Combined Letrozole and Clomid in Women With Infertility and PCOS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combined Letrozole and Clomid in Women With Infertility and PCOS (NCT02802865), a randomized phase 4 study. The primary outcome is Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level.

2. Clinical Question

3. Trial Design

The registry describes NCT02802865 as a completed, randomized, parallel-group phase 4 trial. It lists no masking. The planned enrollment was 70 participants, with 35 assigned to letrozole alone and 35 to letrozole plus clomiphene for the primary outcome. Random allocation can help balance participant characteristics across groups on average, but the registry record does not report the method used to generate or conceal the allocation sequence. It also does not report a blinding procedure; masking is listed as none.

The treatments were given during cycle days 3–7. Both groups received letrozole 2.5 mg orally for 5 days; the combination group also received Clomid 50 mg orally for 5 days over those cycle days. The primary outcome was assessed 7 days following an LH surge or at cycle day 21 if no LH surge was detected. The record does not provide further detail about treatment adherence or how cycles without a detected LH surge were handled beyond this timing description.

The registry lists secondary outcomes concerning follicle development, follicle size, endometrial thickness, conception, clinical pregnancy, multiple gestation, live birth, and pregnancy loss. The posted analyses include endometrial thickness, conception, and clinical pregnancy among those outcomes. A fuller description of the analysis populations, follow-up completeness, and prespecified statistical plan is not reported in the registry record. The dates of study start and primary completion are 2016-08 and 2018-05, and the status is completed.

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 Number of Participants Achieving Ovulation Measured by Mid-luteal Progesterone Level, measured over 7 days following LH surge or at cycle day 21 if no LH surge was detected.

The primary endpoint is the number of participants achieving ovulation, measured using the mid-luteal progesterone level. The registry defines ovulation as a progesterone level at least 3 ng/mL and no ovulation as a level below 3 ng/mL. Measurement was scheduled 7 days following an LH surge or at cycle day 21 when no LH surge was detected.

This is a binary participant outcome: each participant is counted according to whether the recorded progesterone result meets the stated threshold. A binary endpoint makes the group comparison about the frequency of participants meeting that definition, rather than the average progesterone concentration or the number of follicles. The registry’s stated measure is a count of participants, and the posted primary results report 15 of 35 in the letrozole group and 27 of 35 in the combination group.

As a general statistical point, a threshold-based outcome can be straightforward to interpret, but it reduces a continuous laboratory measurement to two categories. Results therefore concern the registry’s operational definition of ovulation, not every possible biological feature of ovulation. Further information about the choice or validation of the threshold is not reported in the registry record.

7. Results Posted in the Registry

• Letrozole + Clomiphene: 77.1% (27/35) versus 42.9% (15/35) on control; risk difference 34.3 percentage points (95% CI 12.8 to 55.8), risk ratio 1.80 (1.18–2.75); unadjusted two-proportion z-test p = 0.003.

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.

Endometrial Thickness

• 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:
  • Letrozole + Clomiphene: mean 8.30 versus 6.20 on control; difference 2.10 (95% CI 0.67 to 3.53), standardized effect d = 0.71; z-test p = 0.004.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Letrozole + Clomiphene than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Conception

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Letrozole + Clomiphene: 12.1% (4/33) versus 8.8% (3/34) on control; risk difference 3.3 percentage points (95% CI -11.4 to 18.0), risk ratio 1.37 (0.33–5.67); unadjusted two-proportion z-test p = 0.659.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Letrozole + Clomiphene and the control. The interval gives the range of effects that remain compatible with the data.

Clinical Pregnancy

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Letrozole + Clomiphene: 9.1% (3/33) versus 2.9% (1/34) on control; risk difference 6.1 percentage points (95% CI -5.2 to 17.5), risk ratio 3.09 (0.34–28.23); unadjusted two-proportion z-test p = 0.288.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Letrozole + Clomiphene and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes span intermediate biological measures and pregnancy-related outcomes. The posted results include endometrial thickness, conception, and clinical pregnancy. The registry also lists follicle development, largest follicle size, multiple gestation, live birth, and pregnancy loss as secondary outcomes, but results for those outcomes are not reported in the registry record. The overall pattern is therefore incomplete: some secondary outcomes have posted comparisons, while the record does not provide results for every listed outcome.

