Restasis for Treatment of Brittle Nails: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Restasis for Treatment of Brittle Nails (NCT00986427), a randomized phase 2 study. The primary outcome is Change From Baseline in the Physician's Global Assessment (PGA) of Target Fingernails #1 and #2.

2. Clinical Question

The registry describes the study as assessing the safety and effectiveness of Restasis® against emulsion alone, identified as Refresh® Dry Eye therapy. Its stated rationale was that daily application might enhance nail growth and improve nail texture in affected and unaffected nails. Those statements describe the investigators’ aims and expectations, not established outcomes.

The primary measure was the Physician’s Global Assessment (PGA) of the 2 target fingernails. The scale assessed signs of brittle nails, including lamellar onychoschizia, ridging, longitudinal splitting, fragility or breakage, and thickness. Lower scores indicate less severe signs. The main comparison therefore concerns changes in an ordinal severity score, rather than a direct measurement of nail growth or a participant-reported benefit.

Secondary questions concerned quality of life related to nail disease, nail growth in the previous 4 weeks, and physician-rated improvement. These complement the primary assessment by addressing other aspects of nail condition, but the registry record does not report analyses for them as a single combined clinical question.

3. Trial Design

This was a phase 2, randomized, single-masked, parallel-group trial with 24 participants enrolled. The registry lists 12 participants in the Restasis® arm and 12 in the Refresh® arm for the primary endpoint. Random allocation means treatment assignment was intended to use chance rather than investigator choice. The record does not report the method used to generate or conceal the allocation sequence.

The masking entry is “single,” but the registry record does not identify which participants in the trial were masked. It is therefore not possible to establish from the posted record whether masking applied to participants, clinicians, outcome assessors, or another role. The record also does not describe how masking was maintained, or whether it was assessed during the study.

Both arms were assigned topical application to target nails for 24 weeks, with a 12 week follow-up period afterward. The primary outcome was assessed at baseline and week 24. The secondary nail-growth and physician global improvement outcomes were reported at week 24; the quality-of-life outcome was reported as change from baseline at week 24.

The trial status is completed. The registry lists a start of 2009-07 and primary completion of 2010-07. The sponsor is Julian M. Mackay-Wiggan. These registry entries describe the design and administration of the study; they do not establish that every enrolled participant completed treatment or contributed data to every outcome. Participant flow, outcome-specific missingness, and analysis populations are not reported in the registry record.

The record does not report the protocol’s sample-size justification, the planned primary analysis, or a detailed statistical analysis plan. It also does not report whether interim analyses were planned or conducted. As a result, the posted arm summaries and comparisons can be described, but their relationship to any prespecified analytic decisions cannot be fully evaluated from 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.

Overall Study

Reasons for not completing this period:

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 From Baseline in the Physician's Global Assessment (PGA) of Target Fingernails #1 and #2, measured over Baseline, week 24.

The primary endpoint is change from baseline in the Physician’s Global Assessment (PGA) of target fingernails #1 and #2, assessed at week 24. These were the 2 fingernails with the most severe signs of brittleness. The PGA is a static evaluation of severity, based on signs including lamellar onychoschizia, ridging, longitudinal splitting, fragility or breakage, and thickness.

The scale runs from 0 to 5: 0 means none, 1 mild, 2 mild to moderate, 3 moderate, 4 moderate to severe, and 5 severe. A negative change indicates a decrease in grade and is described in the registry as improvement; a positive change indicates worsening. Both arm means were negative, so the posted summaries indicate decreases in average PGA scores from baseline in each arm.

A physician-rated severity score is useful because it provides a structured assessment of visible nail signs rather than relying only on an unstructured description. The change measure also places the week 24 score in relation to baseline. However, the endpoint remains a scored clinical assessment. It does not itself measure nail growth, capture every aspect of nail disease, or establish how participants experienced the changes.

The registry record does not report the detailed scoring procedures, assessor training, or reliability of the PGA assessments. That limits evaluation of how consistently the scale was applied. The posted result is best read as a summary of changes in the recorded severity score, with the scale’s direction and assessment limitations kept in view.

