Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy (NCT02332928), a randomized phase 3 study. The primary outcome is Comparison of FACIT-Fatigue Subscale.

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3, randomized, parallel-group trial with triple masking. The sponsor was Virginia Commonwealth University. Enrollment was recorded as 80, and the status is terminated. The registry lists a start date of 2015-03-25 and a primary completion date of 2021-06-02. It does not state why the trial was terminated, so the status alone should not be taken as evidence about the reason or the results.

Participants were assigned to 20 mg melatonin or placebo. The brief description says that eligible participants were electronically randomized in a 1:1 ratio, with stratification according to treatment duration—less than 3 weeks or equal to or greater than 3 weeks—and prior chemotherapy. The intervention schedule was intended to begin the night before the first radiotherapy treatment, continue nightly through radiotherapy, and extend for 2 weeks after its completion. The placebo schedule was described in parallel. Radiotherapy was given as clinically indicated.

The primary outcome was the FACIT-Fatigue subscale, a continuous score. The record describes measurement at baseline and 2 weeks after radiotherapy completion, with a variable timeframe of approximately 58 weeks. The primary outcome description focuses on average change from baseline. The posted outcome counts are 39.0 for melatonin and 38.0 for placebo, fewer than the planned enrollment of 80. The registry record does not explain the difference between planned enrollment and the number contributing to this outcome.

There are 7 outcome measures recorded and 0 reported analyses. Several secondary outcomes concern fatigue scores at later or different assessments, agreement between fatigue instruments, symptoms, and health-service use. The registry record does not report the original sample-size justification, detailed allocation procedures, the analysis population, or a fuller 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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Comparison of FACIT-Fatigue Subscale, measured over Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks).

The primary endpoint is the average change in the FACIT-Fatigue subscale from baseline, compared between the melatonin and placebo groups. FACIT-Fatigue is part of the Functional Assessment of Chronic Illness Therapy instrument. The registry describes a 13-item fatigue subscore, with item responses rated from 0 to 4 and a total score ranging from 0 to 52. Higher scores indicate less fatigue. The broader instrument also includes physical, social, emotional, and functional quality-of-life domains, but the primary endpoint is the fatigue subscale rather than the full quality-of-life score.

A change score expresses how the measured score differs from its baseline value. Comparing average change between randomized groups is intended to describe whether the groups followed different average score patterns over the assessment period. The outcome timeframe is described as baseline and 2 weeks after radiotherapy completion, with the timing varying and approximately 58 weeks stated in the record. The posted mean change was -4.39 in the melatonin group and 0.74 in the placebo group. Since higher scores denote less fatigue, a negative change represents a movement toward a lower score; interpreting that movement requires keeping the scale direction in mind.

The instrument is described in the registry as well validated and widely used in cancer-related fatigue research. Such a measure offers a structured way to quantify reported fatigue, but a score is not a complete account of an individual’s experience. The registry record does not report a threshold for a clinically important difference, so the size of the group contrast cannot be classified by such a threshold from this record.

7. Results Posted in the Registry

• 20 mg Melatonin: mean -4.39 versus 0.74 on control; difference -5.13 (95% CI -9.24 to -1.02), standardized effect d = -0.56; z-test p = 0.014.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Comparison of Functional Assessment of Chronic Illness Therapy (FACIT-F) Scores in Fatigue From Baseline Until 2 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 20 mg Melatonin: mean -2.78 versus 1.30 on control; difference -4.08 (95% CI -8.93 to 0.77), standardized effect d = -0.38; z-test p = 0.099.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between 20 mg Melatonin and the control. The interval gives the range of effects that remain compatible with the data.

Comparison in Functional Assessment of Chronic Illness Therapy (FACIT) in Fatigue From Baseline Until 8 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 20 mg Melatonin: mean 0.65 versus 4.58 on control; difference -3.93 (95% CI -7.49 to -0.37), standardized effect d = -0.49; z-test p = 0.031.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for 20 mg Melatonin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Comparison of the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a Scores Obtained at Baseline and at the Completion of RT.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • 20 mg Melatonin: mean 3.51 versus -0.52 on control; difference 4.03 (95% CI 0.87 to 7.19), standardized effect d = 0.57; z-test p = 0.013.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for 20 mg Melatonin than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover more than one fatigue instrument and more than one follow-up time. Their results do not form a completely consistent pattern: the earlier FACIT comparison is less conclusive by its interval, while the later FACIT and PROMIS comparisons have intervals that exclude zero. This is not necessarily a contradiction, because the assessments occur at different times and the instruments do not measure fatigue in exactly the same way. The registry also lists symptom scores, agreement between two fatigue instruments, and hospital admissions, emergency visits, and days off work. Results for several of these listed outcomes are not reported in the registry record.