The posted endometrial-thickness comparison points toward a higher group mean for the combination regimen. The conception and clinical-pregnancy counts are small, and their recalculated uncertainty intervals include zero. This does not establish that those outcomes are the same between groups; it means the posted data do not precisely distinguish the group contrast. Nor should an intermediate measure or the primary progesterone endpoint be assumed to guarantee a corresponding difference in conception, pregnancy, or birth outcomes.

Secondary outcomes usually carry less weight than a prespecified primary outcome because they are additional questions and may be tested in parallel. As a general statistical point, testing multiple outcomes increases the chance of obtaining apparently notable findings by chance unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. Consequently, nominal p-values for secondary comparisons are best treated as exploratory evidence, not as independent confirmation of the primary result.

The differing denominators also matter when comparing outcomes: the secondary analyses use 34 participants in the letrozole group and 33 in the combination group, whereas the primary analysis uses 35 per group. The reasons for those differences are not reported in the registry record. Without further information about outcome availability and missingness, the results across endpoints should not be assumed to represent exactly the same analysis population.

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

• Number of Developing Follicles
• Size of Largest Developing Follicle
• Endometrial Thickness
• Conception
• Clinical Pregnancy
• Multiple Gestation
• Live Birth
• Pregnancy Loss

9. Statistical Interpretation

10. Statistical Methods Explained

For the primary endpoint, the outcome is binary at the participant level: the recorded progesterone value either meets the registry’s definition of ovulation or does not. The posted counts are 15 of 35 for letrozole and 27 of 35 for letrozole plus clomiphene. A group proportion is the count meeting the endpoint relative to the number assessed in that group. The recalculated comparison expresses the difference between those proportions as a risk difference of 0.343.

What does the risk difference express?

As a general statistical explanation, a risk difference is an absolute contrast between two event proportions. A value above zero in this comparison means the observed proportion was higher in the combination group. It is expressed on the proportion scale, rather than as a ratio. Its confidence interval, 0.128 to 0.558, describes a range of values compatible with the data and the calculation’s assumptions. It does not remove uncertainty or account for design features that are not included in the calculation.

The recalculated risk difference is an unadjusted estimate based on the posted group counts. It does not account for possible differences in baseline characteristics, nor does it incorporate an adjusted model. Whether the trial prespecified or conducted other adjusted analyses is not reported in the registry record. The record does report the sponsor’s own primary comparison separately, using a corrected chi-squared method and reporting a rate ratio.

How does the sponsor’s rate ratio differ?

A rate ratio compares event rates on a relative scale; here the sponsor reports a rate ratio of 1.80, with a 95% confidence interval from 1.18 to 2.75. The recalculated risk difference instead describes an absolute contrast between the observed proportions. These are different measures, so their numerical values cannot be compared as if they were two estimates of the same quantity. The sponsor reports p = 0.007 for the primary analysis, while the unadjusted recalculation has p = 0.003. Different measures and analysis procedures can produce different numerical summaries even when the comparison points in the same direction.

A p-value is a measure of how inconsistent data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor is it a direct measure of the size or importance of an effect. A p-value also does not describe the range of plausible values as directly as a confidence interval. Interpretation should therefore consider the estimate, its uncertainty, the outcome definition, and the design—not a thresholded p-value alone.

What do the secondary analyses add?

Endometrial thickness is a continuous outcome reported as a mean and standard deviation. The posted means are 6.2 mm for letrozole and 8.3 mm for the combination group, with 34 and 33 participants assessed. The recalculated mean difference is 2.1 mm, with a 95% confidence interval from 0.666 to 3.534. A mean difference describes the contrast between group averages; it does not describe the range of individual measurements. The sponsor’s reported test is a two-sided t-test with p = 0.006. As a general explanation, a t-test compares means while accounting for variability and the number of observations under its assumptions.

Conception and clinical pregnancy are binary outcomes. For conception, the posted counts are 3 of 34 and 4 of 33; for clinical pregnancy, they are 1 of 34 and 3 of 33. Their recalculated risk-difference intervals include zero, and the sponsor’s reported p-values are 0.709 and 0.356, respectively. Small event counts make these estimates imprecise. The registry lists other secondary outcome topics, but details of every listed outcome are not reported in the registry record.