7. Results Posted in the Registry

• Refresh® Arm: mean -1.40 versus -1.40 on control; difference 0.00 (95% CI -0.63 to 0.63), standardized effect d = 0.00; z-test p = 1.000.

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.

Change From Baseline in Quality of Life (QOL) Related to Nail Disease

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Refresh® Arm: mean -0.90 versus -1.60 on control; difference 0.70 (95% CI -0.60 to 2.00), standardized effect d = 0.43; z-test p = 0.292.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Refresh® Arm and the control. The interval gives the range of effects that remain compatible with the data.

Growth of the Treated and Untreated Nail in the Previous 4 Weeks

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Restasis® Arm Untreated Nail: mean 2.90 versus 3.10 on control; difference -0.20 (95% CI -1.49 to 1.09), standardized effect d = -0.12; z-test p = 0.761.
  • Refresh® Dry Eye Treated Nail: mean 2.90 versus 3.10 on control; difference -0.20 (95% CI -1.21 to 0.81), standardized effect d = -0.16; z-test p = 0.697.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Restasis® Arm Untreated Nail and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Refresh® Dry Eye Treated Nail and the control. The interval gives the range of effects that remain compatible with the data.

Number of Subjects Achieving Improvement in the Physician's Global Improvement Assessment (PGIA)

• 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:
  • Refresh® Arm: 75.0% (9/12) versus 83.3% (10/12) on control; risk difference -8.3 percentage points (95% CI -40.7 to 24.0), risk ratio 0.90 (0.60–1.36); unadjusted two-proportion z-test p = 0.615.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Refresh® Arm and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several dimensions beyond the primary physician-rated severity score: quality of life related to nail disease, nail growth, and physician-rated improvement. Taken together, they show why a single severity score cannot represent every possible outcome of interest. Changes in a score, a measurement of nail growth, and a participant count meeting an improvement definition are different kinds of evidence and should not be treated as interchangeable.

The posted secondary comparisons do not establish a uniform pattern of differences between the arms. Their uncertainty and the small arm counts make them descriptive rather than conclusive. These outcomes may add context to the primary result, but they do not resolve the uncertainty around the primary comparison or convert equal primary means into evidence of equivalence.

The registry record lists no reported analyses for the secondary outcomes. Consequently, the posted summaries and unadjusted comparisons do not show whether formal testing was prespecified, whether all planned secondary measures are represented, or how any secondary findings were intended to contribute to the study’s overall conclusions.

Multiple outcome comparisons raise a general interpretive concern: when many hypotheses are examined, the chance of at least one apparently notable result can increase if no adjustment or prespecified hierarchy is used. The registry record does not report a multiplicity strategy. Unadjusted secondary p-values therefore carry less weight than a clearly prespecified primary analysis, particularly when the study’s analysis plan and outcome hierarchy are not available. The secondary measures are best considered exploratory context, not independent confirmation of a treatment effect.

Sample-size illustrations attached to secondary comparisons are planning aids based on observed effects, not evidence that the study was adequately powered for those outcomes. They cannot compensate for the absence of a reported analysis plan or establish that a particular secondary finding is reliable.

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

• Change From Baseline in Quality of Life (QOL) Related to Nail Disease
• Growth of the Treated and Untreated Nail in the Previous 4 Weeks
• Number of Subjects Achieving Improvement in the Physician's Global Improvement Assessment (PGIA)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a change score represent?

A change score compares a participant’s later measurement with that participant’s baseline measurement. In this trial, the primary change is reported at week 24 on the PGA scale. Negative values mean the grade decreased, which the registry defines as improvement; positive values mean the grade increased, which it defines as worsening. An arm mean averages the individual changes in that arm. It describes the group’s average, not what happened to every participant.

What do the arm summaries tell us?

The registry reports a mean and standard deviation for each arm. The mean is a measure of the center of the recorded changes. The standard deviation describes how spread out those changes are around the mean. A larger standard deviation generally reflects more variation among participants, while a smaller one reflects less variation. It does not show the full distribution or identify the experience of any particular participant.

