Comparative Study of Specular Microscopes for Measurements of Cell Density, Coefficient of Variation and Hexagonality: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparative Study of Specular Microscopes for Measurements of Cell Density, Coefficient of Variation and Hexagonality (NCT02276638), a registered phase not stated study. The primary outcome is Center Method Corneal Endothelial Cell Density.

2. Clinical Question

The study’s stated purpose was to collect clinical data supporting an FDA 510(k) submission for the Nidek CEM-530 center point and corner point methods. Its secondary objective was to evaluate adverse events. The registry identifies three outcome measures, but the primary outcome description is the only outcome detail included in the record details. The study title also refers to coefficient of variation of endothelial cell area and percentage hexagonality.

The central statistical question is whether density measurements from the named microscope methods are similar or differ in the participant groups. Answering that quantitatively would require reported measurements and a clearly specified comparison. The registry record does not provide those results or the analysis details. Accordingly, the available information describes the study question and measurement target, but does not establish the size or precision of any difference.

3. Trial Design

The registry describes a completed clinical study sponsored by Nidek Co. LTD. The recorded study start was 2014-09, and primary completion was 2014-10. Enrollment was 79. The stated primary objective was to collect clinical data supporting an FDA 510(k) submission for the Nidek CEM-530 center point and corner point methods; the secondary objective was adverse-event evaluation.

The listed devices were the Nidek CEM-530 and Konan CELLCHEK XL. The arm descriptions identify three participant groups: 18-28 years old and non-pathologic, 29-80 years old and non-pathologic, and 29-80 years old and pathological. Each arm description names both devices. These details identify the devices and participant categories, but do not specify how device use was assigned, whether measurements were paired, or whether a particular method was used with each device in each participant.

Allocation is not stated. The registry information also cautions that the arms are not a like-for-like control comparison. It would therefore be inappropriate to interpret the listed groups as randomized treatment arms or to infer a controlled device effect from the group labels alone. The record does not describe masking, measurement order, eligibility criteria, or the rationale for the participant categories; those details are not reported in the registry record.

The primary outcome is a continuous measure: center method corneal endothelial cell density, with the mean and standard deviation specified and a timeframe of single time point - 1 day. The registry notes that not all participants indicated in the Participant Flow Module were analysed for this outcome. It does not provide a full account of the analyzed population or explain exclusions. These design details limit what can be inferred about comparability and the scope of the outcome assessment.

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

Analysis population for the primary outcome, as defined in the registry: Not all participants indicated in the Participant Flow Module were analysed.

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 Center Method Corneal Endothelial Cell Density, measured over single time point - 1 day.

The primary endpoint is center method corneal endothelial cell density, expressed in cells/mm2. It is specified as a continuous outcome summarized by its mean and standard deviation, with the timeframe recorded as single time point - 1 day. The registry identifies the outcome but does not include its numerical mean, standard deviation, or a device comparison estimate.

In general, cell density is a quantitative measurement, so a mean can describe the central level of the measurements in an analyzed group. A standard deviation describes how spread out individual measurements are around that mean. Neither summary alone describes whether two measurement methods agree closely for individual participants: group means can be similar while individual paired measurements vary. Agreement questions ordinarily require results suited to the study’s measurement structure, which is not specified in the registry record.

The study title additionally names coefficient of variation of endothelial cell area and percentage hexagonality. The registry lists three outcome measures, but further details for those outcomes are not reported in the registry record. The primary endpoint is therefore best read as the stated measurement target, not as evidence of a particular measurement result or degree of agreement.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, so its reported summary type is a mean with standard deviation. In general, the mean represents the arithmetic center of a set of measurements. The standard deviation describes their dispersion around that center. Together, these summaries can convey a group’s average measurement and variability, but they do not show the full distribution or the relationship between two measurement methods for each participant. The registry does not provide the actual mean or standard deviation for the primary endpoint.

What would a comparison estimate mean?

In general, a comparison estimate expresses the size and direction of a difference or association according to a chosen analysis. Its interpretation depends on the design. If measurements are taken from the same participant using two devices, an analysis can use the within-participant pairing; if different participant groups are compared, the analysis must account for the between-group design. The registry record does not state whether measurements were paired or how device use was arranged. It therefore does not identify which comparison model, if any, was used.

For device measurement studies, average differences and individual-level agreement answer related but distinct questions. A small average difference can coexist with substantial variation in paired readings. Conversely, variability in individual readings does not by itself establish a systematic shift in the average. General agreement assessment requires information about paired measurements and an appropriate agreement analysis. Neither those data nor such an analysis is reported in the registry record, so no agreement conclusion can be drawn from the endpoint name alone.

How should uncertainty be understood?

In general, a confidence interval describes uncertainty around an estimated quantity under the assumptions of a statistical model. A narrow interval indicates greater precision than a wide interval, while the interval’s location indicates which values are compatible with the data and model. A p-value, when reported, assesses compatibility between observed data and a specified null model; it is not a measure of effect size, clinical importance, or probability that a hypothesis is true. The record does not report an estimate, confidence interval, p-value, or analysis method for the primary outcome.

