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 St. John's Wort in Relieving Hot Flashes in Postmenopausal Women With Non-Metastatic Breast Cancer (NCT00110136), a na phase 2 study. The primary outcome is Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00110136 |
| Phase | Phase 2 |
| Condition | Breast Cancer, Hot Flashes |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 9 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Wake Forest University Health Sciences |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns women with a history of breast cancer who experience hot flashes. Its title specifies postmenopausal women with non-metastatic breast cancer, while the primary-outcome population is described as all registered participants. The registry record does not report further eligibility details or how the analysis population was defined in practice.
Intervention
Participants were assigned St. John's Wort in a one-group study. The arm description specifies one 300mg tablet three times per day. The record does not report adherence, treatment interruptions, or whether participants actually took the assigned regimen throughout the study.
Comparator
There was no concurrent comparison group in the registered design. Allocation is recorded as NA and the model as single group. Consequently, the design does not provide a randomized contrast between St. John's Wort and placebo, usual care, or another treatment. A before-and-after comparison, if results were available, would compare observations over time within the study rather than outcomes against a concurrent control.
Primary question
The primary objective was to assess change in hot-flash frequency over four weeks. Frequency was recorded in a daily hot flash diary, with the primary outcome described at baseline and four weeks and expressed as a mean number of occurrences with standard deviation. Numerical outcome estimates and an inferential result are not reported in the registry record. The clinical question is therefore identifiable, but its answer cannot be established from the posted registry results.
3. Trial Design
This phase II study evaluated St. John's Wort in a single-group design. The registry record identifies Wake Forest University Health Sciences as the sponsor and records enrollment of 9. The trial status is terminated. Its recorded start date is 2006-03-16 and its primary completion date is 2008-04-01. The registry record does not report why the study was terminated, so the status alone should not be taken to indicate a particular reason or outcome.
Allocation is recorded as NA, the model as single group, and masking as none. There is no registered randomized control arm for a like-for-like comparison. The arm description says that a participant was given one 300mg St. John's Wort tablet three times per day. Information about adherence, treatment duration beyond the primary four-week assessment window, and other treatment received is not reported in the registry record.
The primary outcome concerns hot-flash frequency from a daily diary at baseline and four weeks. Other registered outcomes cover hot-flash score, toxicities, quality of life measured by MCS and PCS, and mood measured by the POMS Short Form. The record lists 6 outcome measures and 5 analyses, but detailed analysis specifications and numerical results are not reported. Enrollment describes the registered study size; it does not establish how many participants contributed data to any particular endpoint.
A single-group before-and-after design can describe change over time among observed participants. In general, without a concurrent control group, such a change cannot by itself distinguish an intervention-related effect from time trends, measurement variation, other influences, or changes in who contributed observations. This is a design limitation, not a claim about what occurred in this study.
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 | St. John's Wort |
|---|---|
| STARTED | 9 |
| COMPLETED | 9 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All registered participants
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.
Population: All registered participants are used in the analysis.
| Characteristic | Unit | St. John's Wort |
|---|---|---|
| Participants analysed | 9 | |
| Age, Continuous | years | 55.2 (SD 7.0) |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 8 |
| Age, Categorical: >=65 years | Participants | 1 |
| Sex: Female, Male: Female | Participants | 9 |
| Sex: Female, Male: Male | Participants | 0 |
| Race/Ethnicity, Customized: White | participants | 9 |
| Region of Enrollment: United States | participants | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Effect of St. John's Wort on Hot Flash Frequency as Recorded in a Daily Hot Flash Diary From Baseline to 4 Weeks, measured over Baseline and four weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | number of occurrences |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the effect of St. John's Wort on hot-flash frequency, recorded in a daily hot flash diary at baseline and four weeks. The measure is the number of occurrences, treated as a continuous outcome and summarized using a mean and standard deviation. The stated primary objective is to assess change over a four-week period in patients given St. John's Wort.
Frequency captures how often hot flashes occur, while a diary is a way to record repeated events over the observation period. In general, measurements at baseline and follow-up make it possible to describe whether the recorded mean changes over time. The mean gives a measure of the group’s average frequency; the standard deviation describes variation among recorded values around that mean. Neither statistic alone conveys the full distribution of individual responses.
