Prospective Trial of Vaccine Responses Against Pneumococcus and Influenza in Adult Cancer Patients 65 Years of Age and Older: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Trial of Vaccine Responses Against Pneumococcus and Influenza in Adult Cancer Patients 65 Years of Age and Older (NCT00741039), a non-randomized phase 2 study. The primary outcome is Determine Response Rate of Patients > or = to 65 Yrs Diagnosed.

2. Clinical Question

The study asks how adults aged 65 years and older with prostate, lung, and/or breast cancer respond to influenza and pneumococcal vaccination. Its stated aim also includes learning how well vaccination protects against disease, but the registry record does not report disease-prevention results.

These details define the question the registry planned to address, but they do not establish what response was observed. The posted results do not report participant-level response counts, response rates, or a comparison of response between the cancer and volunteer groups. They also do not report whether vaccine responses differed by cancer type or by the vaccine regimen received. Accordingly, the registry description supports an account of the intended population and outcome, not a conclusion about the magnitude of vaccine response or protection.

3. Trial Design

This is a Phase II prospective study with non-randomized allocation and no masking. The registry describes a parallel model. Enrollment is listed as 126. The study was sponsored by Memorial Sloan Kettering Cancer Center and is marked completed. The registry lists a start of 2008-08 and primary completion of 2012-08.

The patient group consisted of adults aged 65 years and older with a diagnosis of prostate, lung, and/or breast cancer. The other group consisted of MSKCC employee volunteers aged 65 years and older without a cancer diagnosis. Both group descriptions mention immunization with inactivated influenza vaccine and/or PPV23. The record does not describe random assignment to vaccination groups, nor does it establish that the volunteers and cancer patients were otherwise comparable. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The listed intervention descriptions refer to inactivated influenza vaccine with the 23-valent pneumococcal vaccine, and to inactivated influenza vaccine with PPV23 (Pneumovax). The arm descriptions specify influenza vaccine by intramuscular administration and pneumococcal vaccine by subcutaneous or intramuscular administration. The record does not report how the choice between vaccine regimens or administration routes was determined.

The primary outcome is a response measure for Pneumovax, assessed 8-16 weeks following vaccination. Although the study description discusses influenza and pneumococcal vaccination, the registry record gives no corresponding influenza response definition in the primary outcome description. It also does not report clinical infection outcomes as primary results.

The registry marks one outcome measure and zero analyses. The posted record does not include response estimates, a statistical analysis plan, or results comparing the groups. Details such as eligibility criteria beyond the diagnoses and age description, participant flow, follow-up completeness, and the rationale for the planned enrollment 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:

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 Determine Response Rate of Patients > or = to 65 Yrs Diagnosed, measured over 8-16 weeks following vaccination..

The primary outcome description concerns complete response to Pneumovax, measured 8-16 weeks following vaccination. A participant meets the stated response definition through seroconversion or a greater than three-fold rise in titer against at least 5 of the listed serotypes: 4, 14, 19, 23, 6B, 18C, and 9V. The outcome is specified as a number of participants, so the intended summary is a count of people meeting the response definition.

General: An antibody titer is a laboratory measure used to describe the amount of a particular antibody in a sample. Seroconversion generally refers to a change from a negative to a positive test result under the assay’s definition. A multi-serotype criterion makes the response definition depend on results for several pneumococcal types rather than a single type. These are general descriptions; assay procedures and the precise operational definition of seroconversion are not reported in the registry record.

A response endpoint provides a way to describe an immune measurement after vaccination. It is not by itself a direct count of infections prevented, severity reduced, or deaths avoided. The registry’s stated study aim includes protection against disease, but no disease-prevention endpoint result is reported. Nor does the record post the observed number meeting the complete-response definition, the denominator used for that calculation, or an estimate of uncertainty. The biological response criterion is therefore identifiable, while its observed frequency and its relationship to clinical protection are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: A prospective study defines its intended observations before following participants for those observations. A parallel design follows groups in the same general study period rather than having each participant serve as their own comparison at different treatment periods. These design labels describe the structure; they do not, on their own, establish that the groups are comparable or that an observed difference is caused by vaccination.

What does non-randomized allocation imply?

General: Random allocation is a method for assigning participants to groups so that, in expectation, measured and unmeasured characteristics are not systematically used to choose a group. With non-randomized allocation, this protection against systematic group differences is absent. The registry identifies a cancer patient group and a healthy employee volunteer group, and explicitly says the arms are not a like-for-like control comparison. A direct difference between those groups would therefore need cautious interpretation, even if a result were posted. The record does not report an adjustment strategy or covariates used to address possible differences.

How is the primary response defined?

The primary outcome is a participant count for complete response to Pneumovax, assessed 8-16 weeks following vaccination. Complete response is defined as seroconversion or a greater than three-fold rise in titer against at least 5 of the listed serotypes. General: A binary response outcome classifies each participant as meeting or not meeting a stated criterion. A count of participants meeting that criterion can be converted to a response rate only when the relevant denominator is known and specified. The registry record does not post the response count or denominator, so a response rate cannot be interpreted from this record.

