Comparison of EVD Catheter Diameter on Occlusion and Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparison of EVD Catheter Diameter on Occlusion and Replacement (NCT03248739), a randomized na study. The primary outcome is Number of Participants With Permanent Catheter Occlusions.

2. Clinical Question

The trial asked whether external ventricular drain catheter diameter was associated with permanent catheter occlusion. It compared a large catheter with a small catheter and recorded whether participants experienced permanent occlusion, defined as failure of catheter patency that could not be restored by manipulation or flushing.

The primary endpoint is a participant count, not a measure of how many occlusion episodes each participant experienced or how long a catheter remained patent. The registry record lists catheter replacement and temporary occlusion among secondary outcomes, along with procedure-related and symptomatic hemorrhage. Those outcomes address related but distinct events; they do not change the definition of the primary endpoint.

3. Trial Design

The registry record describes a randomized, open-label, parallel-group device trial sponsored by Wake Forest University Health Sciences. It lists an enrollment of 33 and a terminated status. The recorded study start was 2017-06-12, and primary completion was 2022-11-04. The reason for termination is not reported in the registry record.

Participants were assigned to a large or small external ventricular drain catheter. The posted primary outcome population is described as participants randomized to large- or small-bore catheters. The registry record does not report whether the analysis followed an intention-to-treat approach, whether participants were excluded after randomization, or how any deviations from assigned catheter use were handled.

The primary endpoint was the number of participants with permanent catheter occlusion, assessed up to 4 weeks. The record defines permanent occlusion as a non-functioning catheter whose patency could not be restored through manipulation or flushing. The outcome is therefore binary at the participant level: a participant either met the stated definition or did not.

The record lists five outcome measures, including the primary endpoint and secondary outcomes. Secondary measures include catheter replacement, temporary occlusion, procedure-related hemorrhage, and symptomatic hemorrhage. Posted numerical results are available for catheter replacement and temporary occlusion, but numerical results for the hemorrhage outcomes are not reported in the registry record. The sample-size justification, recruitment target rationale, and planned statistical analysis 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.

Before assignment: 33 subjects were consented to study with 33 being randomized.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Randomized to Large or Small Bore Catheters

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 With Permanent Catheter Occlusions, measured over Up to 4 weeks.

The primary endpoint counts participants with permanent catheter occlusion during follow-up of up to 4 weeks. The registry definition requires a non-functioning, non-patent external ventricular drain for which patency cannot be restored through catheter manipulation or flushing. This distinguishes permanent occlusion from a temporary interruption that resolves with those measures.

Counting participants with the event gives a binary outcome for each participant. It summarizes whether the defined event occurred, rather than the number of episodes, duration of obstruction, or time until occlusion. The endpoint is relevant to the trial’s stated question because it directly records the event the comparison was designed to assess: permanent catheter occlusion by catheter diameter.

In general, a prespecified, clearly defined endpoint helps make the groups’ outcomes comparable and reduces ambiguity about what qualifies as an event. Here, the definition draws a boundary between permanent and temporary occlusion. The registry record also lists replacement and temporary occlusion separately, so those outcomes should not be treated as interchangeable with the primary endpoint.

The posted primary counts are 0 participants in the large-catheter group and 2 participants in the small-catheter group. Those counts describe the observed outcomes in this trial; by themselves, they do not establish the size or certainty of a difference in the broader population. Interpretation also depends on the uncertainty around the comparison and on design and analysis details that are not reported in the registry record.

7. Results Posted in the Registry

• Small: 12.5% (2/16) versus 0.0% (0/17) on control; risk difference 12.5 percentage points (95% CI -3.7 to 28.7); unadjusted two-proportion z-test p = 0.133.

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.

Number of Participants With Catheter Replacements

• 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:
  • Small: 18.8% (3/16) versus 5.9% (1/17) on control; risk difference 12.9 percentage points (95% CI -9.3 to 35.0), risk ratio 3.19 (0.37–27.58); unadjusted two-proportion z-test p = 0.258.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Small and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Temporary Occlusions

• 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:
  • Small: 0.0% (0/16) versus 11.8% (2/17) on control; risk difference -11.8 percentage points (95% CI -27.1 to 3.6); unadjusted two-proportion z-test p = 0.157.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Small and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcome pattern is not uniform in direction: the replacement comparison points toward more events in the small-catheter group, while temporary occlusion points in the opposite direction. These outcomes describe different events, and neither is interchangeable with the primary definition of permanent occlusion. Their variation does not resolve the uncertainty in the primary comparison.

The registry lists catheter replacement, temporary occlusion, procedure-related hemorrhage, and symptomatic hemorrhage as secondary outcomes. Numerical results are posted for replacement and temporary occlusion. Numerical results for the two hemorrhage outcomes are not reported in the registry record. The posted secondary results therefore offer only a partial view of the outcomes listed.