These secondary results provide context around the primary comparison, but they should not be treated as independent confirmations of it. Multiple endpoints and follow-up times increase the chance of obtaining apparently notable findings by chance. The registry record does not describe a multiplicity adjustment or a hierarchy that would establish which secondary outcomes were confirmatory. Unadjusted secondary results therefore carry less weight than a clearly specified primary comparison.

Secondary measures can also answer different questions. A comparison of fatigue scores asks whether average scores differ; agreement between instruments asks whether their measurements align. Health-service use and days off work are distinct outcomes and cannot be inferred from a fatigue score. Differences in timing, measurement, and outcome type make a single overall conclusion from all secondary measures inappropriate. The registry record does not report enough analysis detail to assess whether these outcomes were analyzed as planned or how missing data affected each one.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Comparison of Functional Assessment of Chronic Illness Therapy (FACIT-F) Scores in Fatigue From Baseline Until 2 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.
• Comparison in Functional Assessment of Chronic Illness Therapy (FACIT) in Fatigue From Baseline Until 8 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.
• Comparison of Edmonton Symptom Assessment System (ESAS) Scores Obtained at Baseline Until Completion of RT.
• Comparison of the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a Scores Obtained at Baseline and at the Completion of RT.
• Determine the Level of Agreement in Reported Fatigue Scores When 2 Different Survey Instruments Are Used to Measure Fatigue.
• Compare the Number of Hospital Admissions, Emergency Center Visits, and Medical Days Off Work Between Patients Receiving Melatonin Compared to Placebo.

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change compare?

A mean is the arithmetic average of a continuous measurement across participants. In a change-score analysis, each participant’s later measurement is compared with that participant’s baseline measurement, and the group average change is then compared between arms. A mean difference between groups describes the separation in those average changes. Here, the posted comparison is -5.13 points for melatonin relative to placebo. The sign depends on the order of subtraction: a negative value indicates a lower average change in the melatonin group than in the placebo group. The score’s meaning also depends on its direction; for FACIT-Fatigue, higher scores denote less fatigue.

Change scores can be useful because they describe movement from baseline, but they are not identical to comparing follow-up scores alone. They can also be affected by baseline differences, measurement variability, and which participants have measurements at each time. The registry record does not provide baseline group means, individual participant data, or a detailed account of how the change scores were analyzed. It therefore does not permit a fuller assessment of those issues.

What does the confidence interval express?

A confidence interval gives a range of values compatible with the estimate under the calculation’s assumptions. The primary interval extends from -9.238 to -1.022. Its width reflects uncertainty about the size of the mean difference, not a range that contains a known proportion of individual participants’ responses. An interval that excludes zero is evidence against a zero mean difference under the stated calculation, but it does not by itself establish clinical importance, eliminate bias, or prove that the underlying value lies within the interval.

The comparison is reported with an unadjusted p-value of 0.014. A p-value describes how unusual a result at least as far from the null value would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not quantify the probability that the finding is due to chance. The record does not report whether this comparison was prespecified in a detailed analysis plan or whether other analyses were considered.

Why does the standard error matter?

The registry reports arm-level dispersion as standard error. Standard error describes the uncertainty in an estimated group mean, rather than the spread of individual scores. A smaller standard error generally indicates a more precise estimate of the mean, while participant-to-participant variation can be much larger. The posted arm standard errors for the primary outcome are 1.24 for melatonin and 1.69 for placebo. Those values should not be interpreted as standard deviations or as a description of the range of individual fatigue scores.

The mean difference and its confidence interval depend on both the estimated group means and their uncertainty. In general, increasing the number of observations can improve precision, but the practical gain depends on variability, study design, and the completeness of observations. The registry record does not provide a full analysis specification, so the exact model or any adjustments used by the study team cannot be described.

