Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis (NCT04002141), a randomized phase 2 study. The primary outcome is Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole.

2. Clinical Question

The trial's broader question was whether ovarian hyperstimulation was associated with changes in endometriosis-related symptoms, and whether letrozole use during stimulation affected symptoms and reproductive outcomes. The primary endpoint addresses the treatment comparison in pain scores, rather than every part of that broader question. The registry describes the pain measure as a 0-10 visual acuity scale, with 0 indicating no pain and 10 the worst imaginable pain. Scores were recorded at baseline ultrasound on day 2 of the menstrual cycle and at day 12, described as the average day of the trigger shot.

A no-endometriosis control group was also included to evaluate symptom patterns, but it was not part of the primary letrozole-versus-placebo comparison. The primary result therefore speaks to the observed mean change among the analyzed endometriosis groups; it does not by itself answer whether ovarian stimulation changes symptoms relative to no stimulation or establish effects on egg, embryo, or pregnancy outcomes.

3. Trial Design

The registry describes a completed, randomized, parallel-group phase 2 trial with enrollment of 60. The study concerned endometriosis and ovarian hyperstimulation. The start date was 2019-09-17, and primary completion was 2023-10-01. The sponsor was the University of California, San Francisco.

Participants with endometriosis were assigned to a letrozole or placebo group. The registry also lists a no-endometriosis control group, whose participants completed symptom surveys but were not described as receiving either study tablet. The letrozole arm description specifies 5mg daily throughout ovarian stimulation and for 2 weeks following retrieval; the placebo arm description specifies one tablet daily over that period. The arm descriptions state that participants were blinded to their randomization. The registry's masking classification is single, while its brief summary calls the study double blinded. These descriptions differ, and the registry record does not clarify the discrepancy.

The main pain outcome was based on paired survey time points: baseline ultrasound and day 12, described as the average day of the trigger shot. The primary endpoint analysis included participants who completed stimulation and filled out both baseline and trigger pain surveys. The posted primary comparison has 17.0 participants in the letrozole group and 16.0 in the placebo group. This outcome-specific analysis population is smaller than the total enrollment, and the reason for each exclusion or difference is not reported in the registry record.

The registry lists secondary outcomes concerning pain patterns, egg quantity and maturity, follicular fluid, embryo grade, and pregnancy outcomes. It does not report the trial's original sample-size justification, detailed randomization procedure, allocation ratio, or full statistical analysis plan. These design details should not be inferred from the posted 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: only includes those who completed stimulation and filled out survey for baseline and trigger pain

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 Average Delta in Endometriosis Pain Score Pre and Post Stimulation With and Without Use Of Letrozole, measured over Baseline ultrasound (day 2 of menstrual cycle) and day 12 (average day of trigger shot)..

The primary endpoint is the average delta in endometriosis pain score from before stimulation to the trigger time point, comparing participants with endometriosis who received placebo with those who received letrozole. Pain was measured on a 0-10 visual acuity scale. The specified time points were baseline ultrasound on day 2 of the menstrual cycle and day 12, described as the average day of the trigger shot.

A change score is intended to capture how the measured score differs between the two time points, rather than comparing only the score at one time. The registry reports the mean change and standard deviation for each group, along with a mean difference between groups. The registry does not explicitly define the subtraction order used to form the delta. Therefore, the negative group means should be read as the posted change values, without assuming a direction of symptom improvement from the sign alone.

This endpoint was chosen to assess pain across ovarian stimulation in patients with endometriosis and to compare the letrozole and placebo groups. It does not measure every symptom, and it is not itself a measure of egg quality, embryo development, or pregnancy. The analysis also applies only to participants who completed stimulation and both required surveys, as stated in the registry description.

7. Results Posted in the Registry

• Endometriosis Letrozole: mean -2.50 versus -2.70 on control; difference 0.20 (95% CI -2.46 to 2.86), standardized effect d = 0.05; z-test p = 0.883.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Average Delta in Endometriosis Pain Score Pre and Post Stimulation of Patients Receiving Placebo Compared to No Endometriosis

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • No Endometriosis Control: mean -0.60 versus -2.70 on control; difference 2.10 (95% CI -0.67 to 4.87), standardized effect d = 0.52; z-test p = 0.138.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between No Endometriosis Control and the control. The interval gives the range of effects that remain compatible with the data.

