Feasibility of Cocooning Immunization Strategy With Influenza Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility of Cocooning Immunization Strategy With Influenza Vaccine (NCT00570037), a non-randomized na study. The primary outcome is Influenza Vaccine Coverage (Percent) for New Mothers of Newborns.

2. Clinical Question

The study addresses a practical prevention strategy: increasing vaccination among people in close contact with newborns. The record’s rationale notes that influenza vaccine is not approved for infants under 6 months of age and describes vaccination of household contacts as a cocooning strategy. The evaluation focuses on program implementation and maternal vaccine coverage rather than a reported comparison of infant influenza illness. Although household contacts are part of the program, the named primary outcome is specifically coverage among new mothers. The registry record does not report a separate primary coverage result for household contacts.

3. Trial Design

This was a completed, parallel, non-randomized study sponsored by Duke University. The registry record lists enrollment of 544 and records the phase as NA. The study ran from 2007-10 through primary completion in 2008-04. It compared a hospital implementing an immunization program with a hospital where vaccination was available through routine clinical care. There was no masking.

The intervention hospital used standing postpartum vaccine orders for birth mothers, a vaccine clinic on the postpartum ward for household contacts, and mailed reminders for household contacts. The comparison hospital had no study immunization program. The intervention was trivalent inactivated influenza vaccine. The brief description identifies Durham Regional Hospital and Duke University Medical Center as birthing hospitals serving Durham and surrounding counties in central North Carolina, and describes Duke University Hospital as a comparison setting. The registry arm descriptions distinguish the hospitals by program status; the record does not provide further detail about how hospital assignment or site selection was determined.

Because allocation was non-randomized and the program was implemented at the hospital level, differences between hospitals could be associated with differences in vaccine coverage. The registry record explicitly cautions that the arms are not a like-for-like control comparison. It does not report whether the analysis adjusted for measured differences between hospitals or participants. The record lists three outcome measures and no statistical analyses. The exact methods for recruitment, outcome collection, and analysis are not reported in the registry record.

The design is therefore best read as a comparison of coverage across two different care settings, one of which introduced a package of vaccination strategies. It is not a randomized estimate of the isolated effect of any one component, such as standing orders or mailed reminders. The record does not report a separate comparison that can distinguish the contribution of each component.

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 Influenza Vaccine Coverage (Percent) for New Mothers of Newborns, measured over Pregnancy period through 6 to 8 weeks postpartum.

The primary endpoint is influenza vaccine coverage among new mothers delivering at the hospital. It is defined as the percentage reporting that they received an influenza vaccine during pregnancy, in hospital after delivery, or during the 6 to 8 week postpartum period. This is a binary outcome at the individual level: a mother either meets the endpoint definition by reporting vaccination within those periods or does not. The reported summary is a percentage.

Coverage is a relevant measure for an implementation program because the program is intended to make vaccination more accessible and encourage uptake among mothers and household contacts. It captures whether vaccination was reported within the specified time window, rather than measuring the number of program components used or the incidence of influenza. The endpoint description does not establish that vaccination was verified through medical records, and the registry record does not report further information about how reports were collected or confirmed.

The defined outcome combines vaccination received at different times and places: during pregnancy, after delivery in hospital, or in the postpartum period. A coverage percentage therefore represents the combined endpoint definition, not a separate estimate for each setting or period. The registry record does not report the primary endpoint result, its uncertainty, or the number of mothers included in its analysis. Without those results, the endpoint definition can be explained, but the observed coverage in either hospital and the difference between them cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level measure summarized as a percentage. In general, a coverage percentage is calculated from the number of participants meeting the endpoint definition relative to the number with outcome information, with the result expressed as a proportion or percent. The registry record does not report the numerator, the outcome denominator, or the resulting percentage for either hospital, so no outcome calculation can be reconstructed or checked from the record.

What does a confidence interval communicate?

In general, a confidence interval expresses statistical uncertainty around an estimate. For a coverage percentage or a difference in percentages, a narrow interval indicates greater precision under the statistical model, while a wide interval indicates less precision. The interval’s meaning depends on the analysis and its assumptions, and it does not account automatically for systematic differences between groups. No confidence interval for the primary outcome is reported in the registry record.

Why does the design matter for the comparison?

Random allocation can help balance measured and unmeasured characteristics across groups on average. This study was non-randomized: the program and routine-care comparison were associated with different hospitals. Consequently, a difference in coverage could reflect the program, differences in the hospital settings, or both. This is a general limitation of non-randomized comparisons, not proof that a particular source of bias occurred. The record does not report an adjustment strategy, a model specification, or details of measured covariates.