The endpoint is clinically interpretable as a count of occurrences, but interpretation depends on how diary records were completed and how missing days were handled. Those details are not reported in the registry record. Nor are the baseline and follow-up estimates, a change estimate, its uncertainty, or a test result reported. Thus the outcome definition is available, but the amount and precision of any observed change cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and design but does not report numerical results for the primary endpoint. It gives no mean hot-flash frequency at baseline or four weeks, no estimated change, no standard error or confidence interval, and no test result. The posted results therefore do not establish the direction, size, or precision of change in hot-flash frequency. This absence of a numerical result is not evidence that the frequency stayed the same, nor does it establish that it changed.
The registered design is single group, with no concurrent randomized comparator. Even if a before-and-after estimate were available, it would describe change among participants with measurements; it would not alone identify what would have happened over the same period without St. John's Wort. In general, symptoms can vary over time, measurement can fluctuate, and other influences can coincide with treatment. Without a suitable control comparison, these explanations cannot be separated by a simple pre/post contrast.
The registry describes the endpoint as a mean number of occurrences with standard deviation. A mean can be a useful summary, but it does not show whether changes were similar across participants or concentrated in a few observations. A standard deviation describes variability, not the precision of the estimated mean. Precision would ordinarily be assessed with an uncertainty interval or a suitable model-based estimate; such a result is not reported in the registry record.
Enrollment is recorded as 9, but this does not establish the number with complete diary records at either time point or the number included in an analysis. The primary population is described as all registered participants, while actual analysis-population details are not reported. Missing observations could affect both the estimate and its precision, and the handling of missing diary entries is not reported.
Safety entries show 0 serious adverse events among 9 at risk and 6 participants with other adverse events among 9 at risk. These counts describe the registry’s safety reporting; they do not substitute for a benefit estimate or establish the nature, timing, or severity of each event. The record does not report a detailed account of adverse-event collection or follow-up. Overall, the available record supports a description of the study’s aim and design, but not a quantitative conclusion about the primary outcome.
9. Statistical Methods Explained
The endpoint is a continuous measure summarized by a mean and standard deviation. The registry describes the outcome as the number of hot-flash occurrences recorded in a daily diary, with observations at baseline and four weeks. The record does not specify the statistical model, the exact contrast used for analysis, or the inferential procedure. General explanations below describe concepts that may be relevant to this type of endpoint; they are not claims about methods actually used in the study.
What does a mean summarize?
In general, the arithmetic mean represents the average of observed measurements. For a diary-based frequency outcome, it can summarize the average recorded number of occurrences over a defined observation period. A mean is sensitive to unusually high or low values, and it does not reveal the shape of the distribution. Two groups of participants could have the same mean while differing in how much individual values vary or in how values are distributed. The registry’s outcome description does not state whether diary counts were converted to a particular daily summary before calculating the mean.
The standard deviation describes spread among observations around the mean. It is not a measure of how precisely the mean has been estimated. Precision also depends on the amount and pattern of available information and on the assumptions of the analysis. A confidence interval, when reported, gives a range of values compatible with the data under the method’s assumptions and conveys uncertainty about an estimate. No confidence interval for the primary endpoint is reported in the registry record.
How could repeated measurements be compared?
In general, a before-and-after study may estimate change by comparing each participant’s follow-up measurement with that participant’s baseline measurement, or by comparing group summaries at the two times. These approaches answer related but not identical statistical questions. A paired analysis uses the fact that two measurements come from the same participant; its uncertainty depends on the variability of within-participant changes. A comparison of separate time-point summaries does not directly use that pairing unless the analysis accounts for it. The registry does not report which approach was used, whether participant-level changes were calculated, or whether any adjustment was made.
For repeated observations, the number of recorded diary days and completeness of each diary can matter. In general, participants with more complete records may contribute differently from those with fewer observations, depending on the analysis method. A protocol might define a minimum level of diary completion or a rule for deriving a participant-level frequency, but those details are not reported in the registry record. It is therefore not possible to infer how daily entries were converted into the primary summary.
Why do uncertainty and study design matter?
An estimate describes the observed data; an uncertainty interval or test addresses how compatible the data are with a range of possible underlying effects under stated assumptions. Statistical significance, if assessed, would not by itself describe clinical importance. Conversely, a non-significant result would not prove that there is no effect. The primary estimate and its uncertainty are not reported in the registry record, so neither the magnitude nor the statistical precision of a possible change can be evaluated.
The single-group structure limits causal interpretation. General statistical reasoning distinguishes an observed change from a treatment effect: a treatment effect is a contrast between outcomes under different treatment conditions, whereas a single-group pre/post change compares measurements across time. The latter can be affected by natural symptom fluctuation, external influences, diary behavior, or regression to the mean. These are general possibilities, not findings about this trial. A concurrent control group and a prespecified comparison would help address some alternative explanations, but this record does not describe such a group.