In general, secondary outcomes can help describe a broader pattern, but they often have less evidential weight than a prespecified primary outcome. Multiple comparisons increase the chance of observing apparently notable results by chance when each is considered separately. The registry record does not report a multiplicity adjustment or an analysis plan explaining how secondary outcomes were to be interpreted. The recalculated secondary p-values are unadjusted, so they should be treated as exploratory descriptions rather than as standalone confirmatory evidence.

The secondary estimates are also based on small event counts and have broad confidence intervals that include no difference. They do not provide a precise estimate that would settle the primary question. In addition, the posted secondary findings cannot establish a consistent pattern across all listed outcomes because two outcomes have no numerical results in the registry record. The secondary data add context, but they do not materially remove the uncertainty around permanent occlusion.

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

• Number of Participants With Catheter Replacements
• Number of Participants With Temporary Occlusions
• Number of Participants With Procedure-related Hemorrhages
• Number of Participants With Symptomatic Hemorrhages

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports the primary outcome as participant counts, with a binary event status for each participant. The posted results give 0 events among 17 participants in the large-catheter group and 2 among 16 in the small-catheter group. The recalculated comparison is expressed as a risk difference: the estimated event risk in the small group minus that in the large group. A positive value means a higher observed event risk in the small group under that contrast.

In general, a risk difference expresses an absolute difference in event probabilities, rather than a relative comparison. It is directly interpretable on the probability scale, but its precision depends on the event counts and group sizes. With sparse outcomes, estimates can be sensitive to a small change in the number of events. The recalculated risk difference is 0.125. Its confidence interval runs from -0.037 to 0.287, indicating that the data are compatible with values below and above no difference. The interval’s confidence level is not reported in the registry record.

The registry’s own reported primary analysis is Fisher Exact, with p=0.23, and is labeled as an equivalence analysis. In general, Fisher’s exact test evaluates evidence against a specified null association using the observed allocation of categorical outcomes; it does not rely on the same approximation as many large-sample tests. A p-value describes how unusual the data would be under the test’s null model, subject to the test’s assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the probability that a treatment effect exists.

The unadjusted recalculated p-value is 0.133. That value is not the sponsor’s reported Fisher Exact p-value, and the two should not be conflated. The recalculation uses the posted summary counts to give a simple unadjusted comparison. The registry record does not report enough detail to reconstruct all aspects of the sponsor’s analysis, including any equivalence margin. A p-value above a conventional significance threshold does not establish no effect. Likewise, the equivalence label alone does not establish equivalence without the margin and corresponding analysis details.

What does a confidence interval add?

In general, a confidence interval conveys the range of effect estimates that are reasonably compatible with the data under the method used. It communicates uncertainty in the effect estimate, whereas a p-value summarizes evidence relative to a specified null hypothesis. The primary interval is wide enough to include both a negative difference and a positive one. That is a sign that the trial does not estimate the primary contrast precisely. The interval should not be read as a list of equally likely values or as a guarantee that the true effect lies within it.

How should the secondary planning figures be read?

The registry includes a planning illustration for catheter replacement based on the observed effect, not the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustration gives participants per arm for 80% and 90% power when planning for 100%, 75%, or 50% of the observed effect. These values are prospective planning illustrations, not observed power and not evidence that a future study would achieve the stated power under different assumptions. Because the effect used for planning comes from a small trial, it may be an unstable basis for design. The registry record does not report the trial’s original sample-size justification.

In general, over-dispersion is an issue for outcomes where variability exceeds what a model assumes, and it can make standard errors too small if ignored. The posted outcomes are participant event counts with binary status; the record does not describe a dispersion model or report dispersion estimates. No claim about an adjusted model or an over-dispersion correction is warranted from the registry record.

The registry record lists one reported analysis for the primary outcome and no reported analyses for the posted secondary outcomes. It does not report a complete analysis plan, multiplicity procedure, missing-data method, or model covariates. Accordingly, the estimates and p-values should be understood as the reported primary analysis and simple unadjusted recalculations, not as evidence that unreported adjustment or sensitivity analyses were conducted.

11. Confidence Intervals and Precision

The primary recalculated risk difference is 0.125, with a confidence interval from -0.037 to 0.287. The interval spans no difference and extends to a positive difference. This breadth means the observed data do not pin down the primary effect closely. A point estimate alone would obscure this uncertainty, particularly because the event counts are sparse.

In general, a confidence interval reflects both the observed data and the method used to calculate it. It is not a range of values that can be treated as equally plausible, and it does not guarantee that the true effect lies within the interval. The confidence level for the posted recalculated intervals is not reported in the registry record, so it should not be assigned a level by assumption.

