An Observational Study of OPTIVE PLUS® for the Treatment of Dry Eye Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Observational Study of OPTIVE PLUS® for the Treatment of Dry Eye Disease (NCT01711424), a registered phase not stated study. The primary outcome is Number of Participants Very Satisfied or Satisfied With OPTIVE PLUS®.

2. Clinical Question

The clinical question is about participants' reported satisfaction with treatment, rather than a direct comparison between assigned treatments. The registry describes satisfaction in relation to dry eye signs and symptoms and uses a four-point scale: Very satisfied, Satisfied, Dissatisfied or Very dissatisfied. The primary outcome combines the first two response categories in its stated definition. The number of participants in that combined category is not reported in the registry record, so the recorded information does not establish the observed level of satisfaction.

The study concerns use in a routine clinical setting, where physicians made treatment decisions according to their current standard of care. This setting may describe experience in practice, but it does not by itself answer what would have happened to similar patients under another treatment or no treatment. Without a stated comparator, a comparative treatment effect cannot be estimated from the information reported. The record also names Tear Break Up Time (TBUT) and Schirmer Score as secondary outcomes, but their results are not reported in the registry record. Consequently, the clinical question that can be identified is narrower than a question about comparative effectiveness or changes in all dry eye measures.

3. Trial Design

The record classifies this study as observational and describes OPTIVE PLUS® use in patients with dry eye disease in a routine clinical setting. The physician determined treatment in line with current standard practice. The study record identifies one intervention, OPTIVE PLUS®, and describes patients prescribed it. It does not describe a randomized assignment process or a separate control group. Allocation is not stated, and the record explicitly cautions that this is not a randomized comparison and that arms are not a like-for-like control comparison.

The listed enrollment is 1209. The study start is recorded as 2012-09, the primary completion as 2013-03, and the status as COMPLETED. These record details describe the study's administrative and enrollment information; they do not provide the outcome findings. The primary outcome is the number of participants very satisfied or satisfied with OPTIVE PLUS® at Week 4. Its stated population is all participants with data available for that measure, which need not be the same as the enrollment listed for the study. The number with outcome data is not reported in the registry record.

The record lists four outcome measures and zero analyses. Alongside the satisfaction outcome, the named secondary outcomes are physician satisfaction, TBUT and Schirmer Score. Their numerical results and analysis details are not reported in the registry record. The available description does not specify how participants were recruited, the clinical criteria used to include them, how long each participant was observed, or how the outcome data were collected beyond the stated Week 4 timeframe for the primary outcome. Those details should not be inferred from the observational label or from the routine-care setting.

Because treatment was chosen by physicians rather than assigned through a stated randomized process, the design is descriptive rather than a direct randomized treatment comparison. Patient characteristics, treatment choices and care circumstances could differ in ways that affect outcomes. The record does not describe a comparator or an adjustment strategy to address such differences. This means the design can characterize recorded experience among participants with available outcome data, but the information recorded does not isolate an effect attributable to OPTIVE PLUS®.

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: Patients with dry eye prescribed OPTIVE PLUS® in accordance with physician standard practice. There was no investigational drug administered in this study.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants with data available for this outcome measure.

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 Number of Participants Very Satisfied or Satisfied With OPTIVE PLUS®, measured over Week 4.

The primary endpoint is the number of participants who rated their satisfaction with OPTIVE PLUS® as Very satisfied or Satisfied at Week 4. The satisfaction question relates to treatment for dry eye signs and symptoms. Responses were described on a four-point scale, with Dissatisfied and Very dissatisfied as the other categories. The endpoint therefore represents a count in the two more favorable response categories, rather than a measurement of symptom change or a continuous score.

A satisfaction endpoint can capture a participant's overall experience of treatment in a way that may not be represented by a single clinical measurement. In general, patient-reported or clinician-reported satisfaction can reflect a judgment about perceived benefit, burden and expectations. It is not interchangeable with an objective sign, and it does not on its own show that a measured clinical change occurred. In this record, satisfaction is the primary outcome, while TBUT and Schirmer Score are named as secondary outcomes. The record also names a secondary measure of physician satisfaction.

