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 A Phase II, Dose Ranging Study Of CP-690,550 Eye Drops In Patients With Dry Eye Disease (NCT01135511), a randomized phase 2 study. The primary outcome is Changes in Corneal Staining Scores for Study Eye From Baseline at Week 8.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01135511 |
| Phase | Phase 2 |
| Condition | Dry Eye Syndromes |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 285 |
| Arms in the primary outcome | 9 |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Participants with dry eye disease were enrolled. The primary endpoint population was described as intent-to-treat: participants who received at least 1 dose of study treatment. The study eye was the eye with the worse (higher) corneal staining score at baseline.
Intervention
CP-690,550 eye drops were studied at 0.001%, 0.003%, and 0.005%. Results are posted separately for participants in Japan and Korea.
Comparator
The study included CP-690,550 eye-drop vehicle and sodium hyaluronate eye drops 0.1% in Japan. A CP-690,550 vehicle group was also reported in Korea.
Primary question
At Week 8, how did mean change from baseline in corneal staining score compare across the reported treatment groups? Lower scores indicate less staining, and a negative change from baseline was defined as improvement.
The registry describes a Phase II, dose-ranging study intended to evaluate dose-response, efficacy, and safety. The primary comparison is about the average change in a clinical sign of dry eye, rather than a direct measure of how participants felt or functioned. Secondary outcomes included other corneal and conjunctival staining measures, tear-film measures, and ocular comfort.
The posted results include treatment groups from Japan and Korea. The recalculated contrasts use the Japan vehicle group as the reference, including for the reported Korean groups. Those contrasts therefore should not be read as comparisons against a vehicle group from the same country. The registry record does not report an adjusted, location-specific analysis that would resolve that distinction.
3. Trial Design
This was a randomized, double-masked, parallel-group Phase II study. The official title describes a vehicle- and comparator-controlled, dose-ranging design, with sodium hyaluronate eye drops as the active comparator. The registry lists enrollment of 285 and five intervention categories: three CP-690,550 concentrations, vehicle, and sodium hyaluronate. Posted primary outcome results distinguish groups in Japan and Korea.
The registry lists the study as completed. Its recorded start was 2010-07, and primary completion was 2011-04. These dates describe the registry record and do not provide further detail about recruitment or follow-up. The treatment-arm descriptions are blank in the record, so additional particulars of the regimen are not reported in the registry record.
Random allocation and masking can help limit systematic differences in treatment assignment and assessment, but the posted record does not describe the allocation method or how masking was maintained. It also does not report a statistical analysis plan, an explanation of the planned sample size, or interim analyses. The primary endpoint population is described as participants who received at least 1 dose; missing primary endpoint values were imputed using last observation carried forward.
The results list group means and standard deviations for the continuous primary outcome. The contrasts discussed in the statistical interpretation are recalculated, unadjusted comparisons based on those posted group summaries. They are not a substitute for a sponsor-reported adjusted analysis. No reported analyses are listed in the registry record, so whether the sponsor conducted additional analyses, and what models or covariates they may have used, is not reported in 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.
Before assignment: In this study, during the 2-week run-in period, enrolled participants were administered artificial tears 4 times daily after signing informed consent.
Only the first 6 of 9 groups are shown.
Overall Study
| Stage | CP-690,550 Eye Drops Vehicle Group in Japan | CP-690,550 Eye Drops 0.001% Group in Japan | CP-690,550 Eye Drops 0.003% Group in Japan | CP-690,550 Eye Drops 0.005% Group in Japan | Sodium Hyaluronate Eye Drops 0.1% Group in Japan | CP-690,550 Eye Drops Vehicle Group in Korea |
|---|---|---|---|---|---|---|
| STARTED | 41 | 42 | 41 | 40 | 39 | 21 |
| COMPLETED | 41 | 39 | 33 | 37 | 38 | 20 |
| NOT COMPLETED | 0 | 3 | 8 | 3 | 1 | 1 |
Reasons for not completing this period:
| Reason | CP-690,550 Eye Drops Vehicle Group in Japan | CP-690,550 Eye Drops 0.001% Group in Japan | CP-690,550 Eye Drops 0.003% Group in Japan | CP-690,550 Eye Drops 0.005% Group in Japan | Sodium Hyaluronate Eye Drops 0.1% Group in Japan | CP-690,550 Eye Drops Vehicle Group in Korea |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 1 | 2 | 0 | 0 | 1 |
| Lack of Efficacy | 0 | 1 | 1 | 2 | 0 | 0 |
| Protocol Violation | 0 | 0 | 3 | 0 | 0 | 0 |
| Pregnancy | 0 | 0 | 0 | 1 | 0 | 0 |
| could not visit the clinic | 0 | 1 | 2 | 0 | 0 | 0 |
| noncompliance with study drug taken | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: Participants who received at least 1 dose of study treatment. A last observation carried forward (LOCF) was used to impute missing data.
