This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Immunogenicity to Human Papillomavirus Vaccine (Gardasil) Among IBD Patients on Immunosuppressive Therapy (NCT00727636), a non-randomized na study. The primary outcome is Antibody Titer to HPV 6.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00727636 |
| Phase | NA |
| Condition | Inflammatory Bowel Disease |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 53 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boston Children's Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with inflammatory bowel disease (IBD) receiving immunosuppressive therapy. The study aims described in the record specify ages 9-26. The prospective cohort received vaccination during the study; the retrospective cohort had blood drawn during the study after receiving vaccination from a primary medical provider.
Intervention
The intervention was Gardasil, identified in the record as the quadrivalent human papillomavirus virus-like particle vaccine. The record describes prospective participants as receiving the vaccine during the study. It does not report a vaccination schedule or dose-level details in the outcome description.
Comparator
The study aims describe comparison with historical controls. The registry also lists prospective and retrospective cohorts, but labels the allocation nonrandomized and the model single-group. These cohorts should not be read as randomized, exchangeable treatment arms. The record does not describe a concurrent randomized control group.
Primary question
The primary outcome is geometric mean antibody titer to HPV 6 at Month 7, measured in milli-Merck units/mL and accompanied by a 95% confidence interval. The record does not report the numerical titer or confidence interval. It also describes intended assessment of vaccine-associated adverse events, disease activity and flare-ups after vaccination, but does not provide results for those aims in the primary outcome entry.
In statistical terms, the central question is whether the measured antibody response in the study population can be characterized and compared with the historical information discussed in the study aims. The registry record does not provide the historical-control estimates, the details of any comparison, or a numerical antibody result. Therefore, it does not support a quantitative comparison of the cohorts or a conclusion about the magnitude or precision of an immune response. The study is described as a pilot investigation, and its nonrandomized structure is important when interpreting any comparison that might be made from data outside this record.
3. Trial Design
The registry describes a completed, nonrandomized study with a single-group model and no masking. It lists enrollment of 53 and identifies inflammatory bowel disease as the condition. The intervention is Gardasil vaccine. The arm descriptions distinguish a prospective study cohort, whose participants received the vaccine during the study, from a retrospective cohort, whose participants had blood drawn during the study after receiving the vaccine from their primary medical provider.
These descriptions indicate different routes into observation, not randomized assignment to competing treatments. The prospective and retrospective cohorts may differ in when vaccination occurred and how information was collected. The record does not give enough detail to determine the extent of those differences or whether they affected the antibody measurements. It also does not report the number enrolled in each cohort or explain how historical controls were selected.
The study aims describe measuring immune response in people aged 9-26 with IBD who were receiving immunosuppressive agents, and comparing that response with historical controls. The aims also include evaluating vaccine-associated adverse events, disease activity and flare-ups after each dose. However, the registry's primary outcome entry is specifically antibody titer to HPV 6 at Month 7. Results for the other stated aims are not reported in the registry record.
The registry lists the study as completed. Its start is recorded as 2008-07 and primary completion as 2010-06. These dates describe the registry record and do not establish when every participant was vaccinated or assessed. The timing of individual vaccinations, follow-up visits, and blood draws beyond the primary outcome timeframe is not reported in the registry record.
Because allocation was nonrandomized and the model is listed as single-group, the cohort labels should not be treated as proof of a controlled trial comparison. No randomization procedure, masking process, or concurrent control group is described. The study design can characterize observations collected in these cohorts, but the registry record alone does not establish a causal contrast between treatment strategies.
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
| Stage | Prospective Cohort | Retrospective Cohort |
|---|---|---|
| STARTED | 37 | 15 |
| COMPLETED | 33 | 15 |
| NOT COMPLETED | 4 | 0 |
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.
| Characteristic | Unit | Prospective Cohort | Retrospective Cohort | Total |
|---|---|---|---|---|
| Participants analysed | 37 | 15 | 52 | |
| Age, Categorical: <=18 years | Participants | 33 | 6 | 39 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 9 | 13 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age Continuous | years | 14.9 (SD 3.1) | 18.9 (SD 3.5) | 16.1 (SD 3.6) |
| Sex: Female, Male: Female | Participants | 37 | 15 | 52 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 37 | 15 | 52 |
6. Primary Endpoint
The registry lists the primary outcome as Antibody Titer to HPV 6, measured over Month 7.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | milli-Merck units/mL |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is antibody titer to HPV 6 at Month 7. Antibody titer is a measure of the concentration or level of antibodies measured in a sample; the registry specifies milli-Merck units/mL as the unit. It specifies the summary as a geometric mean with a 95% confidence interval.
