This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Comparative Study of Thymosin Beta 4 Eye Drops vs. Vehicle in the Treatment of Severe Dry Eye (NCT01393132), a randomized phase 2 study. The primary outcome is Safety.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01393132 |
| Phase | Phase 2 |
| Condition | Dry Eye, Sjogren's Syndrome, Graft vs. Host Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 9 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Michigan Cornea Consultants, PC |
| Results posted | Yes |
2. Clinical Question
Population
Patients with severe dry eye and ocular surface defects were the intended population. The listed conditions also include Sjogren's Syndrome and Graft vs. Host Disease. The registry record does not report further eligibility details or the characteristics of the participants enrolled.
Intervention
Participants assigned to Thymosin Beta 4 received a preservative-free, sterile eye drop solution containing Tβ4 for direct instillation into each eye, six times daily for 28 days.
Comparator
The comparison group received vehicle, described as the same excipients as RGN-259 without Tβ4. The vehicle was also instilled into each eye six times daily for 28 days.
Primary question
The primary outcome was safety, recorded as a sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56. Assessment included intra-ocular pressure by applanation tonometry, a complete ophthalmologic evaluation including fundoscopy, and adverse events at baseline and subsequent study visits. The registry's stated hypothesis concerned possible corneal surface healing; the posted primary endpoint, however, was safety.
3. Trial Design
The registry describes a randomized, triple-masked, parallel phase 2 study comparing Thymosin Beta 4 eye drops with vehicle. The record lists an enrollment of 9 and marks the study completed. The study start is recorded as 2011-03, and primary completion as 2012-12. The sponsor is Michigan Cornea Consultants, PC.
The intervention was a preservative-free, sterile solution containing Tβ4, administered directly into each eye six times daily for 28 days. The vehicle comparator contained the same excipients as RGN-259 but no Tβ4 and was administered on the same schedule. The posted arm results identify 6 participants in the Thymosin group and 3 in the placebo group. These group sizes describe the posted arm records; the registry record does not provide further details about recruitment, participant flow, or the analysis population.
Randomization means assignment was intended to use a chance-based process, while masking is intended to limit the influence of treatment knowledge on participants or study personnel. The record labels masking as triple but does not identify which roles were masked or describe how masking was maintained. It also does not report the randomization procedure, allocation concealment, eligibility criteria, treatment adherence, or protocol deviations.
The study listed Corneal Fluorescein Staining, Ocular Discomfort Index and Tear Film Break up Time as secondary outcomes. The registry record does not report their numerical results in the registry record for this analysis. It likewise does not report a detailed statistical analysis plan, a sample-size justification, or whether any interim analyses were planned.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Pre-assignment Details: Subjects were evaluated upon entering the study after a two week washout period.
Overall Study
| Stage | Thymosin | Placebo |
|---|---|---|
| STARTED | 6 | 3 |
| COMPLETED | 6 | 3 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Thymosin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 6 | 3 | 9 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 | 2 | 7 |
| Age, Categorical: >=65 years | Participants | 1 | 1 | 2 |
| Age, Continuous | Years | 54.2 (SD 11.6) | 63.7 (SD 6.65) | 57.33 (SD 11.18) |
| Sex: Female, Male: Female | Participants | 4 | 2 | 6 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Region of Enrollment: United States | participants | 6 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Safety, measured over Day 1, Day 14, Day 28 and Day 56.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | event |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is labeled Safety and is defined as the sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56. The description includes measurement of intra-ocular pressure by applanation tonometry, a complete ophthalmologic evaluation including fundoscopy, and adverse-event assessment at baseline and all subsequent study visits. The registry specifies the unit as an event and the outcome type as a number.
A safety endpoint is used to describe unwanted events and clinically monitored findings during a study. Recording events across study visits can capture events that arise at different points during follow-up. The endpoint definition combines adverse-event observations with specified eye examinations; the registry record does not explain how findings from these sources were classified, whether repeated observations of the same event were counted once or more than once, or how severity and relatedness were assessed.
