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 Fremanezumab, Migraine and Sleep (NCT04693533), a na phase 4 study. The primary outcome is Fremanezumab and Sleep.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04693533 |
| Phase | Phase 4 |
| Condition | Migraine Disorders, Sleep Disorder |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 22 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Beth Israel Deaconess Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
People with migraine were the intended population. The registry lists Migraine Disorders and Sleep Disorder as conditions and records planned enrollment of 22. The specific eligibility criteria and characteristics of participants who actually took part are not reported in the registry record.
Intervention
The intervention was fremanezumab, listed as Fremanezumab Prefilled Syringe [Ajovy]. The study description places daily assessments around treatment injections, with a baseline period before treatment and follow-up periods after the first, second, and third injections. The dose and other treatment details are not reported in the registry record.
Comparator
There was no placebo or control group. The registry describes an open-label, single-group, within-person study, so the planned comparison was each participant’s sleep quality during treatment against their pre-treatment period. Allocation is listed as NA, and the record does not describe a randomized comparison.
Primary question
The primary question was whether sleep quality improved during treatment compared with the pre-treatment period, as measured by the Insomnia Severity Index. The study summary also describes an interest in the relationship between fremanezumab’s ability to prevent migraine and improved sleep. The registry record does not report outcome results, so it does not establish the direction or size of any observed change or relationship.
3. Trial Design
This was a phase 4, open-label, single-group study sponsored by Beth Israel Deaconess Medical Center. The registry lists planned enrollment of 22 and a status of terminated. It records a start date of 2021-07-29 and a primary completion date of 2024-04-01. The reason for termination, the number of participants who enrolled or received treatment, and the timing of termination are not reported in the registry record.
The study summary describes a within-person design using daily assessments of migraine and sleep outcomes. It sets out a baseline period from days 0 to 30, followed by treatment periods identified as injection 1 on days 31-60, injection 2 on days 61-90, and injection 3 on days 91-120. The primary outcome timeframe is described as 1 month before and 3 month after treatment. These are planned observation windows in the registry description; the record does not report how much observation was completed.
In a within-person design, a participant’s measurements before treatment serve as the comparison for their measurements during treatment. This can account for stable differences between participants, but it does not create a concurrent untreated control group. Because the study was open label and had no placebo or control group, changes over time could reflect treatment, changes in migraine or sleep for other reasons, expectations, or other events. The registry’s interrupted time-series description indicates repeated assessments around treatment intervals, but detailed analytical procedures are not reported in the registry record.
The record lists 2 outcome measures and 0 analyses. Apart from the primary outcome description, details of the other outcome measure are not reported in the registry record. The registry also does not report a protocol-based sample-size justification or explain why the study was terminated.
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 | Treatment Effect |
|---|---|
| STARTED | 22 |
| COMPLETED | 22 |
| NOT COMPLETED | 0 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Treatment Effect |
|---|---|---|
| Participants analysed | 22 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 22 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 18 |
| Sex: Female, Male: Male | Participants | 4 |
| Race/Ethnicity, Customized: white | Participants | 19 |
| Race/Ethnicity, Customized: Black or African American | Participants | 1 |
| Race/Ethnicity, Customized: Asian | Participants | 0 |
| Race/Ethnicity, Customized: native Hawaiian or other Pacific Islander | Participants | 0 |
| Race/Ethnicity, Customized: American Indian or Alaskan native | Participants | 0 |
| Race/Ethnicity, Customized: multiracial | Participants | 0 |
| Race/Ethnicity, Customized: unknown | Participants | 0 |
| Race/Ethnicity, Customized: other | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Fremanezumab and Sleep, measured over 1 month before and 3 month after treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint concerns improvement in sleep quality during treatment compared with the pre-treatment period. Sleep quality is measured with the Insomnia Severity Index, a questionnaire in which participants answer 7 questions, each using a score from 0 to 4. The total score ranges from 0-28. The registry describes categories of 0-7 for no clinically significant insomnia, 8-14 for subthreshold insomnia, 15-21 for clinical insomnia of moderate severity, and 22-28 for clinical insomnia of severe severity.