For the primary outcome, both arm means are -1.4. The standard deviations are 0.9 for Restasis® and 0.67 for Refresh®. Equal means do not establish that the arms had identical participant-level results. In particular, the reported standard deviations show that outcomes varied within each arm, and the registry does not provide participant-level data or a distribution of individual changes.

How should the mean difference be read?

The posted comparison reports the mean difference as 0.0, with a 95% confidence interval from -0.635 to 0.635. The comparison is presented as Restasis® relative to Refresh®. A difference of zero means that the posted arm means are the same. Negative and positive values in the interval represent possible differences in opposite directions, under the assumptions used to calculate the interval.

A confidence interval is a measure of statistical uncertainty around an estimate. In general, an interval calculated by a method with the stated coverage will include the true parameter in that proportion of repeated uses of the method, assuming its conditions hold. It is not a probability statement about the fixed true difference after the interval has been calculated. The interval is also not a range that contains every participant’s response. It concerns uncertainty in the group comparison.

What does the p-value add?

The unadjusted p-value is 1.0. In general, a p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that null hypothesis and the analysis assumptions were true. It does not measure the probability that the null hypothesis is true, the size of an effect, or the clinical importance of a result. The registry record does not report a detailed analysis plan for this test. The p-value is identified as unadjusted, so it should not be read as accounting for a multiplicity procedure.

For this comparison, the p-value and the confidence interval are consistent with the equal posted means and the uncertainty in the estimated difference. Neither statistic proves equivalence. A formal equivalence analysis requires a prespecified margin and a design and analysis suited to that question; such a margin is not reported in the registry record.

Why does small-study uncertainty matter?

With 12 participants listed in each primary-outcome arm, the estimate is based on a limited amount of information. General statistical reasoning predicts that smaller samples tend to produce less precise estimates, particularly when participant outcomes vary. The confidence interval conveys uncertainty directly; the sample count helps readers understand why an apparently exact equality between rounded group means should not be treated as proof of identical effects.

The standard deviations and confidence interval should be considered together. The standard deviations describe variability within arms, while the confidence interval describes uncertainty in the between-arm comparison. They answer different questions. Neither provides a complete account of the data distribution or resolves possible concerns about missing measurements, because participant flow and missing-data handling are not reported in the registry record.

What do the planning illustrations mean?

The registry includes planning illustrations for secondary comparisons. They are based on the observed effects and state assumptions of a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Their entries describe participants per arm for 80% power and participants per arm for 90% power under specified fractions of the observed effect. They are planning illustrations, not numbers of participants observed, and not evidence that the trial had a particular probability of detecting an effect.

These illustrations are especially sensitive to the observed effect used as their starting point. An effect estimated in a small trial can be unstable, and a planning calculation based on it is not a substitute for a prespecified design justification. The registry record does not report the trial’s own sample-size justification. No planning illustration is posted for the primary endpoint.

The primary interpretation should therefore center on the recorded arm means, mean difference, confidence interval, and the limits of the available reporting. General principles help explain these quantities, but the registry record does not establish all details of how the primary analysis was conducted.

11. Confidence Intervals and Precision

The primary mean difference is 0.0, and its 95% confidence interval extends from -0.635 to 0.635. The interval includes zero, matching the fact that the two posted arm means are equal. It also includes differences in either direction. This means the point estimate is not the only value compatible with the data under the interval’s calculation assumptions.

Precision concerns how narrowly the result estimates the underlying between-arm difference. A confidence interval that spans a range of values communicates uncertainty around the point estimate. The interval does not establish that all included differences are equally plausible, and it does not describe the range of individual participant changes. It concerns uncertainty in the estimated mean difference.

The arm summaries are based on 12 participants in each arm for this outcome. That sample size, alongside the reported standard deviations of 0.9 and 0.67, provides context for interpreting the interval. The registry record does not report participant-level outcomes or missing-data information, so it is not possible to assess whether the posted estimates represent all randomized participants or whether unavailable measurements could affect interpretation.