The posted primary values are 0 for the Thymosin group and 0 for the placebo group. These values describe the recorded event counts under the registry's outcome definition. They do not, on their own, establish that the underlying risks are identical, nor do they describe the precision of a treatment comparison. The registry record does not report a confidence interval or an inferential comparison for this count outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary safety values are 0 events for the Thymosin group and 0 for the placebo group. The adverse-event record also lists 0 serious adverse events and 0 other adverse events among those at risk in each group. These are descriptive counts in the registry record. They indicate what was reported for the enrolled groups under the stated outcome definitions, not a precise estimate of how often events might occur in a broader population.
The record does not provide a numerical between-group effect estimate or a confidence interval. It also states that values are missing or not estimable for a two-arm comparison of this count outcome. Therefore, a comparative effect cannot be interpreted from these posted counts. In particular, the absence of a reported difference is not evidence that the groups are equivalent or that a difference has been ruled out.
Small group sizes limit the information available about uncommon events. When no events are observed, the data can still be compatible with nonzero underlying event risks; the extent of uncertainty depends on the amount and quality of follow-up and on how events were defined and collected. The registry record does not provide enough detail to quantify that uncertainty. No confidence limits or other inferential statistics for safety are reported.
The study's stated hypothesis concerned whether Thymosin Beta 4 might promote corneal surface healing and support changes in visual acuity and dry-eye symptoms. These hypotheses should not be confused with the posted primary outcome. The primary endpoint was safety, and the secondary outcomes named in the record concern staining, discomfort and tear-film breakup time. Their numerical results are not reported in the information available for this analysis. As a result, the safety counts do not answer whether the intervention changed those clinical measures.
There is also no basis in the registry record to make claims about a treatment effect on visual acuity, surface healing or symptoms. The study is marked completed, but completion status does not substitute for outcome estimates. The record does not report participant-level data, group characteristics, follow-up completeness, or a detailed account of the analysis population. Those omissions matter when judging how broadly the descriptive safety counts can be interpreted.
9. Statistical Methods Explained
What does a count outcome represent?
A count outcome records how many events were observed under a defined rule. The primary endpoint is described as a sum of adverse events over specified study visits. That structure differs from an outcome that records a continuous measurement, such as a change in a score, or a binary outcome that classifies each participant as having or not having an event. The precise meaning of a count depends on what qualifies as an event and how repeat events are handled. Those operational details are not reported in the registry record.
A count may be reported for each treatment group, as it is here, without also reporting an estimate of the contrast between groups. A comparative analysis would need to specify the effect being estimated and the method used to account for the count data and study design. The registry record does not provide such a method for the primary outcome. It explicitly indicates that values are missing or not estimable for a two-arm comparison of this count endpoint.
Why does over-dispersion matter?
General statistical explanation: count models often begin with assumptions about how much variation is expected for a given average event rate. Over-dispersion occurs when the observed variation is greater than that assumption allows. If it is ignored, uncertainty estimates may be too narrow and tests may be poorly calibrated. Possible sources include substantial differences between participants or clustering of events, but whether either occurred in this study is not reported in the registry record.
Choosing a count model requires information about the outcome definition, follow-up, and design, as well as a stated analysis plan. The posted results do not report event-time or participant-level data, so the appropriateness of a particular model cannot be assessed from these counts. No count-model estimates, dispersion assessments, or model diagnostics are reported.
How should uncertainty be understood?
General statistical explanation: a confidence interval describes a range of effect values that are compatible with the data under a specified model and procedure. It conveys precision, rather than a guarantee about the true value. A point estimate alone does not show how uncertain the estimate is; the sample size, event frequency, design and analysis all matter. A confidence interval is not reported for the primary endpoint in this registry record.
When both groups have zero recorded events, a simple observed difference in counts would not by itself capture uncertainty about future or underlying event rates. Inference requires a defined model or other method and appropriate assumptions. The registry record reports no estimable two-group comparison, so there is no posted interval or test result to interpret. No additional arithmetic or re-analysis can recover a sponsor's analysis from group counts alone.
What can a planning illustration say?
