Feasibility of iFS™ for Intrastromal Arcuate Keratotomy (ISAK) Procedures: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility of iFS™ for Intrastromal Arcuate Keratotomy (ISAK) Procedures (NCT01210820), a non-randomized na study. The primary outcome is Change in Refractive Astigmatism.

2. Clinical Question

In practical terms, the study asks whether the specified laser procedure can be evaluated in participants with these forms of refractive astigmatism and whether cylinder measurements change over the stated follow-up. The registry’s brief summary says the results will demonstrate that the procedure is safe; that wording describes the stated expectation, not a numerical finding. The available record does not include the primary endpoint results needed to assess change, nor does it give enough information to judge whether feasibility criteria were met. The study should therefore be read as a registered investigation with a defined clinical question, rather than as a reported estimate of treatment effect.

3. Trial Design

The registry describes a prospective, single-center study of intrastromal arcuate keratotomy performed with the iFS™ femtosecond laser system. The allocation is non-randomized, masking is absent, and the model is parallel. The study is marked completed. The recorded enrollment is 21, and the two named groups represent different clinical histories rather than randomized treatment assignments.

The Natural Astigmatism group consists of participants with refractive astigmatism and no prior ophthalmic surgery; the description allows that participants may also have cataracts. The Post cataract with residual astigmatism group consists of participants who have undergone cataract removal and continue to have residual astigmatism. The registry lists 17 participants at risk for adverse events in the natural-astigmatism group and 4 in the post-cataract group. Those group descriptions and counts do not establish that the arms are exchangeable or directly comparable.

The study began in 2010-07, with primary completion in 2012-06. Phase is recorded as NA. Abbott Medical Optics is listed as sponsor. The primary endpoint is change in refractive astigmatism at 6 months. The record lists 2 outcome measures and 0 analysis entries, but does not provide the numerical primary outcome result. Further details about eligibility criteria, procedural settings, follow-up completion, and the statistical analysis plan are not reported in the registry record.

Because allocation was not randomized and the arms differ by prior cataract surgery, an observed contrast between groups, if one were reported, could reflect differences in participant characteristics as well as any difference associated with the procedure. The registry itself flags that these are not like-for-like controls. The design can describe observations in the enrolled groups, but the record does not support a randomized causal comparison.

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 Change in Refractive Astigmatism, measured over 6 months.

The primary endpoint is change in refractive astigmatism at 6 months. It is defined as change in mean cylinder, assessed by manifest refraction, compared with baseline; the unit is diopter of cylinder change. This is a continuous outcome, and the registry identifies the parameter as a mean with standard deviation as the dispersion measure.

In general, a continuous endpoint retains information about the magnitude of a measured characteristic rather than reducing participants to categories such as improved or not improved. A mean describes the group’s average measured value or change. A standard deviation describes how spread out individual observations are around that average. These summaries answer different questions: the mean characterizes the group average, while the standard deviation characterizes variability among measurements.

In general, a baseline-referenced change measure helps describe how a measurement differs from its starting value over follow-up. Manifest refraction is the assessment named in the record for measuring cylinder. The endpoint is therefore relevant to the study’s stated focus on refractive astigmatism, but it is not itself a complete account of feasibility or safety. Interpretation would also depend on the actual estimate, its uncertainty, the number of participants with evaluable follow-up, and how missing measurements were handled. Those outcome details are not reported in the registry record, so no numerical average change or precision estimate can be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measure: change in mean cylinder at 6 months. It specifies the mean as the parameter of interest and the standard deviation as the measure of dispersion. The entry does not report a numerical result for either summary. The following explanations describe general statistical concepts and do not imply that a particular analysis was carried out for this study.

What does a mean change describe?

In general, a mean change summarizes the average within-participant difference between a follow-up measurement and baseline, when such paired observations are available. It can describe the average direction and size of change in the analyzed group. It does not show whether every participant changed in the same direction, nor does it describe the full distribution of individual responses. The registry specifies comparison with baseline but does not report how the change was calculated for participants without measurements at both time points.

The standard deviation is a descriptive measure of spread. In general, a larger standard deviation indicates more variation among individual measurements around the group mean; a smaller one indicates less spread. It is not the same as the standard error or a confidence interval. Because neither the mean change nor its standard deviation is reported, the registry entry does not permit evaluation of the average change or the observed variability.

What would a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity under the assumptions of the method used. Its width reflects both variability and the amount of information available. A narrow interval indicates greater statistical precision than a wide interval, but precision alone does not establish that an estimate is clinically important. A confidence interval for a mean change would help readers judge which values are compatible with the data and analysis. No such interval is reported in the registry record.

A p-value, if reported, would relate the observed data to a specified statistical null hypothesis under the test’s assumptions. It would not quantify the size of an effect, establish clinical importance, or measure the probability that the null hypothesis is true. No p-value or testing method is reported for the primary endpoint. The absence of a registered analysis entry also means there is no posted statistical test to interpret.

Why does the non-randomized design matter?

