Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease (NCT03287635), a na phase 4 study. The primary outcome is Dry Eye Comfort Questionnaire, SANDE.

2. Clinical Question

3. Trial Design

This is a completed phase 4 study sponsored by Toyos Clinic. The registry lists an enrollment of 19 and identifies dry eye disease as the condition. The study started on 2018-07-01, had a primary completion date of 2020-02-01, and is marked COMPLETED. These dates describe the record; they do not supply the timing or completeness of individual participant follow-up.

The design is recorded as single-group, with allocation marked NA and masking marked NONE. There is no registered control arm, and the record does not describe a randomized comparison. As a result, the primary outcome is a within-participant change question: dryness scores at baseline are to be compared with scores at the final study visit among patients receiving Acthar gel. The registry does not report a control-based estimate of what would have happened over the same period without the intervention.

The registered primary outcome is the Dry Eye Comfort Questionnaire, SANDE, recorded as scores on a scale and summarized by a mean with standard deviation. The timeframe is stated as 12 weeks total. The population description says patients receiving Acthar gel injections for 90 days were analyzed. The record does not explain how these descriptions align for individual participants, nor does it report the number with complete outcome measurements.

Intraocular pressure is listed as a secondary outcome. The record lists three outcome measures but no analysis entries. The protocol, eligibility details beyond the arm description, dosing schedule, visit schedule beyond the SANDE description, and statistical analysis plan are not reported in the registry record. These absences limit how fully the design and implementation can be reconstructed.

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: Additional subjects were added when study participants dropped out due to subject withdrawal, were lost to follow up and physician decision.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients receiving Acthar gel injections for 90 days were analyzed

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.

Population: Patients experience persistent symptomatic dry eye disease despite treatment with traditional therapies.

6. Primary Endpoint

The registry lists the primary outcome as Dry Eye Comfort Questionnaire, SANDE, measured over 12 weeks total. Measure is change on SANDE scale (0 is no dryness and 100mm is maximal dryness) from baseline to final value. Higher values reflect greater amounts of subjective dryness..

The primary endpoint is change in Dry Eye Comfort Questionnaire SANDE scores from baseline to the final study visit. Participants were asked to rate eye dryness at Visit 1,2 and 3. The rating uses a line extending from 0, meaning no dryness, to 100mm, meaning maximal dryness. The distance from the no-dryness starting point to the participant’s mark is measured in millimeters. Higher scores indicate greater subjective dryness.

The measure is intended to capture participants’ perceived dryness, including the instantaneous discomfort at the time of a particular visit. The record describes the assessment as a general measure of change in both eyes from baseline to the final visit. A mean is an appropriate summary for describing the average score or average change in a group, while a standard deviation describes how dispersed individual scores are around that mean. Those summaries do not, by themselves, establish whether a change is attributable to the intervention.

The endpoint description gives the scale and assessment approach, but the posted results do not include the observed scores, mean change, standard deviation, or a confidence interval. Thus, the direction, magnitude, and precision of the measured change are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information registered for this study is limited. The primary measure is continuous: SANDE produces a score along a scale, and the record specifies a mean and standard deviation as the summary. The design is single-group, and no analysis entries or numerical primary outcome results are reported. The concepts below explain how these elements are generally interpreted; they do not describe unreported procedures used in this study.

What does a mean change represent?

For a continuous outcome measured at baseline and follow-up, a mean change summarizes the average within-participant difference between the two assessments, provided the same participants contribute measurements at both times. The mean can describe the center of the observed changes, but it does not show whether all participants changed similarly. Participants may have changes in different directions or of different sizes. The registry record names mean as the summary statistic, but it does not report the mean change or the individual-level distribution of changes.

The SANDE endpoint is a subjective rating of dryness. The record specifies that a higher score represents greater subjective dryness and that the primary outcome is change from baseline to final value. It does not state the arithmetic convention used to express change, such as whether follow-up minus baseline or the reverse was used. In the absence of a posted estimate and a stated convention, no signed effect should be reconstructed.

What does the standard deviation describe?

In general, a standard deviation describes the spread of observations around their mean. For a change score, it would describe how much participants’ changes vary around the average change. It is not the same as a standard error or a confidence interval: those address the precision of an estimated mean, whereas the standard deviation describes participant-level dispersion. The registered outcome lists standard deviation, but no value is reported, and the record does not clarify whether it refers to baseline scores, final scores, or changes.

Why does the single-group design matter?

A within-group comparison can describe change over time among those measured, but it cannot isolate the intervention’s contribution in the way a suitable concurrent comparison can. In general, changes may coincide with treatment without being caused by it. Natural variation in symptoms, expectations, other care, and changes in measurement experience can also affect before-and-after results. These are general features of uncontrolled comparisons, not claims about what occurred among these participants. Allocation is marked NA, masking is NONE, and no comparator is registered.