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.
Only the first 6 of 10 groups are shown.
| Characteristic | Unit | CP-690,550 Eye Drops Vehicle Group in Japan | CP-690,550 Eye Drops 0.001% Group in Japan | CP-690,550 Eye Drops 0.003% Group in Japan | CP-690,550 Eye Drops 0.005% Group in Japan | Sodium Hyaluronate Eye Drops 0.1% Group in Japan | CP-690,550 Eye Drops Vehicle Group in Korea |
|---|---|---|---|---|---|---|---|
| Participants analysed | 41 | 42 | 41 | 40 | 39 | 21 | |
| Age, Customized: Between 18 and 44 years | participants | 14 | 14 | 11 | 11 | 11 | 5 |
| Age, Customized: Between 45 and 64 years | participants | 9 | 14 | 12 | 16 | 14 | 10 |
| Age, Customized: >=65 years | participants | 18 | 14 | 18 | 13 | 14 | 6 |
| Sex: Female, Male: Female | Participants | 32 | 39 | 37 | 33 | 34 | 20 |
| Sex: Female, Male: Male | Participants | 9 | 3 | 4 | 7 | 5 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Changes in Corneal Staining Scores for Study Eye From Baseline at Week 8, measured over Baseline, Week 8.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was change from baseline in corneal staining score for the study eye at Week 8. The record describes a grading approach based on the National Eye Institute dry eye clinical trials workshop: the cornea was divided into 5 zones, each graded from 0 to 3, and the zone scores were summed. The total score could range from 0 to 15, with higher scores indicating greater staining.
The study eye was defined as the eye with the worse corneal staining score at baseline. Change was calculated as the score at observation minus the score at baseline. A negative change therefore meant less staining than at baseline and was defined in the registry as improvement. The reported summary is the mean change, with standard deviation, for each group.
Corneal staining is a clinical sign that can be scored systematically across participants and is relevant to the study’s stated interest in dry eye disease. It is not, by itself, a complete account of symptoms, comfort, or everyday experience. The registry also lists ocular comfort and other eye-related measures as secondary outcomes, which address different aspects of the condition.
The primary analysis population included participants who received at least 1 dose. The record says last observation carried forward was used to impute missing data. It does not report how much data were missing or provide a sensitivity analysis using other missing-data assumptions.
7. Results Posted in the Registry
- CP-690,550 Eye Drops 0.001% Group in Japan: mean -3.00 versus -3.00 on control; difference 0.00 (95% CI -1.06 to 1.06), standardized effect d = 0.00; z-test p = 1.000.
- CP-690,550 Eye Drops 0.003% Group in Japan: mean -3.00 versus -3.00 on control; difference 0.00 (95% CI -1.00 to 1.00), standardized effect d = 0.00; z-test p = 1.000.
- CP-690,550 Eye Drops 0.005% Group in Japan: mean -3.10 versus -3.00 on control; difference -0.10 (95% CI -1.13 to 0.93), standardized effect d = -0.04; z-test p = 0.849.
- Sodium Hyaluronate Eye Drops 0.1% Group in Japan: mean -3.20 versus -3.00 on control; difference -0.20 (95% CI -1.19 to 0.79), standardized effect d = -0.09; z-test p = 0.692.