Comparative Trends in Endometriosis Pain Score Pre and Post Stimulation of Patients With Endometriosis Receiving Either Placebo or Letrozole and Patients Without Endometriosis

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Endometriosis Letrozole: mean -0.70 versus -1.00 on control; difference 0.30 (95% CI -1.32 to 1.92), standardized effect d = 0.14; z-test p = 0.717.
  • No Endometriosis Control: mean -0.60 versus -1.00 on control; difference 0.40 (95% CI -1.47 to 2.27), standardized effect d = 0.15; z-test p = 0.676.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Endometriosis Letrozole and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between No Endometriosis Control and the control. The interval gives the range of effects that remain compatible with the data.

Does Letrozole Impact Egg Quantity in Endometriosis Patients

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Endometriosis Letrozole: mean 0.84 versus 0.88 on control; difference -0.04 (95% CI -0.34 to 0.26), standardized effect d = -0.09; z-test p = 0.795.
  • No Endometriosis Control: mean 0.73 versus 0.88 on control; difference -0.15 (95% CI -0.40 to 0.10), standardized effect d = -0.42; z-test p = 0.238.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Endometriosis Letrozole and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between No Endometriosis Control and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the scope beyond the primary pain comparison. They include pain-score comparisons involving the no-endometriosis control group, longer-term pain trends, egg quantity, follicular fluid, pregnancy outcomes, egg maturity, and embryo grade. This variety reflects several distinct scientific questions, not a single extension of the primary endpoint.

The posted secondary summaries do not form a consistent basis for a strong overall claim about treatment effects. They are based on different outcomes, time frames, and analysis populations, and the registry lists no reported analyses for these secondary records. Some comparisons have estimates near zero and others farther from zero, but uncertainty remains and no adjustment for the number of outcomes or comparisons is reported. The summaries should therefore be treated as exploratory or descriptive rather than as a confirmatory set of tests.

The secondary findings do not overturn the primary interpretation. The primary result is an imprecise comparison of mean pain change between the endometriosis letrozole and placebo groups. Secondary outcomes can add context about symptoms and reproductive measures, but they do not establish a more precise answer to that primary question. Nor can a result from one outcome be substituted for another: pain scores, egg measures, embryo grading, and pregnancy outcomes have different meanings and scales.

Unadjusted secondary results carry less weight because testing many outcomes increases the chance that some patterns will appear even when effects are absent. The registry does not report a prespecified hierarchy, multiplicity correction, or detailed analysis plan for interpreting the family of outcomes. In addition, different sample sizes across outcomes indicate that the data contributing to one measure may not be the same as those contributing to another. The registry record does not explain those differences or describe missing-data methods.

Accordingly, the secondary results are best viewed as signals for further evaluation rather than definitive evidence. The record supports describing their scope and uncertainty, but not selecting an isolated favorable or unfavorable result as proof of a broad treatment effect.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Average Delta in Endometriosis Pain Score Pre and Post Stimulation of Patients Receiving Placebo Compared to No Endometriosis
• Comparative Trends in Endometriosis Pain Score Pre and Post Stimulation of Patients With Endometriosis Receiving Either Placebo or Letrozole and Patients Without Endometriosis
• Does Letrozole Impact Egg Quantity in Endometriosis Patients
• Follicular Fluid
• Pregnancy Outcomes
• Egg Maturity
• Embryo Grade

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports continuous outcomes as means with standard deviations. A mean describes the average observed value in a group; a standard deviation describes how spread out individual values are around that average. Neither quantity alone describes the precision of the comparison. Precision also depends on the number of participants contributing data, and the interval around the estimated difference communicates uncertainty about the group contrast.

The primary endpoint is a change score measured on a 0-10 pain scale. The analysis compares the average change in the letrozole group with the average change in the placebo group. The posted group means are -2.5 and -2.7, and the estimated mean difference is 0.2. The registry does not define the delta subtraction order, so the signs should not be translated into a direction of pain improvement without that definition. A mean difference is expressed in the outcome's scale units; it is not a ratio or a percentage.

The standard deviations for the primary groups are both 3.9. A relatively large spread means individual observed changes vary around the group average. General statistical context: when measurements are variable and group sizes are limited, an estimated difference can remain imprecise even if the group means are close. A narrow mean difference estimate does not follow simply from a small observed difference; the uncertainty interval and sample sizes matter too.