Variability also matters to analysis. In general, over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, standard errors may be too small and uncertainty intervals may be too narrow. This concept is relevant to statistical modeling generally, but the registry does not report a model or evidence about over-dispersion for this study. The primary outcome is continuous and summarized with a standard deviation; no claim about the adequacy of any model can be made from that description.

What does the planning note say?

The record includes a sample-size planning illustration based on the observed effect, rather than the trial’s own design. Its stated 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 described as a stated fraction of the observed effect. For non-time-to-event outcomes, the note describes planning in participants per arm. The illustration is not evidence that the study was designed using those assumptions, and its figures should not be treated as observed power. Sample-size planning based on an observed effect is a conditional illustration: it depends on the effect used and the assumptions chosen. No planning results are included in the record details.

Power is a design property calculated under specified assumptions, not a retrospective measure of whether a study has produced persuasive evidence. In general, a planning calculation asks how many participants per arm would be needed to detect a target effect at a chosen significance level and power, given a model for variability and allocation. It does not show the probability that the observed result is true. The registry record does not report an actual sample-size justification, a target effect for the trial design, or an observed power calculation. It would be incorrect to infer any of these from the planning illustration.

The registry lists 0 analyses. That absence means the record does not specify a statistical test or model for the primary comparison. It also does not report whether analyses were adjusted, how repeated or paired measurements were handled, how outliers were treated, or whether assumptions were checked. These are not details that can be recovered from the primary endpoint’s summary type.

The title names density, coefficient of variation of endothelial cell area, and percentage hexagonality. Such outcomes may have different distributions and may call for different descriptive or inferential approaches; this is a general statistical consideration, not a description of methods used in this study. The registry record does not report the analytic methods for those additional measures. Taken together, the available information describes the intended endpoint and one planning framework, but not the statistical analysis that generated a result.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("18-28 Years Old Non-pathologic", "29-80 Years Old Non-pathologic", "29-80 Years Old Pathological")
n   <- c(28, 27, 19)
m   <- c(3069.5, 2678.6, 2514)
sp  <- c(346.41, 391.33, 351.02)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  18-28 Years Old Non-pathologic  28  3069.500  346.410  2935.176  3203.824
CARM  29-80 Years Old Non-pathologic  27  2678.600  391.330  2523.795  2833.405
CARM  29-80 Years Old Pathological  19  2514.000  351.020  2344.814  2683.186

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 3 outcome measures, and the study title names endothelial cell density, coefficient of variation of endothelial cell area, and percentage hexagonality. The primary outcome description concerns center method corneal endothelial cell density. Details for the other measures, including their definitions, timing, and numerical results, are not reported in the registry record.

When a study evaluates multiple outcomes or multiple comparisons, the chance of at least one apparently notable result can increase if each is tested independently at the same threshold. General approaches to multiplicity include prespecifying a primary outcome, adjusting tests, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among outcomes beyond identifying the primary measure, or an interim-analysis plan. No such procedures should be assumed.

The primary-outcome description states that not all participants indicated in the Participant Flow Module were analysed. The record does not state the number analyzed for this endpoint, the reasons for non-analysis, or how missing measurements were addressed. It does not report whether analyses followed an intention-to-treat, per-protocol, or other population definition. These omissions prevent assessment of how missingness might affect the endpoint summary or comparison.

In general, missing measurements can affect interpretation when the likelihood of missingness is related to participant characteristics or observed values. Appropriate handling depends on the amount and pattern of missing data, the study design, and assumptions about the missingness process. No missing-data method or sensitivity analysis is reported in the registry record. The enrollment figure should therefore not be substituted for an outcome-specific analyzed population.

There are 0 analyses listed. This leaves multiplicity handling, the statistical analysis population, and missing-data procedures unreported. These gaps are material when interpreting any proposed comparison, but the record does not permit quantifying their effect.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 adverse-event entries list 28 participants at risk in the 18-28 Years Old Non-pathologic group, with 0 serious adverse events and 0 other adverse events. For the group titled 29-9- Years Old Non-pathologic, it lists 28 at risk, with 0 serious adverse events and 0 other adverse events. For the 29-80 Years Old Pathological group, it lists 23 at risk, with 0 serious adverse events and 0 other adverse events. The death fields are null for these entries.

These are the recorded counts for the listed safety categories and groups. A zero count means that no event was entered for that category in the registry record; it does not establish that every possible event was sought, reported, or captured. Null death fields do not provide a numerical death count and should not be read as a confirmed zero.

The non-pathologic group title “29-9- Years Old” differs from the 29-80 years old category in the arm descriptions. The registry record does not clarify that discrepancy. These safety figures should also be read separately from the primary measurement outcome: they do not provide information about the accuracy, agreement, or precision of the microscope measurements.

