Safety of Nerivio in Pregnant Women With Migraine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of Nerivio in Pregnant Women With Migraine (NCT05464069), a registered phase not stated study. The primary outcome is Gestational Age at Delivery.

2. Clinical Question

The study asks a comparative safety question rather than a randomized treatment-effect question. It uses retrospective survey information from women who had already experienced pregnancy and delivery. The groups are defined by treatment history: use of Nerivio during pregnancy or use of other migraine therapy. The registry record does not describe randomized allocation, and it cautions that the arms are not a like-for-like control comparison.

The central endpoint, mean gestational age at delivery, describes the average timing of delivery in each group. Secondary outcomes listed in the record include birth weight, miscarriage, preterm birth, birth deficits, still births, developmental milestones following 3 months postnatal, and migraine patterns. The clinical question therefore includes both the timing of delivery and a range of maternal and infant outcomes.

The record does not report group means or variability for the primary endpoint, or comparative estimates for the secondary outcomes. It is consequently not possible to determine from the registry record how the groups differed on these outcomes or how precisely any difference was estimated.

3. Trial Design

This is a retrospective controlled survey study, not a randomized trial. Its stated purpose is to assess the safety of treating migraine with Nerivio during pregnancy and 3 months postpartum by comparing women with migraine who used Nerivio during pregnancy with women who did not. The registry lists an enrollment of 145 and identifies the study as completed. The study start date is 2022-08-01, and the primary completion date is 2022-11-28.

The study used an electronic survey process that included an eligibility questionnaire, an electronic informed-consent form, and a questionnaire. Nerivio-group participants were to be recruited from Theranica's user base. Control-group participants were to be recruited through health care providers, including headache specialists and OBGYNs who were study co-investigators. The record describes the Nerivio group as postpartum patients with migraine who used Nerivio at least 3 times during pregnancy. It describes the comparison group as postpartum patients with migraine who used other migraine therapy during pregnancy and did not use Nerivio before or during pregnancy and at least 3 months postpartum.

The intervention list names Nerivio as a device and Migraine Relief as a drug. The registry record does not explain the role of Migraine Relief in the study or give further details about which other migraine therapies participants used. Allocation is not stated. Because treatment history and recruitment pathways distinguish the groups, the comparison may also reflect differences between the people who entered each group, not just their migraine treatment.

The primary outcome timeframe is retrospective data for up to 42 weeks, collected over 2 months. The record does not report the survey completion dates for individual participants, additional follow-up procedures, or how survey responses were verified. It lists eight outcome measures and one analysis, but detailed analysis methods are not reported.

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 Gestational Age at Delivery, measured over Retrospective Data for up to 42 weeks, collected over 2 months.

The primary endpoint is gestational age at delivery, measured in gestational days. The registry specifies that the endpoint is summarized as a mean with standard deviation and describes it as the mean gestational age at delivery in both study groups. It is a continuous measure: each recorded delivery timing can take a value along a scale, and the group mean gives a summary of the central timing.

Gestational age at delivery is used to characterize when delivery occurred. Comparing group means can describe whether the average timing differed between the women who used Nerivio during pregnancy and those who used other migraine therapy. The standard deviation describes the spread of individual gestational-age values around a group mean. A mean alone does not show that spread, and the standard deviation is not a measure of uncertainty in the mean.

The registry record gives a timeframe of retrospective data for up to 42 weeks, collected over 2 months. It does not report the observed mean or standard deviation for either group, a difference between groups, or a confidence interval. Those missing results prevent assessment of the size and precision of any group contrast from the registry record. The endpoint definition alone does not indicate whether the groups were similar or different, and it does not establish that any observed difference would be caused by treatment.

Gestational age at delivery is only one part of the study's stated safety assessment. The registry also lists pregnancy, birth, developmental, and migraine-related secondary outcomes. A finding about average delivery timing would not by itself describe all those outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods provide a framework for describing observations and comparing groups. The registry record specifies the primary endpoint and its summary measure, but many details needed to reproduce or fully assess an analysis are not reported. General explanations below describe what common statistical concepts mean; they should not be read as a claim that a particular method was used in this study.

What does a mean summarize?

For a continuous outcome such as gestational age at delivery, a mean summarizes the central value across observed participants in a group. It can be useful for comparing the average timing of delivery between groups. A mean does not show the full pattern of individual values, so it is commonly accompanied by a measure of spread. The registry specifies standard deviation for this purpose. Standard deviation describes how dispersed observations are around the mean; it does not directly tell how precisely the mean has been estimated.

Means can be influenced by unusual values, and two groups with the same mean can still have different distributions. A complete interpretation may therefore depend on the distribution of the endpoint and on how the analysis treats values that are missing or atypical. The registry record does not report distributional checks, transformations, or other analysis details for gestational age at delivery.

What would a group comparison estimate?

A comparative analysis would describe the observed difference in gestational age at delivery between the study groups. A confidence interval around that estimate would communicate its statistical precision under the analysis assumptions. In general, a narrower interval indicates greater precision, while a wider interval indicates greater uncertainty. A confidence interval is not a guarantee that the true value lies inside it, and it does not resolve biases caused by group selection or measurement.