For a continuous outcome, variability among individual measurements affects how precisely a group mean is estimated. For a binary outcome, the number of participants and how many meet the endpoint affect the precision of a proportion and its contrast. These general principles help explain why sparse outcomes can have broad uncertainty. They do not establish that any particular analysis assumption was met; distributional checks, model diagnostics, and analysis-plan details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary recalculated risk difference is 0.343, with a 95% confidence interval from 0.128 to 0.558. The interval gives a measure of precision for the absolute group contrast: values across this range are compatible with the observed data under the calculation’s assumptions. Because the interval does not include zero, the recalculation is consistent with a higher observed proportion meeting the ovulation definition in the combination group. This is not a guarantee about the true effect, and the interval does not describe all sources of uncertainty.

The sponsor’s primary rate ratio is 1.80, with a 95% confidence interval from 1.18 to 2.75. This interval is on a relative scale, so it should not be read as an absolute difference. It is also based on the sponsor’s corrected chi-squared analysis, rather than the unadjusted risk-difference calculation. The distinct measures and methods explain why the two intervals have different numerical scales.

For the secondary outcomes, the recalculated mean difference for endometrial thickness is 2.1 mm, with an interval from 0.666 to 3.534. The conception risk difference is 0.033, with an interval from -0.114 to 0.180; the clinical-pregnancy risk difference is 0.061, with an interval from -0.052 to 0.175. The latter two intervals include zero and extend across values in both directions. Their width reflects limited precision in these comparatively sparse event data.

In general, a confidence interval is most useful when read alongside the estimated contrast and the outcome scale. A wide interval indicates that the data are compatible with a broader range of contrasts; it does not mean that every value in the interval is equally likely. Confidence intervals also do not correct for multiple outcome testing or missing data unless the analysis explicitly handles those issues. The registry record does not report such adjustments.

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 participants per arm for the binary outcomes and for endometrial thickness. They are illustrations based on the observed effect, not the original trial’s own design assumptions. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculation uses the stated fraction of the observed effect as the effect to detect. The trial’s own sample-size justification and original design assumptions are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under the listed assumptions, if that effect were present and the assumptions held. The 90% power column gives the corresponding planning figure for a 90% chance. Power is a design-stage probability tied to a particular assumed effect, test, and set of assumptions; it does not express the probability that a result is true.

For the primary outcome, the planning illustration using 100% of the observed effect lists 31 participants per arm for 80% power and 41 per arm for 90% power. Planning for 75% of the observed effect lists 58 and 77 per arm; planning for 50% lists 133 and 177 per arm. The smaller assumed effects require more participants because smaller contrasts are harder to distinguish from sampling variation. The same pattern applies to the secondary-outcome illustrations, whose figures differ according to the observed outcome and effect scale.

These values are not observed power. They are not a retrospective measure of whether the completed trial was adequately powered, and they do not replace a trial-specific design justification. The registry record does not report the original sample-size assumptions.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.429; treatment proportion p₁ = 0.771; average p̄ = 0.600.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6928 = 1.3579.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6490 = 0.5462.
4. n = (1.3579 + 0.5462)² / (0.3429)² = 30.8, rounded up to 31 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
p0 <- 0.428571428571429                          # control proportion
p1 <- 0.771428571428571                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2802865)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 31 (80% power), 41 (90% power)
 75% of observed effect: n per arm = 58 (80% power), 77 (90% power)
 50% of observed effect: n per arm = 133 (80% power), 177 (90% power)
power.prop.test: 30.8 
Simulated power at n = 31 per arm: 0.817 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis compares the letrozole and combination groups using a corrected chi-squared method. It gives a rate ratio of 1.80, a 95% confidence interval from 1.18 to 2.75, and p = 0.007. The unadjusted recalculation from the posted counts gives a risk difference of 0.343, a 95% confidence interval from 0.128 to 0.558, and p = 0.003. The sponsor’s result is reported on a relative scale; the recalculation is on an absolute scale. Their numerical estimates and p-values are therefore not direct substitutes for each other.

The recalculation is a simple unadjusted analysis of the posted summary counts. It is useful as a transparent comparison, but it does not supersede the sponsor’s own analysis. The two analyses point in the same direction: the combination group had more participants meeting the primary progesterone definition. The registry record does not report enough detail to establish whether the sponsor’s analysis included additional adjustments beyond the named method.