Mean difference: CP-690,550 Eye Drops 0.001% Group in Japan
95% CI: -1.06 to 1.06
Recalculated from the posted summary statistics
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.
| Secondary outcome | Type | Effect measure | Estimate (95% CI) | Planning size, 80% power |
|---|---|---|---|---|
| Number of Participants Evaluable for Time to Achievement of 100% Clearing of Corneal Staining for Study Eye | Binary Endpoint | Risk difference | -10.0 pts (-25.0 to 5.0) | 195 per arm |
| Number of Participants Evaluable for Time to Achievement of ≥10 mm Schirmer Wetting Score Without Anesthesia for Study Eye | Binary Endpoint | Risk difference | -5.2 pts (-21.3 to 10.9) | 806 per arm |
| Number of Participants Evaluable for Time to Achievement of ≥3 Unit Decrease in OCI Scores | Binary Endpoint | Risk difference | -6.6 pts (-25.8 to 12.6) | 729 per arm |
Number of Participants Evaluable for Time to Achievement of 100% Clearing of Corneal Staining for Study Eye
- 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:
- CP-690,550 Eye Drops 0.001% Group in Japan: 9.5% (4/42) versus 19.5% (8/41) on control; risk difference -10.0 percentage points (95% CI -25.0 to 5.0), risk ratio 0.49 (0.16–1.50); unadjusted two-proportion z-test p = 0.196.
- CP-690,550 Eye Drops 0.003% Group in Japan: 14.6% (6/41) versus 19.5% (8/41) on control; risk difference -4.9 percentage points (95% CI -21.1 to 11.4), risk ratio 0.75 (0.29–1.97); unadjusted two-proportion z-test p = 0.557.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CP-690,550 Eye Drops 0.001% Group in Japan 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 CP-690,550 Eye Drops 0.003% Group in Japan and the control. The interval gives the range of effects that remain compatible with the data.
Number of Participants Evaluable for Time to Achievement of ≥10 mm Schirmer Wetting Score Without Anesthesia for Study Eye
- 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:
- CP-690,550 Eye Drops 0.001% Group in Japan: 14.3% (6/42) versus 19.5% (8/41) on control; risk difference -5.2 percentage points (95% CI -21.3 to 10.9), risk ratio 0.73 (0.28–1.93); unadjusted two-proportion z-test p = 0.525.
- CP-690,550 Eye Drops 0.003% Group in Japan: 4.9% (2/41) versus 19.5% (8/41) on control; risk difference -14.6 percentage points (95% CI -28.4 to -0.8), risk ratio 0.25 (0.06–1.11); unadjusted two-proportion z-test p = 0.043.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CP-690,550 Eye Drops 0.001% Group in Japan and the control. The interval gives the range of effects that remain compatible with the data.
- The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for CP-690,550 Eye Drops 0.003% Group in Japan than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
Number of Participants Evaluable for Time to Achievement of ≥3 Unit Decrease in OCI Scores
- 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:
- CP-690,550 Eye Drops 0.001% Group in Japan: 69.0% (29/42) versus 75.6% (31/41) on control; risk difference -6.6 percentage points (95% CI -25.8 to 12.6), risk ratio 0.91 (0.70–1.19); unadjusted two-proportion z-test p = 0.504.
- CP-690,550 Eye Drops 0.003% Group in Japan: 73.2% (30/41) versus 75.6% (31/41) on control; risk difference -2.4 percentage points (95% CI -21.3 to 16.4), risk ratio 0.97 (0.75–1.25); unadjusted two-proportion z-test p = 0.800.
- Interpretation:
- The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between CP-690,550 Eye Drops 0.001% Group in Japan 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 CP-690,550 Eye Drops 0.003% Group in Japan and the control. The interval gives the range of effects that remain compatible with the data.
The registry lists secondary outcomes spanning several kinds of evidence: corneal and conjunctival staining, tear break-up time, Schirmer testing, and ocular comfort. Some are continuous changes from baseline; others count participants meeting a stated threshold or achieving a defined clearing outcome. These measures do not all capture the same feature of dry eye disease, so agreement across them could add context, while disagreement would not necessarily be surprising.
The posted secondary results include participant counts for selected outcomes at Week 8. They should be read alongside the primary continuous staining endpoint, not as interchangeable versions of it. A count based on crossing a threshold can change differently from a group mean, and it can discard information about how far participants are from that threshold. The available registry record does not report a unified analysis that combines these outcomes or establishes which secondary comparisons should be prioritized.
