies two secondary outcomes. Numerical results for those secondary outcomes are not reported in the registry record. The record does not describe a prespecified hierarchy of outcomes, a multiplicity adjustment, or a strategy for controlling the chance of false-positive findings across multiple tests.

The primary comparison is labeled unadjusted, with p-value 0.478. The registry does not explain whether this refers only to adjustment for covariates or also to adjustment for multiple comparisons. No broader statistical plan is reported, so it is not possible to establish how the primary endpoint was positioned among the measures or how secondary analyses were intended to be interpreted. In general, examining multiple outcomes can increase the chance that at least one result appears notable by chance; planned adjustment or careful descriptive interpretation can address this issue. That is a general principle, not a claim about what occurred in this trial.

Missing-data handling is also not reported in the registry record. The endpoint counts include 82 conventional-dose participants and 41 low-dose participants, but the record does not state whether these represent all randomized participants, all participants assessed, or a defined analysis population. It does not report whether any endpoint assessments were missing or how potentially unclassifiable reactions were handled. No participant flow details are reported.

The record gives no analysis population definition, such as intention-to-treat or per-protocol, and no sensitivity analyses are reported. These omissions affect assessment of how exclusions, missing observations, or departures from assigned treatment might influence the result. The registry lists zero analysis records, but that entry does not demonstrate that no analysis was performed; it means analysis details are not present in the registry record.

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 non-serious adverse event terms

The posted serious adverse-event counts are zero in the conventional-dose group, among 82 participants at risk, and zero in the low-dose group, among 41 participants at risk. These are the counts recorded in the registry. They do not establish that serious adverse events were impossible or that no such events occurred outside the reporting period or definition used for this record. The serious-event terms list is empty.

Other adverse events are reported for 28 conventional-dose participants among 82 at risk and 15 low-dose participants among 41 at risk. The registry does not supply the event terms, severity breakdown, observation period, or criteria for attributing events to vaccination. It also does not explain whether the counts refer to participants with at least one event or to a different counting rule, beyond the field description that indicates affected participants.

Deaths are recorded as null for both groups, which means death counts are not reported in the registry record; null should not be read as zero. These safety figures are descriptive and do not provide a complete comparative safety analysis. Differences in follow-up, event ascertainment, or definitions cannot be assessed from the posted information. The counts should be interpreted alongside the missing safety-reporting details, rather than as proof of absence or presence of a particular risk.

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

The registry results show that most participants in both dose groups were recorded as having the defined cutaneous take reaction: 81 of 82 in the conventional-dose group and 41 of 41 in the low-dose group. The posted point estimate for the low-dose versus conventional-dose risk difference is 0.012. Its confidence interval, -0.012 to 0.036, includes zero, and the reported unadjusted p-value is 0.478. These statistics indicate uncertainty about the direction and magnitude of the difference in the endpoint proportions.

This is not a demonstration that the doses are equivalent. A conclusion of equivalence requires a prespecified acceptable difference and a suitable analysis. Neither is reported in the registry record. Nor does a non-significant p-value prove that the doses have identical effects. It means that the reported comparison does not provide strong evidence against the no-difference hypothesis under the unadjusted test used; the test method itself is not reported.

The endpoint is a vaccination-site reaction. Its occurrence does not establish whether participants developed protective immunity or were protected against smallpox. Antibody response and cell-mediated immunity are listed as secondary outcomes, but their findings are not reported in the registry record. The record’s stated trial aims include safety, reactogenicity, and immunogenicity, but the posted primary result addresses only the cutaneous reaction measure.

The safety counts are also limited. Zero serious adverse events are reported in each group, while other adverse events are reported for 28 participants in the conventional-dose group and 15 in the low-dose group. With definitions and observation period not reported, these counts cannot establish a full safety profile or explain the nature of the events. Death counts are not reported.

The trial record describes a randomized, quadruple-masked, parallel-group Phase II/III study in healthy volunteers. It does not report allocation implementation, analysis populations, missing-data handling, or a full statistical plan. Accordingly, the posted figures support a narrow reading of the recorded endpoint comparison, not a broader claim about clinical protection, immune response, or overall comparative benefit and harm.