A standardized questionnaire gives sleep symptoms a defined measurement framework and allows repeated assessments to be compared over time. The listed categories can help describe the level of insomnia indicated by a score. However, the registry record does not define the precise numerical criterion that would count as an improvement for the primary analysis. It also does not report whether the planned endpoint was a change in total score, a change in category, or another summary of repeated measurements.
The endpoint is described in terms of participants, while its measurement instrument produces a score. Without results or a fuller analysis description, the registry record does not establish how the scores were converted into the stated primary outcome or how a change was summarized. It reports no primary outcome results; therefore, the endpoint’s observed values and precision are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive constraint is that the registry record describes the question and planned measurement but does not report primary outcome results. It records 0 analyses. No estimate of sleep-quality change, uncertainty interval, or statistical test result is reported in the registry record. Consequently, the posted information does not show whether sleep scores changed during treatment, how large any change was, or how precisely it was estimated.
The planned comparison is within participants: sleep assessments before treatment are compared with assessments during treatment. That structure can be useful for observing how measurements vary over time in the same people. It does not, by itself, show that treatment caused any change. Without a concurrent control group, other influences that change over time can be difficult to distinguish from a treatment-related pattern. The open-label design also means participants knew they were receiving treatment, which can affect self-reported outcomes such as sleep symptoms.
The study summary describes daily assessment and fixed treatment intervals, which could support examination of temporal patterns if the data and analysis were available. But the registry record does not report adherence to daily assessment, the actual timing or number of observations, the handling of trends or repeated measurements, or the statistical model. The results therefore cannot be interpreted as evidence for or against a relationship between migraine prevention and sleep improvement.
The record’s terminated status is important context, but it does not explain why the study ended or how termination affected data collection. The planned enrollment of 22 is not evidence that 22 participants enrolled, completed follow-up, or contributed endpoint data. Those participant-flow details are not reported in the registry record.
Any planning illustrations based on an observed effect should be treated as planning exercises, not as observed power or as proof that the original study was adequately sized. The described assumptions include two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not match the registry’s single-group design without a control arm. The trial’s own sample-size justification is not reported in the registry record.
In short, the registry record supports a description of the intended design and endpoint, but not a conclusion about treatment effects. A reader would need outcome results, participant flow, and analysis details to assess the observed pattern and its uncertainty.
9. Statistical Methods Explained
What does a within-person comparison estimate?
In general, a within-person comparison evaluates how measurements for the same participant differ across periods. Each participant contributes information from before and during treatment, rather than being compared with a separate control group. This approach can reduce the influence of characteristics that remain relatively stable within a participant. It does not remove influences that vary over time, such as changes in migraine, sleep routines, other care, life circumstances, or expectations.
For this study, the registry describes daily migraine and sleep assessments during baseline days 0 to 30 and after treatment across days 31-60, days 61-90, and days 91-120. A statistical analysis of these observations would need to account for the fact that measurements from the same participant are related. Treating every daily observation as independent could make uncertainty appear smaller than it is. The specific method for accounting for repeated measurements is not reported in the registry record.
What is an interrupted time series?
In general, an interrupted time-series design examines repeated measurements over time and asks whether the pattern changes around an intervention or interruption. It can distinguish a change in level from a change in trend when enough observations and an appropriate model are available. A time-series interpretation depends on features such as the pattern before treatment, the timing of intervention, serial dependence, and other events that may coincide with the intervention.
The study summary calls this an interrupted time-series design, with treatment introduced at fixed intervals. The registry record does not report the planned model, whether baseline trend would be estimated, whether changes after each injection would be considered separately, or how autocorrelation and other time-related patterns would be handled. It also does not report whether the actual injection and assessment dates followed the planned schedule.
How should the sleep measure be understood?
The Insomnia Severity Index is the stated measure for the primary sleep outcome. Its 7 questions use responses from 0 to 4, and its total score ranges from 0-28. The registry describes score bands from no clinically significant insomnia through severe clinical insomnia. In general, repeated scores can be analyzed as numerical measurements, while categories can be used to describe severity bands. These approaches answer different questions: a score analysis concerns magnitude of change, while a category analysis concerns movement between defined bands.
