Incidence of Headache Following an Unintentional Dural Puncture: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Incidence of Headache Following an Unintentional Dural Puncture (NCT01977898), a randomized na study. The primary outcome is Participants Who Report Post Dural Puncture Headaches.

2. Clinical Question

The clinical question is about the frequency of a reported headache over a specified period, rather than its severity or longer-term consequences. The registry lists headache-related measures as secondary outcomes, including severity, treatment, symptoms, and duration. Those measures address different aspects of the clinical experience and should not be treated as interchangeable with the primary incidence outcome.

The registry describes the purpose as evaluating whether intrathecal morphine decreases the incidence of post-dural puncture headache. That stated purpose does not establish the direction or size of an effect. The posted counts and comparison estimates are needed to assess what the trial recorded, and their uncertainty matters when interpreting the comparison.

3. Trial Design

This was a randomized, double-masked, parallel-group trial. The registry lists an enrollment of 68 and reports the study status as completed. The study start is recorded as 2011-11, and primary completion is recorded as 2019-03-01. The phase is listed as NA. More detail about the randomization procedure, allocation concealment, or how masking was implemented is not reported in the registry record.

The two interventions were intrathecal preservative-free morphine, 0.3 mL (150 mcg), and normal saline, 0.3 mL. Both were described as administered following an unintentional dural puncture. The registry’s brief summary identifies obstetric patients as the population of interest. Detailed inclusion and exclusion criteria and baseline characteristics are not reported in the registry record.

The primary outcome was the number of participants reporting post-dural puncture headache from delivery to postpartum day 5. The posted outcome counts are 21 of 27 in the morphine group and 27 of 34 in the saline group. These outcome denominators differ from the recorded enrollment of 68. The reason for that difference, including whether it reflects missing outcome data, exclusions, or another analysis-population definition, is not reported in the registry record.

The registry lists 11 outcome measures and 10 analyses. Secondary measures include headache severity and treatment, cranial nerve symptoms, repeat epidural blood patch, headache timing and duration, greatest pain level, and intrathecal catheter dwell time. A detailed statistical analysis plan and the original sample-size justification are not reported in the registry record.

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 Participants Who Report Post Dural Puncture Headaches, measured over 5 days.

The primary endpoint counts participants who reported post-dural puncture headache between delivery and postpartum day 5. It is a binary outcome: each participant is classified according to whether a headache was reported during that period. The registry describes the result as a count of participants with the event, rather than as a continuous measure of pain or a time-to-event measure.

Incidence is useful for asking how frequently an event occurred in each randomized group. It gives a direct comparison of the proportion with a recorded headache during the defined follow-up period. In this trial, the posted counts are 21 of 27 participants in the morphine group and 27 of 34 in the saline group. These are the group-specific outcome counts and denominators used in the posted comparison.

The endpoint’s time window is important to interpretation. It covers delivery through postpartum day 5; it does not describe headache beyond that period. The registry separately lists outcomes concerning severity, treatment, timing, and duration, indicating that the presence of headache is not the only aspect of interest. The endpoint does not, by itself, describe how severe a headache was, what treatment was received, or whether symptoms continued after the specified follow-up.

Using a defined event window makes the comparison interpretable, but a complete assessment also depends on how outcomes were collected and how participants without recorded outcomes were handled. Those details are not reported in the registry record.

7. Results Posted in the Registry

• Saline: 79.4% (27/34) versus 77.8% (21/27) on control; risk difference 1.6 percentage points (95% CI -19.1 to 22.4), risk ratio 1.02 (0.78–1.33); unadjusted two-proportion z-test p = 0.877.

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.