As a general statistical explanation, a geometric mean is often used for measurements that are positive and have a skewed distribution. It summarizes values on a multiplicative scale by transforming them, averaging on that scale, and transforming back. This can make the summary less dominated by very high observations than an arithmetic mean would be. The registry record does not state why this summary was selected or describe the observed distribution of antibody titers.
A confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. Its width is relevant to precision: a narrower interval indicates a more precise estimate under those assumptions, while a wider interval indicates greater uncertainty. The registry identifies a 95% confidence interval as the dispersion measure but does not report its limits or the estimation method.
The endpoint is an immunological measurement, not a direct measure of infection or disease. The registry record does not report a threshold defining an adequate response, nor does it provide a numerical titer or confidence interval for this outcome. Thus the endpoint definition identifies what was intended to be measured, but the record does not show the estimated Month 7 response.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a specific primary endpoint: geometric mean antibody titer to HPV 6 at Month 7, with a 95% confidence interval and units of milli-Merck units/mL. However, it does not report the estimated geometric mean or the interval limits. Without those values, the primary endpoint cannot be quantitatively interpreted from the registry record. The number of outcome measures is listed as 4, while the record lists no analyses.
This distinction matters: an outcome definition describes what investigators intended to measure, whereas an analysis result reports what the measured data showed. The record contains the former but not a numerical estimate for the primary endpoint. It therefore does not establish the magnitude of the antibody response, the precision of that estimate, or how it compares with historical controls. The absence of a posted estimate is not evidence that the response was high, low, or unchanged.
The study is labeled nonrandomized, with a single-group model and no masking. Its cohort descriptions include prospective participants vaccinated during the study and retrospective participants whose blood was drawn after vaccination by their primary medical provider. Those cohorts differ in how vaccination and observation were situated. Any comparison between them, or with historical controls, would need to account for the possibility that groups differed in relevant characteristics or data collection. The registry record does not report an adjusted comparison or the details needed to assess such differences.
The record's stated aims include adverse events, disease activity, and flare-ups after vaccination. The posted safety information identifies serious adverse-event categories for the prospective cohort, but it does not give a detailed account of timing, severity, relatedness, or the clinical context of each report. The retrospective cohort has no participants listed at risk in the adverse-event fields, so those entries cannot be interpreted as evidence that no events occurred in that cohort.
The record also contains planning assumptions for sample-size illustrations: a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed with those parameters. The registry record does not report an observed effect used for such planning, so no numerical planning conclusion can be drawn from the assumptions alone. Such illustrations, where used, are not observed power.
Overall, the registry supports a description of the study question, design labels, endpoint definition, and some safety counts. It does not provide the primary antibody result or an inferential analysis. Statistical conclusions about the endpoint's size, precision, or comparative meaning are therefore not reported in the registry record.
9. Statistical Methods Explained
The registry describes the study as nonrandomized, unmasked, and single-group. These labels shape what statistical comparisons can reasonably mean. In a randomized study, assignment can help balance measured and unmeasured characteristics across groups on average. In this study, allocation was not randomized, so differences between cohorts may reflect factors other than vaccination or immune response. This is a general design consideration; the registry does not report which factors differed or whether any adjustment was made.
What does a geometric mean summarize?
As a general statistical explanation, a geometric mean summarizes values on a multiplicative rather than additive scale. The data are transformed, averaged, and transformed back. This summary is commonly suited to positive measurements that are skewed, although the record does not describe the distribution of the antibody titers or explain the choice of summary. It reports antibody titer to HPV 6 in milli-Merck units/mL and specifies the geometric mean as the parameter.
The endpoint also specifies a 95% confidence interval. In general, a confidence interval gives a range of values compatible with the estimate under the analysis assumptions and describes the estimate's precision. It is not a guarantee that the true value lies in the interval, and it does not by itself establish clinical importance. The interval's limits and the method used to calculate it are not reported in the registry record, so neither its width nor the precision of the estimate can be assessed.