The registry record does not specify which approach formed the primary statistical analysis, how improvement was operationalized, or whether a threshold for a meaningful change was prespecified. It also does not report outcome data. As a result, no change estimate or interpretation of its precision can be reconstructed from the record.
What does an uncertainty interval convey?
In general, a confidence interval expresses the range of values compatible with an estimate under the assumptions of the statistical model. A narrow interval indicates greater precision than a wide interval, though precision is not the same as absence of bias. The interval’s interpretation depends on the endpoint definition, analysis population, model, and data quality. No confidence interval or other uncertainty estimate for the primary endpoint is reported in the registry record.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability is greater than a statistical model expects. It can arise when data are more heterogeneous or more correlated than assumed. If a model understates that variability, standard errors may be too small and intervals too narrow. The primary outcome is described through the Insomnia Severity Index, but the record does not report an analysis model or a dispersion estimate. No conclusion about over-dispersion in this study can therefore be drawn.
How do the planning assumptions fit the design?
The planning illustrations are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not evidence about the trial’s actual power or results. Equal allocation between arms is not aligned with the registry’s single-group, no-control design. The registry record does not report that these assumptions were used to plan the trial, and its own sample-size justification is not reported.
What can be inferred from the analysis record?
The registry records 0 analyses. It does not report a statistical plan, outcome estimates, hypothesis tests, confidence intervals, or adjustment methods. The description of the intended design should not be mistaken for evidence that the described analyses were completed. Without posted analysis results, statistical significance, effect size, and precision cannot be assessed.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 2 outcome measures, but the details of the other measure and the relationships among outcomes are not reported in the registry record. It does not report a hierarchy of outcomes, a multiplicity adjustment, or a plan for selecting which outcomes to emphasize. In general, testing multiple outcomes can increase the chance of finding an apparently notable result by chance. A prespecified hierarchy or adjustment can address that issue, but no such approach is documented in the record.
Missing-data procedures are not reported in the registry record. The study description calls for daily assessments across baseline and treatment periods, but it does not state how missed assessments, incomplete questionnaires, or participant withdrawal would be handled. This matters because missing observations can affect both the estimated pattern over time and its uncertainty, particularly if missingness is related to symptoms or treatment experience.
The analysis population is also not reported in the registry record. It is not clear which participants or observations would be included in the primary analysis, or how participants with incomplete follow-up would be treated. The planned enrollment of 22 does not establish the number contributing data to any outcome.
Because the registry records 0 analyses and does not post primary outcome results, readers cannot assess whether the analysis followed a prespecified plan, whether any outcomes were omitted, or how missing data and multiplicity were addressed.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Treatment Effect | 0 | 22 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment Effect | 0 of 22 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment Effect | 0 of 22 |
The posted safety figures list 22 at risk for serious adverse events and 0 serious adverse events. They also list 22 at risk for other adverse events and 0 other adverse events, with 0 deaths. These are the registry’s reported figures for the Treatment Effect group. The record does not list serious adverse event terms.
These figures should be read as the safety information posted in the registry, not as proof that no adverse events occurred among everyone who may have participated. The record does not report whether all planned participants enrolled, how many received treatment, how long safety was monitored, or whether all safety data were complete. The planned enrollment of 22 is not interchangeable with a confirmed count of participants treated or followed for safety.
The study had no placebo or control group, so these figures do not provide a comparative estimate of safety. They also cannot establish whether an event was caused by treatment. The registry’s terminated status and the reason for termination are not explained in the safety information. The posted counts therefore describe what the record reports, with important uncertainty about exposure, follow-up, and completeness.
12. What the Result Does, and Does Not, Mean
The record describes a study designed to examine whether sleep quality changed during fremanezumab treatment compared with the pre-treatment period, and whether sleep improvement was related to migraine prevention. It identifies the Insomnia Severity Index as the primary sleep measure and describes repeated assessments before and after treatment. These details define the scientific question and intended measurement approach.
They do not establish what happened to participants’ sleep. The registry record does not report the primary outcome results, a change estimate, a confidence interval, or an analysis. It therefore cannot show the direction, size, or precision of any change. It also cannot establish a relationship between migraine prevention and sleep improvement.