Repeat Epidural Blood Patch

• 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:
  • Saline: 10.0% (1/10) versus 9.1% (1/11) on control; risk difference 0.9 percentage points (95% CI -24.3 to 26.1), risk ratio 1.10 (0.08–15.36); unadjusted two-proportion z-test p = 0.943.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Saline and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the assessment beyond whether a headache was reported. They address severity, treatment, cranial nerve symptoms, repeat epidural blood patch, timing and duration of headache, greatest pain level, and intrathecal catheter dwell time. The registry lists 10 secondary outcomes, but detailed results for most of these measures are not reported in the registry record available for interpretation. Consequently, a consistent overall pattern across the full set of secondary outcomes cannot be established from the reported details.

The registry does include a reported analysis for repeat epidural blood patch, using a chi-squared method. That is a distinct outcome from the primary headache-incidence endpoint and should be read as a separate comparison, not as a replacement for the primary result. The registry record does not provide enough detail on the other secondary findings to assess whether they align with, qualify, or differ from the primary comparison.

In general, secondary outcomes can help describe different dimensions of the clinical question, but they do not automatically provide independent confirmation of a primary result. They may be exploratory, and examining multiple outcomes increases the chance that some results appear noteworthy by chance when each is assessed separately. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting secondary outcomes. Accordingly, unadjusted secondary findings carry less weight than a prespecified primary analysis and should be interpreted cautiously, especially when the complete results and analysis plan are unavailable.

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

• Severity of Post Dural Puncture Headache
• Treatment Method for Headache
• Number of Participants With Cranial Nerve Symptoms
• Repeat Epidural Blood Patch
• Presenting Day of Headache
• Number of Participants With Duration in Days of Headache After Unintentional Dural Puncture.
• Greatest Level of Headache Pain Experienced With the Unintentional Dural Puncture
• Intrathecal Catheter Dwell Time

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary because each participant either reported a post-dural puncture headache during the specified period or did not. For a binary endpoint, the observed risk is the number of participants with the event divided by the number assessed in that group. The posted counts are 21 of 27 for morphine and 27 of 34 for saline, corresponding to the reported risks of 0.778 and 0.794.

The posted primary comparison is expressed as a risk difference, with saline minus morphine as the direction of comparison. A positive risk difference means the observed risk is higher in the saline group than in the morphine group; a negative value means it is lower. The recalculated estimate is 0.016. Its interval, -0.191 to 0.224, spans zero, the value corresponding to no absolute difference. The interval also encompasses effects in either direction, so the point estimate should not be read as a precise estimate of the underlying difference.

Two relative measures are also reported. The risk ratio compares the risks directly, and the odds ratio compares event odds. A ratio of 1 represents no group contrast on that ratio scale. The risk ratio estimate is 1.021, with an interval from 0.784 to 1.33; the odds ratio estimate is 1.102, with an interval from 0.322 to 3.772. Because the endpoint is common in both groups, the odds ratio and risk ratio need not be numerically similar. In general, an odds ratio is not the same as a risk ratio and should not automatically be interpreted as a direct relative change in risk.

The registry reports Fisher Exact for the primary analysis. In general, Fisher’s exact test evaluates the association between group assignment and a binary outcome using the observed table of counts, with a method suited to categorical data. The registry reports a superiority analysis and p = .877. A recalculated unadjusted comparison gives p = 0.877. A p-value is evaluated against a null model of no group association; it does not quantify the probability that a treatment effect exists, and it does not establish equivalence when it is not small.

Confidence intervals describe a range of effect estimates compatible with the observed data under the method’s assumptions. In general, a narrow interval indicates greater precision, while a wide interval indicates less precision. The confidence level for the posted intervals is not reported in the registry record, so no confidence level is assigned in this interpretation. The important feature for this comparison is that the risk-difference interval crosses zero and allows appreciable contrasts in either direction.

The recalculated comparisons are unadjusted comparisons based on the posted summary counts. They do not account for covariates or other adjustments. The registry record does not report an adjusted primary analysis or a detailed prespecified analysis plan. If a registry-reported analysis and a recalculation differ, the sponsor’s own analysis takes precedence; in this case, the discrepancy flag is false and the two primary p-values are numerically concordant as recorded, with different formatting.

