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 Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia (NCT00507546), a randomized phase 4 study. The primary outcome is Amount of Wakefulness After Sleep Onset (WASO).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00507546 |
| Phase | Phase 4 |
| Condition | Insomnia, Spinal Cord Injury, Tetraplegia |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 12 |
| Arms in the primary outcome | 2 |
| Lead sponsor | US Department of Veterans Affairs |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned individuals with tetraplegia and sleep disruption. Its brief summary describes the target group as people who lack endogenous melatonin production. The primary outcome population was participants who completed the entire protocol; the registry record does not report additional eligibility details for that analysis.
Intervention
Ramelteon was given nightly at 8 mg during the active-treatment period. The study describes this as replacing melatonin function with a melatonin agonist. The registry record does not report further details about treatment adherence or how the intervention was administered beyond the nightly schedule.
Comparator
The comparator was nightly placebo. In the crossover sequence, participants received ramelteon and placebo in different orders, with a placebo washout interval between treatment periods. The record does not report whether participants or staff could identify treatment assignment during the study.
Primary question
The primary question was whether wakefulness after sleep onset differed between ramelteon and placebo. This endpoint was measured in minutes and summarized as the median of the average WASO during the three weeks of each treatment. The registry record reports a Friedman analysis but does not report a treatment-effect estimate or confidence interval.
3. Trial Design
The registry record describes a completed randomized, triple-masked, crossover trial sponsored by the US Department of Veterans Affairs. Enrollment was 12. The study began in 2007-07 and had primary completion in 2010-12. Its listed conditions include insomnia, spinal cord injury, tetraplegia, and sleep disorders.
The treatment sequences were ramelteon then placebo and placebo then ramelteon. In the first sequence, participants received 8 mg of nightly ramelteon for three weeks, followed by two weeks of nightly placebo as washout, then three weeks of nightly placebo. In the other sequence, participants received nightly placebo for three weeks, two weeks of nightly placebo as washout, then 8 mg of nightly ramelteon for three weeks. The primary outcome timeframe is listed as 10 weeks.
A crossover design allows treatment comparisons within a participant across treatment periods, rather than relying only on comparisons between separate groups. Random allocation concerns the assigned sequence. The record identifies triple masking, but does not report who was masked or how masking was maintained. It also does not report the randomization method, sequence-balance details, or procedures for assessing carryover between periods. Those details should not be inferred from the design label alone.
The primary outcome population is described as all participants who completed the entire protocol. The posted arm summaries list 3 participants for ramelteon and 2 for placebo. These outcome counts are distinct from the enrollment figure, and the registry record does not explain the difference. The design information establishes the intended comparison, but the limited posted outcome counts constrain how much can be learned from the observed summaries.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Subjects excluded if baseline measure detected the presence of melatonin metabolite in their urine.
Overall Study
| Stage | Arm 1 | Arm 2 |
|---|---|---|
| STARTED | 4 | 4 |
| COMPLETED | 2 | 3 |
| NOT COMPLETED | 2 | 1 |
Reasons for not completing this period:
| Reason | Arm 1 | Arm 2 |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Protocol Violation | 1 | 0 |
| Physician Decision | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: All participants who completed the entire protocol.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Arm 1 | Arm 2 | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 4 | 8 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 4 | 4 | 8 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 51.25 (SD 9.74) | 55.5 (SD 15.5) | 53 (SD 12) |
| Sex: Female, Male: Female | Participants | 0 | 1 | 1 |
| Sex: Female, Male: Male | Participants | 4 | 3 | 7 |
| Region of Enrollment: United States | participants | 4 | 4 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Amount of Wakefulness After Sleep Onset (WASO), measured over 10 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | Minutes |
| Endpoint classification | not reduced to a single comparison |
Wakefulness after sleep onset, abbreviated WASO, measures time spent awake after a person has first fallen asleep. It is reported in minutes. The registry record defines the primary outcome as the median of the average WASO during the three weeks of either placebo or ramelteon treatment, with a 10-week timeframe. The analysis population is described as participants who completed the entire protocol.
WASO focuses on sleep continuity rather than only the time needed to fall asleep or total time in bed. As a general statistical and clinical concept, a measure of wakefulness during the sleep period can capture disruptions that a simple report of sleep onset would not describe. The use of a median summarizes the center of the observed values while reducing sensitivity to unusually high or low observations compared with an arithmetic mean. It does not, by itself, describe the full pattern of participant-level values.
