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 Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance (NCT04864405), a randomized phase 4 study. The primary outcome is Change in Endocrine Toxicity and Tolerability at 12 Weeks.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04864405 |
| Phase | Phase 4 |
| Condition | Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 245 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Ottawa Hospital Research Institute |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerned people with early-stage breast cancer receiving endocrine therapy. The primary endpoint population was participants who answered the FACT-ES questionnaire at baseline and twelve weeks. The registry record reports an enrollment of 245, but does not report further eligibility details in the information for this outcome.
Intervention
Participants assigned to morning administration were instructed to take endocrine therapy within one hour of waking. The trial examined timing as a practical feature of treatment-taking, with endocrine toxicity and tolerability as the primary outcome.
Comparator
The comparator was evening administration, defined as taking endocrine therapy within one hour of bedtime. The comparison was between assigned timing groups; the registry record does not describe a blinded comparison.
Primary question
Did the mean change in total FACT-ES score from baseline to twelve weeks differ between morning and evening administration? FACT-ES scores range from 0 to 184, with higher scores indicating better outcomes. The posted group means changed by -2.2 in the morning group and -5.0 in the evening group. The estimated mean difference for evening compared with morning was -2.8 units.
This is a question about a patient-reported measure of endocrine symptoms and tolerability over a specified follow-up period. It is not, by itself, a comparison of cancer control or survival. The registry record lists health-related quality of life, compliance, and cost-effectiveness among the secondary outcomes, but does not provide their numerical results in the record summarized for this analysis. The question is therefore narrower than whether either timing is preferable overall: it asks whether the reported change in this particular symptom measure differed between the randomized groups.
3. Trial Design
The trial is identified in the registry as NCT04864405 and is titled “Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance.” Its official title describes REaCT-CHRONO as a pragmatic, randomized, multicentre trial. The record lists the phase as PHASE4, the allocation as randomized, the masking as none, and the model as parallel. The sponsor is Ottawa Hospital Research Institute.
The two intervention groups differed in the assigned time for taking endocrine therapy. Morning administration was defined as taking the medication within one hour of waking; evening administration was defined as taking it within one hour of bedtime. The open-label design means that masking was not used according to the registry. The record does not provide further details about how adherence to the assigned timing was monitored or whether the timing instruction was followed throughout the trial.
The registry reports enrollment of 245. The primary endpoint result lists 103 participants in the morning group and 102 in the evening group for the outcome measure. These outcome counts are associated with the posted endpoint; the record does not explain the difference between enrollment and the numbers reported for this measure. The endpoint population is described as participants who answered the FACT-ES at baseline and twelve weeks.
The trial started on 2021-06-30, had primary completion on 2022-09-05, and is marked completed. The registry lists six outcome measures and four secondary outcomes: change in endocrine toxicity and tolerability, change in health-related quality of life scores, the number of participants compliant with endocrine therapy, and cost-effectiveness. Numerical results for those secondary outcomes are not reported in the registry record. The record does not report the trial's original sample-size justification or its original statistical analysis plan.
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 | Morning Administration of Endocrine Therapy | Evening Administration of Endocrine Therapy |
|---|---|---|
| STARTED | 122 | 123 |
| COMPLETED | 115 | 112 |
| NOT COMPLETED | 7 | 11 |
Reasons for not completing this period:
| Reason | Morning Administration of Endocrine Therapy | Evening Administration of Endocrine Therapy |
|---|---|---|
| Withdrawal by Subject | 4 | 6 |
| Did not want endocrine therapy | 3 | 5 |
Analysis population for the primary outcome, as defined in the registry: The participants who answered the FACT-ES at baseline and 12 weeks.
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 | Morning Administration of Endocrine Therapy | Evening Administration of Endocrine Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 122 | 123 | 245 | |
| Age, Continuous | years | 61.1 (SD 12.5) | 61.0 (SD 11.2) | 61.1 (SD 11.9) |
| Sex: Female, Male: Female | Participants | — | — | 0 |
| Sex: Female, Male: Male | Participants | — | — | 0 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Canada | participants | 122 | 123 | 245 |
| Type of endocrine therapy: Tamoxifen | Participants | 93 | 94 | 187 |
| Type of endocrine therapy: Anastrozole | Participants | 20 | 22 | 42 |
| Type of endocrine therapy: Letrozole | Participants | 9 | 7 | 16 |
| Type of endocrine therapy: Exemestane | Participants | 0 | 0 | 0 |
| Type of endocrine therapy: LHRH | Participants | 10 | 12 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Change in Endocrine Toxicity and Tolerability at 12 Weeks, measured over Baseline to 12 weeks after treatment initiation.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is change in total Functional Assessment of Cancer Therapy - Endocrine Symptoms questionnaire score from baseline to twelve weeks after treatment initiation. FACT-ES is described as a validated subscale of the Functional Assessment of Chronic Illness Therapy measurement system. It contains 46 items, each using a five-point Likert-type scale from 0, “not at all,” to 4, “very much.” The total score ranges from 0 to 184, and higher scores indicate better outcomes.