Hot-flash counts are event counts. In general, count data can have a distribution different from the normal distribution assumed by some simple methods, particularly when counts are asymmetric or when variability exceeds what a basic count model expects. Over-dispersion means that observed variability is greater than a model’s basic assumption; ignoring it can make uncertainty estimates too small. Other approaches can model counts or repeated observations directly. The registry record does not state whether a count model, a normal approximation, or another method was used, and the endpoint is described as a mean with standard deviation rather than by a named model.
What do planning calculations mean?
General sample-size planning calculations ask how much information a future study might need to detect a prespecified effect under chosen assumptions. The registry’s planning description characterizes its illustration as based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a description of this single-group study’s registered design. The record does not report the illustration’s numerical results or the effect value used.
A planning sample size is not an observed result and is not observed power. It does not show that the study had a particular probability of detecting an effect after data collection, nor does it replace an estimate and its confidence interval. The sample-size assumptions do not establish that the original trial was designed using those assumptions; the record explicitly identifies the calculation as a planning illustration rather than the trial’s own design. A sample-size justification for the trial itself is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 6 outcome measures and 5 analyses. The named outcomes extend beyond the primary hot-flash-frequency endpoint to hot-flash score, toxicities, quality of life measured by MCS and PCS, and mood measured by the POMS Short Form. The record does not explain how the listed outcome measures correspond to the analyses or identify a multiplicity adjustment. A statistical plan describing outcome hierarchy, prespecified contrasts, or control of false-positive findings is not reported in the registry record.
In general, testing several outcomes or comparisons increases the chance that at least one result may appear statistically notable by chance. Multiplicity methods can address that issue, but the appropriate approach depends on which outcomes and contrasts were planned and on the inferential goal. Without a detailed analysis plan and numerical results, the registry record does not support judging whether multiplicity affected interpretation.
Missing-data methods are also not described. For a diary endpoint, missingness could involve incomplete days, absent baseline or follow-up records, or withdrawal before assessment. The registry does not report how many observations were missing, why they were missing, whether any imputation was used, or whether sensitivity analyses were conducted. These details matter because a complete-record analysis can differ from an analysis that makes assumptions about unobserved values.
The primary population is described as all registered participants, and enrollment is recorded as 9. The record does not report the number included in the primary analysis or define an analysis population beyond that description. It also does not report whether participants were analyzed according to treatment assignment, as treated, or under another rule. Consequently, the relationship between enrollment, available diary data, and the reported analysis cannot be evaluated.
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 |
|---|---|---|---|
| St. John's Wort | 0 | 9 | 0.0% |
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 |
|---|---|
| St. John's Wort | 6 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | St. John's Wort |
|---|---|---|
| Dry Mouth | Gastrointestinal disorders | 4 of 9 |
| Insomnia | General disorders | 4 of 9 |
| Dizziness | Nervous system disorders | 3 of 9 |
| Fatigue | General disorders | 2 of 9 |
| Headache | Nervous system disorders | 2 of 9 |
| Prutitus | Skin and subcutaneous tissue disorders | 2 of 9 |
| Diarrhea | Gastrointestinal disorders | 1 of 9 |
| Hot Flashes | General disorders | 1 of 9 |
| Pain | General disorders | 1 of 9 |
| Photosensiivity | Eye disorders | 1 of 9 |
The registry records 0 serious adverse events among 9 at risk in the St. John's Wort group. It records 6 participants with other adverse events among 9 at risk. These are counts as entered in the registry, not rates recalculated from them. No serious adverse-event terms are listed. The record does not report a number for deaths, so deaths are not reported in the registry record.
These entries should be read as a summary of reported safety counts, not as a complete account of tolerability. The record does not give event descriptions for the other adverse events, their timing, duration, severity, relatedness to treatment, or whether a participant experienced more than one event. It also does not explain the safety monitoring or collection procedures. Therefore, the count of participants with other events does not reveal the number or pattern of individual events.
Zero serious adverse events in the registry entry means that none are recorded in that category for this group; it does not establish that serious risk is absent. With no randomized comparison group, the safety counts do not allow a comparative assessment against another treatment or no treatment. They should also be considered separately from the unreported primary hot-flash-frequency results.