The registry record does not report a group contrast, confidence interval, or p-value for the primary endpoint. It also does not report whether the comparison was adjusted for participant characteristics. Without these results and methods, readers cannot determine the estimated contrast, its precision, or whether any adjustment was made.

Why does over-dispersion matter?

Over-dispersion is a general issue for count outcomes when the observed variation exceeds what a chosen statistical model expects. If a model assumes less variability than the data contain, its uncertainty estimates can be too small, making results appear more precise than warranted. Methods that account for extra variation can improve uncertainty estimates when their assumptions fit the data. The registry record does not specify a model for count outcomes, or report whether over-dispersion was assessed. This concept is therefore relevant as general statistical context, not as a description of the study's analysis.

What do the planning assumptions mean?

The sample-size material is described as a planning illustration computed from an observed effect, not as the study's own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm. Such calculations explore what a future study might require under chosen assumptions. They are not observed power, do not show the probability that the present study detected an effect, and do not establish that the study was designed around those assumptions.

The registry record does not report the protocol's sample-size justification or whether the planning assumptions match the original study design. It also does not report the observed primary endpoint effect needed to evaluate the planning illustrations. No planning illustration can replace the missing outcome estimates and uncertainty measures.

What does the retrospective design imply?

In a randomized study, allocation is intended to make treatment groups comparable in expectation, subject to chance. In this retrospective controlled survey, the record does not state that participants were randomly assigned; instead, the arms are defined by prior treatment use. Group differences may therefore reflect treatment selection or other characteristics as well as any treatment-related differences. Statistical adjustment can sometimes address measured differences, but cannot automatically eliminate unmeasured confounding. The record does not describe whether adjustment was performed.

Recall and reporting are also general considerations for retrospective surveys: participants may report past experiences imperfectly, and those who respond may differ from those who do not. These are possible design-related sources of bias, not documented findings about this study. The registry record does not report validation of survey responses or an assessment of nonresponse.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Postpartum Females With Migraine Who Used Nerivio ", "Postpartum Females With Migraine Who Used Other Mi")
n   <- c(59, 81)
m   <- c(271, 273)
sp  <- c(13, 9)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Postpartum Females With Migraine Who Used Nerivio   59  271.000  13.000  267.612  274.388
CARM  Postpartum Females With Migraine Who Used Other Mi  81  273.000  9.000  271.010  274.990

11. Multiplicity, Missing Data and Analysis Populations

The registry lists eight outcome measures, including the primary endpoint and secondary measures related to birth weight, pregnancy outcomes, developmental milestones, and migraine patterns. It also lists one analysis. The record does not report a multiplicity plan, such as whether any adjustment was made when examining several outcomes or comparisons. Without that information, the interpretation of any individual statistical test would depend on analysis details that are not reported. No test results for the primary or secondary outcomes are given in the registry record.

Missing-data handling is not reported. The registry record does not state how many participants completed each survey item, whether primary endpoint data were unavailable for any participants, or how incomplete responses were treated. Missingness can affect a comparison if the availability of data is related to participant characteristics or outcomes. General approaches include analyzing available observations under stated assumptions, imputing missing values, or conducting sensitivity analyses; the record does not establish that any of these approaches was used.

The analysis population is also not reported. The enrollment figure is 145, but the registry record does not give group-specific numbers contributing to the primary endpoint or specify an inclusion rule for each analysis. The serious adverse event figures use at-risk counts of 59 and 81 for the two groups, but these figures should not be assumed to describe the analysis population for gestational age at delivery or every secondary outcome.

The record does not describe protocol deviations, exclusions, or sensitivity analyses. These omissions make it difficult to determine how complete the outcome data were and how robust the findings might be to different analysis choices. They do not demonstrate that data were missing or that analyses were inappropriate; they mean that these matters are not reported in the registry record.

12. 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.

The registry records serious adverse events as 0 of 59 at risk in the group of postpartum females with migraine who used Nerivio during pregnancy, and 0 of 81 at risk in the group who used other migraine therapy during pregnancy. Deaths are listed as 0 in both groups. The other adverse event counts are also recorded as 0 in each group. No serious adverse event terms are listed.

These entries should be read as registry counts, not as proof that serious events were impossible or that the groups had equal risk. A count of zero in the recorded data can occur even when an event remains possible. It does not establish the safety of a treatment, and it does not describe events that were not captured by the study's collection process.

The record does not report the definitions used for adverse events, the completeness of event ascertainment, or additional details about the safety follow-up. The study is retrospective and based on an electronic survey, so interpretation depends on what participants reported and what was recorded. The serious adverse event figures also do not substitute for results on the listed pregnancy and infant outcomes, which are not reported in detail.

