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 Cholecalciferol and Flu Vaccine in Treating Healthy Participants (NCT01561989), a randomized na study. The primary outcome is Effect of 25-hydroxy Vitamin D3 Levels on Immunologic Response (Antibody Responses) to Injectable Seasonal (2011-2012) Trivalent Influenza Vaccine (Observational Component).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01561989 |
| Phase | NA |
| Condition | Healthy, no Evidence of Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Roswell Park Cancer Institute |
| Results posted | Yes |
2. Clinical Question
Population
Healthy participants with no evidence of disease were the intended population. The official title identifies healthy employees working at Roswell Park Cancer Institute. The record lists enrollment as 11, but also states that no subjects were treated before study closure because of lack of accrual. It therefore does not describe a treated study population from which vaccine responses could be evaluated.
Intervention
The planned intervention descriptions assign participants to daily oral cholecalciferol for 12 weeks, followed by seasonal trivalent influenza vaccine given by injection. One arm description specifies 400 IU daily and the other specifies 4,000 IU daily. Questionnaire administration is also listed as an intervention, but its timing and role are not reported in the registry record.
Comparator
The intervention descriptions distinguish the two cholecalciferol doses, with vaccination planned after supplementation in each arm. The adverse-event record uses a different pair of group labels: cholecalciferol plus flu vaccine and flu vaccine alone. The registry record does not explain how those safety groups correspond to the planned dose arms.
Primary question
The listed primary outcome asks whether 25-hydroxy vitamin D3 levels relate to antibody responses to injectable seasonal trivalent influenza vaccine. It is identified as an observational component and names the 2011-2012 vaccine. The listed timeframe is 4 weeks after vaccination. Because no participants were treated, the record contains no antibody-response findings with which to answer that question.
The clinical question therefore has both an observational and an intervention aspect. The observational component concerns vitamin D status at vaccination and subsequent immune response. The planned intervention component concerns giving different daily cholecalciferol doses before vaccination. These are related questions, but they are not interchangeable: an association between vitamin D level and antibody response would not by itself establish the effect of assigning a supplement dose.
The record also lists outcomes involving flu-like illness and genetic or metabolic measures. Their inclusion indicates broader planned interests, but no results for those outcomes are reported. With treatment not begun before closure, the key finding is not an estimate of vaccine response or supplement effect; it is that the planned clinical comparison was not carried out.
3. Trial Design
The registry describes a randomized, double-masked, parallel study sponsored by Roswell Park Cancer Institute. Its status is terminated. The recorded start was 2011-10 and primary completion was 2013-07. The enrollment field lists 11, while the primary outcome description states that no subjects were treated before study closure because of lack of accrual. These entries describe different aspects of the record and should not be read as evidence that 11 participants received the study interventions.
The planned intervention arms involved daily oral cholecalciferol for 12 weeks, followed by seasonal trivalent influenza vaccine by intramuscular injection. One arm description specifies 400 IU and the other 4,000 IU. The listed primary outcome, however, is an observational assessment of vitamin D level and antibody response to the 2011-2012 seasonal vaccine. The intervention descriptions refer to the 2012-2013 seasonal vaccine. The registry record does not clarify this difference in vaccine seasons or explain the relationship between the observational and intervention components.
Random allocation ordinarily means a chance-based process is used to assign participants to study groups. Masking ordinarily means that some people involved in the study are kept unaware of assigned treatment, though the record does not specify who was masked or how masking was maintained. A parallel design ordinarily compares groups followed during the same study period. These are general descriptions of design terms; because no participants were treated, the registry record cannot show how the design operated in practice.
The phase is listed as not applicable. Eligibility criteria beyond the description of healthy participants with no evidence of disease, recruitment procedures, allocation details, and the intended sample-size justification are not reported in the registry record. Nor is a full account of study conduct reported. The termination and lack-of-accrual statement are central to interpreting all planned comparisons: the record describes a design, but not a completed randomized treatment comparison.
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.
Before assignment: unable to meet accrual objective. study closed.