The secondary outcome Repeat Epidural Blood Patch is also binary. Its registry-reported method is Chi-squared. In general, a chi-squared test compares observed categorical counts with counts expected under a null model of no association. The registry reports p = .525 for that secondary analysis. This test result is separate from the primary Fisher Exact analysis; different endpoints and methods should not be combined into a single conclusion.

General statistical caution applies to all these analyses: estimates depend on the participants included, the accuracy and completeness of outcome ascertainment, and the assumptions of the chosen methods. The registry record does not report detailed handling of missing outcomes, an intention-to-treat definition, or the confidence level for the posted intervals. Those omissions limit how fully the reported estimates can be audited or interpreted.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.016, with an interval from -0.191 to 0.224. The interval is wide relative to the point estimate and includes zero. It also includes negative and positive values, which correspond to possible differences in either direction when the contrast is saline minus morphine. Thus, the observed estimate alone gives a less complete picture than the range of estimates compatible with the data.

The relative measures likewise show substantial uncertainty: the risk ratio is 1.021, with an interval from 0.784 to 1.33, and the odds ratio is 1.102, with an interval from 0.322 to 3.772. The ratio intervals include 1, the value for no ratio contrast. The broad intervals indicate that the data do not tightly pin down the size or direction of the group contrast.

In general, a confidence interval is an uncertainty range produced by a statistical procedure. It does not mean that every value in the range is equally likely, and it does not guarantee that the true effect lies within the interval. Its interpretation depends on the method and its assumptions. The confidence level associated with these intervals is not reported in the registry record.

The outcome counts are 21 of 27 in the morphine group and 27 of 34 in the saline group. The enrollment recorded for the trial is 68, and the registry record does not explain why the primary outcome denominators differ from enrollment. The uncertainty in the estimates, together with the unreported accounting of participants without a recorded endpoint, should temper confidence in a precise interpretation. The findings support describing the observed group results, but not treating the point estimate as a definitive measure of the underlying contrast.

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 primary effect, not the original design calculation. For this binary outcome, the figures are participants per arm, rather than total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column describes the planned number of participants per arm under which the calculation would have an 80% chance of detecting the specified effect, if that effect and the planning assumptions held. The 90% power column uses a higher probability of detection under those same assumptions and therefore requires more participants per arm. These are design-planning quantities, not claims about the trial’s achieved power.

The rows set the target effect at 100%, 75%, and 50% of the observed effect. The smaller the effect a future study aims to detect, the more participants per arm the calculation requires. That pattern is visible in the planning figures: the requirements increase as the target fraction gets smaller. Because the observed risk difference is close to zero, planning directly from it produces very large participant requirements; this illustrates how a small assumed contrast can drive a large design calculation.

The figures are not observed power. They do not measure how much power this completed trial actually had, and they do not establish the probability that the trial’s result is correct. They are conditional planning illustrations whose usefulness depends on the chosen effect size and stated assumptions. They should be interpreted alongside the wide uncertainty in the observed effect estimate, rather than as evidence that any particular future study size is definitively adequate.

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 = 0.778; treatment proportion p₁ = 0.794; average p̄ = 0.786.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5801 = 1.1369.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5799 = 0.4881.
4. n = (1.1369 + 0.4881)² / (0.0163)² = 9,890.1, rounded up to 9,891 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 <- 0.777777777777778                          # control proportion
p1 <- 0.794117647058823                          # 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(1977898)
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 = 9,891 (80% power), 13,240 (90% power)
 75% of observed effect: n per arm = 17,706 (80% power), 23,702 (90% power)
 50% of observed effect: n per arm = 40,110 (80% power), 53,695 (90% power)
power.prop.test: 9890.1 
Simulated power at n = 9,891 per arm: 0.799 (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 registry reports Fisher Exact for the primary superiority analysis, with p = .877. The unadjusted recalculation from the posted summary statistics gives p = 0.877. The discrepancy flag is false, so there is no flagged difference between the sponsor’s analysis and the recalculated result. The formatting of the reported value differs, but the numerical values agree at the precision recorded.

