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 Occipital Nerve Stimulation (ONS) for Migraine: OPTIMISE (NCT01775735), a randomized na study. The primary outcome is Change in the Number of Moderate-to-severe Headache Days Per Month.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01775735 |
| Phase | NA |
| Condition | Migraine Disorders |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 28 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Boston Scientific Corporation |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with intractable chronic migraine. The primary-outcome population was narrower: participants who completed baseline and the six-month assessment and had at least 70% of the required electronic diary data. The registry record says that data for five subjects were not calculated because of missing diary data.
Intervention
The intervention was continuous occipital nerve stimulation with the Boston Scientific Precision system for six months after randomization. The study summary describes stimulation as being used alongside anti-migraine medications.
Comparator
The control group received intermittent stimulation from the same type of system: stimulation for 20 seconds every 90 minutes during the six months after randomization. This is an active stimulation comparator, not a no-device control.
Primary question
The primary question was whether the number of moderate-to-severe headache days per month changed from baseline to six months after randomization, and how the reported change differed between continuous and intermittent stimulation. The registry reports arm-level median changes, but says statistical analysis was not performed because the sample was too small to draw statistically relevant conclusions. It does not report an inferential estimate of the between-group difference.
3. Trial Design
OPTIMISE was registered as a randomized, double-masked, parallel-group study of occipital nerve stimulation for migraine disorders. The listed phase is not applicable. The registry record lists Boston Scientific Corporation as the sponsor and an enrollment of 28. The recorded study start was 2013-04-10, and the primary completion date was 2015-12-01. The study status is terminated; a reason for termination is not reported in the registry record.
Both groups used the Boston Scientific Precision occipital nerve stimulation system for six months after randomization. The treatment group received continuous stimulation. The control group received intermittent stimulation for 20 seconds every 90 minutes. The study summary describes the device as being used in conjunction with anti-migraine medications. The record does not describe further details of medication management or whether medication use was standardized between groups.
Random allocation is intended to make groups comparable on average, while masking is intended to limit the influence of treatment knowledge on participants’ reports or study assessments. These are general purposes of the design features, not evidence that any particular procedure was successful in this trial. The method used to generate the allocation sequence, concealment procedures, and the identities of people who were masked are not reported in the registry record.
The primary outcome was a change in monthly moderate-to-severe headache days from baseline to six months after randomization. The record lists one outcome measure and no posted analyses. It does not report a protocol-level statistical plan, sample-size justification, or interim-analysis plan. The enrollment figure is not itself evidence of the number included in the primary-outcome 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: 28 subjects were consented in the study. 13 failed screening and 15 were randomized. Statistically relevant conclusions cannot be made from this small sample size.
Intervention (6 Months)
| Stage | Treatment | Control |
|---|---|---|
| STARTED | 8 | 7 |
| COMPLETED | 8 | 7 |
| NOT COMPLETED | 0 | 0 |
Open Label (24 Months)
| Stage | Treatment | Control |
|---|---|---|
| STARTED | 8 | 7 |
| COMPLETED | 7 | 3 |
| NOT COMPLETED | 1 | 4 |
Analysis population for the primary outcome, as defined in the registry: All subjects who completed Baseline and 6 months post-randomization and had ≥70% of eDiary data. Data for 5 subjects was not calculated due to missing eDiary data. Statistical analysis was not performed as the sample size is too small to draw any statistically relevant conclusions.
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.