14. Why This Trial Matters Statistically

This trial is statistically notable as a comparison between two dose levels of the same vaccine with a common, observable binary endpoint. The primary outcome is defined through specified vaccination-site findings, and results are reported as participant counts in each group. This makes the contrast understandable in terms of whether a reaction was recorded, while also requiring attention to the precise case definition and assessment window.

The near-boundary event pattern is important for interpretation: the registry reports a reaction for 81 of 82 conventional-dose participants and 41 of 41 low-dose participants. A result near the upper limit of a binary proportion can make an observed difference sensitive to a small number of participants and to how outcome classification is handled. General statistical methods address such data through suitable interval and test procedures, but the registry does not identify the methods used.

The comparison also illustrates why estimates and uncertainty should be read together. The risk-difference estimate is 0.012, while its interval ranges from -0.012 to 0.036. Reporting the point estimate alone would conceal uncertainty about whether the low-dose group’s underlying reaction proportion is higher or lower. The unadjusted p-value of 0.478 is not a substitute for that interval or for a judgment about clinically meaningful differences.

The record’s omissions are also instructive for registry interpretation. Secondary outcomes are named but numerical results are not reported, and analysis populations, missing-data methods, multiplicity handling, and statistical procedures are not specified. These gaps show why an outcome count and a p-value cannot fully convey the design and conduct of a clinical analysis. The posted figures are informative for the primary recorded comparison, but they do not answer every safety, immunogenicity, or protection question raised by the trial’s stated aims.

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 registry record does not report key details needed to evaluate the primary analysis fully. The endpoint population is blank, and no analysis population definition is given. It is therefore unclear whether the posted group denominators refer to all randomized participants, participants assessed for the endpoint, or another analysis set. Participant flow and any exclusions are not reported.

Missing-outcome handling is not described. Although the endpoint counts include 82 participants in the conventional-dose group and 41 in the low-dose group, the record does not state whether any reactions were unassessed, indeterminate, or missing. It also does not report how the reaction definition was applied in practice, who assessed the photographs and measurements, or whether assessments were independently reviewed. The stated masking level does not supply those implementation details.

The statistical method for the risk difference, its confidence interval, the arm-level intervals, and the p-value is not reported. No protocol, analysis plan, sample-size justification, interim-analysis information, or multiplicity strategy is included. The registry includes planning assumptions based on the observed effect, but the trial’s original design justification is not reported. These planning illustrations cannot establish the study’s original power or explain why enrollment was set at 123.

The timeframe for safety ascertainment and definitions for serious and other adverse events are not reported. Serious-event counts are zero in both groups, but deaths are null and therefore not reported. Other adverse-event counts lack event terms and severity details. Numerical results for the named secondary outcomes are also absent. Finally, the registry does not report a clinical interpretation threshold for the take-reaction contrast, so the practical importance of the confidence interval cannot be determined from the record alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Efficacy of CJ-50300 in Healthy Volunteers — NCT00607243.
• Registry record last updated 2013-07-09; status last verified 2013-07.
• Results first posted 2013-07-09.
• 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

NCT00607243 is a completed, randomized, quadruple-masked, parallel-group Phase II/III trial sponsored by Seoul National University Hospital. It enrolled 123 healthy volunteers and compared conventional-dose CJ-50300 at 2.5 x 100000 pfu/dose with diluted low-dose CJ-50300 at 2.5 x 10000pfu/dose. The recorded start is 2008-01, with primary completion in 2008-06.

The primary endpoint was cutaneous take reaction, defined by specified vaccination-site findings during post-vaccination days 6-8; the timeframe is listed as 7-9 day. The registry reports reactions in 81 of 82 conventional-dose participants and 41 of 41 low-dose participants. The low-dose versus conventional-dose risk difference is 0.012, with a confidence interval from -0.012 to 0.036 and an unadjusted p-value of 0.478.

Serious adverse events are reported as zero in both groups. Other adverse events are reported for 28 conventional-dose and 15 low-dose participants; deaths are not reported. Antibody Response and Cell-mediate Immunity are listed as secondary outcomes, but their numerical results are not reported in the registry record.