A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer (NCT02172911), a non-randomized phase 1, phase 2 study. The primary outcome is Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

This was an open-label phase I/IIA study of INO-3112 delivered by electroporation in women with cervical cancer. The record describes a parallel design with nonrandomized allocation and no masking. Enrollment was 10. The study status is completed; the start date was 2014-06-06 and primary completion was 2017-09-07. In a nonrandomized study, participants are not assigned to groups by chance, so differences between cohorts may reflect their underlying clinical circumstances as well as any differences in treatment history.

The two cohorts represent distinct clinical settings. Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 who had received standard chemoradiation with curative intent. Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had received salvage therapy. The record describes a four-dose series of INO-3112 in each cohort, but the cohort descriptions are truncated, so additional administration details are not reported in the registry record.

The study’s stated focus was safety, tolerability, and immunogenicity. The primary outcome was the percentage of participants with at least one TEAE, assessed up to 36 weeks. Secondary outcomes included changes in HPV-16 and HPV-18 E6 and E7 antigen-specific spot-forming units per million peripheral blood mononuclear cells, and E6- and E7-specific antibody titers assessed by ELISA. The registry lists 17 outcome measures, but the primary endpoint result and secondary outcome results are not reported in the registry record. A statistical analysis plan, allocation procedures beyond the nonrandomized designation, and sample-size justification are not 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received at least one dose of study treatment plus EP.

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 Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE), measured over Up to 36 weeks.

The primary endpoint measures the percentage of participants who experienced at least one treatment-emergent adverse event up to 36 weeks. The registry defines an adverse event as an untoward medical occurrence after administration of a pharmaceutical product; an event does not have to be caused by the product to meet that definition. A TEAE is an event reported for the first time after the first study-drug dose, or a pre-existing event that worsened after that dose.

Counting participants with one or more events gives a participant-level summary of whether any qualifying event occurred during the stated follow-up period. It does not, by itself, describe the total number of events, their severity, duration, or causal relationship to treatment. Those questions require separate information. The registry identifies the safety population as participants who received at least one dose of study treatment plus electroporation.

The endpoint is presented as a percentage with a 95% confidence interval. In general, a confidence interval expresses uncertainty around an estimated percentage under the analysis method used; it does not establish that an event was caused by treatment. Neither the primary percentage nor its confidence interval is reported in the registry record. The endpoint’s intended measure is clear, but its observed value and precision cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help distinguish what a study observed from what can be inferred. In this study, the registry describes a primary endpoint based on a participant-level binary outcome: whether each participant had at least one TEAE during follow-up. The endpoint is expressed as a percentage. The actual percentage and its confidence interval are not reported in the registry record, and the analysis method used to calculate them is not reported in the registry record.

What does a percentage measure?

As a general statistical principle, a percentage for a binary outcome describes the share of an analyzed group with the event. It compresses each participant’s outcome to whether at least one qualifying event occurred. This is useful for a clearly defined event criterion, but it does not communicate how many events each affected participant experienced, how severe or prolonged they were, or when they occurred. It also does not establish whether the event was caused by the intervention. The registry’s TEAE definition is based on timing after the first study-drug dose, not on a stated requirement that the event be treatment-related.

The safety population is defined as participants who received at least one dose of study treatment plus electroporation. This population definition matters because results depend on who is included in the denominator. The record does not provide a primary endpoint denominator or outcome count, so neither can be checked against the safety-population definition. The cohort-specific serious-event counts are separately available, but they are not the missing primary endpoint estimate.

How should a confidence interval be understood?

As a general statistical principle, a confidence interval describes uncertainty around an estimate under a specified statistical procedure. A narrow interval indicates greater precision under that procedure than a wide interval; the interval does not guarantee that the underlying value lies within its limits, nor does it measure the probability that a treatment caused an event. For a percentage based on a small group, uncertainty can be substantial. The registry names a 95% confidence interval for the primary endpoint but does not report its limits or the method used to construct it. The precision of the primary estimate therefore cannot be evaluated.

What does the design allow?

The study is nonrandomized and open-label. As a general statistical principle, random allocation can help balance prognostic characteristics between groups on average, while masking can reduce some forms of bias in treatment delivery or outcome assessment. Neither feature is present as described in this record. Moreover, the cohorts were defined by different clinical contexts: newly diagnosed disease after chemoradiation with curative intent versus persistent and/or recurrent disease after salvage therapy. Their observed outcomes should not be interpreted as a controlled comparison of treatment strategies.

The registry describes the study as parallel, but parallel groups do not by themselves make a comparison randomized or controlled. Without random assignment and a comparable control group, differences across cohorts may reflect disease status, prior treatment, or other characteristics that are not described in the record. The registry does not report an adjusted comparison or a statistical model intended to address such differences.