Why do unadjusted secondary comparisons need caution?

Several secondary measures and assessment times are listed. When many outcomes are examined, some may appear unusual by chance even if there is no underlying difference for any of them. This is the general multiplicity problem. Adjustments can control error rates across multiple comparisons, or researchers can designate a small number of outcomes as confirmatory and treat others as exploratory. The registry record does not report a multiplicity strategy. Consequently, unadjusted secondary p-values and intervals should be considered less conclusive than a single prespecified primary comparison.

The secondary measures also differ in what they capture. FACIT-Fatigue and PROMIS Fatigue-Short Form 8a are separate instruments; ESAS is a symptom assessment, and the listed outcomes also include agreement between survey instruments and health-service use. Scores from different instruments are not automatically interchangeable, and agreement between instruments is a distinct question from whether group averages differ. The record does not provide details of scoring transformations or a plan for combining these outcomes.

What is not described about the analysis?

The registry lists 0 reported analyses, although outcome summaries and comparisons are posted. The record does not state whether the primary analysis followed intention-to-treat principles, whether it used a repeated-measures model, how missing observations were handled, or whether baseline covariates were included. It also does not report an original sample-size justification, interim analyses, or a complete statistical plan. Those omissions mean that the posted summary results cannot be used to reconstruct every analytic choice or assess whether all randomized participants were handled as intended.

General statistical interpretation assumes that the comparison and its uncertainty calculation are appropriate for the design and data. Randomization supports causal comparisons when assignment is implemented as planned and follow-up and analysis preserve the randomized groups. Masking can reduce some sources of bias, but the registry’s triple-masked label does not identify exactly who was masked or whether masking remained effective. The record does not provide enough detail to evaluate these aspects fully.

11. Confidence Intervals and Precision

The primary mean difference is -5.13 points, with a 95% confidence interval from -9.238 to -1.022. This interval indicates that the estimated contrast is not precisely pinned to one value: differences throughout that range are compatible with the calculation. The interval lies on the negative side of zero, but its width still leaves uncertainty about the magnitude. Precision is different from clinical importance, and the registry record does not state a threshold for interpreting the size of a FACIT-Fatigue difference as clinically important.

The interval is based on the posted group summaries and is an unadjusted re-calculation. It describes uncertainty under the assumptions of that calculation; it does not account for unreported aspects of trial conduct or analysis. It also does not describe the range of individual participant outcomes. Individual scores may vary around their group mean, and a confidence interval for a mean difference is not a prediction interval for an individual.

The primary outcome counts are 39.0 in the melatonin group and 38.0 in the placebo group. The planned enrollment was 80. The record does not explain why the primary outcome counts differ from planned enrollment or whether missingness could affect the comparison. The confidence interval reflects the posted summary information, not additional uncertainty about unreported missing-data mechanisms, deviations from the intended protocol, or unreported analyses.

Intervals for secondary comparisons also vary in whether they include zero. That pattern should be considered alongside the number of listed outcomes and the absence of a reported multiplicity plan. A confidence interval can convey statistical uncertainty for an individual comparison, but it does not automatically account for the fact that several comparisons were examined. The secondary findings therefore have less confirmatory weight than the primary comparison.

12. 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.

The planning estimates are participants per arm for 80% power and participants per arm for 90% power. They are based on the observed effect and the stated fraction of that effect to detect. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For time-to-event outcomes, the planning convention is total events; these estimates are for continuous outcomes and are expressed as participants per arm.

The 80% power column describes the planned chance of detecting the specified effect under the planning assumptions if that effect is real. The 90% column uses a higher target chance of detection under those same assumptions. These are prospective design concepts: they are not the probability that the trial’s result is correct and do not measure how likely the observed result is to replicate. This is not observed power.

The rows use different fractions of the observed effect as the effect to detect. Planning for a smaller effect requires more participants because a smaller separation between group means is harder to distinguish from random variation. Estimates based on 100% of the observed effect are therefore smaller than estimates based on 75% or 50% of that effect. The displayed values are illustrations under the specified assumptions, not a record of the original trial’s design calculations.

The registry record does not report the trial’s original sample-size justification or its own design assumptions. The enrollment target was 80, but the record does not explain how that target was chosen. The planning illustrations should not be used to infer the trial’s intended power, nor should they be treated as proof that the trial was adequately or inadequately sized for its original objective.