General statistical explanation: a sample-size calculation can illustrate how many participants per arm might be needed to detect an assumed effect under specified statistical assumptions. Such an illustration is planning information, not an outcome of the completed study and not a measure of observed power. The record describes a planning approach based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect.
No numerical planning estimates are reported in the record available for this analysis. The record therefore does not support a claim about the number of participants per arm required for 80% power or any other target. Nor does this general planning description establish that those assumptions governed the trial's original design. The study's own sample-size justification is not reported in the registry record.
What does randomization contribute?
General statistical explanation: random assignment can reduce systematic differences between groups at the point of assignment, on average, when implemented as intended. It does not ensure that groups will be similar in every characteristic, especially in a small study. Interpretation also depends on the allocation process, adherence, follow-up and analysis population. The record labels the study randomized, but does not report the procedure or enough participant detail to assess balance.
Masking can reduce the risk that expectations influence reporting or assessment. The record labels the study triple-masked, but does not specify which participants or personnel were masked or whether masking was maintained. These labels describe design features; they do not remove uncertainty arising from limited data or missing reporting.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists three secondary outcomes: Corneal Fluorescein Staining, Ocular Discomfort Index and Tear Film Break up Time. The primary outcome is Safety. The record does not provide the numerical results for these secondary measures in the information available for this analysis, nor does it report outcome-specific estimates, confidence intervals or tests for them.
When a study assesses several outcomes or conducts several statistical tests, the chance of at least one apparently unusual result can increase. General statistical explanation: multiplicity procedures can address this issue by controlling a specified error rate, or investigators may identify a primary outcome and treat other findings as exploratory. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a statistical analysis plan that explains how multiple comparisons were handled. It is therefore not possible to determine whether any adjustment was planned or used.
Missing-data methods and the analysis population are also not described. The posted arm records report 6 participants for Thymosin and 3 for placebo, but the registry record does not explain whether these are randomized, treated, or analyzed participants; whether any participants withdrew; or whether outcome data were incomplete. It does not report an intention-to-treat, per-protocol, or safety population definition. Without those details, the relationship between enrollment, follow-up and the posted outcome counts cannot be fully assessed.
The record does not report whether interim analyses were planned or conducted. It also does not describe a prespecified approach to missing observations. These omissions limit evaluation of how the reported results were selected and analyzed, but they do not establish that any particular procedure was or was not used.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Thymosin Beta 4 | 0 | 6 | 0.0% |
| Placebo | 0 | 3 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Thymosin Beta 4 | 0 of 6 |
| Placebo | 0 of 3 |
The serious adverse event figures list 0 affected participants in the Thymosin Beta 4 group, with 6 at risk, and 0 affected participants in the placebo group, with 3 at risk. The figures for other adverse events likewise list 0 affected participants in both groups, with the same at-risk counts. These are the posted registry values, not adjusted estimates of comparative risk.
Zero recorded events in the study groups does not show that the underlying chance of an event is zero. With limited observations, uncommon events may not appear during the recorded follow-up. The registry record does not report confidence intervals, detailed event definitions, severity categories, relatedness assessments, or follow-up completeness. The primary safety description includes assessments at Day 1, Day 14, Day 28 and Day 56, but the adverse-event summary does not provide a fuller account of exposure time or individual event timing.
Deaths are listed as not reported in the registry record; they should not be interpreted as zero deaths. The posted counts support a descriptive statement about what was recorded, but they do not establish equivalence in safety between the groups or characterize risks beyond this study.
12. What the Result Does, and Does Not, Mean
The result establishes that the registry record posts zero primary safety events in each group and zero serious and other adverse events in the adverse-event summary. The record describes a randomized, triple-masked, parallel phase 2 comparison of Thymosin Beta 4 eye drops with vehicle in a severe dry eye study. These registry entries describe the trial and its posted safety counts.
The result does not provide an estimable between-group comparison for the primary count outcome. It does not show that the groups have the same underlying event risk, that clinically important differences are excluded, or that no adverse events could occur outside the observed study experience. No confidence interval or inferential result is reported for the primary safety comparison.