In general, random allocation can help balance measured and unmeasured characteristics between groups, although it does not guarantee perfect balance. Here, allocation is explicitly non-randomized. The arms are defined by whether participants have natural astigmatism or residual astigmatism after cataract removal, so they differ by clinical history. The registry warns that the arms are not a like-for-like control comparison. A simple contrast between their outcomes, if available, could therefore reflect group composition as well as any procedural association.

Adjustment can sometimes address measured differences, but it cannot automatically remove confounding, especially when relevant factors were not measured or are not included in the model. The registry lists 0 analyses and does not report an adjustment plan or model. It is therefore not possible to assess whether covariate adjustment was planned or performed. No adjusted treatment comparison should be inferred from the group descriptions alone.

What does over-dispersion mean in general?

Over-dispersion arises when observed variability is greater than a statistical model expects. It is relevant to some kinds of count or event data and can make standard errors too small if ignored. The primary endpoint is continuous, and the record does not identify an over-dispersion model or report data suggesting over-dispersion. The concept is therefore a general consideration, not a stated feature of this analysis. For a continuous outcome, interpretation instead depends on the distribution of measurements, the validity of the chosen model, and the assumptions used to estimate uncertainty; the registry does not report those model details.

How should planning illustrations be read?

The record describes sample-size planning illustrations using a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence about the outcome. In general, such calculations ask how much information might be needed to detect a target effect under assumptions about variability and analysis. They do not describe the power observed after the study was completed. Because the registry does not report the primary effect estimate or its dispersion, the basis for evaluating those illustrations is not available in the record.

General planning calculations can be sensitive to assumptions about the target effect, variability, allocation, and statistical method. If assumptions differ from the eventual study conditions, the planned sample size may not provide the anticipated precision or detection probability. The record does not report a protocol-based sample-size justification, a target effect specified before enrollment, or whether the planning illustration governed enrollment. Those matters are not reported in the registry record.

What can be concluded from the posted summaries?

The available information defines the study design, endpoint, follow-up time, groups, and recorded adverse-event counts. It does not supply the continuous outcome summaries or inferential results. A sound statistical interpretation must distinguish those design details from the missing numerical results. Without the endpoint estimate, its dispersion, and an account of the analyzed observations, the magnitude and precision of change cannot be characterized. The record also does not support a causal comparison between the non-randomized groups.

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("Natural Astigmatism", "Post Cataract With Residual Astigmatism")
n   <- c(17, 4)
m   <- c(-0.97, -0.81)
sp  <- c(0.43, 0.35)
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  Natural Astigmatism  17  -0.970  0.430  -1.191  -0.749
CARM  Post Cataract With Residual Astigmatism  4  -0.810  0.350  -1.367  -0.253

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and identifies change in refractive astigmatism as the primary endpoint. It lists 0 analysis entries. The record does not describe a multiplicity procedure, a hierarchy among outcomes, or which outcomes were included in formal hypothesis tests. A multiplicity plan is not reported in the registry record.

In general, evaluating multiple outcomes or multiple statistical tests can increase the chance of at least one apparently notable result arising by chance. A prespecified testing strategy can help readers understand how such testing was handled. The record does not provide enough information to determine whether multiplicity was addressed in a protocol or analysis plan, so no particular approach should be assumed.

The record does not report the number of participants with primary endpoint measurements at baseline or 6 months, reasons for missing measurements, or methods used to handle missing data. It also does not identify an intention-to-treat, per-protocol, or other analysis population. The population field for the primary outcome is blank. These details are not reported in the registry record.

In general, missing observations can affect the interpretation of an average change if the participants with observed measurements differ from those without them. Methods for handling missing data rely on assumptions, and the assumptions should be stated to judge how robust an estimate may be. Since neither missingness information nor the analysis population is reported, the available record cannot show which participants contributed to an endpoint estimate or how incomplete follow-up was treated.

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 5% reporting threshold.

The registry records 0 serious adverse events and 0 other adverse events for Natural Astigmatism, with 17 at risk in that group. It records 0 serious adverse events and 0 other adverse events for Post Cataract With Residual Astigmatism, with 4 at risk in that group. These figures describe the adverse-event entries in the registry; they should not be read as proof that no adverse events could occur.

The record does not report the adverse-event definitions, the collection or monitoring procedures, the duration of safety surveillance, or whether all participants contributed the same observation time. Without those details, the event counts cannot be interpreted as a comprehensive assessment of safety. The groups also differ by clinical history and are non-randomized, so their recorded figures are not a controlled safety comparison.

Deaths are recorded as null, not as 0. Accordingly, deaths are not reported in the registry record. The brief summary states an expectation that the study results will demonstrate safety, but that statement is not an event analysis or a reported safety conclusion. The recorded adverse-event counts are limited information and should be interpreted alongside the absent definitions and follow-up details.