Masking can matter particularly for self-reported outcomes because participants know which intervention they receive and may form expectations about their symptoms. The record does not report whether outcome assessors were masked or whether additional procedures were used to standardize questionnaire administration. It would be inappropriate to assume either that such steps occurred or that they did not beyond the registered masking designation.

How should uncertainty be assessed?

In general, a confidence interval gives a range of values compatible with the data under the analysis assumptions, and it communicates the precision of an estimate. A narrow interval indicates greater precision than a wide interval, but the interval does not resolve limitations caused by an uncontrolled design or biased measurement. No confidence interval is reported for the SANDE outcome. A p-value, which addresses compatibility with a specified null model under statistical assumptions, is also not reported. Statistical significance cannot be inferred from a mean and standard deviation alone, and neither value is available.

Repeated assessments may be analyzed in different ways in general, including a direct comparison of baseline and final measurements or a model that uses measurements across visits. These methods can make different assumptions and use different amounts of the available data. The endpoint description mentions Visit 1,2 and 3, but the registry does not report which observations were used in an analysis or what model, if any, was used. The statistical plan and any adjustment for baseline characteristics are not reported in the registry record.

Why is over-dispersion relevant?

Over-dispersion is a general issue for count outcomes when observed variability exceeds what a chosen probability model expects. It is not the central modeling concern for the primary endpoint here, which is a continuous score. For a continuous outcome, the analyst would instead consider the distribution of scores or changes, outliers, repeated measurements, and whether the chosen summary and model fit the data. The record does not provide participant-level measurements or model details, so those features cannot be assessed.

Sample-size planning also cannot be reconstructed from the enrollment figure alone. The registry record does not report a sample-size justification, target precision, or planned detectable effect. The enrollment of 19 is a study descriptor, not evidence of statistical power. Any planning illustration based on an observed effect would be a retrospective illustration rather than an account of the trial’s original design, and no such calculation should be treated as observed power.

10. Confidence Intervals for Each Arm

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

R code and output

arm <- c("Acthar Gel 80 U/ml")
n   <- c(12)
m   <- c(44.77)
sp  <- c(3.13)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Acthar Gel 80 U/ml  12  44.770  3.130  42.781  46.759

11. Multiplicity, Missing Data and Analysis Populations

The record lists the SANDE measure as primary and intraocular pressure as a secondary outcome. It also lists three outcome measures, but the posted record does not provide numerical results for the SANDE outcome or details of analyses for the other measures. A list of outcomes alone does not establish which measures were formally tested, what hypotheses were specified, or whether the results were adjusted for multiple testing.

When several outcomes or analyses are examined, the chance of a seemingly notable result can increase. In general, multiplicity procedures can control the interpretation of a family of statistical tests, but the choice depends on the prespecified questions and analysis plan. Whether any such procedure was planned or used is not reported in the registry record. No p-values or inferential results are available for evaluating this issue.

Missing-data handling is also not reported. The primary outcome description says that patients receiving Acthar gel injections for 90 days were analyzed, but it does not give the analysis denominator or the number of participants with measurements at each visit. It does not explain how missing questionnaire items, missed visits, or incomplete follow-up were treated. The enrollment count of 19 should not be substituted for an outcome-specific analysis count.

The registry does not identify an intention-to-treat or other analysis population, nor does it describe exclusions from the outcome analysis. The available population wording is not enough to establish how participants who did not complete the stated injection period were handled. These omissions leave uncertainty about how representative any analyzed group would be of all enrolled participants.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The safety figures list 19 participants at risk for serious adverse events and 0 affected. For other adverse events, 19 participants were at risk and 1 was affected. The registry lists 0 deaths. These are participant counts as recorded; they are not comparative estimates because the study has no registered control group.

The record does not provide the event descriptions for the other adverse event, and the list of top serious adverse event terms is empty. An empty list of terms does not add detail about the event represented by the other-adverse-event count. The record also does not specify the safety observation period or provide event-level timing, severity, or relatedness information in the available safety summary.

These counts describe what the registry reports for this study. They do not establish that no other safety events occurred outside the recorded categories or observation process. With no comparator and no additional event detail reported, the counts should be read descriptively, not as evidence that the intervention caused or prevented an event.

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

The record describes a phase 4, single-group study of Acthar gel in patients with dry eye disease and identifies change in SANDE dryness scores as the primary outcome. It also records an enrollment of 19 and lists intraocular pressure as a secondary outcome. Those details define the study question and its basic structure.