What can the planning calculations say?

As a general statistical principle, a sample-size calculation asks how many participants or events a future study might need under specified assumptions. The planning illustrations associated with the posted material use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. They are planning illustrations, not observed power and not a measure of the probability that this completed study detected an effect. No numerical planning estimates are reported in the registry record. Because this study is nonrandomized and does not provide a like-for-like control comparison, such illustrative calculations should not be read as evidence that a causal contrast was established.

In general, the choice of effect size matters: planning for a smaller effect requires more information than planning for a larger effect, all else being equal. That conceptual relationship does not establish the trial’s original design rationale. The registry does not report a sample-size justification or enough information to reconstruct one. The planning assumptions should therefore remain distinct from the study’s observed results, which are incompletely reported.

Why do event definitions and follow-up matter?

The primary endpoint is tied to a specified period, up to 36 weeks, and to the first dose of study drug. In general, a time window affects which events qualify and how participants with incomplete follow-up are handled. The registry does not report whether every participant completed the full period, how partial follow-up was treated, or how missing outcome information was handled. Those details are necessary to assess whether the percentage uses comparable observation time across participants.

The serious-event summaries use counts of participants at risk and participants affected within each cohort. These summaries are useful descriptions of what was recorded, but they do not replace a time-to-event analysis, provide adjusted risk estimates, or establish causality. No time-to-event analysis or adjusted model is reported in the registry record. More detailed statistical interpretation would require the endpoint results, analysis population details, missing-data approach, and prespecified analysis methods.

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("Cohort I: INO-3112: Curative Intent", "Cohort II: INO-3112: Salvage Therapy")
n      <- c(7, 3)
events <- c(7, 3)
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  Cohort I: INO-3112: Curative Intent  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7
ARM  Cohort II: INO-3112: Salvage Therapy  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary TEAE endpoint and secondary immunogenicity outcomes. It does not report how the analyses were prioritized beyond identifying the primary endpoint, or whether any adjustment for multiple comparisons was planned. When several outcomes are examined, the chance of finding at least one apparently notable result can increase; as a general statistical principle, multiplicity methods can help control that issue. The record does not report such methods or results for the listed outcomes.

The registry lists no analyses. It does not report a statistical analysis plan, model specifications, decision rules, or whether analyses were adjusted for baseline characteristics. The primary endpoint’s estimate and confidence interval are also absent. The reported outcome descriptions therefore do not establish which planned analyses were performed or how results were selected for reporting.

Missing-data methods are not reported in the registry record. In general, interpretation of a percentage depends on knowing who was included in the denominator and how participants with incomplete follow-up or unavailable outcome measurements were handled. The safety population is defined as participants who received at least one dose of study treatment plus electroporation, but the record does not state the primary endpoint denominator or give details of missing observations.

The stated safety population is relevant to the TEAE outcome. The registry does not report analysis populations for the secondary immunogenicity measures or whether all enrolled participants contributed to those outcomes. Without those details, the extent and potential consequences of missing outcome data cannot be assessed. The available record does not support assumptions about imputation, exclusions, or sensitivity analyses.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disseminated intravascular coagulation (33.3%), intestinal perforation (33.3%), abdominal pain (14.3%), endometritis (14.3%), pneumonia (14.3%).

The serious adverse event summaries report participant counts separately for each cohort. In Cohort I, 3 of 7 participants at risk were affected by a serious adverse event; in Cohort II, 2 of 3 participants at risk were affected. These are descriptive counts from groups with different clinical circumstances, not a randomized comparison. They do not estimate a causal effect of INO-3112 or electroporation.

The registry also lists term-specific percentages: Disseminated Intravascular Coagulation and Intestinal Perforation at 33.3% each, and Abdominal Pain, Endometritis, and Pneumonia at 14.3% each. The record does not explain whether participants could contribute more than one term, nor does it provide event-level timing or causal attribution. These figures should not be interpreted as treatment-related rates without that information.

Deaths are recorded as 0 for Cohort I and 1 for Cohort II. A death count alone does not establish a relationship to study treatment. The primary TEAE percentage and its 95% confidence interval are not reported in the registry record, so these serious-event summaries cannot stand in for the primary safety endpoint.

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

The record supports a description of the study’s design, clinical cohorts, intended safety endpoint, and selected serious adverse event summaries. It does not report the primary TEAE percentage or its 95% confidence interval, so it cannot show how frequently participants experienced at least one TEAE over the stated follow-up period or how precise that estimate was. The secondary immunogenicity results are also not reported in the registry record.