Even if a before-and-during-treatment change were reported, a single-group, open-label design would require cautious interpretation. Without a concurrent control group, the observed pattern could reflect influences other than treatment. Repeated measurements can clarify timing and trajectories, but they do not by themselves eliminate confounding or other time-related explanations.
The planned enrollment of 22 is not confirmation of the number enrolled, treated, or included in an analysis. The registry marks the study as terminated but does not report the reason or participant flow. The posted safety counts likewise do not establish the completeness of safety follow-up.
Accordingly, the record supports a description of the intended research question, design, and endpoint, but not a claim that fremanezumab did or did not improve sleep. The absence of reported results is a limit on what can be concluded, not evidence that an effect was absent.
13. Why This Trial Matters Statistically
This study is statistically interesting because it proposes frequent, within-person measurement of sleep and migraine around treatment periods. Repeated observations can describe trajectories rather than relying only on a single before-and-after measurement. The registry’s fixed observation windows and interrupted time-series framing make timing central to the intended analysis.
That design also highlights important analytic demands. Daily observations from the same participant are related, and sleep measures may vary over time even without treatment. A credible analysis would need to describe how repeated measurements, underlying trends, timing, and missing observations were handled. Those methods and the results are not reported in the registry record, so readers cannot evaluate whether the design’s potential was realized.
The study also illustrates the difference between a planned contrast and a controlled comparison. Comparing each participant with their own baseline can be informative, but without a control group it cannot separate a treatment-associated pattern from all other changes over time. Open-label measurement of a self-reported outcome adds another reason to interpret any eventual change with care.
Finally, the registry’s terminated status, lack of posted outcome analyses, and absent sample-size justification limit assessment of both the evidence and the study’s execution. Planning calculations based on a two-arm equal-allocation assumption do not describe this single-group design. The central statistical lesson is that a thoughtful measurement schedule can frame a useful question, while the design, analysis, and transparent reporting determine how confidently that question can be answered.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is that primary outcome results and statistical analyses are not reported in the registry record. Without estimates and uncertainty measures, the intended sleep comparison cannot be evaluated. The record lists 0 analyses, and it does not state how the primary endpoint was operationalized beyond the general description of improvement.
The study has no placebo or control group and is open label. Within-person comparison can account for stable individual differences, but it cannot rule out time-varying explanations for changes in sleep. Self-reported sleep quality may also be influenced by participants’ expectations or awareness of treatment.
Although daily assessments and treatment intervals are described, the registry does not report actual assessment completeness, treatment adherence, participant flow, or the handling of missing observations. The status is terminated, but the reason is not reported. Planned enrollment of 22 should not be treated as the number who completed the study or contributed outcome data.
The record does not report the statistical model for repeated measures, how trends or correlation were handled, whether effects after each injection were analyzed separately, or how multiplicity was addressed across the 2 listed outcome measures. It also does not report an analysis population or sample-size justification. These gaps prevent evaluation of the analysis plan, precision, and potential for selective reporting.
Finally, the listed safety counts have no concurrent comparison and do not establish the completeness or duration of safety monitoring. Together, these limitations mean that the registry record documents the planned question and design more fully than it documents the resulting evidence.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Fremanezumab, Migraine and Sleep — NCT04693533.
- Registry record last updated 2026-02-27; status last verified 2026-02.
- Results first posted 2026-02-27.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT04693533, titled “Fremanezumab, Migraine and Sleep,” is a phase 4, open-label, single-group study sponsored by Beth Israel Deaconess Medical Center. The registry lists planned enrollment of 22, a start date of 2021-07-29, a primary completion date of 2024-04-01, and status terminated.
The study summary describes daily migraine and sleep assessments before and after treatment, with the Insomnia Severity Index as the primary sleep measure. There was no placebo or control group. The primary question concerned sleep quality during treatment compared with the pre-treatment period.
The registry record lists 2 outcome measures and 0 analyses. Primary outcome results, the reason for termination, participant flow, detailed analysis methods, and the trial’s sample-size justification are not reported in the registry record. Posted safety figures list 0 serious adverse events, 0 other adverse events, and 0 deaths, with 22 at risk for each adverse-event category.