Post-Operative Cognitive Dysfunction in Normal Aging Patients Undergoing Elective Orthopedic Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Post-Operative Cognitive Dysfunction in Normal Aging Patients Undergoing Elective Orthopedic Surgery (NCT04267328), a registered phase not stated study. The primary outcome is Presence of Post Operative Cognitive Dysfunction (POCD).

2. Clinical Question

3. Trial Design

The registry identifies the study as Post-Operative Cognitive Dysfunction in Normal Aging Patients Undergoing Elective Orthopedic Surgery, sponsored by HealthPartners Institute. Its status is completed. The recorded study start date is 2020-01-06, and the primary completion date is 2023-05-09. Enrollment is listed as 47.

The listed intervention is elective orthopedic surgery, with an arm description for patients having surgery. The registry explicitly cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Allocation is not stated. These details do not support a comparative estimate of surgery versus an untreated or alternative-treatment group.

The brief summary describes the study as evaluating the incidence of post-operative cognitive dysfunction and associated risk factors in aging patients without a prior history of mild cognitive impairment or dementia. The primary outcome is the presence of post-operative cognitive dysfunction at three months, defined using change in cognitive test performance from baseline. The registry lists one outcome measure and no analysis entries.

Other design details—including the specific eligibility criteria, recruitment process, follow-up procedures, and planned statistical analysis—are not reported in the registry record. A sample-size justification is also not reported in the registry record. The enrollment figure describes the registered study enrollment; it does not, on its own, establish how many participants completed follow-up or contributed data to the primary outcome.

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

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 Presence of Post Operative Cognitive Dysfunction (POCD), measured over 3 months.

The primary endpoint is the presence of post-operative cognitive dysfunction, recorded as a count of participants. The registry defines a case as a decline of 1.5 or greater standard deviation on any one of the cognitive tests performed, comparing baseline with three months after surgery. It also reports a score range of 0-100 and states that a higher score indicates more cases of incident post-operative cognitive dysfunction.

This endpoint is intended to identify cognitive change after surgery rather than simply describe a single test score at one time point. A baseline-to-follow-up definition makes each participant’s later performance interpretable in relation to their own starting assessment. Using a threshold can also make the outcome easier to classify as present or absent for a count-based analysis.

In general, a threshold-based endpoint depends on the choice of threshold, the tests included, and how test results are measured. The phrase any one means that a qualifying decline on one cognitive test is sufficient under the registry definition. The registry does not report which tests were used, how many tests were administered, how scores were combined or checked, or how missing test results were handled. Most importantly, it does not report the number of participants who met the definition, so the endpoint result cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are not described in the registry record. No analysis entries are listed, and no model, test, adjustment strategy, or uncertainty estimate is reported for the primary outcome. The explanations below are general statistical context, not a description of methods confirmed to have been used in this study.

What does a count endpoint represent?

The primary outcome is specified as a count of participants meeting the endpoint definition. For a count to be interpretable, it is useful to know the number assessed, the number meeting the definition, and how participants with incomplete assessments were treated. The registry lists enrollment as 47, but does not report the primary outcome count, the number with evaluable cognitive tests, or the handling of incomplete follow-up. The enrolled group therefore cannot automatically be treated as the denominator for the outcome.

In general, a count can be described alongside the number of participants assessed, while a proportion places that count in relation to its denominator. Neither should be inferred when the relevant values are absent. A proportion based on an assumed denominator could misrepresent the frequency if some enrolled participants did not complete follow-up or lacked the required test data.

Why does the endpoint definition matter?

The registry defines an outcome as decline of 1.5 or greater standard deviation on any one cognitive test between baseline and three months after surgery. A threshold converts a continuous change in test performance into a classification. This can make an outcome easier to communicate, but participants near the threshold may be classified differently from participants with changes farther from it. In general, interpretation depends on the tests, scoring procedures, baseline measurements, and rules for missing values. These operational details are not reported in the registry record.

The any one test rule also has statistical implications. In general, if several tests are checked and a positive result on any test is sufficient, the overall chance of at least one threshold crossing can be greater than the chance for an individual test considered alone. This is a multiplicity issue. Its practical importance depends on the number and relationship of the tests and on any adjustment or prespecified outcome hierarchy. Those details are not reported in the registry record, so the effect cannot be quantified.