The endpoint focuses on endocrine symptoms and tolerability as experienced by participants. A change score compares a participant's follow-up score with their baseline score, so it represents change over the specified interval rather than a score at a single visit. A negative group mean change indicates that the average score decreased over that interval; given the scale direction, a decrease is in the direction of a worse score. The posted group means are -2.2 for morning administration and -5.0 for evening administration.
Using a patient-reported measure is relevant to a trial concerned with tolerability, because symptoms and their effects are experienced by participants. The endpoint does not directly measure every possible consequence of treatment timing. The registry lists compliance and health-related quality of life as secondary outcomes, but their results are not reported in the registry record. The endpoint population is participants who answered the questionnaire at both baseline and twelve weeks; details about handling incomplete questionnaire data are not reported in the registry record.
7. Results Posted in the Registry
- Evening Administration of Endocrine Therapy: mean -5.00 versus -2.20 on control; difference -2.80 (95% CI -7.05 to 1.45), standardized effect d = -0.18; z-test p = 0.196.
Mean difference: Evening Administration of Endocrine Therapy
95% CI: -7.05 to 1.45
Recalculated from the posted summary statistics
8. Statistical Interpretation
The posted primary result is a mean change of -2.2 units in the morning administration group and -5.0 units in the evening administration group. The registry reports the mean difference for evening compared with morning as -2.8 units, with a 95% confidence interval from -7.048 to 1.448. The point estimate is in the direction of a greater decrease in score in the evening group. Because higher FACT-ES scores indicate better outcomes, the point estimate is in the direction of a less favorable change for evening administration on this scale. It should be interpreted as an estimate, not as proof of a difference.
The confidence interval includes zero. In general, zero represents no difference in group mean change, so the interval is compatible with no difference as well as with effects in either direction. The interval extends from a negative difference to a positive difference, and therefore does not establish which timing group had the more favorable mean change in the wider population. The estimate is also not very precise: the plausible values represented by the interval span both sides of zero. The registry reports an unadjusted p-value of 0.196. In the usual interpretation of a p-value, this value does not provide strong evidence against a null model of no group difference. It does not give the probability that the null model is true, nor does it measure the probability that the observed result arose “by chance.”
The group standard deviations were 14.1 in the morning group and 16.8 in the evening group. These values describe variability in individual change scores around each group's mean. The reported pooled standard deviation is 15.5, and the standardized mean difference is -0.181. The standardized measure expresses the estimated difference relative to the pooled variability; it does not replace the score-scale estimate or its confidence interval.
The numerical result pertains to the primary FACT-ES change outcome and the endpoint population described in the registry. It does not answer whether timing changes compliance, health-related quality of life, cost-effectiveness, or other outcomes, since numerical results for those outcomes are not reported in the registry record. Nor does it show whether the difference, if any, is important to participants: the registry record does not report a threshold for clinical importance. The result is best read as an uncertain estimate of a modest mean difference on this scale, rather than as a definitive finding for or against either timing approach.
9. Statistical Methods Explained
The primary outcome is continuous: each participant's change in FACT-ES score is measured in units on a scale. The registry reports group means and standard deviations, and the comparison is expressed as a difference in means. This is a direct way to describe how the average change differs between the assigned groups while retaining the questionnaire's original units. The morning group is the reference for the reported comparison, which is stated as evening compared with morning.
What does a mean change describe?
A mean is the arithmetic average of the participant-level change scores in a group. Each change score relates a follow-up measurement to that participant's baseline measurement. A group mean therefore describes the average direction and size of change, not the experience of every participant. Participants can have changes above or below that average. The reported standard deviations—14.1 for morning and 16.8 for evening—describe the spread of participant change scores around their respective group means. They are not confidence intervals and do not indicate the precision of the mean by themselves.
For this endpoint, higher FACT-ES scores indicate better outcomes. The group means of -2.2 and -5.0 are negative changes, indicating average decreases in score in both groups. The between-group estimate is -2.8 units for evening compared with morning. The negative sign gives the direction of the comparison as defined; it should not be read without checking which group is subtracted from which. The registry reports this contrast as evening minus morning, so a negative estimate places the evening group's mean change below the morning group's mean change.