Because the interval includes zero, the result does not demonstrate a statistically discernible difference under the reported comparison. But that is distinct from showing that the treatments are equivalent. Equivalence requires a clinically acceptable margin, specified in advance, and an interval sufficiently narrow to exclude differences outside that margin. No such margin is reported in the registry record. The interval should thus be read as an estimate with uncertainty, not as proof of no difference.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and three secondary outcomes. However, it reports zero analyses and lists no reported analyses for the secondary outcomes. The registry record does not report a statistical analysis plan, the order in which outcomes were to be tested, or a method for controlling the risk of false-positive findings across multiple comparisons.

Multiplicity is a general issue when several outcomes or comparisons are tested. If each is interpreted separately without accounting for the number of tests, the chance of at least one result appearing statistically notable can rise. A prespecified hierarchy or adjustment can address this issue, but no such approach is reported in the registry record. The posted secondary p-values are unadjusted and should be interpreted cautiously; they do not constitute a multiplicity-controlled body of evidence.

Missing-data handling is also not reported. The registry lists 12 participants per arm for the primary result, but it does not describe whether all randomized participants had week 24 measurements, how missing values were handled, or whether any sensitivity analyses were conducted. The record likewise does not identify the analysis population, such as whether the analysis followed all randomized participants or only those with observed outcome data.

These omissions limit assessment of possible bias from missing outcomes and of whether the posted analysis follows the intended design. They do not show that data were missing or that an inappropriate method was used; those details are simply not reported in the registry record. Participant flow, withdrawals, protocol deviations, and reasons for any unavailable measurements are not reported in the registry record.

The registry record also does not report interim analyses, stopping rules, or a prespecified sample-size justification. Without those details, readers cannot determine how the study’s design and analysis decisions were made. The posted estimates remain interpretable as reported summaries, but their full methodological context is unavailable.

13. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hematemasis (8.3%).

The registry lists 1 participant with a serious adverse event in the Restasis® arm and 0 in the Refresh® arm; 12 participants were listed at risk in each arm. The most frequently listed serious adverse event term is “Hematemasis,” at 8.3%. These counts describe the posted safety record and should not be interpreted as a complete account of all possible harms.

The record also lists other adverse events affecting 9 participants in the Restasis® arm and 8 in the Refresh® arm, with 12 at risk in each arm. Those counts are distinct from the serious adverse event counts. The registry does not provide enough detail in the posted summary to determine the severity, duration, outcome, or treatment relationship of each other adverse event.

Deaths are not reported in the registry record. The serious-event figures are small counts from a small study, so they provide limited information about uncommon events or differences in risk. The registry record does not report a detailed safety analysis or enough context to infer causation from the listed counts. These are descriptive figures, not a basis for medical advice.

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

The primary result shows equal posted mean changes in PGA severity score at week 24: -1.4 in each arm. Because negative changes indicate lower severity grades, both means represent a decrease from baseline in the recorded group averages. The mean difference is 0.0, with a 95% confidence interval from -0.635 to 0.635. The data therefore do not show a difference between the reported means, while the interval conveys uncertainty about the underlying difference.

This result does not establish that the treatments are equivalent, that every participant experienced a decrease, or that a particular treatment caused the observed changes. It does not establish the absence of a difference that might matter in a larger or differently designed study. The registry record does not report an equivalence or noninferiority design, nor does it report a margin for either question.

The endpoint measures physician-assessed signs of nail brittleness, not every potential aspect of the condition. Secondary measures address quality of life, nail growth, and physician-rated improvement, but their presence does not change the meaning of the primary comparison. The registry’s stated aims and investigator expectations should also be separated from the posted results: an objective or hypothesis is not itself evidence that the expected effect occurred.

The study enrolled 24 participants, and the primary endpoint summaries list 12 per arm. This limits the amount of information available for estimating treatment differences and uncommon safety outcomes. The confidence interval, rather than the p-value alone, helps convey the uncertainty in the primary comparison. The registry record does not report participant-level data, missing-data methods, or the full analysis plan, so important aspects of precision and potential bias cannot be evaluated.

