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 Circadian Macular Volume Changes in the Choroid (NCT02223546), a registered phase not stated study. The primary outcome is Macular Choroidal Volume.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02223546 |
| Phase | Phase not stated |
| Condition | Choroid Physiology |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Medical University of Graz |
| Results posted | Yes |
2. Clinical Question
Population
Healthy subjects. The registry record lists an enrollment of 15.
Intervention
Measurements of choroidal volume every 3 hours within a 24 hour timeframe. No treatment intervention is described.
Comparator
No like-for-like control comparison is identified. The registry record says allocation was not stated and does not describe a randomized comparison.
Primary question
How does macular choroidal volume, measured in the central 6mm, vary across the 24 hour measurement timeframe in healthy subjects?
The study is titled “Circadian Macular Volume Changes in the Choroid,” and its official title describes a pilot study of diurnal changes in choroidal volume. Its stated focus is measurement over time, rather than comparing a treatment group with a control group. The primary outcome is macular choroidal volume, expressed as a mean in mm^3; the measurement timeframe is described as a daily average based on measurements every 3 hours within a 24 hour timeframe.
The registry summary states that choroidal volume measured fluctuates significantly over a 24 hour time frame. That statement gives the direction of the reported finding only in broad terms: the record does not give the individual measurements, mean values at particular times, or an estimate of the size of the fluctuation. It also does not report the statistical method behind the word “significantly.” Consequently, the question that can be addressed from the registry record is whether the posted summary describes variation over the measurement period, not how large or precisely estimated that variation was.
3. Trial Design
This completed pilot study is registered as NCT02223546. The registry record lists the sponsor as Medical University of Graz, the condition as Choroid Physiology, and enrollment as 15. The recorded start is 2013-10 and primary completion is 2014-01. The status is COMPLETED.
The arm description is “healthy subject, every 3 hour measurement.” This describes a measurement schedule, not a treatment assignment. Allocation is not stated, and the record explicitly indicates that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Accordingly, a treatment-versus-control interpretation is not supported by the design information recorded.
The primary outcome is Macular Choroidal Volume. It is described as a continuous measure, with the reported parameter specified as a mean and dispersion specified as a standard deviation. The timeframe is a daily average of measurements every 3 hours within a 24 hour timeframe. The outcome description places the measurement in the central 6mm of the macula. Subfoveal Choroidal Thickness is listed as a secondary outcome.
The registry record lists 3 outcome measures, but the names and definitions of all of them are not available in the registry record recorded for this analysis. It lists 0 analyses. The record does not report the recruitment approach, detailed eligibility criteria, measurement instrument or procedures, analysis population, or a statistical analysis plan. These omissions limit how fully the study's conduct and analysis can be reconstructed. The registry describes the study as a pilot; no design justification or sample-size rationale is reported in the registry record.
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 | Healthy Subject |
|---|---|
| STARTED | 15 |
| COMPLETED | 15 |
| NOT COMPLETED | 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 | Healthy Subject |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | years | 26 (SD 1) |
| Sex: Female, Male: Female | Participants | 7 |
| Sex: Female, Male: Male | Participants | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Macular Choroidal Volume, measured over daily average out of measurements every 3 hours within a 24 hour timeframe.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | mm^3 |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is macular choroidal volume in the central 6mm, reported as a mean in mm^3. The stated timeframe is a daily average derived from measurements every 3 hours within a 24 hour timeframe. The registry identifies the outcome as continuous and specifies standard deviation as the measure of dispersion.
As a general statistical point, a continuous measurement retains information about the magnitude of observed values rather than classifying each observation into a small set of categories. A mean can describe the central level of such measurements, while a standard deviation describes how spread out measurements are around that mean. These summaries answer different questions: the mean describes level, and the standard deviation describes variability. Neither alone describes how values change with time.
For a study focused on diurnal or circadian variation, measuring volume at multiple times can support a description of how the outcome varies across the stated timeframe. However, the record does not provide time-specific means, a summary of within-subject changes, or the individual measurements. It therefore does not allow readers to assess the pattern, timing, magnitude, or precision of changes from the numerical outcome data.
In general, defining the endpoint and its timeframe matters because interpretation depends on what was measured and over what period. Here, the record identifies a central macular volume measure and a 24 hour measurement window, but it does not provide additional operational details about how the daily average was formed. Those details are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry summary states that choroidal volume measured fluctuates significantly over a 24 hour time frame. This is the principal result available in the registry information. It supports reporting that the registry describes temporal fluctuation in the measured volume. It does not, by itself, show the values at each measurement time or quantify the size of the fluctuation.