What would an uncertainty estimate add?

In general, a confidence interval describes uncertainty around an estimate, such as an event proportion or a difference between groups. It is not a guarantee that the true value lies in a particular interval; rather, it reflects the behavior of a statistical procedure over repeated samples under its assumptions. An interval can help readers distinguish a precise estimate from one with substantial uncertainty. The registry record reports no primary outcome estimate or confidence interval, so neither the observed frequency nor its precision can be evaluated.

A statistical test, in general, assesses how compatible observed data are with a specified null hypothesis, given the model assumptions. A p-value is not the probability that the null hypothesis is true and does not measure clinical importance. Because no test results or analysis entries are reported, there is no p-value to interpret for the primary outcome.

What can be inferred without a control group?

In general, an outcome measured in a single group can describe what was observed in that group when results and denominators are available. It does not by itself separate changes related to surgery from changes related to aging, other health events, test variation, or other influences. A comparison group can help address some alternative explanations, but only when its design and analysis support a valid comparison. The registry specifically cautions that the arms are not a like-for-like control comparison and says allocation is not stated. No comparative effect can therefore be read from this record.

How should planning estimates be read?

In general, sample-size calculations are planning illustrations based on assumptions about the effect to be detected, the statistical test, the significance level, and allocation. They are not observed results and do not show how much power a completed study actually had. The record’s planning assumptions refer to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect expressed as a fraction of an observed effect. No calculated planning values or observed primary effect are reported in this record. The trial’s own sample-size justification is not reported in the registry record.

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("Patients Having Surgery")
n      <- c(47)
events <- c(15)
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  Patients Having Surgery  47  15  31.9  19.1  47.1  20.4  46.2  20.4  46.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but its definition counts a decline on any one of the cognitive tests performed. In general, when several tests can each qualify a participant for the endpoint, the number of opportunities to cross a threshold matters. An adjustment, a hierarchy of tests, or another prespecified rule can address multiplicity, but the registry does not report whether any such approach was used. The number of cognitive tests is also not reported in the registry record, so the extent of multiplicity cannot be evaluated.

Missing-data handling is not reported in the registry record. The record does not say how participants without a baseline test, a three-month test, or complete data across tests were treated. This matters because the outcome requires comparison of baseline and follow-up performance. If availability of test data is related to participants’ health or cognitive status, analyses limited to complete assessments can differ from results in the full enrolled group. That is a general concern, not evidence that missing data occurred in this study.

The analysis population is not reported in the registry record. Although enrollment is listed as 47, there is no reported number assessed at three months, number included in the primary outcome analysis, or account of exclusions. The registry also does not report an analysis plan, interim analyses, or the handling of protocol deviations. No particular approach should be assumed.

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 0% reporting threshold.

The registry’s serious adverse event summary lists 47 at risk and 0 affected in the Patients Having Surgery group. It lists 47 at risk and 0 affected for other adverse events, and 0 deaths. No top serious adverse event terms are listed.

These are the safety figures recorded in the registry. They should be read as the posted counts, not as proof that no adverse events of any kind occurred. The record does not describe the collection period, event definitions, attribution procedures, or completeness of safety reporting. It also does not provide additional detail about event severity beyond the serious-event classification.

In general, a zero reported count can coexist with uncertainty about the underlying event frequency, particularly when the number observed is limited or when reporting details are incomplete. The listed at-risk counts do not establish that every participant completed all follow-up or safety monitoring. No inference about comparative safety is possible because the registry does not describe a like-for-like control comparison.

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

The registry record establishes that the study was completed, lists enrollment as 47, and defines a primary cognitive outcome assessed at three months after surgery. It also states that the study aimed to assess incidence and associated risk factors in aging patients without a prior history of mild cognitive impairment or dementia. These are descriptions of the study’s scope, not evidence of its findings.

The primary outcome count and the analyses are not reported in the registry record. As a result, readers cannot determine the observed frequency of post-operative cognitive dysfunction, its precision, or whether any risk factors were associated with it. The stated enrollment cannot fill this gap: without an outcome count and a clear analysis denominator, no incidence estimate can be recovered from the record.