Secondary findings carry less weight when many outcomes and treatment comparisons are examined without a reported multiplicity adjustment. An unadjusted p-value assesses a comparison without accounting for the broader set of tests. Looking across many such results increases the chance that some apparently notable result will arise by chance. The registry record does not report a hierarchy of secondary hypotheses or a multiplicity-control procedure.
For these reasons, secondary outcomes are best treated as supportive or exploratory context. They can inform what patterns merit further study, but they do not replace the primary endpoint or resolve its uncertainty. The registry record lists 20 secondary outcomes as posted, but the analysis plan and the extent to which all planned secondary analyses were completed are not reported in the registry record.
Secondary outcomes registered for this trial, for reference (only those above were recalculated):
- Changes in Corneal Staining Scores for Study Eye From Baseline
- Percentage of Participants Demonstrating 100 Percent Clearing of Corneal Staining for Study Eye
- Changes in Conjunctival Staining Scores (Interpalpebral) for Study Eye From Baseline
- Changes in Tear Break Up Time (TBUT) for Study Eye From Baseline
- Changes in Schirmer Test Values Without Anesthesia for Study Eye From Baseline
- Percentage of Participants Who Achieve ≥10 mm Schirmer Test Value Without Anesthesia for Study Eye
- Number of Participants Who Increase of ≥10 mm From Baseline in Schirmer Test Value Without Anesthesia for Study Eye
- Changes in the Ocular Comfort Index (OCI) Total Score From Baseline
9. Statistical Interpretation
Mean change in corneal staining was negative in every posted primary-outcome group. By the registry’s definition, each negative mean indicates a reduction in staining from baseline. The means were -3.0 for the Japan vehicle group, -3.0, -3.0, and -3.1 for the three CP-690,550 groups in Japan, and -3.2 for sodium hyaluronate in Japan. The Korean group means were -2.4 for vehicle and -3.0, -2.8, and -2.2 for the three CP-690,550 concentrations. These are within-group changes, not treatment effects relative to a control.
The recalculated unadjusted comparisons use the Japan vehicle mean of -3.0 as the reference. For the Japan CP-690,550 groups, the estimated mean differences were 0.0 at 0.001%, 0.0 at 0.003%, and -0.1 at 0.005%. Their confidence intervals were -1.063 to 1.063, -0.999 to 0.999, and -1.131 to 0.931, respectively. The sodium hyaluronate comparison was -0.2, with a confidence interval from -1.19 to 0.790. Each interval includes no difference.
For the Korean groups compared with the Japan vehicle group, the recalculated differences were 0.6 for vehicle, 0.0 for 0.001%, 0.2 for 0.003%, and 0.8 for 0.005%. Every corresponding confidence interval includes no difference. These comparisons cross country groups, so they do not isolate a treatment contrast within Korea. The record does not report a separate recalculated comparison of Korean treatment groups against a Korean vehicle group.
The unadjusted p-values for the primary comparisons range from 0.209 to 1.0. They do not establish that treatment groups are equivalent: the confidence intervals remain compatible with a range of differences, and the registry record does not report an equivalence margin. Nor do these recalculations establish a dose-response pattern. The posted group means are close in some comparisons, while estimates for other groups are less precise. No sponsor-reported adjusted analysis is listed to take account of design features or other variables.
Overall, the posted primary summaries show reductions from baseline across groups, while the unadjusted contrasts do not clearly distinguish the Japan treatment groups from the Japan vehicle group. The Korean contrasts require additional caution because their reference group is in Japan. These results describe the posted data and their precision; they do not by themselves determine a clinical conclusion.
10. Statistical Methods Explained
These comparisons concern a continuous outcome: change in corneal staining score. A group mean describes the average change among participants in that group, while the standard deviation describes the spread of individual changes around that mean. The standard deviation is not the uncertainty in the mean and is not a confidence interval.
What does a mean difference represent?