General: A confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval. No confidence interval for the response measure is reported. Similarly, a p-value would summarize how compatible observed data are with a specified statistical model or null hypothesis; it does not measure the size or clinical importance of an effect. No p-value or hypothesis test for the primary response is reported in the registry record.

Why does the analysis plan matter?

The registry lists zero analyses. The statistical analysis plan, including any model choice, covariate adjustment, handling of multiple outcomes, and planned subgroup analyses, is not reported in the registry record. Without this information, readers cannot determine whether the posted outcome definition was analyzed as planned, whether comparisons were adjusted, or how uncertainty was to be quantified. This is not evidence that a particular method was or was not used; the methods are simply not reported in the registry record.

General: Over-dispersion occurs when count variation is greater than a model assumes. In a binary-outcome setting, dependence among observations or variation across groups can also make simple uncertainty calculations too narrow if the analysis assumes independent, similarly distributed observations. The registry does not report a model or provide information allowing assessment of these issues. No conclusion about over-dispersion or dependence can therefore be drawn for this study.

How should planning illustrations be read?

The sample-size assumptions describe planning illustrations using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is stated as a fraction of the observed effect. General: A sample-size calculation estimates the amount of information needed to detect a specified effect under chosen assumptions. When an illustration is based on an observed effect, it is conditional on that effect estimate and its uncertainty; it does not show that the completed study had a particular probability of detecting an effect. These figures are planning illustrations, not observed power. The registry record does not report the trial’s own sample-size justification or the effect estimate needed to evaluate the illustrations.

For this record, no recalculated response estimate or analysis result is posted. Thus there is no sponsor analysis to compare with an unadjusted recalculation, and no basis for reconstructing an effect from summary statistics. Any estimate requiring unreported counts or denominators would go beyond the registry record. The main statistical reading is therefore about the design and the limits of what is available: a clearly described response criterion, a non-randomized group structure, and no reported primary outcome analysis.

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("Adult Cancer Patients 65 Years of Age and Older", "Healthy Volunteers")
n      <- c(100, 25)
events <- c(63, 24)
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  Adult Cancer Patients 65 Years of Age and Older  100  63  63.0  52.8  72.4  53.2  71.8  53.2  71.8
ARM  Healthy Volunteers  25  24  96.0  79.6  99.9  80.5  99.3  80.4  99.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one outcome measure, but it does not report a multiplicity strategy. The record also describes interest in both influenza and pneumococcal vaccine responses and in protection against disease, while the primary outcome description specifically defines pneumococcal response. It does not explain whether other outcomes were planned, how multiple comparisons would be handled, or whether any outcome hierarchy was specified. Those analysis details are not reported in the registry record.

The number of analyses is listed as zero. The record does not post an analysis population, participant flow, response denominators, or a method for handling missing measurements. It is not reported whether participants without follow-up titers were excluded, counted as nonresponders, or handled by another method. It is also not reported whether missingness differed across groups or vaccine regimens. Without those details, the completeness and comparability of outcome ascertainment cannot be assessed.

The registry does not specify an intention-to-treat, per-protocol, or other analysis population. It does not report how protocol deviations, incomplete vaccination, or unavailable laboratory measurements were handled. These omissions are important because the analyzed population and missing-data rules can affect the interpretation of a response count. No conclusion about the direction or size of any such effect is possible from the record.

General: Multiplicity arises when several outcomes, groups, or analyses are examined; doing so can increase the chance of apparently notable findings unless interpretation accounts for the analysis plan. Missing-data methods likewise depend on why observations are unavailable and on assumptions about the unobserved values. These are general statistical considerations, not claims about what occurred in this study. The registry record does not report enough information to assess either issue empirically.

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.

The registry lists 0 serious adverse events and 0 other adverse events for the adult cancer patient group, with 95 at risk. For healthy volunteers, it lists 0 serious adverse events and 0 other adverse events, with 25 at risk. These are the posted event counts and corresponding at-risk figures; they should not be interpreted as an estimate of comparative safety between the groups.

A zero reported count means that no events are listed in that category in the registry record. It does not establish that no events occurred outside the recorded definitions or collection period, and it does not establish that an intervention has no risk. The record does not report how adverse events were defined, actively solicited, graded, attributed, or followed over time. It also does not describe whether reporting was complete for all participants.

Death counts are not reported in the registry record. The listed adverse-event counts do not replace the primary immune-response outcome and do not provide a basis for estimating protection from infection. Differences between the cancer patients and healthy volunteers would also require caution because the study was not randomized and the registry identifies the groups as not like-for-like controls.

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

The record documents a prospective Phase II study of vaccine responses in adults aged 65 years and older with selected cancers, alongside healthy employee volunteers without a cancer diagnosis. It defines a Pneumovax complete-response measure based on seroconversion or a greater than three-fold titer rise against at least 5 listed serotypes, with assessment 8-16 weeks following vaccination. It also reports the study as completed.