Population: Randomized subjects
| Characteristic | Unit | Treatment | Control | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 7 | 15 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 7 | 7 | 14 |
| Age, Categorical: >=65 years | Participants | 1 | 0 | 1 |
| Sex: Female, Male: Female | Participants | 8 | 7 | 15 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race/Ethnicity – American Indian or Alaska native | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race/Ethnicity – Asian | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race/Ethnicity – Black or African American | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race/Ethnicity – Hispanic or Latino | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Race/Ethnicity – Native Hawaiian or other Pacific Islander | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Race/Ethnicity – White | Participants | 7 | 7 | 14 |
| Race/Ethnicity, Customized: Race/Ethnicity – Other | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 8 | 7 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Change in the Number of Moderate-to-severe Headache Days Per Month, measured over from Baseline to 6 months post-randomization.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Standard Deviation |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is the change in the number of moderate-to-severe headache days per month from baseline to six months after randomization. The registry defines such a day as a calendar day with headache pain lasting at least four hours and peak severity that is moderate or severe, or a day on which the subject took a triptan or ergot regardless of headache duration or severity.
Baseline was based on the first 30 calendar days of electronic diary entries, provided the diary contained at least 70% of data. The six-month value used the 30 calendar days immediately before the six-month visit, with the same diary-completeness threshold. Comparing two defined diary periods gives a consistent way to describe change over time. A threshold for diary completeness also makes clear that values were not calculated for every participant regardless of missingness.
The outcome is reported as a median change with a standard deviation. A median describes the middle of the observed changes and is less affected by unusually large or small values than a mean. A standard deviation describes spread; it is not a confidence interval and does not, by itself, show the precision of the median or the uncertainty in a treatment comparison. The record does not report a confidence interval for the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome summaries are a median change of -5.2 days in the continuous-stimulation group, with a standard deviation of 7.3 and four participants, and a median change of 0.0 days in the intermittent-stimulation control group, with a standard deviation of 10.8 and six participants. These are separate arm-level summaries. They do not provide a statistical estimate of the difference between groups.
The registry record explicitly states that statistical analysis was not performed because the sample size was too small to draw statistically relevant conclusions. It reports no p-value, confidence interval, or model-based estimate for the primary comparison. Consequently, the arm summaries do not establish whether the observed pattern is compatible with a meaningful difference, with little or no difference, or with substantial uncertainty. The direction of one group’s median change cannot substitute for an analysis comparing randomized groups.
The reported spread is large relative to the scale of the median changes, but standard deviations around arm summaries are not a formal measure of uncertainty in the between-group effect. In particular, a standard deviation is not a confidence interval. With small groups, individual observations can have substantial influence on summaries, and the available record does not permit a reliable assessment of how stable these medians would be in another sample.
The primary endpoint is a change from baseline, rather than an absolute six-month headache-day count. Change measures can help describe within-person movement over time, but causal interpretation depends on the comparison between randomized groups and on appropriate analysis. No such inferential comparison is posted. The record also does not state whether any adjustment, covariate model, or other analysis was planned.
These results should therefore be read as descriptive outcome data from a small subset with qualifying diary information, not as a definitive estimate of the relative effects of continuous and intermittent stimulation. The record’s own statement that no statistical analysis was performed is central to interpretation. It does not support a conclusion that the approaches differ, or that they are equivalent. The reason for study termination and the status of any further analyses are not reported in the registry record.
9. Statistical Methods Explained
The study design and the reported outcome summaries answer different questions. Randomization assigns participants to groups so that a comparison can, under suitable implementation and analysis, estimate a treatment contrast. The arm-level medians reported for OPTIMISE describe the observed changes within each group. Without a reported between-group estimate and its uncertainty, those summaries alone do not quantify the treatment contrast.
What does the median describe?
For a set of observed changes, the median is the central value when observations are ordered. It is a measure of location, not a measure of precision. A median can be useful when data are skewed or contain extreme observations, because its value is less sensitive to the magnitude of extremes than a mean. The registry reports median changes, but does not report the underlying participant-level data or a confidence interval for either median.
The standard deviation describes how dispersed observations are around a mean. It is commonly reported with means, and its interpretation alongside a median is less direct. It does not provide the range of possible values for the population median and should not be read as the uncertainty around the treatment comparison. A confidence interval, when calculated with an appropriate method, expresses uncertainty about an estimate; none is posted for this primary result.
Why is a group comparison important?