The record does not describe a randomized, like-for-like control comparison. It therefore cannot answer how the observed outcome compares with what would occur under an alternative approach. More generally, a before-and-after assessment in a group undergoing surgery cannot by itself attribute any cognitive change to surgery, because other influences may also affect test performance over time.

In general, statistical evidence should be interpreted by considering the endpoint definition, the observed estimate, its uncertainty, the analysis population, and the design. Here, the endpoint definition is available, but the outcome estimate, uncertainty, and analysis details are not. The safety summary records zero affected for serious and other adverse events and zero deaths, but the record does not describe reporting completeness or monitoring procedures.

The appropriate reading is therefore limited: the registry records a completed study and a defined research question, but does not report the primary results needed to answer that question. No conclusion about the presence, absence, or frequency of cognitive dysfunction follows from the missing outcome result.

14. Why This Trial Matters Statistically

This study raises statistical issues that are important when research concerns cognitive change after surgery. The outcome compares performance at baseline with performance at three months and uses a threshold based on standard deviation. Such a definition requires transparent reporting of the tests, scoring, assessment timing, and rules for incomplete data. Without those details, readers have limited ability to reproduce or assess the classification.

The rule that a decline on any one test qualifies as an event makes multiplicity relevant. In general, the more opportunities there are for a threshold to be crossed, the more important it is to report how the tests were selected and whether a prespecified adjustment or decision rule was used. The registry does not provide these details, making it difficult to judge how the endpoint should be interpreted.

The study also illustrates why design and analysis information matter alongside an enrollment figure. A count-based endpoint needs a reported numerator and denominator, while a meaningful estimate of precision requires an uncertainty measure. The registry reports neither the primary result nor an analysis entry. Its note that the arms are not a like-for-like control comparison also limits the questions that can be answered through comparison.

Finally, a completed status does not mean that results are available in the registry record. Clear reporting of outcomes, analysis populations, missing data, and safety collection would be needed to assess what the study found and how much confidence to place in those findings. These reporting elements are central to evaluating evidence, independent of the clinical topic.

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 specific to this registry record constrain interpretation. The primary outcome is defined, but the number of participants meeting it is not reported. There is also no reported denominator for participants with complete baseline and three-month assessments, no effect estimate, and no uncertainty interval. The study’s incidence objective therefore cannot be assessed from the posted results.

The cognitive tests are not named, and the number of tests and their scoring procedures are not reported. Because the definition uses a decline on any one test, these omissions prevent assessment of how broadly the endpoint was tested and how test-level results were converted into a participant-level outcome. The registry also does not report how incomplete assessments were handled.

The record states that the arms are not a like-for-like control comparison and that allocation is not stated. It cannot support an estimate of a comparative treatment effect. Details needed to assess the intended risk-factor analyses are also absent: no analysis entries, model specifications, or risk-factor results are reported.

Enrollment is listed as 47, but the record does not say how many participants completed follow-up or entered the outcome analysis. The sample-size justification is not reported in the registry record. The safety counts are listed, but event collection and follow-up procedures are not described. These gaps do not show that a particular problem occurred; they limit what can be established from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Post-Operative Cognitive Dysfunction in Normal Aging Patients Undergoing Elective Orthopedic Surgery — NCT04267328.
• Registry record last updated 2024-04-19; status last verified 2022-09.
• Results first posted 2024-04-19.
• 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 record describes a completed study of post-operative cognitive dysfunction in older adults undergoing elective orthopedic surgery. HealthPartners Institute is listed as sponsor, enrollment is 47, and the primary completion date is 2023-05-09. The primary outcome is the presence of cognitive dysfunction at three months, defined as a decline of 1.5 or greater standard deviation on any one cognitive test from baseline.

The record lists one outcome measure and no analysis entries. It does not report the primary outcome count, risk-factor analyses, or statistical uncertainty. The registry states that the arms are not a like-for-like control comparison and that allocation is not stated. Safety figures list 0 serious adverse events, 0 other adverse events, and 0 deaths among the recorded at-risk counts. The missing outcome and analysis details prevent assessment of the study’s stated incidence question.