For the primary outcome, the registry record does not indicate a discrepancy between the posted results and the recalculation. The sponsor’s reported analysis remains the appropriate reference for the trial’s own analysis, while the recalculation provides a separate view using a different effect measure and unadjusted method. Neither summary on its own resolves concerns about uncertainty, outcome scope, missing data, or generalizability.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome and several secondary outcomes. The primary outcome is ovulation measured by mid-luteal progesterone. Secondary topics include follicle measures, endometrial thickness, conception, clinical pregnancy, multiple gestation, live birth, and pregnancy loss. The posted record includes eight secondary outcome measures, but the registry entries do not provide complete results for every listed topic. The order and hierarchy of the secondary hypotheses are not reported in the registry record.

Multiplicity arises when several outcomes or comparisons are tested. As a general statistical explanation, each additional test creates another opportunity for a result to appear notable by chance, even when no corresponding effect exists. A prespecified adjustment or a clear hierarchy can help control how such findings are interpreted. The registry record does not report whether any multiplicity correction was planned or applied. The secondary p-values should therefore be read as individual, unadjusted findings rather than as evidence adjusted for the full set of outcomes.

There are also differences in the group counts across outcomes. The primary analysis uses 35 participants per group; the posted secondary comparisons use 34 in the letrozole group and 33 in the combination group. This indicates that the reported denominators differ by outcome, but the reasons are not reported in the registry record. It is not possible from these registry entries alone to distinguish missing measurements, exclusions, or other causes. A missing-data plan, imputation method, and sensitivity analyses are not reported.

The analysis population is also not described in sufficient detail to determine whether the primary analysis followed an intention-to-treat approach or another population definition. The record does not report how protocol deviations, incomplete treatment, or unavailable progesterone measurements were handled. These details affect how closely an estimate represents the randomized comparison and how robust it may be to missing outcomes.

These limitations do not invalidate the posted results, but they constrain interpretation. In particular, the primary result can be described as the observed comparison using the recorded denominators, while the treatment of missing data and the inferential consequences of multiple testing remain uncertain.

16. 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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (3.1%), gallstones (3.0%).

The registry reports serious adverse events for 1 participant among 33 at risk in the letrozole group and 1 among 32 at risk in the letrozole-plus-clomiphene group. It reports zero deaths in each group. The listed serious adverse event terms are appendicitis at 3.1% and gallstones at 3.0%. The record does not assign those listed terms to a treatment group in the registry record, so they should not be attributed to either regimen.

The other adverse-event figures are 21 among 33 at risk in the letrozole group and 19 among 32 at risk in the combination group. These are counts, not estimates adjusted for differences in exposure time or event severity. The registry record does not give further details about event definitions, timing, duration, or whether participants could contribute more than one event. The at-risk denominators also differ from the primary endpoint group sizes.

As a general statistical point, adverse-event counts in a small trial can describe what was recorded but may provide limited precision for uncommon harms. The posted counts should not be read as proof that an event cannot occur when none is reported, nor as a reliable comparison of rare-event risks. The registry’s safety figures are descriptive; additional information about systematic safety monitoring and analysis is not reported in the registry record.

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

The posted primary data show that 27 of 35 participants assigned to letrozole plus clomiphene and 15 of 35 assigned to letrozole alone met the registry’s progesterone-based definition of ovulation. The sponsor’s rate-ratio analysis and the unadjusted recalculation both point toward a higher observed frequency in the combination group. The corresponding confidence intervals express uncertainty around those estimates, and they do not remove the limitations of a trial with these group sizes.

The endpoint is a laboratory-defined measure of ovulation. It is not itself conception, clinical pregnancy, live birth, or a measure of overall health. The posted conception and clinical-pregnancy results have low counts and substantial uncertainty. The registry lists additional outcomes, but complete results for all of them are not reported in the registry record. A difference in the primary endpoint should therefore not be treated as proof of a difference in later reproductive outcomes.

As a general statistical point, a randomized comparison can support an estimate of the effect of assignment within the trial when allocation, follow-up, and analysis are handled appropriately. Here, allocation is listed as randomized, but details about sequence generation, concealment, analysis populations, missing data, and treatment adherence are not reported. These gaps leave uncertainty about how closely the posted estimates represent the full randomized comparison.