What does the study structure allow?
The prospective cohort received the vaccine during the study, while the retrospective cohort had blood drawn during the study after vaccination by a primary medical provider. The registry also describes the study aims as comparing immune response with historical controls. These descriptions do not establish that the cohorts were comparable. A retrospective sample may be assembled under different eligibility, timing, or measurement conditions from a prospective sample. The record does not explain how participants entered the cohorts, how historical controls were identified, or whether their measurements were collected in a comparable way.
As a general principle, a nonrandomized comparison can be affected by confounding: factors related both to group membership and to the outcome can make a group difference difficult to attribute to the exposure being studied. Statistical adjustment can address some measured differences, but cannot automatically remove unmeasured differences. The registry lists no analyses, so it does not report whether adjustment, stratification, or any other comparative method was used.
What can the reported analysis information establish?
The registry identifies the primary endpoint and its planned summary, but does not post a numerical endpoint estimate. It lists 4 outcome measures and 0 analyses. Those entries do not provide a test statistic, p-value, confidence-interval limits, or an adjusted effect estimate. Consequently, there is no reported inferential result from which to evaluate whether the antibody response differed from a comparator or how uncertain such a difference might be.
As general statistical context, a p-value measures how incompatible the observed data are with a specified null model, conditional on that model and its assumptions. It is not the probability that the null hypothesis is true, nor is it a measure of effect size. A confidence interval conveys a range of estimates and their precision, but also depends on the model and data. Neither concept can be applied to a numerical conclusion because the registry does not report a numerical antibody result or analysis.
How should planning assumptions be read?
The record describes planning illustrations based on a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It says the target effect is a stated fraction of the observed effect. These describe assumptions for planning calculations, not reported properties of the study's actual design or results. In particular, sample-size calculations are planning illustrations, not observed power. The registry record does not report the observed effect used for these calculations or a completed calculation result in the registry record for this trial.
As a general explanation, power planning estimates the sample size needed to detect an effect under specified assumptions about the effect, variability, significance level, and allocation. If an assumed effect is smaller, the required sample size generally increases, all else equal. But this general relationship does not produce a trial-specific number without the inputs. The record does not report a statistical analysis plan or a sample-size justification for the study itself. It is therefore not possible to determine whether the study's enrollment was selected to attain a particular power.
Why can over-dispersion matter?
As general statistical context, over-dispersion occurs when data vary more than a model assumes. If a model underestimates variability, standard errors may be too small and confidence intervals too narrow. This is relevant in some count or clustered-data settings, but the registry does not report an analysis of that type for the primary antibody endpoint, a model fit, or evidence of over-dispersion. It should not be assumed to have occurred in this study.
In short, the statistical information in the registry is sufficient to identify the primary endpoint's summary and some design characteristics, but not to reconstruct the analysis. The numerical endpoint estimate, confidence-interval limits, analysis methods, and comparative results are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 4 outcome measures and 0 analyses. It identifies antibody titer to HPV 6 at Month 7 as the primary outcome, but does not report numerical results for that endpoint or the other outcome measures. It does not describe a statistical analysis plan, a hierarchy among outcomes, or an approach to multiplicity. These details are not reported in the registry record.
As a general statistical explanation, multiplicity arises when several outcomes, time points, groups, or hypotheses are examined. Testing many hypotheses can increase the chance of at least one apparently unusual result under a collection of null hypotheses. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address this concern, but the registry does not state whether any such method was used. The presence of a named primary endpoint alone does not reveal how other outcomes were analyzed.
The registry does not report missing-data counts, reasons for missing measurements, or methods for handling missing values. It also does not provide an analysis population definition, such as which participants contributed to the Month 7 antibody estimate or whether any participants were excluded from that analysis. Enrollment is listed as 53, but that figure cannot establish how many contributed to a particular outcome.