Nor do the safety counts answer the study's stated questions about corneal surface healing, visual acuity or dry-eye symptoms. The registry lists corneal staining, ocular discomfort and tear-film breakup time as secondary outcomes, but their numerical results are not reported in the information. The registry record does not provide evidence from these counts about those outcomes.
Interpretation is also limited by unreported details about participant characteristics, eligibility, follow-up, outcome classification and analysis populations. The record does not report the statistical analysis plan or the study's sample-size justification. Completion status alone cannot resolve those uncertainties. The posted data are best read as a small set of descriptive safety counts, rather than as a precise estimate of comparative safety or as evidence about clinical benefit.
13. Why This Trial Matters Statistically
This trial illustrates an important distinction between reporting event counts and estimating a comparative effect. A registry can show zero events in each group while still providing no estimable between-group analysis. Without an effect estimate and its uncertainty, readers cannot determine how precisely the study distinguishes possible group differences.
The example also shows why a count endpoint requires clear definitions. The primary safety description combines adverse-event observations with eye examinations over specified visits. Readers need to know how findings were counted, whether repeated reports referred to the same event, and how follow-up was handled. Those details are not reported in the registry record, so the posted count has limited interpretability beyond its stated definition.
Small studies can be useful for describing feasibility and observed outcomes, but they usually contain limited information about uncommon events. A zero count is a valid descriptive result; it is not the same as proving no risk or proving equal risk between groups. Appropriate uncertainty estimates and transparent reporting of the analysis population are important for interpreting even a simple count.
Finally, the trial's stated biological hypothesis and primary endpoint address different questions. The hypothesis concerned possible healing and symptom-related outcomes, while the primary endpoint was safety. Reporting the outcomes separately, with clear estimates and uncertainty, helps prevent safety counts from being mistaken for evidence about efficacy.
14. 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 reports an enrollment of 9, with posted arm records of 6 for Thymosin and 3 for placebo. This is limited information for characterizing uncommon safety events, and the record does not provide uncertainty estimates for the observed counts. The posted primary values are zero in both groups, while a two-group comparison is marked as not estimable.
Important design and reporting details are absent. The registry does not report eligibility criteria, baseline participant characteristics, the randomization procedure, allocation concealment, masking roles, adherence, withdrawals, or completeness of follow-up. It also does not explain how adverse events were defined, classified or counted across visits. These gaps make it difficult to assess the risk of bias or the degree to which the posted counts represent the intended study population.
The registry lists secondary clinical measures, but their numerical results are not reported in the information available for this analysis. The statistical analysis plan, analysis populations, handling of missing data, and approach to multiple outcomes are also not reported in the registry record. No numerical sample-size planning estimates or study-specific sample-size justification are reported.
These limitations restrict interpretation to the descriptive values and design details actually recorded. They do not establish that unreported procedures were absent; they mean the registry record does not allow those procedures or their consequences to be evaluated.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Comparative Study of Thymosin Beta 4 Eye Drops vs. Vehicle in the Treatment of Severe Dry Eye — NCT01393132.
- Registry record last updated 2015-12-23; status last verified 2015-12.
- Results first posted 2015-12-23.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01393132 is a completed randomized, triple-masked, parallel phase 2 study sponsored by Michigan Cornea Consultants, PC. It compared Thymosin Beta 4 eye drops with vehicle in patients with severe dry eye and ocular surface defects. The record lists enrollment of 9, a start date of 2011-03 and primary completion in 2012-12.
The primary outcome was Safety, defined as a sum of adverse events observed at Day 1, Day 14, Day 28 and Day 56, with specified eye examinations and adverse-event assessment. Posted primary values are 0 for Thymosin and 0 for placebo. Serious and other adverse-event counts are also posted as 0 in each group. The registry record does not provide an estimable between-group comparison or confidence interval.
Corneal staining, ocular discomfort and tear-film breakup time are listed as secondary outcomes. Their numerical results, the statistical analysis plan, missing-data methods and analysis populations are not reported in the registry record.