The result also does not establish that the same contrast will occur in other groups of women or in other clinical settings. The registry record does not report enough eligibility detail to assess how broadly the enrolled population represents people with infertility and PCOS. The findings should be understood as a comparison of recorded outcomes in this completed trial, not as a general clinical instruction or a guarantee of an individual outcome.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of endpoint and effect measure matters. The primary outcome is a binary progesterone-based definition of ovulation, and the sponsor reports a relative measure while an unadjusted recalculation expresses the comparison as an absolute risk difference. Each answers the group-comparison question on a different scale. The distinction is important for understanding what the numerical estimate means, rather than treating every effect measure as interchangeable.

The record also demonstrates how an outcome can be statistically distinct from a downstream outcome. Ovulation, conception, and clinical pregnancy are related questions, but they are not the same endpoint. The posted primary comparison is more precise than the sparse pregnancy outcomes, and the latter do not provide a clear, precise estimate of their group differences. This highlights why a biological or intermediate endpoint cannot automatically stand in for a later outcome.

From a biostatistical perspective, the record offers an opportunity to compare a sponsor-reported analysis with a simple unadjusted recalculation, while keeping the sponsor’s own analysis as the primary reference for the trial. It also makes visible the roles of confidence intervals, small event counts, varying denominators, and the absence of reported multiplicity and missing-data details. These features affect the strength and scope of interpretation even when the direction of the primary comparison is clear in the posted counts.

Finally, planning illustrations based on an observed effect show how assumed effect size influences a future sample-size calculation. They are useful as design illustrations, but they are not evidence about the trial’s original planning or its observed power. Separating design-stage planning from post-trial interpretation is an important statistical discipline.

19. 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 defined by a progesterone threshold, and the record does not report the rationale or validation for that threshold. A threshold-based classification does not retain the full range of laboratory values, and the result is specific to the registry’s stated definition and timing. The registry describes assessment after an LH surge or on cycle day 21 when no surge was detected, but does not report additional handling details.

The primary outcome denominators are 35 per group, while the posted secondary outcome denominators are 34 and 33. The reasons for these differences are not reported in the registry record. There is no reported missing-data plan, analysis-population definition, or sensitivity analysis to indicate how unavailable outcomes were handled. The record also does not report adherence or protocol-deviation details.

The trial is listed as randomized and unmasked, but the sequence-generation and allocation-concealment methods are not reported. The record does not provide baseline characteristics in the registry entries, so the degree of balance between groups cannot be assessed from these results alone. Blinding is listed as none, and the record does not describe any other steps taken to reduce measurement or performance bias.

The primary comparison is based on 35 participants in each group. Pregnancy-related secondary outcomes have small event counts, and the uncertainty intervals are broad. Multiple secondary outcomes are listed, but a multiplicity strategy or hierarchy is not reported. Results for every listed secondary outcome are not available in the registry record, limiting a complete assessment of the overall outcome pattern.

The trial’s original sample-size justification and statistical analysis plan are not reported. The available planning illustrations use the observed effects and cannot establish what assumptions informed the trial’s original enrollment. These record-level limitations restrict interpretation; they do not change the counts that were posted.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Combined Letrozole and Clomid in Women With Infertility and PCOS — NCT02802865.
• Registry record last updated 2019-09-27; status last verified 2019-09.
• Results first posted 2019-09-27.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT02802865 is recorded as a completed, randomized, parallel-group phase 4 trial with no masking and an enrollment of 70. It compared letrozole alone with letrozole plus clomiphene in women with infertility and PCOS. Each regimen included letrozole 2.5 mg orally for 5 days on cycle days 3–7; the combination regimen also included Clomid 50 mg orally for 5 days on those cycle days.

The primary endpoint was participants meeting a mid-luteal progesterone definition of ovulation. The posted counts were 15 of 35 with letrozole and 27 of 35 with the combination. The sponsor reported a rate ratio of 1.80, with a 95% confidence interval from 1.18 to 2.75 and p = 0.007. The unadjusted recalculation expressed the comparison as a risk difference of 0.343, with a 95% confidence interval from 0.128 to 0.558.

Secondary pregnancy outcomes have small counts and substantial uncertainty. The registry record does not report a multiplicity strategy, missing-data approach, analysis-population definition, or original sample-size justification.