As general context, missing observations can affect precision and can bias an estimate if their absence is related to participant characteristics or outcomes. The degree and direction of any such effect depend on the pattern of missingness and the methods used. Since the registry does not describe those details, the impact of missing data cannot be assessed from this record. The analysis population, missing-data handling, and multiplicity approach are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Prospective Cohort | 5 | 37 | 13.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Prospective Cohort | 11 of 37 |
| Retrospective Cohort | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Prospective Cohort | Retrospective Cohort |
|---|---|---|---|
| Admitted to hospital | Gastrointestinal disorders | 2 of 37 | 0 of 0 |
| Admitted to hospital | Respiratory, thoracic and mediastinal disorders | 1 of 37 | 0 of 0 |
| Admitted to hospital | Reproductive system and breast disorders | 1 of 37 | 0 of 0 |
| Went to emergency department | Respiratory, thoracic and mediastinal disorders | 1 of 37 | 0 of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Prospective Cohort | Retrospective Cohort |
|---|---|---|---|
| Abdominal pain | General disorders | 3 of 37 | 0 of 0 |
| Rectal bleeding and diarrhea | Gastrointestinal disorders | 2 of 37 | 0 of 0 |
| leg pain | Musculoskeletal and connective tissue disorders | 1 of 37 | 0 of 0 |
| Asthma related symptoms | Respiratory, thoracic and mediastinal disorders | 1 of 37 | 0 of 0 |
| Axillary abscess | General disorders | 1 of 37 | 0 of 0 |
| Rash on their chin | Skin and subcutaneous tissue disorders | 1 of 37 | 0 of 0 |
| Migraine | General disorders | 1 of 37 | 0 of 0 |
| Swelling and severe pain in arm | General disorders | 1 of 37 | 0 of 0 |
Serious events with the highest arm-level rate: admitted to hospital (5.4%), went to emergency department (2.7%).
The safety fields list a prospective cohort with 37 at risk. They report 5 affected for the serious adverse-event field and 11 affected for the other adverse-event field. The registry also lists “Admitted to hospital” at 5.4% and “Went to emergency department” at 2.7% among the top serious terms. These are registry entries, not estimates of causal risk attributable to vaccination.
The retrospective cohort has 0 at risk in the adverse-event fields. Those zeros do not show that no adverse events occurred among retrospective participants; they indicate that the registry safety fields do not list participants at risk for that cohort. The study description says the retrospective participants had blood drawn after vaccination by their primary medical provider, and the registry does not provide a corresponding safety follow-up account for them.
The record does not report the timing of the serious events, their duration, severity grading, relationship to vaccination, or whether the event categories overlap. The listed percentages should therefore be read as reported values for the named terms, not as a complete safety profile or a comparison between cohorts. The affected counts and at-risk counts are not enough to determine causality or to characterize all possible adverse events.
More broadly, a safety count describes events observed and recorded under a particular follow-up process. Interpretation depends on how events were defined, collected, and assessed. Those details are not reported in the registry record. No medical advice or treatment conclusion follows from these registry entries alone.
12. What the Result Does, and Does Not, Mean
The record establishes that investigators studied Gardasil vaccination in the context of inflammatory bowel disease and immunosuppressive therapy. It specifies an antibody endpoint, a measurement time at Month 7, a geometric-mean summary, and a 95% confidence interval. It also describes prospective and retrospective cohorts and reports selected safety fields. These details clarify the study's subject and intended measurements.
The record does not report the numerical primary antibody result or its confidence interval. As a result, it cannot show the size of the measured response or how precisely it was estimated. It also does not provide a numerical comparison with historical controls. The absence of a reported result is not evidence for a particular direction or magnitude of effect.
The design labels also limit interpretation. Allocation is nonrandomized, the model is single-group, and masking is absent. The cohort descriptions differ in how participants received vaccination and were observed. Any apparent difference between cohorts or historical controls could be influenced by how groups were formed, how measurements were collected, or other factors. The registry record does not report an analysis that addresses those possibilities.
The study aims mention vaccine-associated adverse events, disease activity, and flare-ups, but the registry entries summarized for this trial do not provide complete results for those aims. The serious adverse-event fields offer only limited counts and listed terms, without the clinical details needed to assess timing, relatedness, or completeness.
Accordingly, the record supports a description of the question and study structure, but not a definitive quantitative conclusion about antibody response, comparison with historical controls, or safety. A named endpoint is not itself a finding. Estimates, their uncertainty, and the methods behind them would be needed to assess what the observed data mean. Those results and methods are not reported in the registry record.