Participants can change over time for many reasons, including changes unrelated to the assigned stimulation pattern. A randomized comparison is intended to distinguish the outcome pattern in one assigned group from the pattern in another. The relevant inferential quantity would describe the contrast between groups, with an uncertainty measure. The registry says statistical analysis was not performed and gives no such estimate. It is therefore not possible to use the posted medians as a substitute for an inferential comparison.
A p-value, if reported, would describe how compatible data are with a specified null model under its assumptions; it would not measure the probability that a treatment effect is true. A confidence interval would communicate a range of values compatible with the data and analysis assumptions. Neither is reported for the primary comparison. No method for an adjusted analysis, handling of repeated observations, or treatment of outcome distributions is reported in the registry record.
How should missing diary data be understood?
The endpoint definition requires adequate diary completion in both assessment periods. The registry says values were calculated only when the diary contained at least 70% of data, and that data for five subjects were not calculated because of missing diary data. This threshold defines which diary records could contribute to a calculated endpoint; it does not establish that missingness was unrelated to symptoms or treatment assignment. If people with incomplete diaries differ from those with adequate diaries, summaries among those retained may not represent all randomized participants. The record does not report an analysis addressing that possibility.
The primary-outcome population is described as subjects who completed baseline and six months after randomization and had at least 70% of diary data. The record does not provide a full participant flow or explain how all randomized participants were handled in analyses. It also does not report imputation or sensitivity analyses for missing outcomes. These details matter because an analysis restricted to complete or sufficiently complete records can answer a different question from an analysis that retains all randomized participants.
What can planning calculations show?
Planning calculations estimate the number of participants or events that a hypothetical study would require under stated assumptions. They are not observed trial results and are not evidence of the power achieved by the completed study. The planning assumptions associated with this record use a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. These are planning assumptions, not a reported protocol justification for OPTIMISE.
Such calculations depend on the assumed effect and variability, among other design choices. A calculation based on the observed effect is especially uncertain when the observed sample is small; the observed effect may not be a stable estimate of the effect to plan for. The registry record does not report the trial’s own sample-size justification. Accordingly, planning illustrations should not be read as a retrospective test of whether the trial was adequately designed.
General statistical concepts do not fill in unreported methods. The registry does not report an analysis plan, multiplicity procedure, interim monitoring approach, or a model for the primary outcome. No such method should be inferred from the endpoint summaries.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one outcome measure, no posted secondary outcome measures, and zero posted analyses. Those details describe what appears in the registry record; they do not establish whether additional outcomes or analyses were planned outside the record. A multiplicity strategy for multiple endpoints, time points, or analyses is not reported in the registry record. No interim-analysis plan is reported either.
Missing diary data affected the primary outcome. The registry states that values were calculated only when diary data met the at-least-70% completeness criterion in the specified assessment period, and that data for five subjects were not calculated because of missing diary data. The primary-outcome population is described as participants who completed baseline and six months after randomization and met the diary threshold. The arm summaries list four participants in treatment and six in control.
These eligibility rules mean that the reported endpoint summaries apply to participants with the required follow-up and diary completeness, not necessarily to everyone randomized. The record does not explain the missingness pattern by group, give a complete account of participant disposition, or report imputation or sensitivity analyses. It is therefore not possible to assess from the registry whether the missing diary data could have altered the observed summaries.
The reason for termination, the trial’s planned analysis population, and any strategy for handling missing outcomes are not reported in the registry record. No assumption about those procedures should be inferred from the published endpoint values alone.