Overall Study
| Stage | Arm I | Arm II |
|---|---|---|
| STARTED | 5 | 6 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 5 | 6 |
Reasons for not completing this period:
| Reason | Arm I | Arm II |
|---|---|---|
| accural target not met. | 5 | 6 |
Analysis population for the primary outcome, as defined in the registry: No subjects were treated prior to study closure due to lack of accrual.
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 | Arm I (400 IU Cholecalciferol and Vaccine Therapy) | Arm II (4,000 IU Cholecalciferol and Vaccine Therapy) | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 6 | 11 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 | 6 | 11 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex/Gender, Customized: unknown | participants | 5 | 6 | 11 |
| Region of Enrollment: United States | Participants | 5 | 6 | 11 |
6. Primary Endpoint
The registry lists the primary outcome as Effect of 25-hydroxy Vitamin D3 Levels on Immunologic Response (Antibody Responses) to Injectable Seasonal (2011-2012) Trivalent Influenza Vaccine (Observational Component), measured over At 4 weeks post-vaccination.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The listed primary outcome concerns the effect of 25-hydroxy vitamin D3 levels on antibody responses to an injected seasonal trivalent influenza vaccine. It is identified as an observational component, and its stated measurement time is 4 weeks after vaccination. Antibody response is an immune measure; examining it can describe whether measured vitamin D status is associated with a measured response after vaccination. The registry record does not define the antibody measure, its units, the threshold for a response, or how it would be summarized.
The rationale for measuring an antibody response is that it provides a laboratory outcome related to immune response after vaccination. As a general statistical point, a prespecified endpoint helps distinguish the principal question from secondary or exploratory questions and indicates what outcome an analysis is intended to estimate. Here, however, the record does not give a numerical endpoint definition or a planned effect measure.
The outcome description says that descriptive statistics and chi-square tests would be used to assess differences in self-reported flu-like illnesses. This does not directly specify an analysis for the antibody-response outcome named in the primary title. The registry record does not explain whether that description applies to another outcome, nor does it report an antibody analysis. Most importantly, the record says no subjects were treated before closure. There is consequently no reported primary endpoint result to interpret, and no basis in the record for estimating an association or a treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record supports a clear conclusion about study completion: the trial was terminated, and its primary outcome description says no subjects were treated before closure because of lack of accrual. It does not support a conclusion about whether cholecalciferol changed antibody responses, whether vitamin D status was associated with those responses, or whether the planned dose groups differed. No primary outcome estimate, confidence interval, test result, or analysis is reported in the registry record.
The enrollment field lists 11. That entry does not override the explicit statement that no subjects were treated. Enrollment and treatment exposure are not necessarily the same event; in this record, the treatment statement means that the enrollment figure cannot be interpreted as a count of participants who completed supplementation and vaccination. The record does not explain the enrollment field further.
The adverse-event entries list 5 people at risk in the group labelled cholecalciferal plus flu vaccine and 6 in the group labelled flu vaccine alone. Both groups have 0 serious adverse events, 0 other adverse events, and 0 deaths recorded. Those entries should be read as safety-record counts, not as evidence that the planned intervention was administered. In particular, the primary outcome text says no subjects were treated, and the registry record does not specify the safety risk period or reconcile these group labels with the planned 400 IU and 4,000 IU arms.
In general, a confidence interval describes the range of effect estimates compatible with the data under the chosen statistical model and assumptions. No confidence interval is reported for the primary outcome. Without an estimate and its uncertainty, readers cannot assess the magnitude or precision of an association or effect. Likewise, the absence of a reported p-value is not evidence for either the presence or absence of an effect.
The record lists a planned use of descriptive statistics and chi-square tests for differences in self-reported flu-like illnesses. It does not report that these analyses were performed. Even if a test had been planned, a test alone would not describe the size or precision of a difference; those require outcome estimates and uncertainty measures. No such results are reported.
Thus, the appropriate statistical interpretation is about the limits of the available evidence rather than efficacy or lack of efficacy. The design intended to study immune responses and related outcomes, but lack of accrual prevented treatment and the registry record reports no outcome analyses. The registered aims should not be confused with results.
