Chronic Pain Risk Associated With Menstrual Period Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chronic Pain Risk Associated With Menstrual Period Pain (NCT02214550), a randomized phase 4 study. The primary outcome is Change in Participant Bladder Pain Sensitivity From Baseline..

2. Clinical Question

These aims combine a mechanistic question about sensitization with a treatment question about oral-contraceptive regimens. They should not be treated as interchangeable. The primary outcome is a measured bladder-pain score over visits; future chronic pelvic pain risk is part of the study rationale, not the stated primary endpoint. The registry lists a total enrollment of 353, but the arm descriptions do not provide outcome results for that enrollment. How the analysis population was formed for each outcome is not reported in the registry record.

3. Trial Design

The study is listed as a Phase 4, randomized, single-masked, parallel-design trial. It is marked completed. The registry lists a start date of 2014-07 and primary completion of 2020-11. Total enrollment is 353. The identity of the masked party, the randomization procedure, allocation concealment, and the precise criteria for assignment to study groups are not reported in the registry record.

The intervention descriptions include a dysmenorrhea plus cross-organ sensitization group receiving no oral-contraceptive intervention, a group receiving cyclic Microgestin 1/20, and a group receiving continuous Microgestin 1/20. A painful bladder syndrome group is described as receiving continuous Microgestin 1/20. These descriptions specify monitoring with monthly questionnaires for 1 yr, quantitative sensory testing at 6 months and 12 months, and yearly follow-up questionnaires for 5 years. The registry also describes a Pain Discovery Aim involving reproductive-age women and several pain or control groups. Its description is truncated, so the full recruitment and grouping process is not reported in the registry record.

Randomized allocation can support comparisons between assigned groups when the analysis preserves that assignment and appropriately accounts for missing outcomes. It does not by itself establish that groups were similar in every characteristic, that masking was maintained, or that the reported outcome analyses followed assignment. Those details are not reported in the registry record. The registry lists 3 outcome measures and 9 analyses, but does not state how those analyses map to each group, visit, or endpoint. No allocation ratio or detailed statistical analysis plan is reported in the registry record.

The record's description of the study rationale refers to dysmenorrhea, repeated cross-organ sensitization episodes, and chronic pelvic pain. It also states that cyclical oral contraceptives were expected to reduce sensitization and chronic-pain risk. These statements describe the investigators' rationale and expectation; they are not findings. The record does not provide a single primary treatment contrast, an analysis population definition, or a description of how follow-up over the stated period was incorporated into the primary analysis.

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: Patients were drawn from a separate cross-sectional, observational study that included women who mostly had moderate-to-severe dysmenorrhea, but also included some healthy controls, and patients with other chronic pain conditions who served as positive controls for that study. Those with D+COS and PBS in the four intervention arms first participated in the strictly observational study, yielding all baseline data. The Intervention arm participants are NOT included in the "no intervention' arms.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Some participant data were missing due to task error or attrition.

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: For PBS-continuous microgestin 1/20, one of the 15 participants who signed consent and came for a screening visit, changed her mind about taking microgestin and did not come for a baseline visit, so the final sample size for that subgroup is n=14

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Change in Participant Bladder Pain Sensitivity From Baseline., measured over 0 (baseline), 6 month, and 12 month visits.

The primary endpoint is change in participant bladder pain sensitivity from baseline. It is measured as a score on a scale, with the record specifying a Visual Analog Scale from 0 through 100: 0 is no pain and 100 is the worst pain imaginable. Ratings from the bladder filling test are compared across the initial, 6 month, and 12 month visits. The recorded rating at first urge is the outcome measure.

A pain rating provides a way to quantify a participant's reported experience at a defined point in a testing procedure. Repeated measurement makes it possible to describe how scores vary over visits. A mean can summarize the average score for a group, while a standard deviation describes variation among scores around that mean. These summaries do not, by themselves, indicate whether a change is statistically distinguishable from random variation or whether a difference between groups is precise. Those judgments require an analysis and uncertainty estimates, which are not reported in the registry record.