The sponsor’s primary analysis reports p=0.23 from a Fisher Exact test but no estimate or confidence interval. The registry record labels this analysis equivalence, but does not report an equivalence margin. Without that margin and corresponding interval-based details, the p-value cannot establish that differences of a clinically relevant size have been ruled out.

The secondary recalculations also have broad intervals. For catheter replacement, the risk difference is 0.129 with a confidence interval from -0.093 to 0.350. For temporary occlusion, the risk difference is -0.118 with a confidence interval from -0.271 to 0.035. These intervals likewise include no difference. The secondary estimates should be interpreted cautiously, especially because they are unadjusted and the record does not report a multiplicity plan.

Small event counts and limited group sizes constrain precision. More precise estimation would generally require more information, but the appropriate design size depends on assumptions and goals not reported in the registry record. The replacement planning illustration is not a substitute for the missing original design rationale and does not turn the trial’s observed results into a precise estimate.

12. Analyses Reported by the Sponsor

The registry’s own primary result is a Fisher Exact analysis labeled as equivalence, with p=0.23. It reports no primary effect estimate or confidence interval. The simple recalculation from the posted group counts gives a risk difference of 0.125, a confidence interval from -0.037 to 0.287, and an unadjusted p-value of 0.133. These are different statistical summaries, so their p-values are not direct substitutes for one another.

The recalculation is useful for describing the observed absolute contrast and its uncertainty using the posted counts. It does not replace the sponsor’s reported analysis. The registry record does not report an equivalence margin, so the equivalence label cannot be independently interpreted as a formal demonstration that the groups are sufficiently similar. A non-significant p-value alone does not establish equivalence.

The registry record does not indicate a discrepancy flag for the primary result. Even so, the sponsor’s analysis and the simple recalculation answer their questions through different procedures. The record does not provide enough detail to assess whether the sponsor’s test included additional choices or assumptions beyond the method name and reported p-value. The most defensible reading is to retain the sponsor’s reported result as the registry analysis while treating the recalculation as a separate, unadjusted description of the posted counts.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and one reported primary analysis. It also names four secondary outcomes. The record does not report whether the primary outcome was selected before data were examined, how secondary outcomes were prioritized, or whether any adjustment for multiple comparisons was planned or performed. That information is not reported in the registry record.

In general, testing several outcomes separately without adjustment can increase the chance of finding at least one apparently unusual result even when there is no underlying difference. This does not make secondary outcomes uninformative, but it changes how strongly an isolated unadjusted result should be interpreted. The posted secondary recalculations are unadjusted, and the registry record does not provide a multiplicity strategy. They should therefore be read as descriptive and exploratory.

The record describes the primary population as participants randomized to large- or small-bore catheters. It does not report whether the primary analysis included all randomized participants, whether exclusions occurred, or how protocol deviations were handled. The analysis population and any per-protocol or modified analysis sets are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The posted group counts give outcome denominators, but the record does not explain whether outcome status was available for every randomized participant or how unknown status, withdrawals, or incomplete follow-up were handled. It would not be appropriate to assume that all randomized participants had complete outcome ascertainment solely from the posted counts.

The registry record does not report a full statistical analysis plan, interim-analysis plan, sample-size justification, or sensitivity analyses for missing outcomes. It also does not report the reason for trial termination. These gaps limit assessment of whether the posted analyses were prespecified, how robust the findings are to alternative assumptions, and how the terminated status affected the planned analysis.

14. 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.

The adverse-event figures report no serious events among 17 participants at risk in the large-catheter group and none among 16 participants at risk in the small-catheter group. The record also reports no other adverse events affecting participants in either group and no deaths in either group. These are the posted registry counts for the adverse-event categories recorded.

Zero recorded events in these groups do not establish that the risk of an event is absent. In general, rare outcomes can remain uncertain when the number of observed events is small, and event reporting depends on follow-up and ascertainment. The registry record does not provide additional detail about adverse-event definitions, collection procedures, or completeness of reporting.

The named secondary hemorrhage outcomes are procedure-related hemorrhages and symptomatic hemorrhages. Numerical results for those outcome measures are not reported in the registry record. The adverse-event figures should not be assumed to replace those endpoint-specific results or to answer whether either hemorrhage endpoint occurred under its stated definition.

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

The posted results describe a randomized comparison of large and small external ventricular drain catheters, with permanent occlusion as the primary endpoint. The observed counts were 0 of 17 in the large group and 2 of 16 in the small group. The unadjusted recalculated risk difference is 0.125, but its confidence interval ranges from -0.037 to 0.287. The data therefore leave substantial uncertainty about the size and direction of the underlying difference.