For interpretation, the endpoint's denominator matters: the registry defines the population as all participants with data available for this outcome. The number with available data and the number meeting the endpoint are not reported in the registry record. Without those results, the observed satisfaction count and the degree of uncertainty around it cannot be assessed. Nor can satisfaction be compared with a control group's experience, because no comparator group is described.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an observational study, names a binary-style primary endpoint as a participant count, and lists zero analyses. It does not report a statistical analysis plan, an estimated outcome effect, or an inferential result. The explanations below describe general statistical ideas relevant to reading this kind of record; they do not assert that any particular method was used in this study.

What does a participant count represent?

The primary outcome is the number of participants in the Very satisfied or Satisfied response categories at Week 4. A count depends on the number of participants whose responses were available. For interpretation, readers generally need both the number meeting the outcome and the applicable denominator. The registry describes the outcome population as all participants with data available, but it does not report how many participants had such data or the count meeting the endpoint. The listed enrollment of 1209 is a study enrollment figure, not a reported outcome denominator.

For a binary outcome, analysts may report a count, a proportion, or a comparison between groups. Each answers a different descriptive or inferential question. A count alone does not indicate how common an outcome was unless the denominator is also known. A proportion still does not establish a causal effect, particularly when it comes from a group without a suitable comparison. No primary outcome count, proportion, or comparison is reported in the registry record.

What would uncertainty measures add?

General explanation: an estimate is subject to sampling variability, and a confidence interval conveys a range of values compatible with the data under the model and assumptions used. Narrower intervals indicate greater precision under those assumptions; wider intervals indicate less precision. The interval does not correct bias from an unsuitable design, incomplete outcome data or confounding. A p-value, when used, describes how compatible data are with a specified null model and its assumptions; it is not the probability that a treatment works or that the null hypothesis is true.

There is no reported estimate or confidence interval for the primary outcome, and no p-value is reported. The registry lists zero analyses. Therefore, readers cannot use the record to assess statistical uncertainty, evaluate a null-hypothesis test, or determine whether an estimate is compatible with a range of clinically important values. The missing inferential output should not be interpreted as a negative test result.

Why does the observational design matter?

General explanation: random assignment can help balance measured and unmeasured characteristics between groups, on average, when comparing interventions. In an observational study, treatment choices arise outside a stated random allocation process. People receiving a treatment may differ from people not receiving it, and those differences can be related to outcomes. This is confounding: an association between treatment and outcome can partly reflect other characteristics rather than a treatment effect.

Here the record describes physician-directed use in routine care and does not describe a comparator group, allocation procedure or adjustment approach. It therefore does not report the elements needed to interpret a between-group causal estimate. Even a complete descriptive satisfaction count would not show what the same participants' outcomes would have been under another treatment. The registry's caution that arms are not a like-for-like control comparison reinforces that comparisons between any groups should not be treated as randomized evidence.

What is over-dispersion, and is it relevant?

General explanation: over-dispersion arises when observed variation is greater than a statistical model expects. It can matter for count outcomes when counts vary more widely than a simple model assumes, and unaccounted over-dispersion can make uncertainty estimates too optimistic. The registry does not report a model for the primary outcome, a dispersion estimate, or an analysis of count variation. The primary endpoint is described as a number of participants meeting a response definition, but that description alone does not establish that a count-regression model was used or that over-dispersion was assessed.

How should planning illustrations be understood?

The record describes a sample-size planning illustration based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It also says that time-to-event illustrations use the total number of events and that other illustrations use participants per arm. Those assumptions describe a planning calculation, not the design or allocation of this observational study. They do not establish that the study was planned with those assumptions, and the record does not report the study's own sample-size justification.

A planning illustration is not observed power. In general, a sample-size calculation asks how much information might be needed under specified assumptions; it does not show the probability that a completed study has established a treatment effect. The observed effect used as a planning basis, the numerical planning results and any justification for those assumptions are not reported in the registry record. Because the study has no described randomized comparison, an equal-allocation two-arm illustration should not be mistaken for the actual study design.