The record gives no primary-outcome mean, standard deviation, confidence interval, p-value, or time-specific result. It also lists 0 analyses. There is therefore no numerical estimate available to judge how large the reported variation was or how precisely it was estimated. The term “significantly” appears in the registry summary, but the record does not state the statistical test, threshold, model, or uncertainty estimate associated with that wording. It should not be translated into a claim about clinical importance or a specific level of statistical evidence.
In general, statistical significance and effect magnitude are distinct. A significance statement concerns evidence relative to a specified statistical model and null hypothesis; it does not communicate the size of an effect or its practical importance. A confidence interval, when reported, describes the uncertainty around an estimate under the analysis assumptions. Neither the estimate nor such an interval is reported for this primary outcome in the registry information.
The measurement schedule is described as every 3 hours within a 24 hour timeframe, and the outcome timeframe refers to a daily average. If repeated measurements are collected from the same subject, the observations may be correlated rather than independent. General statistical methods for repeated measurements account for that dependence. The record does not say whether measurements were analyzed as repeated observations, reduced to daily averages, or handled by another method, so no particular approach can be attributed to the investigators.
The study is not described as a randomized comparison, and no like-for-like control comparison is identified. Thus, the reported fluctuation should be read as a description of measurements over time, not as an estimate of a contrast between assigned treatments. The record does not establish that any observed variation was caused by a particular factor.
The enrollment is 15, and the registry labels the study a pilot. A small pilot can be informative about measurement and patterns worth studying, but the registry record does not report a sample-size justification or precision target. Without outcome estimates and their uncertainty, the precision of the reported pattern cannot be assessed from the posted information. The result is best understood as a qualitative registry summary, with the numerical magnitude, analysis details, and limits of uncertainty not reported in the registry record.
9. Statistical Methods Explained
The registry describes the primary outcome as a continuous measure summarized by a mean, with standard deviation as the dispersion measure. It does not identify a statistical test or model. The explanations below are general statistical context, not claims about methods used in this study.
What do the mean and standard deviation describe?
For a continuous outcome, the mean is an average that indicates the central level of the measurements included in its calculation. The standard deviation describes the spread of values around that mean. A mean without a measure of spread gives little information about how variable the underlying observations are; a standard deviation without the mean does not show the central level. Together, they can describe a distribution in a compact way, but they do not fully characterize it in every circumstance.
In this study, the registry says the primary parameter is a mean and the dispersion is a standard deviation. It does not report the resulting mean or standard deviation. Nor does it give a distribution plot, individual measurements, or a description of outliers. As a result, readers cannot assess the observed scale of variation or whether the mean is an adequate summary of the recorded values.
Why does repeated measurement matter?
General statistical methods distinguish between independent observations and repeated observations on the same subject. Measurements from the same person can be related: a value at one time may carry information about a value at another time. Treating related measurements as independent can lead to uncertainty estimates that do not reflect the data structure. Methods for repeated measurements can model the correlation or summarize observations at the subject level, depending on the question and design.
The registry describes measurements every 3 hours within a 24 hour timeframe and refers to a daily average. It does not explain whether each time point was analyzed separately, whether measurements were first combined into an average, or whether a repeated-measures model was used. It also does not specify how the analysis accounted for within-subject dependence. These details are not reported in the registry record, so the statistical handling cannot be evaluated.
What does a significance statement establish?
In general, a statistical test evaluates data against a specified null hypothesis under stated assumptions. A p-value, if reported, measures how compatible the observed data are with that hypothesis under the model; it is not the probability that the hypothesis is true. A p-value alone also does not convey the magnitude of an effect or the precision of an estimate. Interpretation depends on the question, analysis, assumptions, and other evidence.
The registry summary uses the word “significantly” to characterize fluctuation. No p-value, test statistic, null hypothesis, or analysis method is reported in the registry record. It is therefore not possible to explain what specific test produced the statement or to evaluate its assumptions. The summary should be reported as the registry's wording, not expanded into a more specific statistical claim.
What would an uncertainty interval add?
In general, a confidence interval gives a range of values compatible with an estimate under the method's assumptions and stated confidence procedure. It helps readers consider both the estimated magnitude and its precision. An interval that is relatively narrow indicates greater precision than a broad interval for the same type of estimate, although an interval does not eliminate uncertainty or establish clinical importance.
No confidence interval or numerical effect estimate for the primary outcome is reported in the registry information. Precision therefore cannot be assessed, and no interval should be inferred from the summary statement. The standard deviation named in the endpoint description is not a substitute for a confidence interval: it describes dispersion of measurements, whereas an interval around an estimate describes uncertainty in that estimate.
