Determine Toxicity and Antibody Responses With a KLH Conjugated Bivalent Vaccine Containing GD2 Lactone, GD3 Lactone With Immunological Adjuvant QS-DG or OPT-821 in Patients With Disease Free AJCC Stage III or IV Cutaneous Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Determine Toxicity and Antibody Responses With a KLH Conjugated Bivalent Vaccine Containing GD2 Lactone, GD3 Lactone With Immunological Adjuvant QS-DG or OPT-821 in Patients With Disease Free AJCC Stage III or IV Cutaneous Melanoma (NCT00597272), a na na study. The primary outcome is Toxicity.

2. Clinical Question

3. Trial Design

This completed pilot trial enrolled patients with melanoma and is described as a single-group study. The title specifies patients with disease-free AJCC stage III or IV cutaneous melanoma. The registry lists enrollment as 34, the start as 2007-12, primary completion as 2012-11, and status as completed. The phase is recorded as NA.

The listed biological intervention is KLH conjugates with GD2L and GD3L. The trial title describes the bivalent vaccine as being used with QS-DG or OPT-821, but the registry intervention entry does not identify an adjuvant assignment for each cohort. The record lists cohorts 1A, 1B, 1C, 2A, 2B, 2C, and 3. It does not explain how these cohorts were formed or establish that they represent treatment arms suitable for direct comparison.

Allocation is recorded as NA, and the study model is single group. Masking is listed as none. Thus, the registry does not describe a masked or randomized comparison. A single-group pilot can describe observed outcomes within the enrolled cohort, but without a concurrent control group it cannot separate outcomes associated with the intervention from outcomes that might also occur without it.

The primary outcome is toxicity over 2 years, expressed as a number of participants and graded according to CTCAE version 3.0. The record does not report a statistical analysis plan, eligibility criteria in detail, the treatment schedule, or cohort-specific intervention details. These elements are not reported in the registry record, so the cohort labels should not be used to infer them.

4. Participant Flow and Accounting

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

Only the first 6 of 7 groups are shown.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Toxicity, measured over 2 years.

The primary endpoint is toxicity, recorded as the number of participants, with a timeframe of 2 years. The registry description says toxicity was to be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This grading framework classifies adverse events by their severity, so it can organize safety observations in a consistent way. The record does not specify which toxicity grades were included in the primary count or provide a threshold defining a primary toxicity event.

A count of participants with an event is a binary-outcome summary at the participant level: each person is classified according to whether the outcome occurred. Such a summary can be useful in a pilot study because it makes the observed frequency of a safety outcome easier to describe than a list of individual reports. However, it does not convey the timing, duration, recurrence, or full clinical course of events. Those details are not reported in the registry record.

The specified 2-year timeframe is important when interpreting a safety count. It defines the outcome’s stated observation period, but the registry record does not explain how incomplete follow-up was handled or whether every participant was observed for the full period. Nor does it provide a primary-endpoint result or a formal statistical analysis. The posted adverse-event counts offer some safety information, but they do not substitute for a reported analysis of the prespecified primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of study is described?

The registry classifies this as a single-group study, with allocation recorded as NA and masking listed as none. These design features matter because they define what kind of statistical conclusion the data can support. In general, a single-group study describes outcomes among participants receiving the intervention. Without a concurrent control group, it cannot estimate what would have happened to comparable participants under a different treatment or no treatment. Cohort labels do not create a controlled comparison unless the design and allocation process support that interpretation.

The title refers to QS-DG or OPT-821, but the registry’s intervention entry lists KLH conjugates with GD2L and GD3L without specifying cohort-level adjuvant assignment. The design information needed to identify a contrast between these adjuvants is not reported in the registry record. Therefore, comparisons between the listed cohorts should not be treated as randomized or otherwise controlled treatment-effect estimates.

What does a participant count capture?