What can the registry entries establish?

The entries establish the stated study type, intervention, endpoint definition, timeframe, available-data population wording and enrollment. They do not provide a complete account of outcome analysis. The distinction between an endpoint being defined and an endpoint being reported is important: a registered measure specifies what was intended to be assessed, while a result requires observed data and a reported analysis. In this record, the primary result and secondary outcome results are not reported in the registry record. Statistical interpretation must therefore remain descriptive about what was registered and cautious about what cannot be inferred.

10. Multiplicity, Missing Data and Analysis Populations

The record lists four outcome measures and identifies satisfaction at Week 4 as the primary outcome. It also names physician satisfaction, TBUT and Schirmer Score as secondary outcomes. The registry lists zero analyses, and numerical results for the primary and secondary outcomes are not reported in the registry record. The analysis population, estimates and uncertainty measures for those outcomes are therefore unavailable.

Multiplicity is the general statistical issue that arises when several outcomes or comparisons are tested. Conducting many tests can increase the chance of finding at least one apparently notable result by chance, depending on the testing strategy. Researchers may address this through a prespecified hierarchy, adjustment or a distinction between primary and exploratory outcomes. The record identifies a primary outcome and secondary outcomes, but a multiplicity strategy is not reported in the registry record. It is not possible to determine whether any adjustment was planned or applied.

The primary endpoint's stated population is all participants with data available for that outcome. The number of participants with available data, the amount or pattern of missingness, and any method for handling missing data are not reported in the registry record. General statistical principle: if outcome availability is related to participants' experiences or characteristics, analysis restricted to observed responses may differ from analysis of the full enrolled group. The record does not allow assessment of whether missingness could affect the interpretation.

Enrollment is 1209, but it should not be substituted for the outcome-specific denominator. No analysis population beyond the available-data description is reported. The record also does not describe exclusions, imputation, sensitivity analyses or a comparison of participants with and without outcome data. These omissions limit assessment of both outcome completeness and the robustness of any possible estimate.

11. 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

Serious events with the highest arm-level rate: cataract operation (0.2%).

The registry lists OPTIVE PLUS® with 1209 participants at risk for serious adverse events and 2 serious adverse events. It separately lists 1209 at risk for other adverse events and 0 other adverse events. These are the registry's reported figures; they should be read as event entries, not as proof that the intervention caused or prevented an event. The record does not provide further detail about event definitions, follow-up completeness or how attribution was assessed.

The most frequent serious adverse event term listed is “Cataract operation” at 0.2%. That label is a reported event term and does not, by itself, establish a causal relationship to OPTIVE PLUS®. The registry does not report deaths in the available safety entry; death information is not reported in the registry record.

In general, adverse-event counts require context about observation time, event ascertainment, severity definitions and participants' underlying health. A count does not describe the timing or duration of events, and without an appropriate comparison it cannot distinguish treatment-related events from events that would occur in the course of routine care. The record's safety entries should therefore be interpreted narrowly as the listed counts and term, rather than as a comparative risk estimate or a complete account of safety.

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

The record establishes that an observational study examined OPTIVE PLUS® use in patients with dry eye disease in a routine clinical setting. Physicians made treatment decisions according to current standard practice. The primary outcome was defined as the number of participants who were Very satisfied or Satisfied at Week 4, among those with data available. These details identify the intended question and the way the primary response was categorized.

The record does not report the primary outcome count or the number of participants with available data. It consequently does not show how many participants met the endpoint, how common those responses were in the analyzed population, or how precise an estimate might be. It also does not report numerical findings for the named secondary outcomes. The absence of these results means the record cannot establish whether satisfaction was high or low, whether TBUT or Schirmer Score changed, or whether any observed outcome was statistically distinguishable from a comparison value.

The study design also limits what any descriptive result could mean. With no stated comparator and no randomized allocation, participant responses cannot establish what would have happened under another treatment or without treatment. General statistical principle: an observed outcome in a treated group is not automatically a treatment effect, because outcomes may reflect patient characteristics, expectations, other care or the natural course of symptoms. The registry record does not describe an analysis designed to separate these possibilities.