The comparison reports an unadjusted p-value of 0.883. General statistical context: a p-value measures how incompatible the observed data are with a specified null model, under the assumptions of the test. It is not the probability that the null hypothesis is true, nor a measure of the size or clinical importance of a difference. Because the value is unadjusted, it does not account for testing multiple outcomes or contrasts. The registry does not report a multiplicity-adjusted primary analysis or a detailed statistical plan.

The comparison also reports a confidence interval from -2.462 to 2.862. General statistical context: a confidence interval is a range of estimates compatible with the observed data under a specified method and its assumptions. It helps show which effect sizes remain plausible, not just whether an estimate is on one side of zero. The confidence level and interval-construction method are not reported in the registry record, so they should not be inferred from the endpoints alone.

The posted secondary comparisons are also unadjusted mean comparisons. Their estimates and intervals are useful as summaries, but multiple outcomes and pairwise contrasts create opportunities for chance findings. Without a stated hierarchy of outcomes, prespecified contrasts, or adjustment procedure, isolated p-values from these outcomes carry less evidential weight than a prespecified primary analysis. The registry lists seven posted secondary outcomes and no reported analyses for the secondary outcome records.

General statistical context: over-dispersion is most directly relevant to count outcomes analyzed with models that assume a particular count distribution. If observed count variability exceeds that assumption, standard errors and tests can be misleading unless the model accommodates the extra variation. The primary endpoint is reported as a continuous mean and standard deviation, not as a count; no count-model details are reported. Thus, over-dispersion should not be invoked to explain the primary result.

The analyzed primary sample is defined by completion of stimulation and both pain surveys. This is a complete-observation subset as described in the registry. General statistical context: analyzing only participants with complete measurements can introduce bias if completion is related to treatment assignment or the outcome. Whether that occurred cannot be determined from the registry record. Missing-data handling, imputation, sensitivity analyses, and the analysis population definition beyond the stated completion requirement are not reported.

Finally, the comparison results are posted summaries rather than sponsor-reported analysis outputs: the registry lists no reported primary analysis. The simple unadjusted comparisons should be interpreted accordingly. They do not establish whether any covariates were included, whether the original trial design used a different primary method, or whether interim analyses were conducted; these details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary mean difference is 0.2, with a reported interval from -2.462 to 2.862. Because the interval spans zero, the data are compatible with no difference as well as with differences in either direction under the interval's method. The interval's endpoints are far enough apart that the point estimate alone gives an incomplete account of uncertainty. The confidence level and construction method are not reported in the registry record, so the interval should be read as posted rather than assigned an unstated level.

The groups contributing to this comparison included 17.0 participants assigned to letrozole and 16.0 assigned to placebo. Both group standard deviations were 3.9. These summaries show why the estimate should not be read as precise merely because the means are numerically close: the observed variation is substantial relative to the estimated difference, and the comparison has a limited number of observations.

Precision is distinct from statistical significance and from clinical importance. An interval that includes zero does not prove the absence of a difference, while a point estimate near zero does not establish equivalence. The registry does not report a threshold for a clinically important pain-score difference, so the clinical importance of the interval's values cannot be assessed from this record alone.

The confidence intervals for the secondary comparisons are also broad in relation to their estimates, and the registry does not report multiplicity adjustment. Taken together, the posted results offer limited precision for distinguishing small effects from no difference. More precise conclusions would require a larger and appropriately planned analysis, but the original design assumptions and planned precision targets are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial's original sample-size design. For these continuous outcomes, the figures are participants per arm, not total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They show the planning size for detecting the stated fraction of the observed effect under those assumptions.

The 80% power column indicates the number of participants per arm the illustration estimates would be needed to have an 80% chance of detecting the specified effect, if that effect and the assumptions held. The 90% power column uses a higher target probability of detection and therefore generally requires more participants. These are planning quantities, not descriptions of what happened in the trial.

Rows for 100%, 75%, and 50% of the observed effect ask how sample-size needs change if the target effect is the full observed estimate or a smaller fraction of it. Smaller effects are harder to distinguish from random variation, so they require more participants under the same assumptions. In particular, planning directly from an observed effect can be unstable when the estimate comes from a small sample; a smaller target effect is often a more conservative planning scenario.

