A Study on the Safety of Hakim Programmable Shunt System: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Safety of Hakim Programmable Shunt System (NCT04285489), a registered phase not stated study. The primary outcome is Number of Participants With Non-infection Within One Year.

2. Clinical Question

3. Trial Design

This is a multicenter, retrospective registry study listed as completed. Its official title describes a safety study of the Hakim Programmable Shunt System, and its brief summary says it aimed to collect safety information from subjects implanted with the device. The registry lists hydrocephalus as the condition and 130 as the enrollment.

The study began on 2020-05-02 and had a primary completion date of 2020-07-28. The endpoint timeframe is one year. The brief summary describes assessment of adverse events occurring within one year after catheter implantation. The record does not explain how retrospective follow-up was conducted, whether the full timeframe was available for every participant, or how events were identified and verified.

The registry lists a single HAKIM Programmable Shunt System Arm for adverse-event reporting. No control arm or comparator is reported, and allocation is not stated. As a result, the design supports a descriptive reading of the recorded safety information, not a randomized treatment comparison. The registry entries do not establish whether other care or patient characteristics influenced the recorded events.

The sponsor is Integra LifeSciences Corporation. The brief summary names Codman & Shurtleff, Inc. of the United States as the producer of the device. These details identify the registry record and device; they do not establish the completeness or independence of event ascertainment. The registry record does not report a protocol, eligibility criteria, recruitment method, or details of the participating centers.

Although the record is marked completed, that status does not itself indicate that every planned outcome was reported. In particular, the primary endpoint is described, but its observed result is not reported in the registry record. The record lists no statistical analyses.

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: Screened 140 patients, 130 of them were enrolled, including 71 adult patients and 59 minors (subject age below 18). 10 patients were screening failures for inclusion/exclusion criteria deviation.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 130 participants implanted Hakim shunting system for 1 year

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 130 enrolled subjects were included into PPS.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Non-infection Within One Year, measured over 1 year.

The primary endpoint is titled “Number of Participants With Non-infection Within One Year.” Its unit is participants, its measure is a count of participants, and its timeframe is one year. The description calls it a “non-infection rate of a subject within one year,” while the title refers to a number of participants. This wording leaves the precise event definition unclear: the registry record does not explain which events qualify as non-infection or how the endpoint was classified.

A participant count is different from a count of all events. If a participant can experience more than one event, a count of participants with at least one qualifying event treats that participant differently from an event total. The endpoint title indicates a participant-based measure, but the registry record does not provide further operational detail to confirm how repeat events were handled.

A one-year safety endpoint provides a defined period in which events are considered, making the timeframe part of the outcome’s meaning. It does not, by itself, show whether follow-up was complete for all participants or whether the endpoint was assessed consistently. Those details are not reported in the registry record.

The endpoint may be used to describe the recorded occurrence of the specified safety outcome after implantation. However, its observed count and rate are not reported in the registry record. Without the endpoint result and a clear definition, no estimate of its frequency or precision can be stated from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is limited. It identifies a participant-count primary outcome and records adverse-event counts and term percentages, but lists no analyses. No statistical plan, analysis population definition, or confidence interval is reported in the registry record. The interpretation should therefore stay descriptive and should not imply that an unreported statistical test or model was used.

What does a participant count represent?

A binary outcome classifies each participant according to whether a defined event or condition was recorded during a specified period. A count of participants meeting that definition is not the same as a count of all events: one participant may have more than one event, while a participant-based outcome ordinarily counts that person according to whether the criterion was met. The primary endpoint title uses a participant count, but its definition is not detailed enough to determine precisely how events were classified or repeated events treated.

To interpret a participant count as a rate or proportion, a reader needs a clearly defined numerator and denominator that refer to the same analysis population and follow-up period. Here, the endpoint description identifies a population of 130 participants implanted with the system for one year, but does not report the number meeting the endpoint. The denominator details, handling of incomplete follow-up, and endpoint result are not reported in the registry record. No endpoint rate can therefore be stated.

Why does the event definition matter?

Consistent definitions help ensure that events are classified similarly across participants and centers. The primary outcome’s use of “non-infection” is not explained beyond its title and short description. The record does not specify which events count, how infections are distinguished from non-infections, or whether the outcome refers to any non-infection event or another classification. Such ambiguity limits interpretation even before considering statistical uncertainty.

General statistical practice would report an estimate alongside a confidence interval when appropriate. A confidence interval describes the uncertainty associated with an estimate under the assumptions of the method; it does not account automatically for missing events, misclassification, or selection bias. No interval for the primary endpoint or adverse-event counts is reported in the registry record, so their statistical precision cannot be quantified.

Can the adverse-event counts be compared?

