Increasing Optimal Use of HPV Vaccination in Primary Care: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Increasing Optimal Use of HPV Vaccination in Primary Care (NCT04180462), a randomized na study. The primary outcome is Initiation of the HPV Vaccine 2-dose Series..

2. Clinical Question

3. Trial Design

The registry record describes a randomized, single-masked, parallel trial of a multi-component implementation strategy in primary care. It identifies Washington University School of Medicine as the sponsor and lists the study status as completed. The recorded start date is 2020-01-07, and the primary completion date is 2023-02-14. Enrollment is recorded as 20. The record does not explain the enrollment unit or reconcile it with the much larger at-risk counts listed in the adverse-event records.

The randomization was at the practice level, as described in the study information. This cluster-randomized structure matters for analysis: practices, rather than individual preteens, were assigned to the study arms, and observations within the same practice may be related. The registry record does not identify who was masked, describe how randomization was carried out, or provide details about the number or characteristics of practices.

Practices assigned to the intervention group received practice facilitation, education, audit and feedback, and a communication strategy. The wait list control group was offered the intervention in the last two years of the study. The primary outcome was assessed at 24 months post-randomization. Sustainability outcomes for initiation and completion of HPV vaccination are also listed, but their measurement details and results are not reported in the registry record.

The record lists four outcome measures and zero analyses. That means no analysis results are listed in the registry record; it does not establish whether analyses were conducted elsewhere. The record does not report the planned statistical model, allocation ratio, sample-size justification, masking details, or procedures for handling missing data.

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

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 Initiation of the HPV Vaccine 2-dose Series., measured over 24 months.

The primary endpoint is initiation of the HPV vaccine two-dose series. The registry describes it as the proportion of eligible preteens who initiate HPV vaccination before their 13th birthday, measured at 24 months post-randomization. It is intended to capture whether eligible preteens started vaccination during the period relevant to the implementation strategy.

An initiation measure is suited to a strategy intended to affect vaccination practices because it focuses on whether vaccination begins, rather than whether the series is later completed. The registry also lists separate secondary outcomes concerning the sustainability of intervention benefit for initiation and completion. Those are distinct questions: initiation does not establish completion, and a result for one should not be interpreted as a result for the other.

The record does not provide a numerical primary-outcome result, the number of eligible preteens used as the denominator, or details of how eligibility and initiation were ascertained. It also does not explain how the registry’s stated parameter of a participant count relates to the outcome description as a proportion. Without those details and a reported estimate, the endpoint can be described but the size or precision of any between-group difference cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can be understood only in part because the registry record does not list an analysis plan or results. The study is described as cluster-randomized, with practices assigned to the intervention or wait list control group. That feature determines what a suitable comparison must account for: the randomized units are practices, whereas the primary outcome is described for eligible preteens.

Why clustering matters

General explanation: people treated in the same practice may share clinicians, workflows, local procedures, and other conditions. Their outcomes can therefore be more alike than outcomes from people in different practices. A conventional analysis that assumes all participant observations are independent may understate uncertainty when this within-practice similarity is ignored. Cluster-aware methods account for the assignment structure and correlation in the data. The registry record does not report which method the sponsor used, nor does it provide estimates of within-practice correlation or practice-level sample sizes.

What an effect estimate would describe

The primary endpoint is the proportion of eligible preteens who initiated HPV vaccination before their 13th birthday at 24 months post-randomization. A between-group estimate would describe the contrast in that outcome for practices assigned to the multi-component strategy and practices assigned to the wait list. A point estimate alone would not show how precisely the contrast was estimated. A confidence interval, if reported, would convey a range of values compatible with the data and the analysis assumptions. No point estimate or confidence interval for the primary endpoint is reported in the registry record.

Why a p-value would not be enough

General explanation: a p-value summarizes how incompatible the observed data are with a specified null hypothesis under a particular statistical model. It does not give the probability that the null hypothesis is true, and it does not describe the size or practical importance of an effect. In a cluster-randomized study, its interpretation also depends on using an analysis that reflects the clustering. The registry record reports no primary-outcome p-value, statistical test, or model.