This is not observed power. The registry's original sample-size justification and design assumptions are not reported, and the illustration does not establish whether the completed study was adequately designed for its primary question. The figures should be read as hypothetical planning aids tied to the observed summaries, not as evidence that the trial had a particular probability of finding an effect.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.200; pooled standard deviation σ = 3.900.
2. n = 2 × (1.96 + 0.842)² × 3.900² / 0.200² = 5,969.1, rounded up to 5,970 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.2                      # observed difference in means
sigma <- 3.9                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4002141)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 5,970 (80% power), 7,991 (90% power)
 75% of observed effect: n per arm = 10,612 (80% power), 14,207 (90% power)
 50% of observed effect: n per arm = 23,877 (80% power), 31,964 (90% power)
power.t.test: 5970 
Simulated power at n = 5,970 per arm: 0.796 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and eight outcome measures in total, with seven secondary outcomes posted. Those outcomes cover several symptom and reproductive domains, and the registry also reports more than one contrast for some outcomes. Repeated testing can raise the chance of obtaining a small unadjusted p-value by chance. The registry record does not report a multiplicity strategy, such as an adjustment procedure, a testing hierarchy, or rules for interpreting secondary outcomes.

The primary comparison reports an unadjusted p-value. The registry does not report whether the original protocol specified a different primary analysis, whether other analyses were planned, or whether any interim analyses were conducted. It also lists no sponsor-reported analyses for the primary or secondary outcome records. Consequently, the posted summary comparisons should not be assumed to reproduce a prespecified sponsor analysis or to represent a complete statistical analysis plan.

The primary analysis population is described as participants who completed stimulation and filled out surveys at baseline and trigger. The reasons for missing surveys, incomplete stimulation, or exclusion from a particular endpoint are not reported in the registry record. The number of participants contributing to some secondary measures differs across outcomes, but the reasons for those changes are not described. Missing-data handling, imputation, sensitivity analyses, and comparisons of participants with and without complete data are not reported.

The registry record does not state whether the primary analysis was intention-to-treat, per-protocol, or another defined approach. It also does not describe adjustment for baseline values or other covariates. These omissions matter because they limit assessment of how participants were included and how uncertainty was handled. They do not establish that a particular analysis method was or was not used outside the posted record; they mean that the method is not reported in the registry record.

Without a reported analysis plan and missing-data account, the safest reading is to treat the available comparisons as posted summaries with unadjusted inference, and to give the primary endpoint priority over the more numerous secondary results.

15. 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 serious adverse event terms

Serious events with the highest arm-level rate: heavy vaginal bleeding (5.0%).

The registry reports serious adverse event counts for groups with 20 participants at risk each. One serious event affecting a participant is listed in the endometriosis letrozole group; none are listed in the endometriosis placebo group or the no-endometriosis control group. Deaths are reported as zero in all three groups. Other adverse events affecting participants are reported as zero in each group.

The registry also lists Heavy Vaginal Bleeding as a serious-event term at 5.0%. It does not identify the group for that term in the posted summary, so it should not be assigned to a particular arm from these figures. These counts describe events recorded in the registry; they are not a formal comparison of safety between groups. With the reported group sizes and no statistical analysis of adverse events, the counts do not establish whether event rates differ or whether an event was caused by an intervention.

Zero recorded deaths or other adverse events in a group should be read as zero reported events in that group, not as proof that no risk exists. The registry does not report further detail about event timing, severity beyond the serious classification, exposure duration, or the process used to assess relatedness beyond the listed affected counts.

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

The primary result describes an observed comparison of mean pain-score change between participants with endometriosis assigned to letrozole and those assigned to placebo who completed stimulation and the required surveys. The estimated difference was 0.2, and the interval extended from -2.462 to 2.862. This supports a cautious conclusion: the posted data do not precisely determine the direction or size of the difference for this analyzed group.

The result does not establish that letrozole and placebo have equivalent effects. Equivalence requires a prespecified margin and an appropriate analysis, neither of which is reported in the registry record. Nor does the result establish that there is no effect. The interval includes zero but also allows nonzero differences, and the registry does not state what range would be clinically important on the pain scale.