A mean difference compares the average change in one group with the average change in the reference group. In the recalculated comparisons, the Japan vehicle group is the reference. A negative difference means the comparison group’s average change was more negative than the reference group’s average change; for this endpoint, more negative change corresponds to a greater reduction in staining. A difference of 0.0 indicates equal posted means at the displayed precision. Neither direction nor size alone determines whether a difference is clinically important; a threshold for clinical importance is not reported in the registry record.
The posted primary comparisons are simple, unadjusted recalculations from group summary statistics. They do not use individual participant data and are not sponsor-reported adjusted analyses. The recalculated estimates and p-values should therefore be understood as descriptive statistical contrasts, not as confirmation of the analysis used by the study team. The registry record does not report a statistical plan that would allow the recalculations to be matched to a prespecified model.
What does a p-value tell the reader?
A p-value describes how compatible the data are with a specified null hypothesis under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of a difference. The posted primary p-values are unadjusted. Because the study includes multiple treatment groups and outcomes, interpreting each p-value as if it were the only test would understate the potential for chance findings across many comparisons.
A non-small p-value is not proof that groups are equal. It can occur when the true difference is small, when the data are variable, or when the sample gives limited precision. An equivalence or non-inferiority conclusion requires a prespecified margin and appropriate analysis; neither is reported in the registry record.
Why does the standard deviation matter?
Standard deviations in the primary groups range from 1.9 to 2.8 score units. They describe observed variability in change scores. With variability, an average can be estimated less precisely than the group’s point estimate alone suggests. Standard deviation also helps characterize how much participant outcomes differ from one another, but it does not show the full distribution or identify individual responses.
General statistical explanation: greater variation makes it harder to distinguish a group mean from another when the sample sizes are otherwise similar. A confidence interval combines information about variation and sample size to express uncertainty around an estimated contrast. The intervals in the posted comparisons are therefore more informative about plausible contrast sizes than the point estimates alone.
How should the country groups be considered?
The posted group summaries separate results by Japan and Korea. The recalculated contrasts use the Japan vehicle group as reference, even for Korean groups. General statistical explanation: when groups differ in location as well as treatment assignment, a contrast can reflect both treatment and location-related differences. The registry record does not report an adjusted model or a within-Korea reference comparison in these recalculations, so the Korean estimates should not be interpreted as clean within-country treatment effects.
What do the planning illustrations mean?
The sample-size illustrations are planning calculations based on stated fractions of observed effects, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They show participants per arm for 80% power or 90% power under those assumptions. For example, planning for 75% of the observed effect in the Japan 0.005% comparison gives 15,545 participants per arm for 80% power and 20,810 participants per arm for 90% power. These figures are not observed power, do not describe the trial’s actual design justification, and depend on the observed effect being a suitable planning value. The registry record does not report the original sample-size justification.
General statistical explanation: planning from an observed effect can be unstable, especially when an estimate is imprecise. Smaller effects require larger samples to distinguish them from no difference under otherwise similar assumptions. These illustrations are scenarios rather than evidence that the trial had a particular probability of finding an effect.
11. Confidence Intervals and Precision
The confidence intervals around the recalculated primary mean differences are broad relative to several of the point estimates. For the Japan comparisons, the interval for 0.001% runs from -1.063 to 1.063, and the interval for 0.003% runs from -0.999 to 0.999. The interval for 0.005% extends from -1.131 to 0.931, and the sodium hyaluronate interval extends from -1.19 to 0.790. Each includes 0.0, the value corresponding to no mean difference.
The intervals also include values in both directions. For these outcomes, a negative contrast favors a larger reduction in staining in the comparison group, while a positive contrast favors a larger reduction in the reference group. The range of values in an interval conveys uncertainty; it should not be reduced to a yes-or-no interpretation based only on whether it crosses 0.0.
The Korean contrasts have intervals from -0.611 to 1.811 for vehicle, -1.374 to 1.374 for 0.001%, -0.836 to 1.236 for 0.003%, and -0.448 to 2.048 for 0.005%. These also include 0.0 and allow effects in either direction. In addition to this statistical uncertainty, the Korean comparisons use the Japan vehicle group as their reference, limiting their interpretation as within-country treatment contrasts.