9. Statistical Methods Explained
The registry record identifies a randomized, double-masked, parallel design and describes supplementation followed by vaccination. These labels concern intended design features. They do not establish that allocation, masking, or treatment took place. The record explicitly says no subjects were treated before closure, so there is no completed intervention comparison to analyze.
What randomization would contribute
As a general statistical concept, randomization assigns participants to study groups by chance. When implemented as planned, it can reduce systematic differences between groups in factors measured or not measured at baseline. This supports a causal comparison of assigned strategies, subject to appropriate conduct, outcome measurement, and analysis. Randomization does not guarantee that groups will be identical, especially in a small study, and it cannot compensate for a comparison that was never carried out. The registry record does not report the allocation sequence, concealment procedures, or any randomized treatment assignments.
What masking and a parallel design mean
In general, masking is intended to limit the influence of knowledge about treatment assignment on participants’ reports, study conduct, or outcome assessment. The record labels the study double-masked but does not identify which parties were masked or describe how the mask was maintained. A parallel design generally assigns participants to one group and compares groups over the study rather than having each participant receive multiple study regimens. The registry record supplies this design label but does not report implementation details.
The intervention descriptions specify daily cholecalciferol for 12 weeks followed by vaccine. One dose is 400 IU and the other is 4,000 IU. A treatment-effect analysis would normally need a clearly specified comparison, an outcome definition, a population for analysis, and an approach to missing measurements. Those details are not reported in the registry record. More fundamentally, the record says treatment did not begin, so there are no reported assigned-treatment outcomes to compare.
Descriptive statistics and chi-square tests
The primary outcome description names descriptive statistics and chi-square tests for assessing differences in the occurrence of self-reported flu-like illnesses. Descriptive statistics organize observed data, for example by reporting the distribution of an outcome in each group. A chi-square test is a general method for assessing whether categorical outcomes are associated with group membership, under assumptions about the data and the expected cell counts. The record does not state the exact categorical definitions, test variant, or analysis population. It also does not report any test statistic or result. The description of these methods therefore documents an intended approach for illness reports, not evidence that a test was performed or an answer to the antibody-response question.
For an antibody endpoint, a statistical analysis would depend on how antibody response was measured and defined. A continuous measurement, a change from baseline, and a categorical responder outcome can call for different summaries and models. The registry record does not specify which form was intended. It also does not report a model for adjusting for baseline factors, a primary effect measure, or a rule for handling values outside measurement limits. These omissions prevent reconstruction of a primary analysis, even apart from the absence of treated participants.
Precision, uncertainty, and over-dispersion
In general, an estimate describes the observed size of an association or difference, while a confidence interval describes its uncertainty under a statistical model. Narrower intervals typically indicate greater precision, and wider intervals indicate less precision. A p-value addresses compatibility of data with a specified null model; it does not measure the size or importance of an effect. None of these primary-outcome statistics is reported in the registry record.
Over-dispersion is a general issue for count outcomes: observed variation can exceed what a simple model assumes. If that happens, a model that ignores the extra variation can understate uncertainty. It may be relevant to some event-count analyses in general, but the registry record does not report a count model, a dispersion assessment, or enough outcome data to evaluate it. It would be inappropriate to claim that over-dispersion was present or addressed in this study.
Planning calculations are not observed evidence
The record describes sample-size planning assumptions as a two-sided significance level of 0.05, equal allocation, and a normal approximation, with planning based on a stated fraction of an observed effect. Such assumptions describe how a planning illustration can be constructed; they do not establish the trial’s original design justification. The record does not report the intended effect size, the fractions used, or numerical planning estimates. Any planning illustration is not observed power and cannot substitute for an outcome analysis. Because the trial did not treat participants, there is no observed treatment effect on which to base a completed trial’s power interpretation.