What the record does not provide is the observed response count or response rate. It does not report a confidence interval, a test of group differences, or an adjusted estimate. As a result, the posted information cannot establish how often participants met the response criterion, whether response differed between the patient and volunteer groups, or how precise any estimate would be. It also cannot establish vaccine effectiveness against influenza or pneumococcal disease, because clinical protection results are not reported.

General: An immune-response measurement can be informative about a biological response, but it is not interchangeable with a clinical outcome. A serologic criterion does not by itself show that infections were prevented or that their severity changed. The registry’s rationale discusses prevention, but the available record does not give clinical disease results that would answer that question.

The non-randomized design further limits causal interpretation of comparisons between the groups. The groups differ by cancer status and volunteer status as described in the registry, and the record does not report adjustment for these or other characteristics. Any group contrast, if available elsewhere, would need to be interpreted in light of that design rather than treated automatically as an effect of vaccination or cancer status.

The safety counts are also narrow: the registry lists zero serious and zero other adverse events for each group, but does not report event ascertainment methods or death counts. Those entries are not proof of absence of risk. Overall, the study record identifies a population, intervention context, and response definition; it does not report the outcome estimates needed for conclusions about response magnitude, comparative effects, clinical protection, or precision.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between an outcome definition and an outcome result. The registry gives a specific Pneumovax response criterion and assessment window, allowing readers to understand what the investigators intended to measure. Yet it lists zero analyses and does not post the response counts or estimates. A precise endpoint definition cannot substitute for the results needed to estimate response frequency or uncertainty.

The design also highlights why comparator construction matters. The registry distinguishes adults with selected cancers from healthy employee volunteers and identifies the study as non-randomized. It explicitly cautions that the arms are not like-for-like controls. Statistical comparisons do not remove this design limitation simply by producing a numerical contrast; interpretation depends on whether the groups are sufficiently comparable and whether relevant differences are measured and handled. The record does not report those analytical details.

The sample-size assumptions illustrate a separate distinction between planning and evidence. The stated illustrations use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of an observed effect. Such assumptions describe a planning exercise. They are not the observed outcome, and they are not observed power. Since the registry does not report the response estimate or the trial’s own sample-size justification, those assumptions cannot establish the study’s precision or ability to answer its primary question.

Finally, the separation between immune markers and clinical outcomes is important. A measured antibody response is not itself a count of infections prevented. The registry’s aim refers to protection, but clinical protection results are not posted. The record therefore supports careful statistical description of design and measurement, while leaving efficacy, comparative response, and uncertainty unresolved.

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 are specific to the information and design described in this record. Allocation was non-randomized, with cancer patients compared against healthy employee volunteers. The registry explicitly cautions that these are not like-for-like controls. This makes a direct group comparison vulnerable to differences between populations and limits causal interpretation. The record does not report adjustment methods or participant characteristics that could help assess comparability.

The intervention descriptions include inactivated influenza vaccine and/or a pneumococcal vaccine. The record does not explain how participants were assigned to vaccine regimens, whether all participants received the same combination, or how routes of administration varied. It therefore does not support interpretation by regimen or route. The primary response description is specific to Pneumovax; an influenza response definition is not reported in the registry record.

The response outcome is described, but laboratory methods and details of seroconversion are not reported. The registry does not post response counts, denominators, estimates, uncertainty intervals, or analyses. It also does not report participant flow, completeness of follow-up, missing-data handling, or the analysis population. These gaps prevent assessment of outcome precision and of the potential influence of incomplete measurements.

The study rationale includes protection from disease, but clinical infection outcomes are not posted. Safety reporting is limited to the listed event counts; event definitions, ascertainment, follow-up, and death counts are not reported. The registry does not report a multiplicity strategy, statistical analysis plan, or the study’s own sample-size justification. These limitations concern what can be concluded from the registry record; they do not establish what occurred beyond what is recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prospective Trial of Vaccine Responses Against Pneumococcus and Influenza in Adult Cancer Patients 65 Years of Age and Older — NCT00741039.
• Registry record last updated 2015-11-20; status last verified 2015-10.
• Results first posted 2015-11-20.
• 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

The registry describes a completed, prospective Phase II study with non-randomized allocation, no masking, and a parallel model. Enrollment is listed as 126. The study concerns adults aged 65 years and older with prostate, lung, and/or breast cancer and MSKCC employee volunteers of the same age threshold without a cancer diagnosis. Both groups are described as receiving inactivated influenza vaccine and/or pneumococcal vaccine.

The primary outcome description defines complete Pneumovax response as seroconversion or a greater than three-fold titer rise against at least 5 listed serotypes, assessed 8-16 weeks following vaccination. The registry lists one outcome measure and zero analyses, and does not report the response results. It cautions that the groups are not like-for-like controls.

Adverse-event entries list 0 serious and 0 other adverse events for the cancer group, with 95 at risk, and for healthy volunteers, with 25 at risk. Death counts are not reported. The record does not provide clinical protection estimates, response-rate estimates, confidence intervals, or a statistical analysis plan.