How should the standardized difference be read?
The posted standardized mean difference is -0.181, based on a pooled standard deviation of 15.5. A standardized mean difference expresses a contrast in units of pooled variability rather than in questionnaire points. This can help describe the size of a contrast relative to the spread of individual scores. It is less directly interpretable in the scale's original units, so it should be considered alongside the mean difference and its confidence interval. The sign still depends on the comparison's direction. The standardized value does not establish whether the difference matters clinically; a threshold for interpreting clinical importance is not reported in the registry record.
What does the confidence interval add?
The 95% confidence interval for the mean difference is -7.048 to 1.448. In general, a confidence interval describes the uncertainty associated with an estimate under the statistical method used. It is not a range that contains a fixed proportion of individual participants' results. Nor does it mean that every value in the interval is equally plausible. Here, its inclusion of zero indicates that the observed group summaries do not rule out no mean difference under this interval-based analysis. Values on either side of zero are also within the interval, so the direction of the underlying mean difference remains uncertain.
What does the p-value test?
The reported p-value is unadjusted and equals 0.196. In general, a p-value measures how unusual data at least as incompatible with a specified null model would be if that model and the test's assumptions held. It is not the probability that the null model is correct, and it does not quantify the size or practical importance of an effect. The record does not report a detailed statistical model or adjustment strategy for this outcome. The p-value should therefore be read as the registry's posted unadjusted value, not as a complete description of every analytic choice.
The record lists the outcome parameter as a mean and dispersion as standard deviation. The comparison uses the reported group summaries and includes standard errors of 1.389 for morning and 1.663 for evening. A standard error describes uncertainty in an estimated mean, unlike a standard deviation, which describes variability among participant scores. No confidence limits are posted for the individual group means. The record does not report whether any covariate adjustment, model-based correction, or alternative analysis was used for the primary endpoint.
Why can variability affect precision?
As a general statistical point, larger variability in participant outcomes makes a group mean harder to estimate precisely when other features of a study are held similar. Greater variability can also make a between-group contrast less precise. For continuous outcomes, the standard deviation is consequently important context for interpreting a mean difference. The pooled standard deviation is used to express the standardized difference, while the original-unit contrast and its confidence interval remain central to understanding the result in FACT-ES units.
The registry record identifies a randomized, parallel, open-label design but does not report the original statistical analysis plan, assumptions behind the sample-size choice, or details of missing-data methods. Those omissions limit what can be said about whether the posted summary is the only planned analysis, how robust it is to incomplete questionnaires, or how multiplicity was handled. Such details should not be inferred from the numerical result alone.
10. Confidence Intervals and Precision
The estimated mean difference in FACT-ES change is -2.8 units for evening compared with morning administration. Its 95% confidence interval runs from -7.048 to 1.448. This interval is central to judging precision: it includes zero, extends into negative values, and also extends into positive values. The data therefore leave uncertainty about the direction and size of the underlying average difference. The point estimate is only one value within that wider range of estimates compatible with the analysis.
In general, a confidence interval represents the uncertainty in an estimate under the procedure used to construct it. A 95% confidence interval does not mean that 95% of individual participants' changes fall within its limits, and it is not a direct statement that there is a 95% probability that the true difference lies inside this particular interval. Rather, the confidence level describes the long-run behavior of the interval procedure under its assumptions. The registry record does not provide sufficient analysis details to assess all assumptions behind the interval.
The group standard deviations are 14.1 and 16.8, while the standard errors of the group means are 1.389 and 1.663. Standard deviations describe participant-level spread; standard errors describe the precision of estimated means. The posted comparison interval is more informative for the between-group question than either group's spread considered alone. It does not establish equivalence between the timing groups, because no equivalence margin is reported in the registry record. It also cannot establish clinical importance, because a threshold for meaningful change is not reported.
The unadjusted p-value of 0.196 is consistent with the interval's inclusion of zero: neither result supplies strong evidence of a clear mean difference. The result remains uncertain rather than demonstrating that the groups are identical. Additional precision would require evidence that narrows the plausible range, but the registry record does not report a larger confirmatory analysis or further primary-outcome estimates.
11. Planning a Similar Trial: Sample Size
This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 482 | 645 |
| 75% of the observed effect | 856 | 1,146 |
| 50% of the observed effect | 1,925 | 2,577 |
The sample-size figures are planning illustrations based on the observed effect, not the trial's original design calculations. They are participants per arm, not total event counts. The planning assumptions listed in the registry record are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect. The original trial's own sample-size assumptions and justification are not reported in the registry record.