Overall, the record reports selected design labels and an intended method for illness outcomes, but not a complete statistical analysis plan. The exact antibody-response definition, analysis model, effect measure, uncertainty procedure, adjustment strategy, and treatment of missing data are not reported in the registry record. The absence of reported analyses is consistent with the stated closure before treatment; it should not be filled in by assuming a conventional plan.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary outcome and several secondary outcomes, including flu-like illness, vitamin D levels and immune response, and genetic or metabolic measures. It does not report a multiplicity strategy for interpreting results across these outcomes. In general, multiplicity arises when multiple outcomes, comparisons, time points, or tests are considered: the chance of at least one apparently unusual result can rise as the number of tests increases. Prespecified priorities or adjustment procedures can help define how such results should be interpreted, but the record does not describe any such procedure.
The primary outcome description includes an antibody response at 4 weeks post-vaccination, while the method description refers to descriptive statistics and chi-square tests for self-reported flu-like illnesses. The registry record does not clarify the relationship between these descriptions. It also lists outcomes associated with more than one study component and vaccine season. These unresolved details mean the intended hierarchy and testing family cannot be reconstructed from the record.
Missing-data methods, analysis populations, and rules for excluding or retaining participants are not reported in the registry record. Such details ordinarily clarify how incomplete outcome measurements, protocol deviations, or participants who do not receive planned treatment are handled. Here, the record states that no subjects were treated before closure because of lack of accrual, but does not describe an analysis population or a missing-data procedure. No inference about those methods should be made from the design labels alone.
Because no primary or secondary outcome analyses are reported, multiplicity and missing-data procedures cannot be evaluated through results. The record does not state whether interim analyses were planned or conducted; that information is not reported in the registry record. Nor does it provide a statistical plan explaining which analyses would have been confirmatory and which exploratory.
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 |
|---|---|---|---|
| Cholecalciferal + Flu Vaccine | 0 | 5 | 0.0% |
| Flu Vaccine Alone | 0 | 6 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cholecalciferal + Flu Vaccine | 0 of 5 |
| Flu Vaccine Alone | 0 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cholecalciferal + Flu Vaccine | 0 of 5 |
| Flu Vaccine Alone | 0 of 6 |
The adverse-event record lists two safety groups. The group labelled Cholecalciferal + Flu Vaccine has 5 people at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. The group labelled Flu Vaccine Alone has 6 people at risk, 0 serious adverse events, 0 other adverse events, and 0 deaths. These are the posted counts; they do not establish the amount of treatment exposure or the duration of safety follow-up.
The primary outcome description says no subjects were treated before study closure because of lack of accrual. Accordingly, the safety entries should not be interpreted as a safety comparison after completed study treatment. The registry record does not explain how the at-risk counts were defined, what period they cover, or why the safety group labels differ from the planned 400 IU and 4,000 IU intervention descriptions.
In general, zero events recorded in a group means no events appear in that registry category; it does not prove that an intervention has no risk. Interpreting safety requires context about exposure, follow-up, event definitions, and ascertainment. Those details are not reported in the registry record. The posted figures therefore describe the registry’s safety entries only and do not support a comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The central meaning of the record is that a study was planned to examine vitamin D status, cholecalciferol supplementation, influenza vaccination, and immune response, but was terminated before participants were treated because of lack of accrual. The record does not report a primary outcome analysis. It therefore provides no estimate of the association between 25-hydroxy vitamin D3 levels and antibody response, and no estimate of the effect of either planned cholecalciferol dose.
The absence of outcome results should not be interpreted as a finding of no effect. A study that produces no treatment outcome data cannot establish that the intervention has no effect, just as it cannot establish that it has an effect. The same distinction applies to the listed secondary outcomes. Their presence in the registry describes planned questions, not findings.
The enrollment field lists 11, but the record’s statement that no subjects were treated limits what can be inferred about exposure and outcome data. The adverse-event counts record zero events in the listed categories, yet they do not provide a completed comparison of treated participants. Neither the enrollment entry nor the safety entries supply the missing primary response measurements.
As a general statistical principle, a result is most informative when an effect estimate is paired with an uncertainty measure and a clear account of the analysis population. The registry record reports none for the primary outcome. Readers cannot assess the size, direction, or precision of a primary effect, and cannot distinguish a small effect from an imprecise or unavailable estimate.