The intervention also combines several actions. In general, when multiple strategies are introduced together, a comparison of the overall program cannot isolate the effect of each action unless the design or analysis provides separate contrasts. The registry record describes standing orders, a postpartum vaccine clinic, and mailed reminders, but does not report component-specific analyses. It also does not report whether vaccine availability or delivery differed in other ways across the settings.

How should planning calculations be read?

Any sample-size illustrations associated with the posted material are planning illustrations, not observed power and not trial findings. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These calculations do not establish that the study had a particular probability of detecting an effect after the data were collected. The registry record does not report the original design’s sample-size justification, or whether the study was planned around a particular target effect.

More generally, sample-size planning asks how much information a future study might need under specified assumptions. It depends on the outcome rate, the effect the study is designed to detect, the chosen error rate, allocation, and analysis method. If those assumptions do not match the eventual study or the assumptions are uncertain, a planning calculation may not describe the achieved precision. It cannot substitute for an estimate and confidence interval based on the observed outcome data. No numerical planning results are stated in the registry record.

What analyses are available?

The registry record lists three outcome measures and zero statistical analyses. It names the maternal coverage measure as primary, but does not provide an inferential method, adjusted or unadjusted estimates, a p-value, a confidence interval, or an analysis population. It is therefore not possible to determine from the record whether the intended comparison was a difference in percentages, a model-based contrast, or another form of analysis. No method should be attributed to the study without documentation.

For a binary percentage outcome, general approaches may report each group’s percentage and a direct contrast between groups. The contrast and its uncertainty are often more useful for comparing groups than separate percentages alone, but its validity still depends on how participants were selected, how missing outcome information was handled, and whether the analysis accounts for the design. This is general statistical context, not a description of an analysis reported for this study. The registry record does not contain enough outcome detail to assess these features.

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("Hospital With Immunization Program", "Hospital With No Immunization Program")
n      <- c(238, 306)
events <- c(167, 196)
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  Hospital With Immunization Program  238  167  70.2  63.9  75.9  64.1  75.6  64.1  75.6
ARM  Hospital With No Immunization Program  306  196  64.1  58.4  69.4  58.5  69.2  58.5  69.2

11. Multiplicity, Missing Data and Analysis Populations

The record lists three outcome measures, but it does not report a multiplicity plan or identify the methods used to account for testing multiple outcomes. In general, examining several outcomes can increase the chance of a seemingly notable result arising by chance when each is tested separately. A prespecified hierarchy or adjustment can address some multiplicity concerns, but neither is reported in the registry record. The primary outcome is named, yet the relationship between it and the other listed outcomes is not explained in the available record.

Missing data are also not described. The registry record does not report how many participants had primary outcome information, whether any outcome reports were incomplete, how missing values were treated, or whether sensitivity analyses were performed. For a reported percentage, the denominator and the handling of missing responses matter: excluding participants without outcome information can yield a different interpretation from treating them as not vaccinated. The record does not state which approach, if any, was used.

The analysis population is not reported in the registry record. It is therefore unclear whether the primary outcome was analyzed among all enrolled participants, among respondents with available information, or according to another definition. The overall enrollment and the safety entries do not resolve that question. The record also does not report a statistical analysis plan, interim analyses, or whether any results were selected for reporting according to a prespecified procedure. These omissions limit assessment of how complete and comparable the outcome data were, and whether the reported analysis—if one was conducted—followed a predetermined plan.

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 0% reporting threshold.

The serious adverse event entries list zero affected participants in both groups. The hospital with an immunization program has 238 participants at risk, and the hospital with no immunization program has 306 participants at risk. These are the figures recorded for the safety entries; they are not primary outcome results and should not be treated as the denominators for maternal vaccine coverage.

A zero count in these entries means that no serious adverse events are recorded for the listed groups in this registry record. It does not establish that no adverse events of any kind occurred, and it does not show that the groups had equivalent safety experience. The record does not list serious adverse event terms, and it does not report a safety observation window or further detail about ascertainment. The entries for other adverse events do not provide additional interpretable event information in the registry record.

Because the comparison was non-randomized, the safety figures should also be read as descriptive group counts rather than as a randomized safety comparison. These entries alone do not establish causation or quantify comparative risk. They should not be used to infer safety beyond what the registry record explicitly records.

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

The study record describes an evaluation of a hospital-based effort to increase influenza vaccination among new mothers and household contacts of newborns. Its primary endpoint is the percentage of new mothers reporting vaccination during pregnancy, after delivery in hospital, or during the 6 to 8 week postpartum period. The program combined standing postpartum orders, a postpartum vaccine clinic for household contacts, and mailed reminders. The comparison setting relied on routine clinical care.