The registry record reports a full range for each treatment summary. A range indicates the span of posted values, but it does not show how values are distributed within that span. Nor does a median and range reveal each participant’s paired change across treatment periods. The registry record does not provide participant-level WASO values or a treatment-effect estimate with a confidence interval, so the summaries do not establish the size or precision of a within-person difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary summaries are a median WASO of 72.3 minutes for ramelteon and 76.5 minutes for placebo. The full range is 20.7 to 92.3 minutes for ramelteon and 24.0 to 117.0 minutes for placebo. These are descriptive summaries for the participants included in each arm’s posted outcome data; they should not be read as estimates that apply precisely to a broader population.
The sponsor-reported analysis used the Friedman method and gives p = 0.70. This result does not provide evidence of a clear separation between the treatment conditions under that analysis. A p-value is not an estimate of the size of a treatment effect, and it does not show that the treatments are equivalent. The registry record does not report a confidence interval or an estimated treatment contrast, so the range of effect sizes compatible with the data cannot be assessed from the posted analysis.
The small numbers in the arm summaries are important when reading the descriptive results. The posted outcome counts are 3 for ramelteon and 2 for placebo, while the enrollment figure is 12. The record does not explain why the primary analysis population has those counts or how participants without posted outcome data were handled. With so few posted observations, summary values can be strongly influenced by individual participants, and estimates of variability or treatment differences are likely to be imprecise. The record does not provide enough detail to quantify that imprecision.
The study used a crossover design, so the intended comparison involves treatment experiences within participants. The arm medians and ranges do not show the paired observations that would clarify how each participant’s WASO changed between conditions. A group-level summary for each treatment cannot substitute for the participant-level pairing. The registry record does not report the paired data or a treatment-effect estimate from the crossover analysis.
The posted result therefore describes the observed summaries and the sponsor’s reported test, not a definitive conclusion about the effect of ramelteon. The p-value should be interpreted alongside the outcome counts, the missing detail about the analysis population, and the absence of a reported effect estimate and confidence interval. The registry record does not report enough information to judge whether the analysis had adequate precision for the intended clinical question.
9. Statistical Methods Explained
The primary outcome is a quantitative measure in minutes, summarized by a median and full range. The median is the middle value after observations are ordered. In general, it is useful when a distribution may be skewed or affected by extreme observations, because a single unusually large value has less influence on the median than on the mean. The median does not communicate how tightly observations cluster around the center. The range gives the lowest and highest posted values, but does not describe the distribution between those endpoints.
What does the Friedman analysis test?
The sponsor-reported method is the Friedman test. In general, this is a rank-based method for comparing related conditions, often used when the same participants contribute measurements under more than one condition. It ranks observations within participant or block and assesses whether the conditions tend to differ in their ranks. That makes the method conceptually relevant to repeated-condition data, but the registry record does not report the exact analysis inputs, how ties were treated, or whether additional factors were included. The method name alone does not establish that all features of the crossover design were addressed.
The reported p-value is 0.70. In general, a p-value describes how compatible the observed test statistic is with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, and it is not the probability that the result occurred by chance. A large p-value does not demonstrate equivalence or rule out an effect. Interpretation depends on the size and precision of an estimated treatment contrast, which the registry record does not report.
Why are effect estimates and confidence intervals useful?
An effect estimate expresses the direction and magnitude of a treatment contrast. A confidence interval describes the uncertainty around an estimate under the statistical procedure used. In general, an interval that is wide indicates limited precision, while a narrower interval indicates greater precision. Neither the sponsor-reported analysis nor the posted primary results include a confidence interval or a reported numerical contrast. The p-value alone cannot show which differences remain compatible with the observed data.
The outcome summaries are medians and ranges for the separate treatment conditions. For a crossover comparison, paired participant-level measurements are especially informative because each participant serves as their own reference across conditions. The posted summaries do not show those paired values, and the registry record does not report a paired treatment-effect estimate. It is therefore not possible to reconstruct the within-participant pattern from the group summaries without making assumptions or accessing data that are not in the registry record.
What does the crossover structure add?
In general, crossover designs can control for stable participant characteristics because treatment conditions are compared within the same person. They also require attention to period effects, sequence effects, and possible carryover from one treatment period to another. The listed sequences include a placebo washout interval, but the registry record does not report a carryover assessment, period-specific results, or the statistical handling of sequence. A washout description alone cannot establish that carryover was absent.
The primary analysis population is described as all participants who completed the entire protocol. This is a completer-based description, not a full account of how all randomized participants were analyzed. The record does not report reasons for non-completion, missing outcome handling, or whether participants with partial data contributed to any analysis. These details matter because excluding incomplete records can affect both the number of observations and the comparability of treatment experiences.