The endpoint is a measure of bladder pain sensitivity, not a direct measure of future chronic pelvic pain incidence. Although the study rationale concerns chronic pelvic pain risk and the secondary outcomes include quantitative sensory testing parameters regarding pelvic hyperalgesia and differences in EEG-recorded cortical activity, those measures do not change what the primary endpoint represents. The registry record does not report primary endpoint means, standard deviations, changes, confidence intervals, or statistical test results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be interpreted from the registry record are limited. It identifies the primary measure as a continuous score summarized by a mean and standard deviation, and gives three measurement occasions: baseline, 6 month, and 12 month visits. It does not report the model, test, contrast, adjustment variables, or analysis population used for the primary result. The explanations below describe general statistical concepts, not methods confirmed to have been used in this trial.

What does a mean describe?

General: A mean is an average of the observed values in a group. For a pain score, it can summarize the group's average recorded rating at a visit or the average change across visits, depending on the analysis. A mean is useful for describing the center of a distribution, but it can conceal differences among participants. Two groups can have the same mean while having different amounts or patterns of variability. The registry specifies mean and standard deviation as the outcome summary, but the actual means and standard deviations are not reported in the registry record.

What does a standard deviation describe?

General: A standard deviation describes how spread out observations are around their mean. It is not the same as the uncertainty in an estimated mean. Uncertainty in a group mean depends on the amount of information contributing to the estimate and the variability of the measurements. For comparing groups, a confidence interval for a difference or change can communicate the estimate's precision. The registry record does not report such intervals for the primary outcome.

Why does repeated measurement matter?

General: Measurements from the same participant are usually related. A participant's baseline score and later scores are not independent observations in the way scores from unrelated participants might be. An analysis of repeated measurements should account for this within-participant relationship, or should define a change score that makes the comparison clear. Methods that ignore correlation can misstate uncertainty. The registry gives the visit schedule but does not report how within-participant correlation was handled.

Comparing change from baseline can address whether average scores moved over time, while comparing groups' changes can address whether the pattern differed by assigned regimen. These are different questions. A time-related change within a group does not, on its own, establish a difference attributable to an intervention; other factors over time could also contribute. A between-group contrast is generally needed to evaluate whether the groups followed different patterns, with the design and analysis assumptions taken into account. The precise primary contrast is not reported in the registry record.

What does randomization contribute?

General: Random assignment is intended to make assigned groups comparable with respect to measured and unmeasured characteristics on average. It supports causal interpretation when the allocation process is maintained, outcome ascertainment and analysis are appropriate, and missing data or departures from assignment do not undermine the comparison. Randomization does not ensure exact balance in a particular trial. The registry labels the study randomized, but the sequence-generation method, concealment procedure, adherence, and analysis according to assigned group are not reported in the registry record.

How should uncertainty be read?

General: A confidence interval communicates a range of effect estimates compatible with the observed data under the statistical model. Its width conveys precision; its position relative to a relevant null value helps assess compatibility with no difference. A p-value is a measure derived under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, nor a measure of the clinical importance of a result. The registry record does not report primary-outcome confidence intervals or p-values, so these interpretations cannot be applied to a primary estimate.

What is over-dispersion, and does it apply?

General: Over-dispersion describes greater variability in data than a statistical model expects. It is especially relevant to some count outcomes, where assuming too little variation can make uncertainty look smaller than it is. The primary endpoint in this record is a continuous pain score, not a count outcome. No distributional diagnostic or model is reported, so there is no basis to claim that over-dispersion was assessed or affected the primary analysis.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. General: Such calculations illustrate the number of participants per arm for a chosen power under specified assumptions. They are planning quantities, not estimates of the probability that this completed trial detected an effect. They should not be described as observed power. The numerical planning outputs and the trial's own sample-size justification are not reported in the registry record. The record also does not state whether its planning illustration reflects the actual design, analysis, missingness, or allocation across the described groups.

The registry lists 9 analyses across 3 outcome measures, but does not describe their methods. It is therefore not possible to determine whether the analyses used a model for repeated measures, compared changes from baseline, adjusted for other variables, or handled multiple comparisons using a particular procedure. Those methods should not be inferred from the endpoint description or from the study's randomized designation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and 9 analyses. Multiple analyses can arise from assessing different outcomes, groups, time points, or contrasts. General: When many statistical hypotheses are tested, the chance of obtaining at least one apparently unusual result by chance can increase. A prespecified hierarchy, a clearly designated primary comparison, or an appropriate multiplicity procedure can help make interpretation more reliable. The registry record does not report whether any such approach was planned or used. It also does not identify the nine analyses or state which result, if any, was designated as the primary inferential comparison.