How should the time pattern be analyzed?
As general context, time-pattern questions can be approached by estimating values at specified times, modeling time as a continuous or categorical predictor, or summarizing a defined change over the measurement window. The choice depends on the scientific question, measurement schedule, data structure, and assumptions. A model may also need to represent the dependence among measurements made on the same subject. These choices affect what the estimated quantity means.
The stated primary endpoint is a daily average of measurements taken every 3 hours over a 24 hour timeframe, while the study title and summary refer to changes over time. The record does not clarify how this endpoint relates to any time-specific comparisons or how the stated fluctuation was estimated. No analysis can be reconstructed from the description alone.
The registry includes a planning illustration based on an observed effect, with assumptions including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial used those design parameters; the record explicitly characterizes the illustration as separate from the trial's own design. Any sample sizes generated under such assumptions are planning illustrations, not observed power. The registry record does not report the trial's own sample-size justification or analysis plan.
10. Confidence Intervals for Each Arm
No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.
| Arm | Participants | Mean | Standard deviation | 95% CI for the mean |
|---|---|---|---|---|
| Healthy Subject | 15 | 10.330 | 2.530 | 8.929 to 11.731 |
R code and output
arm <- c("Healthy Subject")
n <- c(15)
m <- c(10.33)
sp <- c(2.53)
sd <- sp # posted standard deviations
for (i in seq_along(n)) {
se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}
CARM Healthy Subject 15 10.330 2.530 8.929 11.73111. Multiplicity, Missing Data and Analysis Populations
The registry record lists 3 outcome measures, names Macular Choroidal Volume as the primary outcome, and lists Subfoveal Choroidal Thickness as a secondary outcome. The names and definitions of all listed outcomes are not reported in the registry record available for this analysis. The record lists 0 analyses, and does not report how outcomes or time-specific comparisons were analyzed.
Multiplicity arises in general when several outcomes, time points, or statistical comparisons are examined. The more questions assessed, the greater the chance that at least one result may appear statistically notable by chance if no suitable approach is used. Methods may prioritize a primary outcome, adjust inference, or clearly distinguish confirmatory analyses from exploratory ones. The record does not report whether multiplicity was considered or how it was handled; no adjustment method should be assumed.
Missing-data information is not reported in the registry record. There is no description of whether measurements were missing, how missing observations were handled, or whether any sensitivity analysis was performed. The analysis population is also not reported. Although the registry lists enrollment as 15, it does not state how many participants contributed data to the primary endpoint or whether all enrolled participants were included in the analysis. Enrollment should not be treated as proof of complete outcome data.
General interpretation of repeated measurements also depends on whether observations are available across the intended measurement times and how incomplete records are treated. Without these details, the potential influence of missing measurements on the estimated time pattern cannot be assessed. The registry does not report an imputation strategy, exclusion rule, or analysis population definition.
12. 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 |
|---|---|---|---|
| Healthy Subject | 0 | 15 | 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 |
|---|---|
| Healthy Subject | 0 of 15 |
The registry lists a Healthy Subject group with 15 at risk for serious adverse events and 0 affected. It also lists 15 at risk for other adverse events and 0 affected. No serious adverse-event terms are listed. The deaths field is null, so deaths are not reported in the registry record; a null entry is not the same as a reported count of zero.
These figures describe the adverse-event entries in the registry. They do not establish that no events occurred outside the scope of collection or reporting, and the record does not describe the safety-monitoring period, event definitions, or ascertainment procedures. The registry does not provide additional information about how events were collected or reviewed.
In general, an at-risk count identifies the group considered in the adverse-event summary, while an affected count records participants with the specified event category. These counts are not a substitute for a detailed safety description, and they do not indicate the timing, duration, severity, or cause of an event. Because this study is described as measurement-focused in healthy subjects and does not report a treatment comparison, these entries should not be interpreted as comparative evidence about treatments.
13. What the Result Does, and Does Not, Mean
The registry record describes a completed pilot study in healthy subjects, with repeated measurement of macular choroidal volume over a 24 hour timeframe. Its summary reports that choroidal volume fluctuates significantly during that period. This is the result that can be stated directly from the posted information.
The summary does not provide the underlying measurements or a numerical estimate of the amount of fluctuation. It does not show how the values varied across measurement times, the mean or standard deviation, or an uncertainty interval. The size, precision, and detailed shape of the reported pattern therefore cannot be judged from the registry information.