How should planning illustrations be read?
Any sample-size illustrations associated with the posted results are planning calculations based on the observed effect, not observed power from this trial. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. In general, such calculations describe a hypothetical future design under stated assumptions. They do not show that the current trial had a particular probability of detecting an effect, and they do not repair uncertainty from sparse observed data. The registry record does not report a trial-specific sample-size justification or the design assumptions used before enrollment.
Multiplicity is another methodological consideration. When several outcomes or analyses are examined, the chance of finding at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry record lists a secondary outcome of change in subjective morning alertness and reports two outcome measures and two analyses, but it does not report a multiplicity strategy or a prespecified hierarchy. The available information is not enough to determine how the primary and secondary results were intended to be interpreted together.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Friedman | not reported | 0.700 |
The sponsor-reported primary analysis is a Friedman test with p = 0.70. The registry record does not report a separate recalculated treatment contrast or confidence interval, so there is no independently reported estimate to compare directly with the sponsor’s test result. The posted medians and ranges are descriptive summaries, not a replacement for an analysis that accounts for the crossover pairing.
No discrepancy is flagged in the registry record. Where a recalculation differs from a sponsor analysis, the sponsor’s own analysis takes precedence; that situation is not indicated for this result. The p-value should still be read in context: it does not quantify the treatment difference, demonstrate equivalence, or show how precise the comparison is. The registry record does not provide the detailed analysis inputs needed to reproduce the Friedman test.
Any sample-size illustrations based on the observed effect are planning illustrations under stated assumptions. They are not observed power and do not change the interpretation of the reported trial result. The sponsor’s reported test remains the only reported inferential result for the primary comparison in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry record identifies the primary outcome as WASO and lists change in subjective morning alertness as a secondary outcome. It reports two outcome measures and two analyses. It does not report whether the outcomes were ordered in a prespecified testing hierarchy, whether adjustments for multiple testing were planned, or whether any results were exploratory. Without that information, the strength of evidence across outcomes cannot be assessed using a documented multiplicity strategy.
The primary outcome population is described as all participants who completed the entire protocol. The posted outcome counts are 3 for ramelteon and 2 for placebo, compared with enrollment of 12. The record does not report why these numbers differ, which participants were excluded from the primary analysis, or whether the counts refer to all available observations under each treatment. It also does not report reasons for withdrawal, incomplete treatment, or missing WASO measurements.
Missing-data methods are not reported in the registry record. In general, missing outcome data can matter if the chance of being observed is related to a participant’s outcome or treatment experience. A completer-only description does not establish whether missingness was harmless, and it does not show whether sensitivity analyses were conducted. The record does not report imputation, weighting, or other methods for handling incomplete records.
The record also does not report the full statistical analysis plan, a sample-size justification, interim analyses, or adjustments for period and sequence in the crossover design. Their absence from the registry record is not evidence that a particular procedure was or was not used; it means the posted information does not allow readers to verify those aspects of the analysis. These gaps are relevant to interpreting both the p-value and the apparent precision of the treatment summaries.
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 |
|---|---|---|---|
| Arm 1 | 0 | 4 | 0.0% |
| Arm 2 | 0 | 4 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm 1 | 0 of 4 |
| Arm 2 | 0 of 4 |
The adverse-event record lists Arm 1 and Arm 2 separately. Each arm has 4 participants at risk for serious adverse events and reports 0 serious adverse events. Each arm also has 4 participants at risk for other adverse events and reports 0 other adverse events. Death counts are not reported in the registry record. No serious adverse-event terms are listed.
These figures describe the safety entries posted for the arms; they do not establish that no adverse events occurred outside the recorded categories or observation periods. The registry record does not explain the relationship between the safety populations and the primary outcome population, or provide further information about collection and attribution procedures. The number at risk for each safety category should be read as its own posted denominator, not assumed to be the same as the primary analysis count.
With the reported at-risk counts, zero recorded events provides limited information about uncommon harms. The absence of a recorded event in these entries is not proof that an event cannot occur. The safety figures are descriptive and should be interpreted alongside the limited amount of information reported about safety follow-up.
13. What the Result Does, and Does Not, Mean
The registry record documents a randomized, triple-masked crossover comparison of nightly ramelteon and placebo for sleep disruption in individuals with tetraplegia. For the primary endpoint, it reports median WASO values of 72.3 minutes under ramelteon and 76.5 minutes under placebo, with the listed full ranges. The sponsor’s Friedman analysis reports p = 0.70.