The 80% power column gives the planned number of participants per arm for a hypothetical study to have an 80% chance of detecting the chosen effect under those assumptions, if that effect and the assumptions are correct. The 90% power column gives the corresponding planning number for a higher chance of detection. For planning around 100% of the observed effect, the figures are 482 participants per arm for 80% power and 645 participants per arm for 90% power. Planning for 75% of the observed effect gives 856 participants per arm for 80% power and 1,146 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,925 participants per arm for 80% power and 2,577 participants per arm for 90% power.
The pattern reflects a general principle: smaller effects are harder to distinguish from random variation, so detecting them with the same planning assumptions requires more participants. These figures depend on using the observed effect as the starting point, which is uncertain and may not represent the effect in a future study. They are not evidence about the probability that the completed trial detected an effect, and are not observed power.
12. How the Sample Size Is Derived
Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z1−α/2 = 1.960) and the desired power (z1−β = 0.842 for 80% and 1.282 for 90%).
Formula
n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.
Worked calculation for this trial
- Observed difference Δ = -2.800; pooled standard deviation σ = 15.502.
- n = 2 × (1.96 + 0.842)2 × 15.5022 / -2.8002 = 481.2, rounded up to 482 participants per arm for 80% power.
The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).
R code
alpha <- 0.05
z_a <- qnorm(1 - alpha / 2) # two-sided
delta <- -2.8 # observed difference in means
sigma <- 15.502242011695 # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))
# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")
# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4864405)
n <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n)) # difference in sample means
s2 <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1)) # pooled sample variance
tstat <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))
Output from running the code
100% of observed effect: n per arm = 482 (80% power), 645 (90% power)
75% of observed effect: n per arm = 856 (80% power), 1,146 (90% power)
50% of observed effect: n per arm = 1,925 (80% power), 2,577 (90% power)
power.t.test: 482.1
Simulated power at n = 482 per arm: 0.806 (20000 replicates)The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.
13. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures, including the primary change in endocrine toxicity and tolerability at twelve weeks and secondary outcomes covering health-related quality of life, compliance with endocrine therapy, and cost-effectiveness. Numerical results for the secondary outcomes are not reported in the registry record summarized for this analysis. The registry reports zero analysis entries. It therefore does not describe how results for multiple outcomes were analyzed or whether any other outcome results were evaluated.
Multiplicity is the statistical issue that arises when several outcomes, comparisons, time points, or analyses are considered. In general, conducting multiple statistical tests can increase the chance of obtaining at least one apparently unusual result even if there are no underlying effects. A prespecified plan may address that issue by identifying a primary outcome and specifying whether or how other comparisons are adjusted. The record identifies a primary outcome, but does not report a multiplicity adjustment or a detailed plan for interpreting multiple outcomes. It is not appropriate to assume that an adjustment was or was not performed beyond what the record states.
The primary endpoint population is described as participants who answered FACT-ES at baseline and twelve weeks. This defines who contributed to that outcome, but it does not explain how many assigned participants lacked one or both assessments, why any data were missing, or how incomplete questionnaires were handled. The record does not report imputation methods, sensitivity analyses, or a missing-data assumption. These details matter because an analysis limited to participants with both assessments may differ from an analysis that accounts for incomplete follow-up in another way.
The registry record does not report whether the primary comparison followed an intention-to-treat principle, how protocol deviations were handled, or whether a per-protocol population was used. It also does not give the analysis population definitions for secondary outcomes. Such choices can affect interpretation, particularly in an open-label trial where assigned timing and actual timing may not always coincide. The posted result should therefore be read as applying to the reported endpoint population and analysis, without assuming unreported population or missing-data procedures.
14. What the Result Does, and Does Not, Mean
The posted result describes a comparison of average FACT-ES change over the period from baseline to twelve weeks after treatment initiation. The morning group's mean change was -2.2 and the evening group's was -5.0. The estimated difference, evening compared with morning, was -2.8 units, with a 95% confidence interval from -7.048 to 1.448 and an unadjusted p-value of 0.196. Because higher FACT-ES scores indicate better outcomes, the point estimate is in the direction of a greater decrease in the evening group. The uncertainty interval includes zero and values in both directions, so the estimate does not establish a clear difference between groups.
This result does not show that the two timing approaches are equivalent. Demonstrating equivalence requires an explicit margin defining differences small enough to count as equivalent, and no such margin is reported in the registry record. Likewise, the result does not establish that any difference is clinically important or unimportant. The record does not report a threshold for meaningful change on the FACT-ES measure.