Over-dispersion and count outcomes

The primary outcome is described as a proportion, while the record’s parameter field identifies a participant count. It does not explain this difference in presentation or specify the outcome model. General explanation: for count data, over-dispersion means that observed variation exceeds what a chosen model expects. Ignoring it can lead to uncertainty estimates that are too narrow. For a proportion, the relevant modeling choices and variance assumptions depend on the data structure and analysis plan. The registry record does not report whether over-dispersion was assessed or whether any model used for the primary endpoint required it.

Planning illustrations versus trial results

The record describes planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For non-time-to-event outcomes, the illustrations are expressed as participants per arm; time-to-event illustrations use total events. These are planning assumptions, not observed results or evidence of achieved power. Since no observed primary-outcome effect or analysis result is reported in the registry record, the planning illustrations cannot be judged against a posted effect estimate. They also do not establish the trial’s original sample-size justification; that justification is not reported in the registry record.

The study is marked completed, but completion does not itself supply a statistical result. The record lists four outcome measures and zero analyses. It does not report model specification, covariate adjustment, handling of missing outcome data, analysis populations, or any sensitivity analyses. As a result, readers cannot assess whether the analysis followed a prespecified plan or how robust any estimated effect might be. Those details are not reported in the registry record.

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("Intervention Group", "Wait List Control Group")
n      <- c(2151, 1615)
events <- c(1723, 1219)
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  Intervention Group  2151  1723  80.1  78.4  81.8  78.4  81.7  78.4  81.7
ARM  Wait List Control Group  1615  1219  75.5  73.3  77.6  73.3  77.5  73.3  77.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures, including the primary endpoint and secondary outcomes concerning sustainability of benefit for HPV vaccine initiation and completion. It does not report an approach to multiplicity, such as whether a primary comparison was designated as the sole confirmatory test, whether secondary tests were adjusted, or how multiple follow-up periods were handled. Without that information, the registry record does not show how the chance of false-positive findings across multiple analyses was addressed.

Missing-data methods are not reported in the registry record. The record does not state how missing vaccination information, loss to follow-up, changes in eligibility, or incomplete practice-level data were handled. It also does not describe whether missingness was assessed by randomized group or whether sensitivity analyses were planned. General explanation: missing outcome data can affect both the estimated group contrast and its uncertainty, especially if the chance of missingness is related to outcome status or differs between groups.

Analysis populations are likewise not described. The registry does not say whether analyses were based on randomized assignment, intervention received, complete cases, or another defined population. Nor does it explain how the cluster-randomized assignment was reflected in the analysis population or unit of inference. The record’s listed enrollment and adverse-event at-risk counts do not resolve these questions.

The record lists zero analyses. This means that no analyses are listed in the registry record; it does not mean that no analyses were carried out. Without posted estimates, denominators, analysis populations, and missing-data procedures, the primary and secondary outcomes cannot be evaluated statistically from this record.

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 0% reporting threshold.

The registry lists serious adverse-event counts by group and follow-up period. For the intervention group at 24 months post-randomization, the record lists 2151 at risk, zero serious adverse events, zero other adverse events, and zero deaths. For the wait list control group at 24 months post-randomization, the corresponding entries are 1615 at risk and zero in each event category. At 36 months post-randomization, the intervention group has 2211 at risk and zero in each category; the wait list control group has 1410 at risk and zero in each category.

These entries describe what the registry recorded, not a comparative safety analysis. The record does not give event definitions, collection methods, the length of individual observation, or an explanation of the at-risk counts. Enrollment is listed as 20, and the registry does not reconcile that figure with the safety counts. The counts should therefore be read in their recorded context rather than treated as the primary-outcome denominators.

Zero recorded events do not establish that no events occurred outside the registry’s recording process, nor do they quantify the uncertainty around event rates. The registry also lists no serious adverse-event terms. Further safety interpretation is limited because methods and outcome analyses are not reported in the registry record.

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

The record describes a trial designed to evaluate whether a multi-component implementation strategy could increase HPV vaccine use in primary care. It identifies practice facilitation, education, audit and feedback, and a communication strategy as intervention components, and it defines initiation before a preteen’s 13th birthday as the primary outcome at 24 months post-randomization. This establishes the intended question, not its answer.

No primary-outcome estimate, uncertainty interval, or test result is reported in the registry record. The record therefore does not show whether the intervention group had a higher, lower, or similar initiation outcome than the wait list control group. It does not establish the size or precision of any effect, and it cannot support conclusions about the effectiveness of the strategy.