The word “significantly” should not be read as a measure of clinical importance. The record does not state the statistical test, model, p-value, or hypothesis used to support the term. General statistical interpretation distinguishes evidence against a statistical null from the magnitude or practical relevance of a pattern. No conclusion about practical importance can be drawn from the wording alone.
The record also does not identify a like-for-like control group or a randomized comparison. It describes a measurement schedule in healthy subjects. Thus, the reported fluctuation is not an estimate of a treatment effect, and the registry summary does not establish why the measurements vary. The result should not be extended beyond the measured outcome and timeframe.
Finally, the registry does not report the analysis population, missing-data handling, detailed outcome results, or statistical analysis plan. These omissions leave important questions about how the result was obtained and how precisely it was estimated. The appropriate reading is narrow: the registry summary reports significant fluctuation in choroidal volume over a 24 hour time frame, while the magnitude and analytic basis are not reported in the registry record.
14. Why This Trial Matters Statistically
This study is statistically interesting because its question concerns change over time within a measurement schedule rather than a simple contrast between treatment groups. A design with measurements every 3 hours within a 24 hour timeframe raises general issues about how repeated observations are summarized and how their dependence is handled. Those choices influence what an estimate represents and how uncertainty should be described.
The registry identifies a continuous primary outcome and names both a mean and standard deviation as summary measures. That makes the distinction between central level, spread, and time pattern important. A daily average may describe an overall level, while a claim about fluctuation concerns variation over the measurement period. The record does not explain the analytic link between the daily-average endpoint and the reported time-related summary, so that distinction is especially relevant when interpreting the result.
The registry summary's use of “significantly” also illustrates why numerical results and methods matter. Without an estimate, uncertainty interval, or description of the test, readers cannot assess the strength, precision, or magnitude of the finding. Statistical significance is not a substitute for those quantities.
As a pilot study, the record can raise a question for future investigation, but it does not report a sample-size justification or sufficient outcome detail to evaluate precision. The registry includes a planning illustration, but identifies it as separate from the study's own design. Keeping planning assumptions distinct from observed results is essential: a planning calculation is not observed power and does not fill gaps in the outcome reporting.
The design information also cautions against a causal or comparative interpretation. No randomized comparison or like-for-like control is identified. The statistical value of the record is therefore in documenting a time-oriented measurement question and its reported summary, while illustrating the importance of transparent methods and numerical outcome reporting.
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 registry information is brief relative to the questions raised by the study title and summary. It reports a significant fluctuation over a 24 hour time frame but does not provide the measured values, estimated magnitude, standard deviation result, confidence interval, or p-value. Readers cannot determine the scale or precision of the reported pattern from those details.
Methods that would clarify interpretation are not reported in the registry record. These include the statistical test or model, treatment of repeated measurements, analysis population, handling of missing observations, and multiplicity approach. The record does not describe the measurement procedures or give detailed eligibility criteria. It also does not identify all 3 outcome measures by name and definition in the information.
The study is not described as a randomized comparison, allocation is not stated, and the registry notes that the arms are not a like-for-like control comparison. The result therefore cannot support a treatment contrast or establish a cause for temporal variation. The healthy-subject setting and the described measurement schedule define the scope of the record; broader applicability is not established by the information reported.
The registry calls the study a pilot but does not report its own sample-size justification. Its planning illustration is not the trial's design rationale. The absence of detailed outcome results and analysis methods means that the main reported finding cannot be independently evaluated from the registry record alone. These limitations concern what is documented, not proof that additional information or analyses do not exist outside the record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Circadian Macular Volume Changes in the Choroid — NCT02223546.
- Registry record last updated 2020-09-24; status last verified 2020-09.
- Results first posted 2020-09-24.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT02223546 is a completed pilot study titled “Circadian Macular Volume Changes in the Choroid,” with the official title “Pilotstudy: Diurnal Changes in Choroidal Volume.” The sponsor is Medical University of Graz. The registry lists enrollment as 15, the start as 2013-10, and primary completion as 2014-01.
The primary outcome is mean macular choroidal volume in the central 6mm, measured in mm^3. The timeframe is a daily average from measurements every 3 hours within a 24 hour timeframe. Subfoveal Choroidal Thickness is listed as a secondary outcome. The summary reports significant fluctuation in choroidal volume over a 24 hour time frame.
The registry does not report the numerical primary-outcome results, statistical analysis method, analysis population, or missing-data handling. It identifies no randomized, like-for-like control comparison. The reported finding is therefore best read as a brief summary of temporal variation, without a reported estimate of its magnitude or precision.