The record reports one device arm rather than a comparator group. Counts for serious and other adverse events can describe what was recorded in that arm, but they do not estimate a contrast between treatments. A treatment comparison requires suitable groups and an analysis designed to account for how those groups were formed. No such comparison is reported, and the record states that allocation is not stated and that this is not a randomized comparison.

Even within one arm, event categories need careful interpretation. The registry does not say whether a participant could appear in both the serious and other adverse-event counts, whether a death was also counted among those affected, or whether the term percentages refer to participants or events. General statistical practice distinguishes participants experiencing events from total event episodes, because these answer different questions. The record does not provide enough detail to reconcile those quantities.

What can a planning illustration establish?

The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. These are planning conventions, not evidence that the trial used those assumptions in its design. The registry record does not report a sample-size justification or a statistical plan for the study itself. A planning illustration is not observed power and does not supply a missing endpoint result.

In general, power calculations depend on assumptions about the effect, variability, allocation, outcome type, and analysis. If the assumptions differ from the study context, the resulting planning values may not describe what the study could detect. Since no comparator or primary endpoint analysis is reported, the planning conventions should not be used to infer a treatment effect or the certainty of a safety conclusion.

Why might event variability affect analysis?

For event counts, general methods may need to account for variation greater than a simple model expects, sometimes called over-dispersion. It can arise when event counts vary more across participants than the model allows, and can make standard errors and confidence intervals too optimistic if ignored. This is a general consideration, not a claim about the data in this registry. The record does not report a count model or information sufficient to assess over-dispersion.

For a binary participant outcome, the analysis should also align the statistical method with the outcome definition, follow-up, and denominator. The registry’s zero listed analyses means no test, model, or adjustment can be attributed to the posted results. Descriptive counts should not be presented as if they were adjusted estimates or formal evidence of a difference.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Treatment Arm, Single Arm Study")
n      <- c(130)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment Arm, Single Arm Study  130  5  3.8  1.3  8.7  1.7  8.7  1.7  8.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and zero analyses. It does not report a statistical plan, a hierarchy of outcomes, or a plan for handling multiple comparisons. Multiplicity arises when several hypotheses or outcomes are tested, because repeated testing can increase the chance of a result appearing statistically notable by chance. This is a general statistical concern; the record does not show that formal hypothesis testing was conducted or that a multiplicity adjustment was needed or used.

The primary endpoint result itself is not reported in the registry record. The record does not describe whether other outcomes were planned, how outcomes were selected for reporting, or whether any analyses were prespecified. It is therefore not possible to assess selective reporting or to identify an analysis set from the registry information alone.

Missing-data handling is not reported in the registry record. The one-year timeframe is specified, but the record does not say how participants without complete follow-up were handled, whether outcome status was available for everyone, or how missing event information was classified. Missingness can affect an estimate if the availability of data is related to participant characteristics or event status. No assumption about the pattern or impact of missing data can be made.

The analysis populations are also not reported in the registry record. Enrollment is listed as 130, and the primary population description also refers to 130 participants implanted with the shunting system for one year. The record does not explain whether those descriptions correspond to the same analysis set, define exclusions, or indicate how follow-up availability affected inclusion in an analysis.

These gaps do not establish that the study had missing data, selective reporting, or multiplicity problems. They mean that the registry record does not contain the information needed to evaluate those issues. The reported event figures should be understood as registry descriptions, not as results from a documented inferential analysis.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neurological disorders (5.4%), product problems (4.6%), intracranial infection (4.6%), injuries (4.6%), pneumonia (1.5%).

The adverse-event group is the HAKIM Programmable Shunt System Arm. The registry lists 130 participants at risk for serious adverse events and 31 affected; for other adverse events it lists 130 at risk and 9 affected. It also lists 4 deaths. These figures describe what the registry reports, but do not by themselves establish event causation or comparative risk.

The listed serious-event terms and percentages are Neurological disorders at 5.4%, Product problems at 4.6%, Intracranial infection at 4.6%, Injuries at 4.6%, Pneumonia at 1.5%, and tumor at 1.5%. The record does not explain whether these terms can overlap, whether percentages are based on participants or event episodes, or how the terms were selected. They should not be added or treated as a mutually exclusive breakdown.

The record does not state whether deaths overlap with serious or other adverse events, nor does it clarify whether these figures all use the one-year timeframe. The primary endpoint is described separately and its result is not reported. Accordingly, adverse-event listings should be read as descriptive safety information with important denominator, timing, and classification details left unspecified.

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

The posted registry information supports a narrow conclusion: it records a completed, multicenter, retrospective safety study of the Hakim Programmable Shunt System, with enrollment of 130, a one-year primary timeframe, and adverse-event figures for one device arm. It lists 31 participants affected by serious adverse events, 9 affected by other adverse events, and 4 deaths. These figures are descriptive; they are not estimates of a difference between the device and another treatment.