The endpoint focuses on symptoms and tolerability as measured by a patient-reported questionnaire. It is not a direct measure of cancer control, survival, or every aspect of quality of life. Although the registry lists compliance, health-related quality of life, and cost-effectiveness as secondary outcomes, their numerical results are not reported in the registry record. Conclusions about those outcomes cannot be drawn from the primary FACT-ES result.
The trial was randomized and open-label, which describes the assigned comparison and masking status in the registry. Randomization is a design feature intended generally to support fair comparisons between groups, but the posted summary alone does not establish whether the assigned timing was followed or how missing outcome data were handled. The result should be interpreted as evidence about the reported average change in the defined endpoint population, with uncertainty in the estimated contrast—not as advice to individuals about when to take medication.
15. Why This Trial Matters Statistically
This trial asks a practical statistical question: whether the timing of endocrine therapy is associated with a difference in patient-reported endocrine symptoms and tolerability. Its primary measure is a continuous score with a defined direction, and the comparison is reported in both the scale's original units and standardized units. These features allow readers to consider the average contrast, variation among participants, and uncertainty around the estimate rather than relying on a binary conclusion alone.
The registry's result illustrates why a point estimate, confidence interval, and p-value answer different questions. The point estimate indicates the direction and estimated size of the group contrast. The interval shows the range of values compatible with the analysis under its assumptions, while the p-value describes the data's compatibility with a specified null model. Here, the interval spans zero and the unadjusted p-value is 0.196. Neither supports a definitive conclusion about the direction of the underlying mean difference.
The endpoint also has boundaries that matter statistically. It is a change in a particular validated symptom questionnaire over a specified interval, among participants who answered at baseline and twelve weeks. It does not automatically stand in for compliance, broader quality of life, cost-effectiveness, or cancer outcomes. Those are distinct outcomes, and their numerical results are not reported in the registry record.
Finally, the record leaves key analysis details unreported, including the original sample-size justification, missing-data methods, and multiplicity approach. Those omissions make it important to separate what the posted summary estimates from questions that require additional trial reporting. The planning illustrations can help readers understand what future sample sizes might be under stated assumptions, but they cannot retrospectively determine whether the completed study had adequate power.
16. 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 main limitation of the posted result is the uncertainty around the estimated group difference. The 95% confidence interval, -7.048 to 1.448, includes zero, so the direction of the underlying average difference is not established by this estimate. A p-value of 0.196 likewise does not give strong evidence against a null model of no difference. The result should not be framed as proof that timing makes no difference.
The endpoint is based on questionnaire responses at baseline and twelve weeks. The registry describes the analysis population as participants who answered at both time points, but does not report how incomplete responses were handled or explain how that population relates to all randomized participants. Missing-data methods and sensitivity analyses are not reported in the registry record. The record also does not explain the difference between the enrollment figure and the endpoint group counts.
The trial is listed as open-label. The record does not report how adherence to the assigned timing was measured, or whether participants consistently took therapy within the defined window around waking or bedtime. No details are given about treatment types within endocrine therapy or other factors that could help interpret variation in symptoms. Such details should not be inferred from the reported result.
Other limitations of interpretation follow from the outcome reporting available in the registry. The record lists secondary outcomes, but their numerical results are not reported. It does not report the original statistical analysis plan, the sample-size justification, a threshold for clinically meaningful change, or an approach to multiplicity. These gaps restrict assessment of the planned analysis and of the broader effects of timing beyond the primary symptom score.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: Evaluating the Dose Timing (Morning vs Evening) of Endocrine Therapy and Its Effects on Tolerability and Compliance — NCT04864405.
- Registry record last updated 2026-01-08; status last verified 2025-12.
- Results first posted 2026-01-08.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
20. Record Summary
NCT04864405 is a completed, randomized, parallel, open-label phase 4 trial sponsored by Ottawa Hospital Research Institute. It compared endocrine therapy taken within one hour of waking with therapy taken within one hour of bedtime. Enrollment was 245, and the registry lists trial start on 2021-06-30 and primary completion on 2022-09-05.
The primary outcome was change in FACT-ES score from baseline to twelve weeks. The reported mean changes were -2.2 for morning administration and -5.0 for evening administration. The estimated mean difference for evening compared with morning was -2.8 units, with a 95% confidence interval from -7.048 to 1.448 and an unadjusted p-value of 0.196. The interval includes zero, so the result does not establish a clear difference in mean change.
The record lists four secondary outcomes, but their numerical results are not reported. Original sample-size assumptions, missing-data methods, multiplicity procedures, and detailed analysis plans are also not reported in the registry record.