In short, the record documents the design and outcome summaries of a small randomized comparison. Its primary endpoint means were the same as posted, but the findings should not be read as a definitive conclusion about equivalence or as a treatment recommendation.

15. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical statistics: an estimate that shows no difference between two arm means is not the same as strong evidence that the treatments have identical effects. The primary mean difference is 0.0, but the confidence interval spans values on either side of zero. Its width and the limited number of participants matter when judging what the study can establish.

The trial also demonstrates why the endpoint definition and direction of scoring are essential. A negative change in the PGA score represents a decrease in severity grade, while a positive change represents worsening. Without attending to that convention, the signs of the reported changes could be misread. The PGA is a structured physician assessment, but it remains one measure of nail condition rather than a complete description of participant experience.

Comparing an active intervention with an emulsion comparator can answer a focused question about the difference between the assigned arms, provided that the design, analysis, and outcome reporting support that interpretation. In this record, the detailed statistical plan, analysis populations, and missing-data handling are not reported. Those gaps limit how fully readers can evaluate the comparison.

The record further highlights how secondary outcomes and planning calculations should be treated. Secondary measures may add context, but unadjusted findings across several outcomes are less persuasive without a reported multiplicity strategy. Planning illustrations based on observed effects can help explain what future study sizes might look like under stated assumptions, but they are not observed power and do not show that the completed trial was designed around those assumptions.

For biostatistical reading, the central lesson is to separate the point estimate, its precision, the analysis plan, and the clinical meaning of the measure. Together, these determine how much can responsibly be inferred from a posted result.

16. 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 primary comparison is based on 12 participants per arm, limiting the information available to estimate differences and describe variation. The registry reports arm means and standard deviations, but not participant-level data or the distribution of individual changes. As a result, the consistency of the observed changes and the presence of unusually large or small responses cannot be assessed from the registry record.

The record does not report the detailed PGA assessment procedures, assessor training, or measurement reliability. It also does not specify which role was masked, despite listing single masking. These omissions make it difficult to judge how measurement and expectations may have influenced the physician-rated outcome.

Participant flow, withdrawals, protocol deviations, analysis populations, and missing-data handling are not reported in the registry record. Thus, the listed outcome counts do not establish whether all randomized participants contributed data or whether missing observations could affect the estimates. The record also does not report a detailed statistical analysis plan, a sample-size justification, or a multiplicity strategy.

The primary measure captures physician-assessed severity signs in two target fingernails. It does not by itself capture every nail, nail growth, or quality of life. Although the study lists secondary measures in those areas, formal analyses for them are not reported. The registry’s safety summaries are also limited: deaths are not reported, and event details sufficient to assess timing, outcome, or relationship to treatment are not included in the posted summary.

These limitations do not establish that bias or missingness occurred. They define what cannot be checked from the registry record and help keep the interpretation proportional to the information available.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Restasis for Treatment of Brittle Nails — NCT00986427.
• Registry record last updated 2013-08-20; status last verified 2013-07.
• Results first posted 2013-08-20.
• 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.

20. Record Summary

The registry record describes a completed phase 2 randomized, single-masked, parallel study of Restasis® ophthalmic emulsion versus Refresh® Dry Eye therapy for brittle nails. It lists 24 participants enrolled, with 12 in each arm for the primary endpoint. Both treatments were assigned for 24 weeks, followed by a 12 week follow-up period.

The primary outcome was change from baseline in PGA severity score for the 2 target fingernails at week 24. Mean changes were -1.4 in both arms; the mean difference was 0.0, with a 95% confidence interval from -0.635 to 0.635 and an unadjusted p-value of 1.0. The secondary outcomes addressed quality of life, nail growth, and physician-rated improvement.

The registry record does not report a detailed analysis plan, analysis populations, missing-data handling, or a multiplicity approach. Safety entries include 1 serious adverse event in the Restasis® arm and 0 in the Refresh® arm; deaths are not reported in the registry record.