The primary outcome is a number of participants with toxicity, with a stated timeframe of 2 years. For a binary outcome, each participant is categorized according to whether the event occurred within the defined period. A count is straightforward to interpret, but it is only one part of the statistical picture. Its meaning depends on the event definition, the number of participants observed, and the completeness of follow-up. The registry record says toxicity is graded using CTCAE version 3.0 but does not state which grades count toward the primary endpoint or how missing observations are handled.

In general, a count can be accompanied by a proportion and an uncertainty interval to describe the observed frequency and its precision. No primary-endpoint proportion or confidence interval is reported in this record. A confidence interval, in general, represents a range of estimates compatible with the data under a specified statistical method; it helps show how uncertain an estimate may be. It would not resolve design limitations such as the absence of a comparator or unclear outcome ascertainment.

Why does the cohort structure matter?

The adverse-event record presents outcomes by cohort, but the registry does not report how participants were assigned to those cohorts or whether the cohorts were intended to represent treatment alternatives. Small cohort entries can contain few observations, making any apparent difference especially sensitive to individual events. More generally, sparse binary data can yield imprecise estimates and unstable comparisons. The appropriate conclusion from the posted counts is descriptive, not a claim of a cohort effect.

Over-dispersion is a general concern when outcome variability is greater than a simple statistical model expects. It can arise when participants differ in ways the model does not capture or when outcomes cluster. Accounting for it can widen uncertainty and change inferential results. The registry record does not report a model, adjustment for over-dispersion, or any other primary-outcome analysis, so there is no basis for saying whether it was considered.

What can the planning assumptions establish?

The sample-size assumptions describe an illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. For time-to-event outcomes, the planning quantity is the total number of events; for other outcomes, it is participants per arm. These are planning conventions, not evidence that the trial used a two-arm randomized design. The actual study is recorded as single group, and no primary-outcome analysis is listed. Any planning figures should be understood as illustrations rather than observed power or a retrospective demonstration that the trial could detect an effect.

In general, power is a design-stage probability of detecting an effect of a specified size under stated assumptions. It is not a measure of whether an observed result is reliable, and it cannot make a noncomparative design answer a comparative question. The registry does not report its own sample-size justification or statistical plan, so the planning assumptions do not establish why enrollment was set at 34.

What analyses are actually reported?

The registry lists 0 analyses. It does not report a primary-outcome estimate, a hypothesis test, a confidence interval, adjustment for covariates, or a prespecified method for comparing cohorts. The adverse-event counts can be read as descriptive safety records, but they should not be mistaken for adjusted estimates or a formal test. General statistical methods such as regression, exact tests, or survival analysis cannot be attributed to this trial unless the record states that they were used. They are not reported in the registry record.

For safety data, a serious-event count of zero in a cohort is an observed count, not proof that the underlying risk is zero. In general, sparse event data leave substantial uncertainty about the range of plausible event rates, especially when the number at risk is small. The record does not provide uncertainty intervals or enough analysis detail to quantify that uncertainty. The other-event counts are also descriptive and do not indicate severity, duration, or causality unless those features are separately defined.

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 1A", "Cohort 1B", "Cohort 1C", "Cohort 2A", "Cohort 2B", "Cohort 2C")
n      <- c(1, 1, 10, 1, 1, 10)
events <- c(1, 1, 6, 1, 1, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1A  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Cohort 1B  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Cohort 1C  10  6  60.0  26.2  87.8  31.3  83.2  30.8  83.3
ARM  Cohort 2A  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Cohort 2B  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  Cohort 2C  10  7  70.0  34.8  93.3  39.7  89.2  39.0  89.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 0 analyses and does not report a statistical analysis plan. It therefore does not establish which comparisons, if any, were planned, which outcomes were considered primary or secondary beyond the toxicity outcome listed, or whether statistical testing was intended. The title and summary discuss antibody responses, but the listed primary outcome is toxicity; the registry does not report an analysis of antibody response in the outcome information.