The cohort-specific serious-event counts and listed terms document events recorded in the registry. They do not, by themselves, establish that the study intervention caused those events. An adverse event can meet the registry definition without being related to treatment. The record does not provide causal assessments for the listed events. Likewise, the death recorded in Cohort II cannot be attributed to treatment on the information available.

The design also limits comparisons. Participants were not randomized, and the cohorts reflected different disease and treatment settings. Comparing their observed event counts would not provide a like-for-like estimate of what would have happened under an alternative intervention. Differences could arise from the cohorts’ clinical circumstances or other factors not reported in the registry.

These limitations do not erase the descriptive information that is present, but they define its scope. The registry record does not report a statistical analysis plan, missing-data methods, multiplicity procedures, or analyses. It therefore does not support conclusions about treatment efficacy, comparative safety, or immunogenicity results. Any planning calculations should be understood as assumptions for future study design, not as observed power or evidence that an effect was demonstrated. The evidence available is limited to the reported design details and adverse-event summaries.

14. Why This Trial Matters Statistically

This study raises statistical questions that matter when interpreting early-phase, nonrandomized clinical research. Its main endpoint is a participant-level safety percentage, which is straightforward to describe only when the numerator, denominator, follow-up completeness, and uncertainty are available. The registry defines the endpoint and names a 95% confidence interval, but reports neither the endpoint estimate nor its interval. That gap prevents an assessment of both event frequency and precision.

The cohort structure is also important. Participants with newly diagnosed disease after chemoradiation and participants with persistent or recurrent disease after salvage therapy do not form interchangeable comparison groups. Recognizing this prevents a descriptive cohort difference from being mistaken for a treatment contrast. The nonrandomized, open-label design further means that results should be interpreted as observational descriptions rather than as a controlled estimate of causal effect.

Serious adverse events are clinically important, but their statistical meaning depends on clear definitions, denominators, follow-up, attribution, and transparent reporting. The registry gives cohort-specific counts and selected event terms, while leaving the primary safety endpoint result unreported. Those summaries can be read descriptively, but they cannot fill the reporting gap or establish causation.

Finally, the study lists multiple outcomes and no analyses. Reporting which outcomes were analyzed, how missing observations were handled, and whether multiplicity was addressed would help readers distinguish prespecified questions from exploratory ones. The record illustrates why design information, estimates, uncertainty, and analysis methods must be considered together when judging what a small nonrandomized study can establish.

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 limitation for statistical interpretation is that the registry record does not report the primary endpoint result, despite specifying the endpoint and its 95% confidence interval. The primary percentage, its interval, and its analysis denominator are unavailable. The secondary outcome results are also not reported, limiting interpretation of the study’s stated immunogenicity objectives.

The study was nonrandomized and open-label. Its parallel cohorts represented different clinical circumstances, so their outcomes are not a like-for-like comparison. The registry does not report an adjustment strategy for differences between cohorts, and it does not report causal assessments for adverse events. The serious-event counts therefore remain descriptive.

The record does not report a statistical analysis plan, multiplicity procedures, missing-data methods, or details of follow-up completion. These omissions make it difficult to assess how the outcome measures were analyzed and whether incomplete observation could have affected estimates. The cohort descriptions are truncated, so further intervention-administration details are not reported in the registry record. Enrollment was 10, which also limits how much precision can be expected from any participant-level percentage, although the missing confidence interval prevents direct assessment of precision.

Finally, the registry lists 17 outcome measures but no analyses. Without reported results and analytic details, the record cannot establish how the outcomes were handled or support efficacy conclusions. The available safety summaries should not be extended beyond their descriptive scope.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer — NCT02172911.
• Registry record last updated 2021-02-21; status last verified 2021-02.
• Results first posted 2021-02-21.
• 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.

19. Record Summary

This completed, open-label, nonrandomized phase I/IIA study evaluated INO-3112 DNA vaccine delivered by electroporation in women with HPV-16 and/or HPV-18-associated cervical carcinoma. Its two cohorts reflected newly diagnosed disease treated with chemoradiation with curative intent and persistent or recurrent disease treated with salvage therapy. The primary endpoint was the percentage of participants with at least one TEAE up to 36 weeks, with the safety population defined by receipt of at least one dose of study treatment plus electroporation.

The registry record does not report the primary endpoint estimate, its 95% confidence interval, secondary outcome results, or statistical analyses. It does report cohort-specific serious adverse event counts and selected event terms. Because the design was nonrandomized and the cohorts differed clinically, those summaries are descriptive and do not establish causal or comparative treatment effects.