The record remains useful for documenting intended design features, planned outcomes, termination status, and the stated reason for closure. It is not evidence for a clinical benefit or harm from cholecalciferol, and it cannot resolve the broader question of whether vitamin D status predicts vaccine response. Those questions remain unanswered by the posted trial results.
13. Why This Trial Matters Statistically
This record illustrates why design intent and observed evidence must be separated. Randomization, masking, and a planned parallel comparison can support rigorous inference when a trial is conducted and outcome data are collected. They do not themselves produce an estimate. Here, the registry says the study was terminated before any subjects were treated because of lack of accrual, so those design features describe the plan rather than a completed comparison.
The distinction between the observational and intervention questions is also statistically important. Examining vitamin D status in relation to antibody response is an association question. Comparing assigned cholecalciferol regimens is an intervention question. A causal interpretation of the latter depends on treatment assignment and follow-up; an observational association alone would not establish a dose effect. The record contains no results for either question.
The record also shows the importance of aligning endpoint titles, outcome descriptions, and analysis methods. The primary title concerns antibody responses, while the associated description mentions descriptive statistics and chi-square tests for self-reported flu-like illness. The planned arms refer to the 2012-2013 vaccine, whereas the primary outcome refers to the 2011-2012 vaccine. These differences are not resolved in the registry record, making it difficult to reconstruct the intended analysis even if outcome data had been available.
Finally, a termination status and zero adverse-event counts require careful reading. Neither is a substitute for comparative outcome evidence. The safety entries are counts in specified registry categories, while the primary efficacy-related outcome is unreported. Statistically, the most responsible conclusion is that the intended questions were not answered in the posted record. Recognizing that boundary prevents a null result from being confused with an unavailable result.
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 primary limitation is that the registry record says no subjects were treated before closure because of lack of accrual. As a result, no primary outcome estimate or analysis is reported, and the intended intervention comparison cannot be evaluated. The enrollment field lists 11, but the record does not explain that entry in relation to the explicit statement that treatment did not occur.
Several design details needed to interpret the planned questions are not reported in the registry record. These include eligibility criteria beyond the description of healthy participants, the allocation procedure, who was masked, the antibody assay and response definition, the statistical model for antibody responses, and the planned approach to missing measurements. The sample-size justification is also not reported. The stated planning assumptions do not provide a numerical estimate or establish the study’s original design basis.
The registry descriptions do not fully align: the primary outcome concerns the 2011-2012 seasonal vaccine and an antibody response, while the planned intervention arms describe vaccination after supplementation with the 2012-2013 vaccine. The outcome description also mentions chi-square tests for self-reported flu-like illness rather than specifying an antibody analysis. The record does not clarify these differences.
Safety interpretation is limited by the absence of information about exposure and follow-up periods, as well as the difference between safety-group labels and planned dose-arm descriptions. The record does not provide an analysis population, multiplicity plan, interim-analysis information, or detailed outcome ascertainment. These limitations mean that the registry record can document the intended study and its termination, but cannot support conclusions about immune response, treatment effect, or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Cholecalciferol and Flu Vaccine in Treating Healthy Participants — NCT01561989.
- Registry record last updated 2020-03-10; status last verified 2020-03.
- Results first posted 2020-03-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT01561989 is a randomized, double-masked, parallel study sponsored by Roswell Park Cancer Institute and listed as terminated. It planned to study healthy participants, including supplementation with cholecalciferol for 12 weeks followed by seasonal trivalent influenza vaccine. The planned doses were 400 IU and 4,000 IU daily. The primary outcome concerned 25-hydroxy vitamin D3 levels and antibody response 4 weeks after vaccination, as an observational component.
The enrollment field lists 11, but the primary outcome description states that no subjects were treated before closure because of lack of accrual. No primary or secondary outcome analysis is reported. Safety entries list 0 serious adverse events, 0 other adverse events, and 0 deaths in each of the two recorded groups; exposure and follow-up details are not reported. The registry record documents planned questions and study status, but does not provide results answering those questions.