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

The record describes a completed study of specular microscopes, identifies the Nidek CEM-530 and Konan CELLCHEK XL, and names center method corneal endothelial cell density as the primary endpoint. It also records participant categories and selected adverse-event counts. This information clarifies the subject and stated objectives of the study, but it is not a numerical report of comparative measurement performance.

In particular, the posted information does not give a primary-outcome mean, standard deviation, effect estimate, confidence interval, or test result. It therefore cannot show how close the readings were on average, how much measurements varied, or how precisely any difference was estimated. It also does not establish agreement for individual measurements. Those conclusions require outcome data and analysis details that are not reported in the registry record.

The result does not establish that one device or method is more accurate, more precise, or interchangeable with another. Nor does the lack of a reported estimate establish that the devices are equivalent or that there is no difference. Equivalence or non-inferiority requires a defined margin and an analysis designed to evaluate it; those details are not reported in the registry record. A missing or unavailable comparison is not evidence for either similarity or difference.

Interpretation is further constrained by the unspecified allocation and measurement arrangement, the registry’s caution that the arms are not a like-for-like control comparison, and the note that not all participants indicated in the Participant Flow Module were analysed for the primary outcome. The analyzed population, missing-data handling, and statistical methods are not reported. Thus, the record supports a careful account of study scope and endpoint, while leaving the central quantitative comparison unresolved.

14. Why This Trial Matters Statistically

This study is statistically relevant because it concerns measurement rather than a conventional comparison of treatment outcomes. For measurement devices, the question is not only whether group averages differ, but also whether readings correspond closely enough at the individual level for the intended use. General statistical methods distinguish average bias from agreement and from precision. Those distinctions matter when interpreting comparisons of instruments, yet the registry record does not provide the paired results or analysis needed to evaluate them.

The study also illustrates why design details are essential. If both devices measure the same participant, within-participant comparisons can account for some differences between people. If devices are used in separate groups, the comparison has different assumptions and potential sources of confounding. Allocation and measurement arrangement are not reported, so the data structure cannot be established from the registry description. The caution that the arms are not a like-for-like control comparison reinforces the need not to treat group labels as proof of comparability.

Outcome reporting is equally important. The registry identifies three outcome measures and specifies the primary endpoint as a continuous mean with standard deviation, but provides no numerical endpoint results in the record details. Without estimates and uncertainty measures, readers cannot judge effect size, precision, or consistency. The note that not all participants indicated in the Participant Flow Module were analysed also makes transparent reporting of the analysis population important.

Finally, the planning illustration is distinct from the study’s actual design and from evidence about its findings. Planning assumptions can help frame hypothetical future studies, but they cannot substitute for observed outcome estimates or a prespecified analysis. The statistical value of the record is therefore chiefly in clarifying the intended measurement question and showing which design and reporting details remain necessary for an interpretable comparison.

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. The primary endpoint is identified, but its numerical results are not reported in the record details. The mean, standard deviation, comparison estimate, and uncertainty around that estimate are unavailable, preventing assessment of the size and precision of any observed difference.

The device-use structure is unclear. The record names both microscopes in each arm description, but does not state whether the same participants were measured with both devices, how measurements were assigned or ordered, or what comparison was planned. Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. No adjustment strategy or statistical model is reported.

Population reporting is incomplete for interpretation of the endpoint. Although enrollment is listed as 79, the primary-outcome description says that not all participants indicated in the Participant Flow Module were analysed. The outcome-specific denominator, the reasons for non-analysis, and the handling of missing data are not reported. The record does not specify whether results were intended to be pooled or separated by participant group.

There are 0 analyses listed, and the registry does not report a multiplicity plan or analysis details for the additional outcomes named in the study title. Safety reporting includes null death fields and a group label, “29-9- Years Old Non-pathologic,” that differs from the age category in the arm descriptions; the discrepancy is not clarified. These record limitations do not prove that the study lacked procedures or data, but those details are not reported in the registry record and cannot be used to support further conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Comparative Study of Specular Microscopes for Measurements of Cell Density, Coefficient of Variation and Hexagonality — NCT02276638.
• Registry record last updated 2019-03-20; status last verified 2019-03.
• Results first posted 2019-03-11.
• 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 describes a completed study sponsored by Nidek Co. LTD., with enrollment of 79, a recorded start of 2014-09, and primary completion in 2014-10. Its stated purpose was to collect clinical data supporting an FDA 510(k) submission for the Nidek CEM-530 center point and corner point methods, and to evaluate adverse events.

The listed devices were the Nidek CEM-530 and Konan CELLCHEK XL. The primary outcome was center method corneal endothelial cell density in cells/mm2, summarized as a mean with standard deviation at single time point - 1 day. The record notes that not all participants indicated in the Participant Flow Module were analysed. Three outcome measures are listed, but numerical primary-outcome results and analysis details are not available in the record details.

The listed safety groups report 0 serious and 0 other adverse events, while death entries are null. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. These details define the study’s recorded scope but do not quantify device agreement or difference.