The recalculated risk difference, risk ratio, and odds ratio are simple unadjusted contrasts derived from the posted group counts. They help express the size and uncertainty of the comparison on absolute and relative scales, but they are not substitutes for a sponsor-reported adjusted analysis. No adjusted primary analysis is reported in the registry record.

When the sponsor’s own analysis and an unadjusted recalculation disagree, the sponsor’s analysis takes precedence for describing the trial’s reported analysis. Here, the reported and recalculated primary p-values are concordant, while the effect estimates and intervals provide additional context about magnitude and precision. The p-value should not be interpreted alone or as evidence of equivalence; the uncertainty in the effect estimates remains relevant.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes. Testing several outcomes can increase the chance of finding an apparently unusual result even when there is no underlying effect, particularly when each result is considered separately. In general, multiplicity procedures can control or otherwise address that issue, for example by adjusting the testing strategy or by defining a hierarchy of outcomes. Whether such an approach was planned or used is not reported in the registry record.

The registry reports a primary Fisher Exact analysis and a chi-squared analysis for repeat epidural blood patch. It does not report a comprehensive statistical analysis plan, a multiplicity adjustment, or a hierarchy specifying how the secondary analyses should affect conclusions. The secondary outcomes should therefore be interpreted as separate results, with caution about the possibility of chance findings across multiple comparisons.

The record gives an enrollment of 68, while the primary outcome denominators are 27 in the morphine group and 34 in the saline group. The reason the endpoint denominators differ from enrollment is not reported in the registry record. It is not possible to infer from these figures whether the difference reflects missing observations, eligibility decisions, exclusions, or a defined analysis population. The number and handling of participants with missing primary outcomes are not reported in the registry record.

The analysis population is also not defined in detail. The registry record does not say whether the primary analysis followed an intention-to-treat principle, how crossovers or protocol deviations were handled, or whether any imputation was used for missing data. In general, missing outcome data can affect both the group-specific risks and the estimated comparison, especially if the likelihood of missingness is related to outcome or group assignment. Without the relevant accounting and methods, the impact cannot be assessed.

Details of the original sample-size rationale, interim analyses, and the complete prespecified statistical plan are not reported in the registry record. Their absence limits assessment of whether the posted analyses reflect the original analysis strategy.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero serious adverse events among 27 participants at risk in the morphine group and zero among 34 participants at risk in the saline group. It also reports zero other adverse events among 27 participants at risk in the morphine group and zero among 34 participants at risk in the saline group. Deaths are recorded as 0 in each group, and no serious adverse event terms are listed.

These figures describe the events recorded in the registry for the stated groups. They do not establish that no adverse events of any kind occurred outside the categories or reporting period represented in the record. The registry’s detailed methods for adverse-event collection, severity classification, and follow-up are not reported in the registry record. With no reported events in these categories, a comparative safety estimate cannot be inferred from the counts alone; the figures should be read as registry reporting, not as proof of absence of risk.

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

The posted primary results show headache reported by 21 of 27 participants in the morphine group and 27 of 34 in the saline group during the period from delivery to postpartum day 5. The estimated risk difference is 0.016 for saline minus morphine, with an interval from -0.191 to 0.224. The reported Fisher Exact analysis gives p = .877. Together, these results describe similar observed event proportions but leave considerable uncertainty about the size and direction of the underlying difference.

The result does not establish that the interventions are equivalent. A non-small p-value does not prove that there is no effect, and an interval crossing zero does not rule out meaningful differences in either direction. The registry record does not report a clinically important difference threshold or an equivalence margin, so it cannot establish whether the range of effects is clinically negligible.

The endpoint is limited to reported headache through postpartum day 5. It does not answer questions about later headache, and incidence does not describe severity, treatment, or duration. The registry lists secondary outcomes for several of those dimensions, but detailed results for most are not reported in the registry record.