13. 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 z_1−α/2 = 1.960) and the desired power (z_1−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

1. Observed difference Δ = -5.130; pooled standard deviation σ = 9.161.
2. n = 2 × (1.96 + 0.842)² × 9.161² / -5.130² = 50.1, rounded up to 51 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 <- -5.13                      # observed difference in means
sigma <- 9.16107693814797                     # 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(2332928)
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 = 51 (80% power), 68 (90% power)
 75% of observed effect: n per arm = 89 (80% power), 120 (90% power)
 50% of observed effect: n per arm = 201 (80% power), 269 (90% power)
power.t.test: 51 
Simulated power at n = 51 per arm: 0.799 (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.

14. Multiplicity, Missing Data and Analysis Populations

The record lists 7 outcome measures and includes multiple secondary fatigue assessments, as well as symptom, instrument-agreement, and health-service-use outcomes. Examining several endpoints or time points raises a general multiplicity concern: even when there is no true difference, some comparisons may appear statistically notable by chance. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory outcomes, or other rules for interpreting the secondary comparisons. Their unadjusted results should therefore be treated cautiously and should not be read as a collection of independent confirmations.

The registry lists 0 reported analyses. It does not describe the analysis population, whether the primary comparison included every randomized participant, or how participants with incomplete outcome data were handled. The posted primary endpoint counts are 39.0 for melatonin and 38.0 for placebo, while enrollment was 80. The record does not explain the gap between enrollment and outcome counts, whether the counts reflect missing measurements or other analysis decisions, or whether participants were excluded after randomization.

Missing data can affect a comparison if the likelihood of having an outcome recorded is related to group assignment or to the unobserved score. This is a general concern, not evidence that such a pattern occurred in this trial. The record does not report reasons for missingness, methods such as imputation, sensitivity analyses, or follow-up completeness. Without those details, the effect of incomplete data on the posted estimates cannot be assessed.

The record also does not report the original statistical analysis plan, interim analyses, or a detailed description of covariate adjustment and repeated-measures methods. These omissions limit assessment of whether the posted comparisons reflect prespecified analyses and how uncertainty was handled across outcomes and time points. They do not establish that any particular method was or was not used; those details are simply not reported in the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: creatinine increased (2.6%), hyponatremia (2.6%), dizziness (2.6%), nervous system disorders-other, specify (2.6%), confusion (2.6%).

The registry reports serious adverse-event counts of 0 in the melatonin group, among 39 participants at risk, and 3 in the placebo group, among 38 participants at risk. Deaths were recorded as 0 for melatonin and 1 for placebo. Other adverse events were recorded as affecting 37 participants in each group, with 39 and 38 at risk, respectively. These are descriptive counts from the registry and do not, by themselves, establish whether an event was caused by the assigned treatment.

The listed serious-event terms each have a reported frequency of 2.6%: Creatinine Increased, Hyponatremia, Dizziness, Nervous System Disorders-Other, specify, Confusion, and Depression. The record does not provide enough detail to determine the timing, duration, severity beyond the serious-event classification, or relatedness of each event to study treatment. A term appearing in the list should not be interpreted as a comparative risk estimate.

These totals should be read in light of the group sizes and the limited event counts. The registry record does not report a detailed safety-analysis method or a formal comparison of adverse-event rates. Descriptive differences in counts are not proof of a treatment effect, and the absence of a recorded event in one group does not establish that the event cannot occur.

16. What the Result Does, and Does Not, Mean

The posted primary result describes a difference in average change in FACIT-Fatigue scores between participants assigned to melatonin and those assigned to placebo. The estimated mean difference is -5.13 points, with a 95% confidence interval from -9.238 to -1.022. Because the scale is coded so that higher scores denote less fatigue, the negative sign means the melatonin group’s average change was lower than the placebo group’s average change. This is a statement about the observed score comparison, not a general claim about treatment benefit or harm.

The result does not establish the clinical importance of the difference. The record does not state a threshold for a meaningful change on the scale, and statistical compatibility with a nonzero difference does not answer whether patients would notice or value the difference. The result also does not describe every participant’s experience. A group mean can obscure variation between individuals.