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 | 4 | 8 | 50.0% |
| Control | 1 | 7 | 14.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment | 0 of 8 |
| Control | 0 of 7 |
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 | 3 of 8 |
| Control | 3 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment | Control |
|---|---|---|---|
| Status migrainosus | Nervous system disorders | 2 of 8 | 0 of 7 |
| Adverse drug reaction | General disorders | 2 of 8 | 0 of 7 |
| Migraine | Nervous system disorders | 1 of 8 | 0 of 7 |
| Hemiplegic migraine | Nervous system disorders | 1 of 8 | 0 of 7 |
| Migraine without aura | Nervous system disorders | 1 of 8 | 0 of 7 |
| Cellulitis | Infections and infestations | 1 of 8 | 0 of 7 |
| Wound dehiscence | Injury, poisoning and procedural complications | 1 of 8 | 0 of 7 |
| Nephrolithiasis | Renal and urinary disorders | 1 of 8 | 0 of 7 |
| Thrombosis | Vascular disorders | 0 of 8 | 1 of 7 |
| Device related infection | Infections and infestations | 1 of 8 | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment | Control |
|---|---|---|---|
| Implant site irritation | General disorders | 1 of 8 | 1 of 7 |
| Migraine | Nervous system disorders | 0 of 8 | 1 of 7 |
| Carpal tunnel syndrome | Nervous system disorders | 0 of 8 | 1 of 7 |
| Impaired healing | General disorders | 0 of 8 | 1 of 7 |
| Diverticulitis | Infections and infestations | 0 of 8 | 1 of 7 |
| Pneumonia | Infections and infestations | 1 of 8 | 0 of 7 |
| Upper respiratory tract infection | Infections and infestations | 1 of 8 | 0 of 7 |
| Surgical skin tear | Injury, poisoning and procedural complications | 1 of 8 | 0 of 7 |
| Suture related complication | Injury, poisoning and procedural complications | 1 of 8 | 0 of 7 |
| Myofascial pain syndrome | Musculoskeletal and connective tissue disorders | 0 of 8 | 1 of 7 |
Serious events with the highest arm-level rate: status migrainosus (25.0%), adverse drug reaction (25.0%), thrombosis (14.3%), migraine (12.5%), hemiplegic migraine (12.5%).
The serious adverse event figures are reported separately for each group. In treatment, eight participants were at risk and four were affected by a serious adverse event; in control, seven were at risk and one was affected. The record reports zero deaths in each group. These counts are descriptive and do not establish that the groups differ in safety. The record does not provide a statistical comparison or an uncertainty estimate for these figures.
For other adverse events, the record lists eight participants at risk and three affected in treatment, and seven at risk and three affected in control. Serious and other adverse-event summaries should not be combined: they describe different categories in the registry record. The at-risk counts also differ from the primary-outcome group counts, so the safety figures should not be treated as the denominator for the headache outcome.
The listed serious-event terms and percentages are Status migrainosus, 25.0%; Adverse drug reaction, 25.0%; Thrombosis, 14.3%; Migraine, 12.5%; Hemiplegic migraine, 12.5%; and Migraine without aura, 12.5%. These are registry-listed terms, not a comparison of event rates between randomized groups. The record does not report enough detail to determine the timing, duration, relatedness, or clinical course of these events.
12. What the Result Does, and Does Not, Mean
The posted results document a small set of primary-outcome summaries among participants with adequate diary data. The continuous-stimulation group has a reported median change of -5.2 days, and the intermittent-stimulation group has a reported median change of 0.0 days. The record also reports standard deviations and group sizes. It explicitly states that statistical analysis was not performed because the sample size was too small to draw statistically relevant conclusions.
These numbers describe the observed participants; they do not establish that continuous stimulation caused a greater change than intermittent stimulation. There is no reported estimate of the between-group contrast, confidence interval, or p-value. Nor do the summaries establish equivalence: failure to report a statistical comparison is not evidence that the treatments have the same effect.
The outcome uses diary-based counts in defined 30-day windows and a specified threshold for diary completion. Missing diary information meant that some participants did not have a calculated value. Consequently, the arm summaries reflect the endpoint-eligible records rather than necessarily describing everyone randomized. Without information about the missing records and their relationship to outcomes, their effect on the summaries cannot be determined.
The safety counts are also descriptive. They report participants affected by serious and other adverse events, and zero deaths in each group, but do not provide an inferential safety comparison. The serious-event terms and percentages should be read as entries in the registry record, not as evidence of a causal relationship or a comparative risk estimate.