The sponsor reported a Fisher Exact p-value of 0.23 and labeled the analysis as equivalence. The registry record does not report an equivalence margin, so the label cannot be taken as proof that clinically important differences have been excluded. Nor does the unadjusted recalculated p-value of 0.133 demonstrate that there is no difference. In general, failure to show a statistically clear difference is not the same as evidence that groups are equivalent.

The result applies to the recorded endpoint definition and follow-up of up to 4 weeks. It does not establish effects on longer-term catheter function, repeated events, or other outcomes. It also does not provide numerical results for every secondary outcome named in the registry record. The adverse-event counts describe the recorded categories, but cannot establish that adverse events are impossible or that all endpoint-specific safety outcomes were fully reported.

Several aspects needed for a fuller interpretation are not reported in the registry record, including the sample-size rationale, analysis population, missing-data handling, multiplicity strategy, and equivalence margin. These gaps, together with limited event counts and the terminated status, constrain the conclusions that can be drawn. The findings should be read as an imprecise comparison of the posted outcomes, not as a definitive answer about catheter diameter.

16. Why This Trial Matters Statistically

This trial illustrates why event counts, effect estimates, and uncertainty need to be considered together. The primary counts are small, and the recalculated interval includes values on both sides of no difference. The point estimate alone could suggest a clear contrast, while the interval shows that the estimate is not precise. Reporting the scale of the effect and its uncertainty gives a more complete statistical reading than focusing on a single p-value.

The sponsor’s analysis is labeled as an equivalence test, which raises a distinct interpretive issue. Equivalence requires a prespecified margin defining what differences are small enough to count as equivalent. The registry record does not report that margin. This makes the label insufficient, by itself, to support a conclusion of equivalence. The case shows why analysis labels need to be accompanied by the details that define the statistical question.

The trial also highlights the challenge of interpreting secondary outcomes when event counts are sparse and multiplicity procedures are not reported. Different outcomes point in different directions, and not all named endpoints have posted numerical results. Treating each unadjusted comparison as confirmatory would overstate what the record can support.

Finally, the terminated status and missing design details matter for interpretation without automatically invalidating the posted observations. The reason for termination, sample-size justification, missing-data procedures, and full analysis plan are not reported in the registry record. Statistical interpretation must distinguish the information the record does contain from the uncertainties that remain unresolved.

17. 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 posted primary comparison rests on few recorded events, limiting precision. The confidence interval for the recalculated risk difference includes both a negative value and a positive value, so the underlying direction and magnitude remain uncertain. The trial’s enrollment and group counts are small for estimating uncommon binary outcomes, and the observed effect may be unstable.

The record is marked terminated, but the reason for termination is not reported in the registry record. It is therefore not possible to determine from the record whether termination was related to recruitment, feasibility, safety, or another consideration. The original sample-size rationale and stopping rules are also not reported.

The registry labels the primary analysis as equivalence but does not report the equivalence margin. It also does not report the confidence interval for the sponsor’s analysis, a full analysis plan, or whether the posted analysis used all randomized participants. Missing-data handling and protocol deviations are not described. These omissions limit evaluation of the analysis and of the extent to which the results reflect the randomized comparison.

The outcome follow-up is up to 4 weeks, so the record does not establish longer-term catheter outcomes. Numerical results for procedure-related and symptomatic hemorrhage are not reported in the registry record, despite those outcomes being listed. The record describes the placement protocol only partially, and masking was none. Open-label outcome assessment can be a consideration for judgment-based endpoints; the registry does not describe any blinded adjudication procedure.

Finally, multiplicity handling for the listed outcomes is not reported. The secondary recalculations are unadjusted, and the posted numerical secondary results cover only part of the listed secondary outcomes. Together, these limitations call for cautious interpretation rather than a broad conclusion from the primary point estimate alone.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Comparison of EVD Catheter Diameter on Occlusion and Replacement — NCT03248739.
• Registry record last updated 2023-10-25; status last verified 2022-10.
• Results first posted 2023-10-25.
• 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.

21. Record Summary

The registry record describes a randomized, open-label, parallel-group comparison of large and small external ventricular drain catheters, sponsored by Wake Forest University Health Sciences. The record lists enrollment of 33, a terminated status, and primary follow-up of up to 4 weeks.

The primary endpoint was the number of participants with permanent catheter occlusion. The posted counts were 0 of 17 in the large-catheter group and 2 of 16 in the small-catheter group. The simple unadjusted recalculation gives a risk difference of 0.125, with a confidence interval from -0.037 to 0.287 and p=0.133. The sponsor reported a Fisher Exact analysis labeled as equivalence, with p=0.23; the equivalence margin is not reported in the registry record.

The record lists secondary outcomes for replacement, temporary occlusion, and hemorrhage. Numerical results are posted for the first two, while results for the hemorrhage endpoints are not reported in the registry record. The sample-size rationale, analysis population, missing-data approach, multiplicity plan, and reason for termination are also not reported.