The comparison does not resolve how the result would apply to people outside the registry population, to different radiotherapy schedules, or to other cancer settings. The record identifies women with breast cancer receiving radiotherapy, but does not report enough eligibility detail to characterize the full population. It also does not explain why the trial was terminated, why primary outcome counts were below planned enrollment, or how missing data were handled.

Several secondary results add context but are not a substitute for a detailed prespecified analysis. They involve different measures and times, and the record does not report a multiplicity plan. The adverse-event counts are descriptive and do not establish causation or comparative safety. Overall, the record supports a cautious description of the posted group score differences, with uncertainty about magnitude, missing information about analysis and follow-up, and no basis for broader conclusions beyond these data.

17. Why This Trial Matters Statistically

This trial illustrates why a numerical result needs to be interpreted through both the measurement scale and the study design. The FACIT-Fatigue score runs in a direction where higher scores mean less fatigue, so a negative mean difference in change is not self-explanatory. The scale’s direction, the baseline-to-follow-up framing, and the subtraction order all matter when describing the estimate accurately.

It also demonstrates the distinction between a point estimate and its precision. The primary mean difference is accompanied by a confidence interval, which conveys uncertainty in the estimated group contrast. That interval addresses sampling uncertainty under the calculation’s assumptions; it does not settle clinical importance, missing-data bias, or the generalizability of the finding. The absence of a reported clinically important threshold makes it especially important not to equate a statistical result with a patient-relevant conclusion.

The record also makes clear that one trial can present multiple outcomes and assessment times. Secondary comparisons can broaden the picture, but without a reported multiplicity strategy they are not all equally strong evidence. Differences between FACIT and PROMIS scores, symptom measures, agreement analyses, and service-use outcomes require separate interpretation rather than being collapsed into a single verdict.

Finally, the trial record shows the value of transparent reporting about enrollment, analysis populations, missing data, and prespecified methods. Planned enrollment and outcome counts are both reported, but their relationship is not explained. With 0 reported analyses and no detailed statistical plan, readers can describe the posted estimates but cannot fully reconstruct the study team’s analysis. That distinction is central to careful interpretation of registry results.

18. 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.

Several limitations specific to this trial are apparent from the registry record. The trial status is terminated, but the reason for termination is not reported in the registry record. Enrollment was 80, while the primary outcome includes 39.0 participants assigned to melatonin and 38.0 assigned to placebo. The record does not explain the difference between the enrollment target and the number contributing to the primary outcome, nor does it describe missingness or exclusions.

The record lists 0 reported analyses and does not provide a detailed statistical analysis plan. It does not state the analysis population, how repeated measures were modeled, whether baseline covariates were included, or how incomplete measurements were handled. The reported comparison is an unadjusted re-calculation from the posted summaries, so it cannot substitute for unreported details of the sponsor’s analysis.

The outcome schedule is described as baseline and 2 weeks after radiotherapy completion, with timing varying and approximately 58 weeks stated. The registry does not explain the variability in timing or provide a detailed account of actual assessment completion. It also does not report a clinically important difference threshold for FACIT-Fatigue, limiting interpretation of the practical importance of the point estimate.

There are several listed secondary outcomes, but results are not reported for all of them. The record does not describe how multiplicity was handled, whether outcomes were ranked by importance, or whether any interim analyses occurred. The masking label is triple, but the roles masked and the success of masking are not detailed. These reporting gaps do not establish that trial procedures were inadequate; they constrain what can be concluded from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy — NCT02332928.
• Registry record last updated 2023-03-30; status last verified 2023-03.
• Results first posted 2023-03-30.
• 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.

22. Record Summary

The registry describes a phase 3, randomized, parallel-group, triple-masked trial sponsored by Virginia Commonwealth University. Planned enrollment was 80, and status is terminated. The study compared 20 mg oral melatonin with placebo among women with breast cancer receiving radiotherapy. The intended schedule began the night before the first radiotherapy treatment, continued nightly during treatment, and extended for 2 weeks afterward.

The primary outcome was average change in the FACIT-Fatigue subscale. The posted mean difference was -5.13 points for melatonin relative to placebo, with a 95% confidence interval from -9.238 to -1.022 and an unadjusted p-value of 0.014. The record also includes several secondary outcomes and descriptive adverse-event counts, but does not report a detailed analysis plan, missing-data methods, or the reason for termination.