The result also does not answer all of the trial's broader questions. The primary endpoint concerns a change in pain score from baseline to the trigger time point. It is not a direct answer about longer-term symptoms, egg quantity, egg maturity, embryo grade, or pregnancy outcomes. Those topics appear among the secondary outcomes, but the registry does not report sponsor analyses or a multiplicity plan for them.

The findings should not be generalized beyond the population and outcome definition without additional evidence. The primary comparison is restricted to participants with endometriosis who completed stimulation and both surveys. The registry does not report enough information to assess the effects of missing observations or the representativeness of that subset.

These are statistical interpretations of posted summaries, not medical advice. They do not recommend a treatment or establish that a treatment works or does not work. They describe the estimate, its uncertainty, and the limits of what the registry record permits readers to conclude.

17. Why This Trial Matters Statistically

This trial illustrates why an estimated effect and its precision need to be read together. The primary mean difference is close to zero, but the interval is broad enough to include a range of differences. A single point estimate can make a comparison look more settled than it is; the interval and the size of the analyzed groups show the remaining uncertainty.

It also illustrates the distinction between a trial's total enrollment and the number contributing to a particular endpoint. Although enrollment was 60, the primary pain comparison includes 17.0 participants assigned to letrozole and 16.0 assigned to placebo. The registry states that the primary population required completion of stimulation and both surveys. Endpoint-specific participation is therefore essential context when reading any trial result.

The registry's wider set of outcomes provides another statistical lesson: multiple outcomes can illuminate different aspects of a research question, but unadjusted tests across many outcomes are not equivalent to a single confirmatory analysis. A clear analysis plan and transparent reporting of missing data help readers distinguish primary evidence from exploratory patterns. Those details are not reported in the registry record.

Finally, the record contains inconsistent masking descriptions: the classification is single, while the brief summary says double blinded. Flagging such inconsistencies is part of careful evidence reading. Overall, the trial is informative as a small randomized comparison with several related outcomes, while its posted results leave substantial uncertainty about the primary treatment contrast and about the broader questions.

18. 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 comparison is based on a limited number of participants who completed stimulation and both required surveys. The registry does not explain why other enrolled participants did not contribute to this endpoint, or whether missingness was related to assignment or pain scores. This limits assessment of selection and missing-data bias.

The registry's masking descriptions are inconsistent: the trial is classified as single-masked, while the brief summary describes it as double blinded. The record does not clarify who was masked beyond the arm descriptions stating that participants were blinded to randomization. The randomization procedure and allocation ratio are also not reported.

The primary endpoint uses a change score, but the registry does not explicitly state the order of subtraction used to define the delta. That omission limits interpretation of the direction represented by negative values. The confidence level and construction method for the reported intervals are also not stated in the registry record.

The record lists no sponsor-reported analyses, and it does not report the original sample-size justification, full statistical analysis plan, multiplicity handling, interim analyses, or covariate-adjustment strategy. Secondary measures have differing participant counts, with no reported explanation for those differences. The secondary outcome summaries are therefore difficult to evaluate as a coherent confirmatory analysis.

Finally, the primary endpoint covers pain change only through the trigger time point. Other outcomes address longer time frames and reproductive measures, but the posted information does not support treating them as interchangeable with the primary result. These limitations do not invalidate the reported summaries; they define how cautiously they can be interpreted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Assessment and Prevention of Pain During Ovarian Stimulation in Patients With Endometriosis — NCT04002141.
• Registry record last updated 2026-01-28; status last verified 2026-01.
• Results first posted 2026-01-28.
• 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.

22. Record Summary

The registry describes a completed randomized parallel-group phase 2 trial with enrollment of 60, sponsored by the University of California, San Francisco. It compared letrozole with placebo among participants with endometriosis and included a no-endometriosis control group. The primary question concerned mean change in pain score from baseline ultrasound to the trigger time point.

The primary comparison included 17.0 letrozole participants and 16.0 placebo participants. Its estimated mean difference was 0.2, with a reported interval from -2.462 to 2.862 and an unadjusted p-value of 0.883. The estimate is uncertain and does not establish either equivalence or a treatment effect. The registry also posts secondary outcomes and adverse-event counts, but lists no sponsor-reported analyses. Important details about the original statistical plan, missing data, and multiplicity are not reported in the registry record.