The registry record does not report the primary coverage percentages or a comparison estimate. It therefore does not show whether coverage was higher or lower at the hospital with the program, how large any difference might have been, or how precise an estimate would be. The absence of a posted result is not evidence that the program had no effect; it means the registry record does not supply the outcome information needed to judge that question.

Even with a reported difference, this design would not by itself establish that the program caused it. The study was non-randomized, and the two groups were defined by different hospitals. The record itself cautions that the arms are not a like-for-like control comparison. Hospital-level differences could be entangled with the program contrast, and the record does not report adjustment methods or enough participant information to assess their influence.

The endpoint is coverage, not influenza infection or complications in newborns. Thus, it could describe reported maternal vaccine uptake without demonstrating a change in infant health outcomes. The program involved household contacts as well, but the listed primary endpoint concerns new mothers. The registry record does not provide a separate household-contact result in the primary outcome information described.

The appropriate takeaway is limited: the record documents the question, intervention package, comparison setting, and endpoint, alongside serious adverse event counts of zero in both groups. It does not provide the primary outcome findings or the statistical details needed to evaluate the size, precision, or causal interpretation of a coverage comparison.

14. Why This Trial Matters Statistically

This study illustrates a common challenge in clinical and public health evaluation: a program may be introduced in one service setting and compared with routine care elsewhere, rather than assigned randomly to individuals or sites. Such a design can be useful for examining implementation in real hospital contexts, but it complicates causal interpretation. Program status and hospital identity are linked, so any observed contrast could reflect more than the program itself.

The outcome also demonstrates why the endpoint must be kept distinct from the broader rationale. Maternal vaccine coverage is a measurable implementation outcome, while the stated motivation concerns protecting infants who are too young to receive influenza vaccine. A coverage result, even if available, would not by itself measure whether infant influenza illness changed. Keeping these outcomes separate prevents an uptake measure from being treated as direct evidence about a clinical outcome not reported as the primary endpoint.

The intervention is a bundle of strategies. This matters statistically because an overall comparison estimates the contrast associated with the package as implemented, not the separate effect of every component. Distinguishing component effects would require data and analysis that the registry record does not report.

Finally, the registry record shows that a trial description and safety counts do not guarantee that outcome estimates are available for interpretation. Without group-specific coverage, denominators, and measures of uncertainty, readers cannot assess the size or precision of the primary comparison. This example underscores the value of complete outcome reporting, clear analysis populations, and explicit methods for non-randomized comparisons.

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 principal limitation for interpreting the study is that the primary outcome result is not reported in the registry record. No group-specific maternal coverage percentages, outcome denominators, comparison estimate, confidence interval, or p-value are listed. The record also lists no statistical analyses. This prevents assessment of the observed coverage level, the direction or size of a difference, and its precision.

The non-randomized design compares hospitals rather than randomized groups. The registry record explicitly says the arms are not a like-for-like control comparison. Any contrast could be influenced by differences associated with hospital setting, and the record does not report participant characteristics or an adjustment method that would help evaluate this concern. The intervention is a package of strategies, so the design description does not isolate the contribution of individual components.

The endpoint depends on reported vaccination within a combined period. The record does not describe how reports were obtained or verified in sufficient detail to assess outcome measurement, and it does not report whether information was missing or how missing information was handled. The primary analysis population and outcome denominator are also not reported. Although enrollment is listed, it cannot establish the number of participants included in the endpoint analysis.

The record gives limited information about other outcomes and analysis procedures. It lists three outcome measures but does not report a multiplicity approach, an analysis plan, interim analyses, or a sample-size justification. The serious adverse event entries provide counts but no event terms or observation window. These limits do not establish that the study procedures were inadequate; they define what can and cannot be evaluated from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility of Cocooning Immunization Strategy With Influenza Vaccine — NCT00570037.
• Registry record last updated 2013-06-24; status last verified 2011-01.
• Results first posted 2011-02-01.
• 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

NCT00570037 is a completed, parallel, non-randomized study sponsored by Duke University, with enrollment of 544. It compared a hospital using an influenza immunization program with a hospital where vaccination was available through routine clinical care. The program included standing postpartum vaccine orders, a postpartum clinic for household contacts, and mailed reminders. The registry record lists no masking and records the phase as NA.

The primary outcome was maternal influenza vaccine coverage, defined by reported vaccination during pregnancy, after delivery in hospital, or during the 6 to 8 week postpartum period. The primary outcome result and statistical analyses are not reported in the registry record. Serious adverse event entries record zero affected participants in each group, with 238 and 306 participants at risk, respectively. The comparison is non-randomized, and the registry cautions that the arms are not a like-for-like control comparison.