Overall, the record offers limited descriptive information about a randomized study that was terminated. It does not provide enough inferential evidence to determine the comparative effect of the stimulation schedules. The reason for termination and any subsequent analyses are not reported in the registry record.
13. Why This Trial Matters Statistically
OPTIMISE illustrates an important distinction in clinical-trial reporting: randomization is a design feature, while a treatment-effect estimate requires an analysis that compares groups. The registry identifies a randomized, double-masked, parallel-group study, but its primary-outcome entry contains only arm-level medians and standard deviations. It states that no statistical analysis was performed because the sample size was too small to draw statistically relevant conclusions. The design label alone cannot supply the missing comparison.
The endpoint also shows why outcome definitions and data completeness matter. Moderate-to-severe headache days were defined using diary entries and specific symptom or medication criteria, with a minimum diary-completeness threshold. Such operational rules make the endpoint more explicit, while also limiting which records can contribute. The registry reports that five subjects did not have calculated data because of missing diaries and defines the primary population by completion and diary availability.
For statistical readers, the record is a reminder to separate descriptive summaries from uncertainty-aware inference. A median change in one group and a median change in another do not, by themselves, quantify a between-group contrast. Standard deviations do not replace confidence intervals, and the absence of a p-value is not evidence of no difference. The small reported outcome groups and missing diary information further limit what can be concluded from these summaries.
The record is also useful for identifying what remains unknown: the reason for termination, the statistical analysis plan, the sample-size justification, and the handling of missing outcomes are not reported. Those gaps constrain interpretation without changing the descriptive values that are posted.
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 primary outcome is available for small arm groups: four participants in treatment and six in control. The registry itself says statistical analysis was not performed because the sample size was too small to draw statistically relevant conclusions. No inferential between-group estimate or confidence interval is reported, leaving the magnitude and precision of a comparative effect undetermined.
Missing diary data are a specific limitation. The outcome required at least 70% diary completeness, and the registry says data for five subjects were not calculated because of missing diaries. The reported primary population further requires completion of baseline and the six-month assessment. The record does not report the distribution or reasons for missing data by group, an imputation method, or sensitivity analyses. The potential influence of missing outcomes therefore cannot be assessed.
The record gives an enrollment of 28 but does not provide a complete participant-flow account in the posted outcome information. It is not possible to infer from enrollment alone how many participants were randomized, completed follow-up, or contributed to each analysis. The reason the study was terminated is not reported in the registry record.
Further limitations arise from absent methods details. The statistical analysis plan, sample-size justification, allocation-generation procedure, masking details, and approach to multiplicity are not reported. The primary endpoint is summarized using a median and standard deviation, without a reported interval estimate. These omissions prevent a fuller assessment of precision and analytical choices. The safety counts are likewise descriptive and are not accompanied by comparative estimates or uncertainty measures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Occipital Nerve Stimulation (ONS) for Migraine: OPTIMISE — NCT01775735.
- Registry record last updated 2020-11-13; status last verified 2020-11.
- Results first posted 2018-11-02.
- 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
OPTIMISE (NCT01775735) is a terminated randomized, double-masked, parallel-group study of occipital nerve stimulation for migraine disorders, sponsored by Boston Scientific Corporation. The registry lists enrollment of 28 and one primary outcome measure. The treatment group received continuous stimulation and the control group intermittent stimulation for 20 seconds every 90 minutes, for six months after randomization.
The primary outcome was change in monthly moderate-to-severe headache days from baseline to six months. The registry reports a median change of -5.2 days in treatment and 0.0 days in control, with four and six participants respectively. It states that no statistical analysis was performed because the sample size was too small to draw statistically relevant conclusions. Five subjects had no calculated endpoint data because of missing diary data. No secondary outcome measures or analyses are posted. The reason for termination and the trial’s statistical analysis plan are not reported in the registry record.