The safety entry records two serious adverse events and zero other adverse events, with the serious event term “Cataract operation” listed at 0.2%. Those figures do not by themselves show whether events were caused by treatment or how safety compares with another option. Taken together, the record supports a limited account of study structure and registered outcomes, but not a conclusion about efficacy, comparative benefit, or causal safety effects. It also does not support interpreting unreported outcomes as showing no change or no events.

13. Why This Trial Matters Statistically

This study is statistically instructive because it illustrates the difference between an observational description and a comparative treatment evaluation. A routine-care setting can record how treatment is used and what participants or physicians report. However, when physicians determine treatment and no comparator is described, outcome data alone do not identify what would have happened under an alternative. Design and analysis determine which questions can be answered, not only the choice of statistical test.

The primary outcome also demonstrates why definitions and denominators matter. “Very satisfied or satisfied” is a clearly described grouping of responses on a four-point scale, and the Week 4 timeframe is stated. But the registry defines the outcome population as participants with data available without reporting how many had data or how many met the endpoint. A well-defined outcome is useful for interpretation, yet it cannot substitute for the observed result and its denominator.

The record is also a reminder that registration details and results are different kinds of information. A study may be marked COMPLETED and identify primary and secondary measures, while numerical findings and analyses remain unreported in the registry record. In this case, zero analyses are listed. Without estimates and uncertainty measures, statistical precision and the strength of any outcome evidence cannot be evaluated.

Finally, safety listings require careful reading. Event counts, risk populations and a listed event term describe registry entries; they do not by themselves establish causality or comparative risk. Keeping those distinctions clear helps prevent overinterpretation of descriptive records. The main statistical lesson is to align conclusions with the design, the available-data population and the results actually reported.

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 does not report the primary satisfaction count, the number of participants with available primary outcome data, or a numerical result for any named secondary outcome. It also lists zero analyses. This prevents assessment of effect size, precision, statistical uncertainty and the consistency of findings across outcomes. Although enrollment is 1209, the outcome-specific denominator is not reported and should not be assumed to equal enrollment.

The observational design is a further limitation for causal interpretation. Treatment was prescribed according to physician standard practice, and no comparator group or randomized allocation is described. The record does not report participant characteristics, treatment-selection factors, co-interventions or an adjustment strategy. These details are important when considering whether outcomes could be associated with factors other than treatment.

The registry record does not specify recruitment methods, eligibility criteria, the measurement procedures for the secondary outcomes, or how missing outcome data were handled. It does not report whether outcome assessors used standardized procedures or whether participant responses were collected consistently. Missing-data patterns and sensitivity analyses are also not reported. These gaps make it difficult to judge how representative the available responses might be.

For safety, the record provides event counts and a serious adverse event term, but further information about event definitions, timing, attribution, observation time and completeness of reporting is not reported in the registry record. The listed figures therefore cannot support a comprehensive or comparative safety assessment. These limitations concern what can be concluded from this registry record; they do not establish that the study itself did or did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Observational Study of OPTIVE PLUS® for the Treatment of Dry Eye Disease — NCT01711424.
• Registry record last updated 2014-03-17; status last verified 2014-01.
• Results first posted 2014-03-17.
• 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.

18. Record Summary

The registry record describes an observational study of OPTIVE PLUS® for dry eye disease in routine clinical practice. Physicians made treatment decisions according to current standard practice. Enrollment is 1209; the study started in 2012-09, reached primary completion in 2013-03, and has status COMPLETED.

The primary outcome is the number of participants Very satisfied or Satisfied at Week 4, among participants with data available. The record lists four outcome measures and zero analyses. Primary and secondary outcome results are not reported in the registry record. The safety entries list 2 serious adverse events among 1209 at risk and 0 other adverse events among 1209 at risk; “Cataract operation” is listed at 0.2%. With no described comparator and no reported outcome analyses, the record does not establish comparative or causal treatment effects.