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

The registry establishes that a prospective, single-center feasibility study evaluated ISAK performed with the iFS™ femtosecond laser system in participants with refractive astigmatism. It defines change in mean cylinder, assessed by manifest refraction compared with baseline at 6 months, as the primary endpoint. It also records adverse-event counts for the two clinically defined groups. These details show what was studied and what the registry captured.

The registry does not report the numerical result for the primary endpoint. It therefore does not show whether the average cylinder measurement changed, how large any change was, how variable individual measurements were, or how precise an estimate might be. No conclusion about the direction or magnitude of the primary outcome can be drawn from the endpoint definition alone. The record also does not provide an analysis population, follow-up completion information, or an inferential result.

The arm structure does not create a randomized control comparison. Participants were assigned to groups according to clinical history, and the registry cautions that the groups are not like-for-like controls. A difference between groups, if reported elsewhere, would not by itself establish that the procedure caused the difference. The registry entry supplies no adjusted analysis to interpret.

The recorded adverse-event counts are 0 in each listed event category for both groups, but definitions and surveillance details are not reported. Null death entries do not mean that a numerical zero was reported. Thus, the safety information in this record is limited and should not be treated as definitive evidence of safety or as proof that events did not occur outside the reported categories.

In short, the record describes a study question and some design and safety data, but does not provide the primary outcome results needed to quantify the observed effect. The distinction between a registered objective, an expectation stated in a summary, and a reported analysis is essential to interpreting what the record does and does not establish.

14. Why This Trial Matters Statistically

Statistically, this trial matters because it illustrates the difference between a registered endpoint and a reported result. The registry defines a continuous primary measure, its assessment method, comparator to baseline, and follow-up time. Yet it does not provide the mean change or its standard deviation. Without those values, readers cannot assess the observed magnitude, variability, or precision of the primary outcome.

The study also highlights why design features shape interpretation. Non-randomized allocation and groups based on different clinical histories make direct group comparisons difficult to interpret as causal effects. The registry explicitly notes that the arms are not like-for-like controls. Recognizing this limitation is important when reading any future estimate or comparison associated with the study.

The planning assumptions offer another useful statistical distinction. A sample-size illustration based on an observed effect is not the same as the trial’s observed power and is not an outcome result. Planning calculations depend on assumptions about the effect and analysis; they cannot fill in missing endpoint estimates. The record does not report the endpoint estimate needed to assess the effect underlying those illustrations.

Finally, the adverse-event entries show why counts require context. The registry lists zero recorded serious and other events in both groups, but it does not report the event definitions or safety-monitoring details, and the death entries are null. Statistical interpretation therefore depends not only on the numerical entries but on how outcomes were defined, collected, analyzed, and reported. The registry record leaves those key details unresolved.

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.

The registry record offers limited information for evaluating the study’s primary result. Although it defines change in refractive astigmatism at 6 months, it does not report the mean change, standard deviation, confidence interval, or statistical test. The number of participants with evaluable endpoint data and the handling of missing measurements are also not reported in the registry record. This prevents assessment of the endpoint’s magnitude and precision.

The non-randomized design is a specific limitation for comparative interpretation. The arms reflect different clinical histories rather than randomized assignments, and the registry warns that they are not like-for-like controls. The record does not describe an adjustment strategy or provide analyses that could be evaluated for confounding. The registry identifies the study as single-center, which also limits what can be inferred about whether observations would apply in other settings; participant selection and practice details are not reported.

The record does not report procedural details, eligibility criteria, participant flow, follow-up completion, or protocol-defined feasibility criteria. The safety entries lack event definitions and monitoring details. Deaths are listed as null, not as a numerical count. The record’s brief statement of an intended safety demonstration is not a substitute for a reported safety analysis.

Finally, the registry lists 0 analysis entries and does not describe multiplicity handling, an analysis population, a statistical model, or a protocol-based sample-size justification. These omissions do not establish that such plans or procedures did not exist; they mean that they are not reported in the registry record. The available information is therefore insufficient for a full appraisal of analysis conduct or robustness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Feasibility of iFS™ for Intrastromal Arcuate Keratotomy (ISAK) Procedures — NCT01210820.
• Registry record last updated 2013-05-01; status last verified 2013-04.
• Results first posted 2013-04-26.
• 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

NCT01210820 is a completed, prospective, single-center, non-randomized parallel study sponsored by Abbott Medical Optics. Its stated focus is the feasibility of intrastromal arcuate keratotomy performed with the iFS™ femtosecond laser system in participants with refractive astigmatism. Enrollment is recorded as 21.

The primary endpoint is change in mean cylinder by manifest refraction compared with baseline at 6 months. The registry lists 2 outcome measures and 0 analysis entries, but does not report the numerical primary endpoint result. The two clinical groups are Natural Astigmatism and Post Cataract With Residual Astigmatism; the registry cautions that they are not like-for-like controls.

For adverse events, the registry records 0 serious and 0 other events in each group. Deaths are listed as null, so deaths are not reported in the registry record. Missing-data methods, analysis populations, detailed safety methods, and the primary endpoint estimates are not reported.