The findings also depend on how the recorded participants and outcomes were defined. Enrollment is 68, whereas the primary group denominators are 27 and 34. The reason for that difference, the handling of missing outcomes, and the analysis population are not reported in the registry record. This limits assessment of how completely the posted outcome counts represent the randomized groups.

These are results from a randomized trial in obstetric patients following unintentional dural puncture. They should be understood within that population, intervention comparison, endpoint definition, and follow-up period. They are not a general conclusion about other populations or settings.

18. Why This Trial Matters Statistically

This trial offers a useful statistical example of why a point estimate, a p-value, and an uncertainty interval answer different questions. The primary risk difference is close to zero, and the reported p-value is not small, but the interval extends well below and above zero. The point estimate describes the observed contrast; the p-value summarizes the data under a null model; and the interval conveys how imprecisely the effect is estimated.

The trial also illustrates the difference between failing to detect a difference and demonstrating equivalence. Establishing equivalence requires a clinically justified margin and a design and analysis directed at that question. A superiority analysis with a non-small p-value does not supply that evidence. No equivalence margin is reported in the registry record.

Its planning illustrations show how sample-size requirements depend on the effect a future study aims to detect. Smaller target effects require more participants per arm under the stated assumptions. Because planning calculations use an assumed effect and model, they should not be mistaken for observed power or for a guarantee that a study will answer its clinical question.

Finally, the record highlights the importance of transparent reporting. Enrollment and endpoint denominators differ, but the accounting of participants, missing outcomes, analysis populations, and multiplicity methods is not reported. Such information is necessary to assess the reliability and scope of an estimate, regardless of whether the observed group proportions appear close.

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 denominators are 27 for morphine and 34 for saline, while the recorded enrollment is 68. The registry record does not explain this difference or describe the accounting of participants without a recorded primary outcome. Without that information, the effect of missing or excluded observations on the comparison cannot be assessed.

The available primary endpoint covers headache only from delivery through postpartum day 5. It does not establish what happened after that period. The registry lists secondary measures that could add context about severity, treatment, and duration, but detailed results for most of them are not reported in the registry record.

The primary risk-difference interval, -0.191 to 0.224, is broad and includes contrasts in either direction. The confidence level for the posted intervals is not reported in the registry record. No clinically important difference threshold or equivalence margin is reported, limiting interpretation of the practical importance of effects within the interval.

Although the trial is described as randomized and double-masked, the registry does not report details of sequence generation, allocation concealment, masking procedures, or the analysis population. A full statistical analysis plan, multiplicity approach, and original sample-size justification are also not reported. These omissions restrict assessment of whether the reported analyses followed a prespecified plan and how robust the findings are to analytic choices.

The posted safety figures record no serious or other adverse events and no deaths in either group, but the registry record does not report detailed adverse-event collection methods or follow-up. The safety figures therefore describe what is recorded, not the full range of possible harms or the certainty of their ascertainment.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Incidence of Headache Following an Unintentional Dural Puncture — NCT01977898.
• Registry record last updated 2021-11-17; status last verified 2021-11.
• Results first posted 2021-04-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT01977898 is a completed randomized, double-masked, parallel-group trial sponsored by Northwestern University. It compared intrathecal preservative-free morphine, 0.3 mL (150 mcg), with intrathecal normal saline, 0.3 mL, following unintentional dural puncture in obstetric patients. Recorded enrollment was 68.

The primary endpoint was reported post-dural puncture headache from delivery to postpartum day 5. The posted counts were 21 of 27 in the morphine group and 27 of 34 in the saline group. The recalculated risk difference was 0.016, with an interval from -0.191 to 0.224; the registry-reported Fisher Exact analysis gives p = .877.

The primary comparison is imprecise, and the registry record does not report the reason for the difference between enrollment and endpoint denominators, detailed missing-data handling, or a comprehensive analysis plan. Most secondary outcome results are not reported in the registry record.