General statistical explanation: a confidence interval gives a range of estimates compatible with the data under the calculation’s assumptions. It is not a guarantee that the true effect lies in that range, and a wide interval signals limited precision. The registry record does not report a clinically important difference threshold, so the clinical importance of values inside these intervals cannot be assessed from the record alone.
12. Multiplicity, Missing Data and Analysis Populations
The record describes one primary endpoint, but the study also includes several treatment groups and many secondary outcomes. Testing multiple contrasts and outcomes creates a multiplicity issue: even if there is no true treatment difference, some unadjusted results may appear notable by chance. The posted primary comparisons use unadjusted p-values, and the registry record does not report a correction for multiple testing, a prespecified testing sequence, or a hierarchy of hypotheses. Therefore, the p-values should not be treated as if each were the sole confirmatory test.
The registry record lists 51 outcome measures and 20 posted secondary outcomes. It does not report a statistical analysis plan that explains how these measures were selected, how missing observations were handled for each one, or which analyses were intended to be confirmatory. No reported analyses are listed in the registry record. The recalculated summaries do not fill that gap or establish what analyses the study team prespecified.
For the primary endpoint, the stated population was intent-to-treat, defined as participants who received at least 1 dose of study treatment. Missing values were imputed using last observation carried forward (LOCF). LOCF carries a participant’s last observed score forward to a later time point when data are missing. General statistical explanation: this approach assumes the carried-forward value is an adequate stand-in for the unobserved value. If the outcome would have changed after the last observation, the imputed value can misrepresent the later result. The record does not report the amount of missing data or sensitivity analyses using other assumptions.
The record does not report the sample-size justification, interim analyses, or a detailed statistical plan. These items should be treated as not reported in the registry record, rather than inferred from the posted sample-size illustrations or recalculated comparisons.
13. 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 |
|---|---|---|---|
| CP-690,550 Eye Drops Vehicle Group in Japan | 0 | 41 | 0.0% |
| CP-690,550 Eye Drops 0.001% Group in Japan | 0 | 42 | 0.0% |
| CP-690,550 Eye Drops 0.003% Group in Japan | 2 | 41 | 4.9% |
| CP-690,550 Eye Drops 0.005% Group in Japan | 0 | 40 | 0.0% |
| Sodium Hyaluronate Eye Drops 0.1% Group in Japan | 0 | 39 | 0.0% |
| CP-690,550 Eye Drops Vehicle Group in Korea | 0 | 21 | 0.0% |
| CP-690,550 Eye Drops 0.001% Group in Korea | 0 | 19 | 0.0% |
| CP-690,550 Eye Drops 0.003% Group in Korea | 1 | 21 | 4.8% |
| CP-690,550 Eye Drops 0.005% Group in Korea | 0 | 21 | 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 |
|---|---|
| CP-690,550 Eye Drops Vehicle Group in Japan | 11 of 41 |
| CP-690,550 Eye Drops 0.001% Group in Japan | 11 of 42 |
| CP-690,550 Eye Drops 0.003% Group in Japan | 16 of 41 |
| CP-690,550 Eye Drops 0.005% Group in Japan | 8 of 40 |
| Sodium Hyaluronate Eye Drops 0.1% Group in Japan | 9 of 39 |
| CP-690,550 Eye Drops Vehicle Group in Korea | 6 of 21 |
Most frequent serious adverse event terms
| Event term | Organ system | CP-690,550 Eye Drops Vehicle Group in Japan | CP-690,550 Eye Drops 0.001% Group in Japan | CP-690,550 Eye Drops 0.003% Group in Japan | CP-690,550 Eye Drops 0.005% Group in Japan | Sodium Hyaluronate Eye Drops 0.1% Group in Japan | CP-690,550 Eye Drops Vehicle Group in Korea |
|---|---|---|---|---|---|---|---|
| Gastric ulcer | Gastrointestinal disorders | 0 of 41 | 0 of 42 | 1 of 41 | 0 of 40 | 0 of 39 | 0 of 21 |
| Foot fracture | Injury, poisoning and procedural complications | 0 of 41 | 0 of 42 | 1 of 41 | 0 of 40 | 0 of 39 | 0 of 21 |
| Bronchiectasis | Infections and infestations | 0 of 41 | 0 of 42 | 0 of 41 | 0 of 40 | 0 of 39 | 0 of 21 |