13. Why This Trial Matters Statistically
This study raises a statistical question that is important in clinical research: how should an immune-response measurement be interpreted when participants are receiving immunosuppressive therapy and the comparison is nonrandomized? The registry focuses on antibody titer to HPV 6 and specifies a geometric mean with a 95% confidence interval. That endpoint and summary provide a clear outline of the intended primary measurement, even though the numerical result is not reported.
The record also illustrates why design labels matter. Prospective and retrospective cohorts may differ in when vaccination and measurement occurred, and historical controls are not automatically comparable with participants observed in a study. Statistical comparisons depend not only on the outcome measure but also on how groups were assembled and whether measurements were made in comparable circumstances. The registry does not report enough detail to assess these issues fully.
For biostatisticians and clinical researchers, the distinction between an endpoint definition and an analysis result is central. A prespecified-looking outcome label does not provide an estimate, uncertainty interval, or comparison. Here, the primary endpoint is named, but the numerical value and interval are not reported. The registry also lists no analyses, leaving the inferential approach unclear.
The record further shows the limits of interpreting sparse safety entries. Counts and percentages can identify what was recorded, but without definitions, timing, relatedness, and follow-up details they do not provide a complete safety interpretation. These limitations are especially relevant when the study aims include both immune response and disease activity after vaccination.
The statistical importance of the study therefore lies in the question and the need for transparent reporting: clear endpoint estimates, analysis methods, missing-data information, and comparator details are needed to evaluate precision and comparison. The record establishes the study's focus, but it does not report those results.
14. 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 available registry record does not report a numerical estimate for the primary antibody endpoint, its 95% confidence-interval limits, or a comparative analysis. It lists the endpoint and measurement time, but not the result. This is the central limitation for interpreting the study statistically.
The design is nonrandomized and labeled single-group, with no masking. The prospective cohort received vaccination during the study, whereas the retrospective cohort had blood drawn after vaccination from a primary medical provider. The record does not explain cohort selection, historical-control selection, or whether measurement procedures were comparable. These omissions prevent a detailed assessment of comparability and potential confounding.
The registry does not report the number in each cohort, the analysis population for the primary endpoint, or the number with an available Month 7 measurement. It also does not describe missing data, exclusions, or how missing observations were handled. Although enrollment is listed as 53, enrollment alone does not establish the endpoint-specific analysis population.
The primary outcome is antibody titer to HPV 6, while the study aims also mention adverse events, disease activity, and flare-ups. The record does not provide full numerical results for these stated aims or explain how multiple outcomes were handled. The reasons for choosing the geometric mean, the distribution of the antibody measurements, and the method for calculating the confidence interval are not reported in the registry record.
The safety entries have further limitations: the record does not provide event timing, severity, relatedness, or detail about overlap among categories. The retrospective cohort has 0 listed at risk in the safety fields, which limits interpretation of those entries for that cohort. The registry also does not report a statistical analysis plan or a sample-size justification for the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Immunogenicity to Human Papillomavirus Vaccine (Gardasil) Among IBD Patients on Immunosuppressive Therapy — NCT00727636.
- Registry record last updated 2011-05-27; status last verified 2011-05.
- Results first posted 2011-05-27.
- 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.
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18. Record Summary
The registry record describes a completed, nonrandomized, unmasked study with a single-group model and enrollment of 53. The population is people with inflammatory bowel disease receiving immunosuppressive therapy, and the intervention is Gardasil vaccine. The study descriptions distinguish prospective participants vaccinated during the study from retrospective participants whose blood was drawn after vaccination by a primary medical provider.
The primary endpoint is geometric mean antibody titer to HPV 6 at Month 7, measured in milli-Merck units/mL with a 95% confidence interval. The numerical estimate and interval are not reported in the registry record. The record lists 4 outcome measures and 0 analyses.
Safety fields list prospective-cohort counts and two serious-event terms, but do not give sufficient detail to establish timing, relatedness, or completeness. Cohort-specific analysis populations, missing-data methods, comparative methods, and the study's statistical plan are not reported in the registry record. The record identifies the research question and endpoint, but does not provide enough numerical outcome information for a statistical conclusion about the primary response.