The posted results do not report the numerical SANDE scores or change estimate. There is therefore no basis in the registry record to state whether average dryness ratings increased, decreased, or stayed similar, or to quantify how variable or precise any change was. The study completion status does not itself communicate an outcome.

Even a reported before-and-after change would need to be interpreted in light of the design. Because there is no registered control group, the study cannot estimate a treatment contrast against a contemporaneous alternative. In general, an uncontrolled change over time cannot separate intervention effects from symptom fluctuation, expectations, concurrent care, or other changes. This does not determine what happened in this study; it describes what the design can and cannot distinguish.

The safety summary records no participants affected by serious adverse events, one affected by other adverse events, and no deaths among the listed counts. The record does not provide enough event detail to characterize the other adverse event or determine its relationship to treatment. These descriptive figures should not be interpreted as a comparative safety assessment.

Overall, the registry record supports a cautious account of the intended measure, study population description, intervention, design, and recorded safety counts. It does not provide the outcome estimates needed to assess the observed change, its precision, or an intervention effect. Missing analysis details also prevent an independent appraisal of how the outcome data were handled.

14. Why This Trial Matters Statistically

This study is statistically notable for the kind of question it asks and the limits built into its design. Dry eye symptoms are assessed with a subjective score, and the primary question concerns change from baseline to a final visit among participants receiving the intervention. Such a measure can be useful for describing participants’ perceived symptoms, but interpretation depends on the score data and on a clear account of the analysis.

The single-group design makes the distinction between observing change and estimating a comparative effect especially important. A within-person comparison can describe how ratings differ over time. Without a control group, however, it does not show how those same ratings might have changed over that period without the intervention. This is a general causal-inference limitation, not a claim about the direction or cause of any change in this study.

The record also illustrates why enrollment alone is not enough to judge statistical strength. The registry lists 19 enrolled participants, but does not report the number contributing to the primary analysis, the outcome variability, or an uncertainty interval. Without those details, the precision of a mean change cannot be assessed. A sample-size rationale and analysis plan are not reported in the registry record.

Finally, the outcome description is more complete than the numerical reporting: it explains the SANDE scale, the direction of higher scores, and the assessment timeframe, but not the observed values. That distinction matters for readers. A well-defined endpoint clarifies what a study aimed to measure; it cannot substitute for results. The record therefore offers useful design information while leaving the central statistical result unavailable.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this specific study is that the registry record does not report numerical results for the primary SANDE outcome. Baseline and final scores, mean change, variability, and confidence intervals are absent. The outcome’s direction and magnitude therefore cannot be evaluated from the posted results.

The single-group design has no concurrent comparator, and masking is listed as NONE. For a subjective symptom rating, knowledge of treatment may be relevant to how participants report their experience. In general, an uncontrolled design also cannot separate change associated with treatment from other influences over time. These are design limitations, not evidence that any particular bias occurred.

The analyzed population is described as patients receiving injections for 90 days, while the endpoint timeframe is stated as 12 weeks total. The registry does not explain the relationship between those descriptions or report the outcome-specific analysis count. Missing questionnaires, incomplete follow-up, and deviations from the planned treatment period are not described, and the handling of missing data is not reported.

The record does not report the dosing frequency, complete visit schedule, sample-size justification, statistical analysis plan, or adjustment for multiple outcomes. Although intraocular pressure is listed as a secondary outcome and three outcome measures are recorded, numerical results and analysis details are not available for evaluating those outcomes. The safety summary also lacks event descriptions and further context for the other adverse event. These gaps limit independent assessment of efficacy estimates, their precision, and the completeness of safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Clinical Efficacy of H.P. Acthar Gel 80 U/ml to Improve the Signs and Symptoms in Subjects With Dry Eye Disease — NCT03287635.
• Registry record last updated 2021-01-28; status last verified 2021-01.
• Results first posted 2021-01-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry identifies NCT03287635 as a completed phase 4 study sponsored by Toyos Clinic, with 19 enrolled participants and dry eye disease as the condition. It lists Acthar gel 80 U/ml as the intervention and a single-group design with allocation marked NA and masking marked NONE. The study started on 2018-07-01, with primary completion on 2020-02-01.

The primary outcome is change in SANDE dryness score from baseline to final visit, over a stated 12 weeks total. The record describes an analyzed population receiving Acthar gel injections for 90 days and lists intraocular pressure as a secondary outcome. Numerical primary outcome results, analysis methods, and missing-data procedures are not reported in the registry record.

The safety summary records 0 participants affected by serious adverse events, 1 affected by other adverse events, and 0 deaths. The design and available results support descriptive interpretation, but do not provide a comparative estimate of the intervention’s effect.