Most frequent non-serious adverse event terms
| Event term | Organ system | CP-690,550 Eye Drops Vehicle Group in Japan | CP-690,550 Eye Drops 0.001% Group in Japan | CP-690,550 Eye Drops 0.003% Group in Japan | CP-690,550 Eye Drops 0.005% Group in Japan | Sodium Hyaluronate Eye Drops 0.1% Group in Japan | CP-690,550 Eye Drops Vehicle Group in Korea |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 2 of 41 | 4 of 42 | 2 of 41 | 5 of 40 | 1 of 39 | 1 of 21 |
| Eye irritation | Eye disorders | 0 of 41 | 0 of 42 | 0 of 41 | 0 of 40 | 0 of 39 | 3 of 21 |
| White blood cells urine positive | Investigations | 0 of 41 | 0 of 42 | 0 of 41 | 0 of 40 | 3 of 39 | 0 of 21 |
| Leukopenia | Blood and lymphatic system disorders | 0 of 41 | 1 of 42 | 0 of 41 | 1 of 40 | 0 of 39 | 0 of 21 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 41 | 1 of 42 | 0 of 41 | 1 of 40 | 0 of 39 | 0 of 21 |
| Eye discharge | Eye disorders | 0 of 41 | 0 of 42 | 1 of 41 | 1 of 40 | 0 of 39 | 0 of 21 |
| Keratitis | Eye disorders | 1 of 41 | 0 of 42 | 1 of 41 | 0 of 40 | 0 of 39 | 0 of 21 |
| Vision blurred | Eye disorders | 0 of 41 | 0 of 42 | 1 of 41 | 0 of 40 | 0 of 39 | 1 of 21 |
| Headache | Nervous system disorders | 0 of 41 | 0 of 42 | 1 of 41 | 0 of 40 | 1 of 39 | 0 of 21 |
| Anaemia | Blood and lymphatic system disorders | 0 of 41 | 0 of 42 | 0 of 41 | 0 of 40 | 0 of 39 | 1 of 21 |
Serious events with the highest arm-level rate: bronchiectasis (4.8%), gastric ulcer (2.4%), foot fracture (2.4%).
The registry lists participants affected by serious adverse events and other adverse events by group. Serious adverse events were reported for 2 participants in the Japan 0.003% group and 1 participant in the Korea 0.003% group; the other listed groups have 0 affected participants. The corresponding at-risk group sizes are shown in the posted results. These are group-level counts and should not be interpreted as a complete account of the nature, timing, duration, or causal relationship of each event.
The listed serious-event terms include Bronchiectasis at 4.8%, Gastric ulcer at 2.4%, and Foot fracture at 2.4%. The registry record does not give enough context in these figures alone to determine how the terms relate to individual participants or treatment assignment. Death counts are not reported in the registry record.
Other adverse events were reported in each group, with affected-participant counts ranging from 6 to 16 in the posted group entries. Those counts are descriptive; they do not by themselves establish comparative risk or causality. Differences in group size, event definitions, follow-up, and attribution matter when interpreting safety comparisons, and further detail on those aspects is not reported in the registry record.
14. What the Result Does, and Does Not, Mean
The primary outcome results show that mean corneal staining scores decreased from baseline in every reported group. The registry defines a negative change as improvement in this staining measure. The recalculated unadjusted contrasts between the Japan vehicle group and the Japan treatment groups are close to zero, and their confidence intervals include no difference. The Korean contrasts also include no difference, but use a reference group from Japan.
These findings do not establish that the treatments are equal, that a specific dose is effective or ineffective, or that a clinically important difference is absent. The intervals allow a range of possible differences, and the registry record does not provide a clinical-importance threshold. A non-significant unadjusted p-value is not evidence of equivalence. The data also do not establish a dose-response relationship; that question would require an appropriate prespecified analysis, which is not reported in the registry record.
The mean change is one clinical sign, not a complete measure of dry eye disease. Other posted outcomes assess related but distinct signs and participant-relevant measures. They require cautious interpretation because multiple unadjusted comparisons can yield chance findings, and the registry record does not report a multiplicity strategy.