12. What the Result Does, and Does Not, Mean
The study addressed a defined question: whether hot-flash frequency changed over four weeks among participants given St. John's Wort. It used a daily diary and identified mean frequency as the primary measure. The registry also describes the intervention regimen and a range of secondary outcomes. These details clarify what the study set out to assess, but they do not supply the numerical outcome evidence needed to judge the amount or precision of any change.
The registry record does not report a baseline mean, a four-week mean, an estimated change, a confidence interval, or a test result for the primary outcome. It is therefore not possible to say from the posted results whether frequency increased, decreased, or remained similar, or how uncertain an estimate might be. Absence of a numerical result in the registry record should not be interpreted as a null finding.
The design also sets limits on what an observed pre/post change could mean. In general, a single-group study can document a temporal pattern, but without a concurrent comparator it cannot isolate the intervention’s contribution from other changes over time. This limitation applies regardless of whether a within-group change is statistically significant. It does not establish that the intervention had no effect; it means the design does not provide a controlled treatment contrast.
The safety record includes no serious adverse events recorded and reports other adverse events in the study group, but the registry does not provide event-level detail. These counts cannot establish comparative safety or describe all aspects of tolerability. The overall record is informative about the intended population, regimen, endpoint, and single-group design. It is insufficient for a quantitative conclusion about efficacy, for a causal estimate, or for a detailed safety assessment.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a research question and an answer supported by reported data. The registry specifies a primary measure, a baseline and four-week assessment, and a single-group design. Yet numerical estimates for the primary endpoint are not reported in the registry record. Knowing the endpoint definition alone does not reveal the result, its variability, or its uncertainty.
The study also illustrates why design matters to interpretation. A pre/post comparison can describe what happened across time in the observed group, but it is not equivalent to a randomized comparison. General statistical reasoning requires separating a temporal association from a treatment contrast. Without a concurrent comparator, explanations other than treatment can remain possible even when repeated measurements are collected carefully.
Registry reporting is important because counts of outcomes, analysis populations, missing data, and safety events help readers judge how evidence was generated. In this record, enrollment and the primary population description are available, but the number analyzed, diary completeness, missing-data approach, and detailed statistical plan are not reported. Those omissions limit reproducibility and the reader’s ability to assess bias and precision.
The record also labels its sample-size calculations as planning illustrations rather than the trial’s own design. This distinction matters: planning scenarios are not findings from participants and are not evidence of observed power. The study can therefore serve as a reminder to interpret outcome definitions, analysis details, and design together, rather than treating an endpoint label or a planning calculation as a 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 most consequential limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. Without an estimate of baseline and follow-up frequency, a change estimate, and its uncertainty, the magnitude and precision of any observed pattern cannot be assessed. The record also does not give a numerical result for the listed secondary outcomes.
The single-group design has no concurrent randomized comparison. Any within-group change over time, if measured, would not by itself distinguish a treatment-associated effect from time trends, symptom variability, or other influences. Masking is recorded as none, and the record does not describe procedures that might reduce the influence of expectations on diary reporting. These are design considerations, not evidence that a particular bias occurred.
Enrollment is recorded as 9, but the number contributing complete diary data or included in each analysis is not reported. The registry does not explain diary completion requirements, missing-data handling, or whether the analysis population matched the stated population of all registered participants. This makes it difficult to assess how representative the analyzed observations may have been.
The registry lists several outcome measures and analyses but does not report a detailed statistical plan or multiplicity approach. The reason for the terminated status is not reported in the registry record. Safety reporting is limited to group counts: event descriptions, timing, severity details for other events, and deaths are not reported. These limitations mean that the record supports a description of study conduct at a high level, but not a detailed appraisal of outcome estimation or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: St. John's Wort in Relieving Hot Flashes in Postmenopausal Women With Non-Metastatic Breast Cancer — NCT00110136.
- Registry record last updated 2021-09-29; status last verified 2021-09.
- Results first posted 2014-12-29.
- 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
NCT00110136 is a phase II, single-group study sponsored by Wake Forest University Health Sciences. The registry records enrollment of 9, a status of terminated, and no masking. The intervention was St. John's Wort, described as one 300mg tablet three times per day.
The primary endpoint was hot-flash frequency from a daily diary at baseline and four weeks, summarized as a mean number of occurrences with standard deviation. The registry record does not report numerical primary-outcome results, analysis details, or the reason for termination. Safety entries record 0 serious adverse events and 6 participants with other adverse events among 9 at risk; deaths are not reported in the registry record.