For the primary endpoint, measurements are scheduled at baseline, 6 month, and 12 month visits. The registry notes that some participant data were missing because of task error or attrition. It does not report the number of missing scores at each visit, reasons by group, whether missingness differed across assigned groups, or the method used to address missing data. These omissions prevent assessment of how much information contributed to each estimate and whether the observed participants may differ from those with missing measurements.

General: Complete-case analysis uses only participants with the required observed measurements; other approaches may use partial records or model missing values under explicit assumptions. Each approach has conditions under which its estimates are interpretable. A missing-data method cannot be assessed without knowing the analysis used and its assumptions. No imputation, sensitivity analysis, or missingness assumption is reported in the registry record.

The registry record also does not define the analysis populations, such as whether participants were analyzed according to randomized assignment or according to treatment received. It does not describe exclusions after randomization or how adherence was handled. These details matter when reading a treatment comparison, particularly alongside attrition and task errors. There is not enough information to judge the consequences of missing data, multiplicity, or analysis-set choices for the primary result.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent non-serious adverse event terms

The serious adverse event entries report zero affected participants in each of the four intervention groups. The corresponding numbers listed at risk are 5 for D+COS-no OC, 4 for D+COS-cyclic Microgestin 1/20, 8 for D+COS-continuous Microgestin 1/20, and 6 for PBS-continuous Microgestin 1/20. The registry lists no deaths in these groups. These entries describe the recorded safety counts; they do not establish that no serious events occurred outside the reported groups or observation period.

For other adverse events, the registry lists 0 at risk and 0 affected in D+COS-no OC. It lists 4 at risk and 4 affected in D+COS-cyclic Microgestin 1/20, 8 at risk and 8 affected in D+COS-continuous Microgestin 1/20, and 6 at risk and 6 affected in PBS-continuous Microgestin 1/20. These are participant counts in the registry's adverse-event fields, not measures of event severity or duration. The record does not give event descriptions, timing, recurrence, or attribution to treatment.

The counts at risk for safety outcomes are not the same as the overall enrollment and should not be read as the number enrolled in each study arm. The registry record does not explain how those safety denominators were defined or provide additional detail about ascertainment and follow-up. Small reported safety counts cannot by themselves establish the presence or absence of a safety difference between regimens.

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

The study addresses a question about menstrual pain, cross-organ sensitization, and bladder pain sensitivity, with oral-contraceptive regimens described for some groups. Its primary endpoint is a bladder pain rating during a filling test, recorded at first urge and assessed across baseline, 6 month, and 12 month visits. The endpoint is relevant to the stated focus on bladder pain sensitivity, but it is not itself a direct measure of future chronic pelvic pain risk.

The registry record does not report the primary outcome estimates or their uncertainty. It therefore cannot establish whether bladder pain sensitivity changed over time, whether a change differed between groups, or how precisely any such comparison was estimated. The stated enrollment, randomized design, and completed status do not substitute for those results. Nor can the study rationale—that oral contraceptives might reduce sensitization and chronic-pain risk—be treated as evidence that this occurred.

The record describes secondary outcomes concerning quantitative sensory testing parameters regarding pelvic hyperalgesia and differences in EEG-recorded cortical activity. It does not provide their results or the analyses used. It also does not report the exact group contrasts, missing-data methods, analysis populations, or multiplicity approach. Those gaps limit both interpretation of the primary endpoint and comparison among outcomes.

General: A statistically detectable difference and a clinically important difference are not identical concepts. Statistical uncertainty concerns how compatible the data are with different effect values under an analysis; clinical importance concerns whether the size and nature of an effect matter in context. Without estimates, uncertainty intervals, and a clearly specified contrast, neither question can be answered for this primary endpoint from the registry record.

The safety entries report no serious adverse events among the listed at-risk participants in the intervention groups, alongside other adverse-event counts. The record does not provide enough event detail to characterize timing, type, or treatment relationship. These limited entries should be read as registry-reported counts, not as a comprehensive assessment of comparative safety. Overall, the record documents the question, design labels, measurement schedule, and selected safety counts, but it does not report the result needed to judge the primary treatment comparison.