The primary endpoint is a count of participants with “non-infection” within one year, but the result is not reported in the registry record. Its wording is also insufficiently detailed to establish exactly what qualifies. Thus, the central endpoint cannot be used to quantify the recorded frequency of the outcome from this record.

The figures do not establish that the device caused any listed event, nor do they establish that the device prevented or increased events. A retrospective registry without a reported comparator cannot rule out other explanations for an event, including the underlying condition, other care, or differences in participant characteristics. The record does not provide the detail needed to assess those possibilities.

The listing of adverse events also does not establish that every event was captured or that every participant had complete follow-up for the stated timeframe. Completeness of follow-up and event ascertainment methods are not reported in the registry record. Nor does the completed study status resolve those questions.

General statistical interpretation distinguishes the observed information in a registry from a causal treatment effect. A causal claim typically requires a design and analysis that address how treatment was received and how groups may differ. No randomized comparison or comparator arm is reported. The record also lists no analyses, confidence intervals, or adjusted estimates. Therefore, it does not show the precision of an estimated event frequency or support a formal comparison.

The appropriate reading is limited to the outcomes and counts actually recorded, with their definitions and context kept in view. The record does not establish a complete safety profile, quantify the primary endpoint, or determine whether the device changed risk relative to an alternative.

14. Why This Trial Matters Statistically

This study matters statistically because safety registries often collect outcomes that are difficult to interpret without precise definitions, follow-up information, and clear denominators. The record identifies a one-year primary endpoint and reports adverse-event information, but the primary result is absent. That gap illustrates why an outcome’s title alone is not enough to evaluate its frequency or precision.

The distinction between participants affected and event episodes is important in safety reporting. A participant-based count answers how many people met a definition; an event count answers how many episodes were recorded. The registry’s primary outcome is explicitly participant-based, while the adverse-event details do not clarify all counting conventions. Keeping those measures separate avoids treating them as interchangeable.

The study also illustrates the limits of single-arm evidence. A registry can document events among participants who received a device, but without a comparator it cannot estimate a relative difference or separate the device’s contribution from other causes. The retrospective design and unspecified allocation further mean that a randomized contrast is not available in the reported record.

Finally, statistical precision and data quality are distinct considerations. Confidence intervals can describe sampling uncertainty in an estimate, but they cannot repair unclear event definitions, incomplete follow-up, or unreported ascertainment procedures. Here, no statistical analyses or intervals are listed, and the record does not explain those data-collection details. Readers can describe the counts and listed terms, while recognizing that the information does not support a complete inferential safety assessment.

15. 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.

Several limitations are specific to the information recorded for this study. First, the primary endpoint result is not reported in the registry record. Its title refers to participants with “non-infection,” while its description calls it a non-infection rate; the record does not define the classification or explain how the endpoint was determined. This prevents a clear interpretation of what the measure was intended to capture.

Second, the design is retrospective and no comparator is listed. Allocation is not stated, and the record identifies no like-for-like control comparison. The adverse-event counts therefore describe one device arm and cannot establish a comparative effect or causal relationship.

Third, follow-up and event ascertainment details are not reported. Although the primary timeframe is one year and the brief summary refers to events within one year after catheter implantation, the record does not explain completeness of follow-up, methods for identifying events, or handling of participants whose status was unavailable. It also does not say whether the adverse-event figures all use the same timeframe as the primary endpoint.

Fourth, event-counting conventions are unclear. The record does not state whether serious and other adverse-event categories overlap, how deaths relate to those categories, or whether the listed term percentages refer to participants or events. The percentages should not be read as a mutually exclusive distribution.

Finally, no analyses are listed. Statistical methods, analysis populations, missing-data handling, and any sample-size justification are not reported in the registry record. These limitations describe gaps in the available record; they do not prove that the underlying study lacked procedures or that data were incomplete.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study on the Safety of Hakim Programmable Shunt System — NCT04285489.
• Registry record last updated 2021-11-05; status last verified 2021-11.
• Results first posted 2021-09-21.
• 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.

19. Record Summary

The registry identifies NCT04285489 as a completed, multicenter, retrospective registry study of the Hakim Programmable Shunt System for hydrocephalus. Enrollment is 130. The study began on 2020-05-02, with primary completion on 2020-07-28. Its stated aim was to collect safety information after implantation, with a one-year primary timeframe.

The primary outcome is titled “Number of Participants With Non-infection Within One Year,” but its result and a statistical analysis are not reported in the registry record. The adverse-event group lists 31 participants affected by serious adverse events, 9 affected by other adverse events, and 4 deaths. It also lists several serious-event terms with percentages. The record reports one device arm and no comparator, so these figures are descriptive rather than comparative.

Statistical methods, analysis populations, missing-data handling, and detailed event definitions are not reported in the registry record.