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

The registry record establishes that a completed retrospective controlled survey study was designed to compare women with migraine who used Nerivio during pregnancy with women who used other migraine therapy. Its primary endpoint was mean gestational age at delivery, and it listed additional pregnancy, infant, developmental, and migraine outcomes. The record reports serious adverse event counts of zero in each group and no deaths in either group.

Those details do not provide the primary endpoint result. There are no group means, standard deviations, comparative estimates, confidence intervals, or p-values for gestational age at delivery in the registry record. Detailed results for the listed secondary outcomes are also not reported. The available figures therefore do not show whether the groups differed on the primary endpoint or on the broader set of outcomes.

Even if comparative outcome estimates were available, this design would not by itself establish that treatment caused any observed difference. Participants were not described as randomly assigned; they entered groups based on treatment history, and the recruitment routes differed. Such a comparison can be influenced by characteristics associated with treatment choice, survey participation, and other aspects of pregnancy or migraine care. The registry record does not report an adjustment strategy that would address these possibilities.

The adverse event counts are limited to events captured and entered in the registry. A recorded zero does not prove absence of risk, and it does not imply equivalence between groups. Likewise, the enrollment figure does not reveal how complete the endpoint data were or how precise a group comparison would be.

In general, a study's question, endpoint definition, and event counts are distinct from evidence about an effect. Here, the record describes the intended comparison and some safety counts, but does not report the results needed to quantify the primary comparison or assess its precision. The record should therefore be read as an incomplete account of comparative outcomes, not as a definitive statement about treatment safety or effectiveness.

14. Why This Trial Matters Statistically

This study is statistically instructive because a clear clinical question does not guarantee that a registry record contains enough results to answer it. The record defines a continuous primary endpoint, gestational age at delivery, and identifies the group summaries intended for it: mean and standard deviation. But without the observed values, a between-group estimate, and a measure of uncertainty, readers cannot evaluate the magnitude or precision of the comparison.

It also illustrates the distinction between a controlled comparison and randomized allocation. The groups are defined by prior treatment use and recruited through different routes. Statistical comparisons in this setting can describe patterns in the observed groups, but differences may reflect factors beyond treatment. The design does not make those differences disappear, and the registry record does not report whether analysis methods attempted to address them.

The safety counts show another important interpretive distinction. Zero recorded events is a descriptive count, not proof of no risk or of equal risk. Event counts depend on definitions, follow-up, and completeness of reporting. The registry record does not describe those details, so the counts need to be interpreted narrowly.

Finally, the record lists multiple outcomes but does not report how multiplicity, missing data, or the analysis population were handled. These are not merely technical details: they affect how estimates and tests should be understood. The study therefore highlights why transparent reporting of outcome results, uncertainty, data completeness, and analysis choices is essential for responsible interpretation of clinical research.

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 limitations specific to this study follow from the registry description. The retrospective survey design depends on participants reporting prior pregnancy, migraine, treatment, and infant-health information. The record does not describe validation of those reports, so the extent of measurement error cannot be assessed. The survey-based approach may also be affected by who chose or was able to participate; the record does not report a response rate or an assessment of nonresponse.

The groups were defined by treatment history rather than reported random allocation. Nerivio-group participants were to be recruited from Theranica's user base, while comparison participants were to be recruited through health care providers. These different pathways may produce group differences in participant characteristics or participation. The registry record does not describe adjustment for potential confounders or provide information needed to assess how comparable the groups were.

The comparison-group description is incomplete in the registry record, ending before the recruitment description is finished. The record also does not identify the other migraine therapies used by comparison participants. It lists Migraine Relief as a drug intervention but does not explain its role in the study. These omissions limit interpretation of the treatment contrast.

Most importantly, the primary endpoint results and detailed secondary outcome results are not reported in the registry record. The record also does not explain missing-data handling, analysis populations, or multiplicity. Consequently, neither the comparative estimates nor their precision and robustness can be assessed from the registry information. These are reporting limitations; they do not establish that the underlying study failed to collect or analyze the information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety of Nerivio in Pregnant Women With Migraine — NCT05464069.
• Registry record last updated 2025-10-06; status last verified 2022-06.
• Results first posted 2025-10-06.
• 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.

19. Record Summary

NCT05464069, titled “Safety of Nerivio in Pregnant Women With Migraine,” is a completed retrospective controlled survey study sponsored by Theranica. It examines women with migraine who used Nerivio during pregnancy and a comparison group who used other migraine therapy. The registry lists an enrollment of 145, a study start date of 2022-08-01, and a primary completion date of 2022-11-28.

The primary endpoint is mean gestational age at delivery, measured in gestational days. The registry record does not report its group results. Secondary outcomes include birth weight, miscarriage, preterm birth, birth deficits, still births, developmental milestones following 3 months postnatal, and migraine patterns. Serious adverse event counts are recorded as 0 of 59 at risk in the Nerivio group and 0 of 81 at risk in the other-therapy group; deaths are recorded as 0 in each group.

The record does not report detailed outcome estimates, missing-data procedures, analysis populations, or a multiplicity plan. The nonrandomized retrospective comparison and the missing results limit what can be concluded about differences between the groups.