Multiplicity arises in general when many outcomes, time points, subgroups, or comparisons are examined. Repeated testing can increase the chance of an apparently notable result occurring by chance. Statistical plans may address this through a prespecified hierarchy or adjustment, but no such approach is reported in the registry record. The cohort-level adverse-event counts should consequently be treated as descriptive rather than as a set of formal tests.

The record does not report missing-data methods, follow-up completeness, or how participants without complete observation were handled. These details matter for an outcome with a 2-year timeframe: if observation differs among participants, a simple count may not represent the same opportunity for event detection for everyone. No imputation method, censoring rule, or sensitivity analysis is reported.

The analysis population is also not reported in detail. The registry lists enrollment as 34, but does not state which participants were included in each primary-outcome analysis or whether anyone was excluded from safety summaries. A complete-case population, an intention-to-treat population, and a safety population can differ in membership and interpretation. None should be assumed without an explicit definition.

These reporting gaps limit assessment of the analysis choices and of how robust the findings are to missing observations or alternative definitions. They do not establish that no such procedures occurred; the procedures are simply not reported 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 safety entries distinguish serious events from other events and list the number at risk and the number affected in each cohort. The serious-event counts are 0 for cohorts 1A, 1B, 1C, 2A, 2B, 2C, and 3. Their corresponding at-risk counts are 1, 1, 10, 1, 1, 10, and 10. The counts for other events, in the same cohort order, are 1, 1, 6, 1, 1, 7, and 10.

These are cohort-specific counts, not comparative effect estimates. The cohorts are not reported as randomized treatment groups, and the registry does not explain their formation or specify which adjuvant each received. A reader therefore should not interpret differences in counts as evidence that one vaccine formulation caused a different event burden.

A zero recorded serious-event count means no serious event was recorded among the participants listed at risk for that cohort; it does not prove that the true risk is zero. In general, small numbers at risk make event-frequency estimates imprecise. No uncertainty intervals or event-rate analysis are reported. The record also does not provide definitions for the other-event category beyond the adverse-event grouping, or details of severity, timing, duration, or attribution.

Deaths are not reported in the registry record. The serious-event counts should not be read as a complete account of toxicity, because the primary endpoint includes toxicity graded under CTCAE version 3.0 and no analysis of that endpoint is reported.

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

The record documents a completed pilot study of a KLH-conjugated vaccine containing GD2L and GD3L in patients with melanoma. It identifies toxicity over 2 years as the primary outcome and states that toxicity was to be graded using CTCAE version 3.0. The safety entries provide cohort-level counts for serious and other adverse events. These observations contribute descriptive information about events recorded in the study.

They do not constitute a reported analysis of the primary endpoint. The record does not give an endpoint estimate, confidence interval, statistical test, or detailed definition of the toxicity threshold used for the participant count. It also does not state how missing follow-up was handled. As a result, the precision and completeness of the primary safety outcome cannot be assessed from the registry information.

The study is listed as single group, with allocation recorded as NA and no masking. It does not identify a concurrent control group. The cohort names do not establish a controlled comparison, and the intervention entry does not specify which cohort received QS-DG or OPT-821. Consequently, the adverse-event counts do not show that one cohort or adjuvant is safer than another, and they cannot establish a causal effect of the vaccine.

The trial title and summary discuss the goal of raising antibodies against GD2 and GD3. That rationale is not itself a trial result. The listed primary outcome is toxicity, and the registry information does not report an antibody-response analysis. The record therefore does not establish whether antibody levels changed or whether any change was associated with a clinical outcome.

In statistical terms, the posted findings support a limited description of recorded events, not a definitive estimate of comparative benefit or harm. Absence of a reported analysis does not mean that no analysis occurred outside the registry, but any such analysis is not reported in the registry record. Interpretation should remain confined to the outcomes and design details that are recorded.