These results describe the posted data; they do not establish that ramelteon improves sleep, that the treatments are equivalent, or that there is no treatment effect. The p-value is not a measure of clinical importance. Because no treatment-effect estimate or confidence interval is reported, the magnitude and precision of the comparison cannot be judged from the inferential result. The group summaries also do not reveal the paired changes that are central to interpreting a crossover comparison.
The small posted outcome counts and the absence of an explanation for their relation to enrollment limit the conclusions that can be drawn. The registry record does not report missing-data methods, reasons for non-completion, or detailed crossover analyses. Those omissions make it difficult to assess how representative the analyzed observations are or how fully the reported test reflects the design.
The finding is therefore best understood as a descriptive record with a sponsor-reported test result, rather than as a precise estimate of a treatment effect. A nonsignificant result does not prove the absence of an effect, and the available data do not support an equivalence claim. The posted safety entries report no serious or other adverse events in the listed at-risk groups, while death counts are not reported in the registry record. The safety entries are limited observations, not a guarantee about risk.
14. Why This Trial Matters Statistically
This trial is statistically instructive because its crossover design and its posted summaries answer different kinds of questions. The design intends to compare each participant’s experience under ramelteon and placebo, while the registry record presents separate medians and ranges for the treatment conditions. Those summaries do not retain the paired information that would show whether participants generally changed in the same direction or whether individual responses varied.
The result also illustrates why a p-value should not be read alone. The Friedman test reports p = 0.70, but the registry record does not report a treatment-effect estimate or confidence interval. Without an estimate and its uncertainty, the test result cannot communicate the plausible magnitude of a difference. The small posted outcome counts further underscore that a non-significant test is not evidence of equivalence.
Another important issue is the distinction between enrollment and the analysis population. Enrollment is 12, while the posted primary summaries list 3 participants for ramelteon and 2 for placebo. The record describes the analysis population as participants completing the entire protocol but does not explain the reported counts. This makes transparent reporting of participant flow and missing-data handling essential for understanding who contributed to the result.
The record also shows why design labels are not substitutes for methodological detail. Randomization, masking, and a washout interval are described, yet details about sequence allocation, period effects, carryover assessment, and analysis procedures are not reported. These issues are especially relevant to interpreting results from repeated treatment periods. The case highlights how registry results can document key features while leaving uncertainty about the analysis and its precision.
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.
Several trial-specific limitations affect interpretation. The posted primary summaries include 3 participants for ramelteon and 2 for placebo, despite enrollment of 12. The registry record does not explain the relationship between these counts, the reasons participants may not have completed the protocol, or the handling of incomplete outcome data. The small posted counts limit the stability and precision that can be inferred from the summaries.
The reported endpoint summaries are medians and full ranges, not participant-level paired treatment differences. No numerical treatment-effect estimate or confidence interval is reported. Although the sponsor reports a Friedman test, the registry record does not provide enough detail about the analysis inputs or implementation to reproduce it or assess how period and sequence were handled.
The registry record describes a placebo washout interval but does not report a carryover assessment. It also does not report the method of randomization, which parties were masked, or how masking was maintained. A crossover design can be sensitive to period, sequence, and carryover effects, so these missing details limit assessment of the design’s execution and analysis.
The record lists a secondary outcome and multiple outcome measures and analyses but does not report a multiplicity plan. It does not report a trial-specific sample-size justification, interim analyses, or a detailed statistical analysis plan. These details are not reported in the registry record; their absence should not be treated as proof that particular procedures were absent. They do limit the ability to evaluate prespecification, missing-data assumptions, and the intended interpretation of the results.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Functional Melatonin Replacement for Sleep Disruptions in Individuals With Tetraplegia — NCT00507546.
- Registry record last updated 2014-05-22; status last verified 2014-04.
- Results first posted 2014-05-22.
- 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
This completed phase 4 trial evaluated nightly ramelteon versus placebo in a randomized, triple-masked crossover design among individuals with tetraplegia and sleep disruption. The stated primary endpoint was median WASO in minutes over the treatment periods, with the primary analysis population described as participants who completed the entire protocol.
The posted primary summaries report median WASO of 72.3 minutes for ramelteon and 76.5 minutes for placebo, with full ranges of 20.7 to 92.3 and 24.0 to 117.0 minutes, respectively. The sponsor-reported Friedman analysis gives p = 0.70. The registry record does not report a treatment-effect estimate or confidence interval, and it does not explain why the posted primary outcome counts of 3 and 2 differ from enrollment of 12.
The record lists change in subjective morning alertness as a secondary outcome. Safety entries report 0 serious and 0 other adverse events for each listed arm; death counts are not reported in the registry record.