The results are also limited by the use of last observation carried forward for missing primary data and by the absence of reported missingness details or sensitivity analyses. The posted summaries cannot show individual trajectories or how robust the findings are to alternative missing-data assumptions. The recalculated results are descriptive comparisons from group summaries, not a replacement for a sponsor-reported adjusted analysis.
In short, the registry record documents reductions in average staining from baseline and uncertain between-group contrasts. It does not, on its own, support a definitive conclusion about comparative clinical benefit or safety.
15. Why This Trial Matters Statistically
This study is statistically interesting because it combines dose-ranging questions with several active and vehicle comparisons, multiple locations, and a mixture of continuous and threshold-based outcomes. That structure illustrates why a set of group means alone is not enough: the contrast, its uncertainty, the reference group, and the analysis plan all affect interpretation.
The primary results make a useful distinction between within-group change and a comparative treatment effect. Negative average changes occur across all posted groups, but the question of interest is whether the change differs between groups. The recalculated mean differences and confidence intervals address that contrast more directly than comparing the group means by eye. They also show why a small point estimate should not be read as proof of no effect when the interval still spans a range of possibilities.
The location-specific reporting raises another statistical issue. The Korean treatment groups are contrasted with the Japan vehicle group in the recalculated results. A comparison that crosses location cannot cleanly answer the same question as a within-location randomized treatment comparison without appropriate analysis and context. The record does not report such an adjusted analysis.
Finally, this trial illustrates the consequences of many outcomes and unadjusted testing. Secondary measures may add context, but a collection of unadjusted results is not equivalent to a prespecified, multiplicity-controlled evaluation. Planning illustrations based on observed effects likewise demonstrate how sample-size needs depend on the assumed effect; they are scenarios, not observed power or a record of the trial’s original planning.
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 arm descriptions are blank, and the registry record does not report the full dosing schedule, adherence, or other treatment-delivery details. Although the study is described as randomized and double masked, the allocation method and masking procedures are not reported in the registry record.
The recalculated comparisons use the Japan vehicle group as reference for the reported Korean groups. This makes the Korean contrasts difficult to interpret as treatment comparisons within Korea. The posted data do not include a recalculated Korean treatment-versus-Korean-vehicle contrast, and an adjusted analysis accounting for location is not reported in the registry record.
The primary outcome population includes participants who received at least 1 dose, and missing primary data were handled using last observation carried forward. The record does not report the amount or pattern of missing data, or sensitivity analyses that might show whether conclusions depend on that imputation approach. The analysis plan and sample-size justification are also not reported.
Many outcome measures and comparisons are listed, but the registry record does not report a multiplicity strategy or a prespecified hierarchy for interpreting secondary results. The recalculated p-values are unadjusted and based on posted group summaries, not individual participant data or an adjusted model. Thus, they may not reproduce the study team’s analysis.
Finally, the primary endpoint is a clinical sign, and the registry record does not provide a threshold for a clinically important difference. The reported summaries therefore support statistical description but leave important questions about clinical relevance, missing data, and comparative interpretation unresolved.
17. Related Tutorials
18. Related Statistical Calculators
19. Sources
- ClinicalTrials.gov: A Phase II, Dose Ranging Study Of CP-690,550 Eye Drops In Patients With Dry Eye Disease — NCT01135511.
- Registry record last updated 2013-05-07; status last verified 2013-03.
- Results first posted 2013-05-07.
- 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.
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20. Record Summary
The registry describes NCT01135511 as a completed, randomized, double-masked, parallel-group Phase II dose-ranging study in dry eye disease. Enrollment was 285. The primary outcome was mean change in study-eye corneal staining score from baseline at Week 8; negative change was defined as improvement.
Posted group means were negative across the reported Japan and Korea groups. Recalculated unadjusted primary contrasts against the Japan vehicle group have confidence intervals that include no difference. Korean comparisons use a Japan reference group. The record describes an intent-to-treat population of participants who received at least 1 dose and LOCF imputation for missing primary data. The statistical analysis plan, sample-size justification, multiplicity approach, and death counts are not reported in the registry record.