14. Why This Trial Matters Statistically

This trial illustrates how a registry record can contain useful descriptive safety data while leaving important inferential questions unanswered. The record identifies a defined primary outcome, a grading framework, and a stated observation timeframe. Those elements make clear what safety domain the study intended to assess. At the same time, the absence of a reported primary-outcome analysis means readers cannot evaluate an estimated toxicity frequency with its statistical precision.

The single-group design is also central to interpretation. In general, a pilot study can describe feasibility or observed events, but a treatment effect requires an appropriate comparison and a design that supports causal interpretation. Here, allocation is recorded as NA, and the cohort labels are not enough to establish treatment contrasts. This distinction prevents descriptive variation between cohorts from being mistaken for evidence that one formulation is preferable.

The record also demonstrates why intervention detail matters. The trial title refers to QS-DG or OPT-821, whereas the listed intervention describes the conjugated vaccine without cohort-specific adjuvant assignments. Without that mapping, the safety counts cannot be connected to a particular adjuvant contrast.

Finally, safety summaries need context: event definitions, numbers at risk, follow-up completeness, and uncertainty. The registry supplies cohort-level counts and at-risk counts, but not the additional analysis details needed to judge precision or completeness. A zero serious-event count is informative as an observation, yet it cannot establish zero underlying risk. These are general principles for interpreting sparse event data, and they are particularly relevant when the listed cohorts are small.

The statistical lesson is not that the study is uninformative. Rather, the record can support a careful account of what was recorded while making clear that comparative and causal claims are beyond what the reported design and analyses 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.

Several limitations specific to this trial constrain interpretation. The registry identifies a single-group design and does not describe a concurrent comparator. Allocation is recorded as NA, so the cohort entries should not be treated as randomized treatment arms. Cohort formation and the rationale for the seven cohort labels are not reported in the registry record.

The trial title includes QS-DG or OPT-821, but the intervention entry lists only KLH conjugates with GD2L and GD3L. The record does not state which adjuvant was used in each cohort, whether treatment differed across cohorts, or whether any cohort contrasts were planned. This prevents a reliable link between the adverse-event counts and specific intervention components.

The primary endpoint is described as toxicity graded using CTCAE version 3.0 over 2 years, but the record does not define the toxicity threshold counted for the primary outcome. No primary-outcome analysis is listed. The posted adverse-event counts do not supply an analysis of all toxicity grades, and details such as event timing, duration, recurrence, and attribution are not reported.

Although enrollment is listed as 34, the registry does not report a detailed analysis population, follow-up completeness, or methods for handling missing data. It also does not report a sample-size justification, an analysis plan, or methods addressing multiplicity. These omissions limit the ability to assess precision, selection, and robustness. Deaths are not reported in the registry record.

These limitations do not show that information or procedures were absent from the conduct of the study. They indicate that the registry record does not report them, and that conclusions should be limited to the recorded design and descriptive adverse-event counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Determine Toxicity and Antibody Responses With a KLH Conjugated Bivalent Vaccine Containing GD2 Lactone, GD3 Lactone With Immunological Adjuvant QS-DG or OPT-821 in Patients With Disease Free AJCC Stage III or IV Cutaneous Melanoma — NCT00597272.
• Registry record last updated 2016-09-20; status last verified 2016-08.
• Results first posted 2016-08-10.
• 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, single-group pilot study concerns a KLH-conjugated bivalent vaccine containing GD2L and GD3L in patients with melanoma. The trial title describes patients with disease-free AJCC stage III or IV cutaneous melanoma and mentions QS-DG or OPT-821. The registry lists enrollment as 34, status as completed, and toxicity as the primary outcome over 2 years, graded using CTCAE version 3.0.

Allocation is recorded as NA, masking as none, and the study model as single group. The registry lists seven cohorts and reports cohort-level counts for serious and other adverse events. It lists 0 analyses and does not report a primary-endpoint analysis, a statistical plan, cohort-specific adjuvant assignments, missing-data methods, or deaths. The adverse-event entries are descriptive and do not establish a controlled comparison or causal treatment effect.