The record lists secondary outcomes about sustainability of benefit for initiation and completion, but it does not report their results. Initiation and completion are not interchangeable outcomes; starting vaccination does not show whether the series was completed. Likewise, the safety entries of zero recorded events do not answer the primary effectiveness question and do not, on their own, characterize the completeness of safety monitoring.

General explanation: statistical evidence is strongest when the estimated effect, its uncertainty, the analysis population, and the methods are all available for review. A completed status indicates the trial is recorded as completed, but it does not replace those results. The listed planning assumptions are not observed results and cannot establish the effect that the trial found.

The most defensible reading is that the registry record documents the study’s design and intended outcome, but does not provide the outcome analyses needed to determine what the trial found. Interpretation of the intervention’s impact would require results and methods that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises a statistical issue that is important in implementation research: the level at which an intervention is assigned may differ from the level at which outcomes are measured. Here, practices were randomized, while the primary endpoint concerns eligible preteens. That structure makes the practice cluster relevant to both the analysis and the uncertainty around the comparison. General statistical principle: analyses should reflect the randomization structure rather than treating related observations as independent.

The study also distinguishes vaccine initiation from completion and includes sustainability outcomes for both. Those distinctions matter because a strategy could be evaluated at different stages of care and over different periods. The registry record identifies those questions, but does not report results that would allow them to be compared or interpreted.

Registry reporting is itself important for statistical interpretation. A completed trial record without posted outcome analyses leaves readers unable to assess the estimated effect, precision, analysis population, missing-data handling, or the plan for multiple outcomes. In this case, the listed enrollment and safety at-risk counts also cannot be reconciled from the registry information, making it especially important not to substitute one count for another without an explanation.

The record therefore illustrates a distinction between a clearly stated research question and an interpretable result. Design information explains what the study set out to evaluate; estimates and methods are needed to understand what the data show. The missing analysis results limit the statistical conclusions that can be drawn from this trial record.

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 largest limitation for interpretation is that the registry record does not report results for the primary outcome or any analysis. There is no effect estimate, confidence interval, p-value, outcome denominator, or reported comparison. The record lists zero analyses, but that describes what is listed in the registry and does not establish whether analyses were conducted elsewhere.

Important design and analysis details are also absent. The record does not report how randomization was conducted, who was masked, the number and characteristics of practices, the statistical model, or the method used to account for clustering. It does not report the original sample-size justification, allocation ratio, or prespecified analysis plan. Because this is cluster-randomized, missing information about cluster handling is particularly relevant to interpreting uncertainty.

The primary outcome is described as a proportion, but the registry also identifies a participant count as its parameter. No denominator or clarification is reported. The enrollment figure of 20 is not explained in relation to the adverse-event at-risk counts, which differ by group and follow-up period. These figures cannot be reconciled using the registry record alone.

The record does not describe missing-data procedures, analysis populations, multiplicity methods, or outcome ascertainment. The secondary sustainability outcomes are named but not defined in further detail or accompanied by results. Safety entries record zero events but omit event definitions and collection methods. These limitations constrain interpretation of effectiveness, precision, and safety and are specific to the information reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Increasing Optimal Use of HPV Vaccination in Primary Care — NCT04180462.
• Registry record last updated 2025-03-25; status last verified 2025-03.
• Results first posted 2024-02-20.
• 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

NCT04180462 is a completed randomized, single-masked, parallel study sponsored by Washington University School of Medicine. It evaluates a multi-component strategy—practice facilitation, education, audit and feedback, and a communication strategy—to increase HPV vaccine use in primary care. Practices assigned to the wait list control group were offered the intervention in the last two years of the study.

The primary outcome is initiation of the HPV vaccine two-dose series before a preteen’s 13th birthday, measured at 24 months post-randomization. The registry also lists sustainability outcomes for initiation and completion. Enrollment is recorded as 20, with a start date of 2020-01-07 and a primary completion date of 2023-02-14.

The registry record lists zero analyses and does not report primary-outcome results. Safety records list zero serious adverse events, zero other adverse events, and zero deaths across the displayed groups and follow-up periods. Analysis methods, missing-data procedures, and an explanation of the differing enrollment and safety counts are not reported in the registry record.