13. Why This Trial Matters Statistically

This trial is statistically notable for linking a mechanistic hypothesis to a repeated continuous outcome. The proposed pathway involves dysmenorrhea and cross-organ sensitization, while the primary endpoint records bladder pain sensitivity through ratings at first urge during a bladder filling test. The combination makes clear why definitions and contrasts matter: a change in a bladder pain score is not automatically equivalent to a change in chronic pelvic pain risk or to confirmation of the proposed mechanism.

The randomized, parallel-design label indicates an intended structure for comparing assigned groups, and the repeated visits provide an opportunity to describe change over time. General: Repeated observations can improve understanding of trajectories, but they also require methods that account for correlation within participants. Interpretation additionally depends on the actual treatment contrast, the participants contributing to each visit, and the uncertainty around estimates. The registry record does not report those analysis details or the primary outcome results.

The record also illustrates how an outcome may be described more fully than its analysis. It specifies the score range and visit schedule, notes data missing because of task error or attrition, and lists multiple outcomes and analyses. Yet it does not give the group estimates, uncertainty measures, missing-data handling, or multiplicity procedure needed to evaluate the results. The sample-size assumptions are described as planning illustrations based on the observed effect, not as evidence of observed power; the numerical planning outputs are not reported in the registry record.

For clinical researchers and biostatisticians, the central statistical lesson is to separate rationale, measurement, design, and results. The hypothesis explains why the study was undertaken; the endpoint defines what was measured; randomization describes an intended allocation method; and estimates with uncertainty are needed to interpret what the data show. In this record, the first three are partly described, while the primary result is not reported. That distinction prevents a plausible study hypothesis from being mistaken for an observed finding.

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 registry record does not include numerical primary outcome results. No group means, standard deviations, changes from baseline, between-group estimates, confidence intervals, or test results are reported. Consequently, the direction, size, and precision of any primary outcome difference cannot be evaluated. The record identifies the endpoint and its visits but does not specify the principal comparison among the described groups.

Some participant data were missing because of task error or attrition, but the record does not give missing-data counts by group or visit, explain how missing values were handled, or report sensitivity analyses. The analysis populations and treatment-adherence handling are also not reported. These omissions make it difficult to assess how much usable outcome information was available and whether the analysis represented the randomized groups.

The registry lists 3 outcome measures and 9 analyses, without mapping them to specific contrasts or explaining whether the primary analysis was selected in advance. Its multiplicity approach and statistical model are not reported. The single-masked designation is present, but the masked party and procedures are not described. Randomization is stated without details about sequence generation or allocation concealment.

The Pain Discovery Aim description is truncated, and complete eligibility criteria are not reported in the registry record. Safety entries provide participant counts but do not describe event types, timing, or attribution. The total enrollment of 353 cannot be assumed to represent the number with data for any specific outcome or visit. These limitations are specific to what this registry record documents; they leave the primary treatment comparison and its reliability unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Chronic Pain Risk Associated With Menstrual Period Pain — NCT02214550.
• Registry record last updated 2023-06-18; status last verified 2023-05.
• Results first posted 2023-06-18.
• 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.

18. Record Summary

The record describes a completed, randomized, single-masked, parallel Phase 4 study with enrollment of 353. Its primary outcome is change in bladder pain sensitivity, measured by a Visual Analog Scale score during a bladder filling test at baseline, 6 month, and 12 month visits. The study rationale concerns dysmenorrhea, cross-organ sensitization, chronic pelvic pain risk, and oral-contraceptive regimens.

Intervention descriptions include no oral-contraceptive intervention, cyclic Microgestin 1/20, and continuous Microgestin 1/20, including a painful bladder syndrome group receiving continuous treatment. The registry lists secondary outcomes on quantitative sensory testing and EEG-recorded cortical activity. It notes missing participant data due to task error or attrition and lists safety counts for four groups.

Primary outcome estimates, uncertainty measures, analysis methods, missing-data procedures, and the multiplicity approach are not reported in the registry record. The available record therefore describes the study question and selected design features but does not establish the primary outcome findings.