Adherence Assessment With Travalert Dosing Aid: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adherence Assessment With Travalert Dosing Aid (NCT00508469), a randomized phase 4 study. The primary outcome is Adherence.

2. Clinical Question

3. Trial Design

This was a Phase 4 randomized, parallel-group study with no masking. Its stated purpose was to compare adherence when patients used Travalert with a fixed travoprost/timolol combination or with travoprost and timolol as separate medications. The study concerned patients with open-angle glaucoma or ocular hypertension. The registry lists enrollment of 102 participants, a start date of 2007-10, primary completion in 2010-01, and a completed status.

In the fixed-combination arm, participants were instructed to use one drop in the study eye once daily at 9 p.m. For six months. In the separate-medication arm, they were instructed to use travoprost at 9 p.m. and timolol at 9 a.m. and 9 p.m. For six months, using a separate Travalert device for each medication. The primary outcome was assessed over six months and is described as the percentage of adherent patients.

The registry reports per-protocol outcome denominators of 43.0 for the fixed-combination arm and 42.0 for the separate-medication arm. These are not the same as the overall enrollment figure, and the registry record does not explain the relationship between enrollment and those analysis populations. The adverse-event denominators are different again. The record does not report how the random sequence was generated, whether allocation was concealed, or how participants were assigned to the regimens.

The official title names timolol 0.5%, while the intervention list names timolol 0.05%. The arm descriptions do not give a timolol concentration. This inconsistency is not resolved in the registry record. The sponsor is listed as Alcon Research.

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: Baseline characteristics are presented for the per-protocol population.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Per protocol

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 Adherence, measured over 6 months.

The primary endpoint is the percentage of patients classified as adherent over six months. Under the registry definition, a patient had to administer at least 80% of instillations within ±2 hours of the scheduled time to count as adherent. The measure therefore combines the proportion of scheduled doses taken with how closely administration followed the intended schedule. It is a categorical summary of patient-level dosing behavior, not a direct measure of eye pressure, vision, or another clinical outcome.

Adherence is relevant to a regimen comparison because the regimens differ in how many medications and dosing times patients must manage. The study used Travalert to assess the timing of instillations. The endpoint expresses the result as a percentage of adherent patients rather than as a mean adherence score. The registry describes the primary population as per protocol, so the reported percentages apply to that analysis population rather than necessarily to every participant enrolled.

The posted values are 63.0% for Travalert with the fixed combination and 43.0% for Travalert with separate travoprost and timolol. The record does not provide a confidence interval, a numerator for either percentage, or a detailed account of how device records were converted into patient classifications. It also does not report how missing device readings or incomplete records were handled. Those omissions limit assessment of the precision and reproducibility of the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies adherence as a count-type outcome expressed as the percentage of adherent patients. The reported values are 63.0% and 43.0% for the per-protocol groups. The primary outcome definition classifies a patient as adherent if at least 80% of instillations were administered within ±2 hours of the scheduled time. This threshold turns dosing records into a patient-level classification: each patient either meets the stated criterion or does not, and the arm percentage summarizes the share who meet it.

What does the arm percentage convey?

A percentage is a descriptive summary of the observed analysis group. It gives the proportion meeting the endpoint definition, but does not by itself express uncertainty or quantify the strength of evidence for a difference between regimens. Its interpretation depends on the population included, the endpoint definition, and how missing or unusable records were treated. The record names a per-protocol population but does not report a detailed rule for inclusion in that population or for classifying patients whose device data were incomplete.

The endpoint is not a continuous measure of the exact fraction of doses taken. Instead, it reduces dosing behavior to whether each patient met a threshold, then summarizes those classifications as a percentage. Such thresholding can make an endpoint easier to interpret, but it discards detail: two patients with different dosing patterns could receive the same classification if both fall on the same side of the threshold. This is a general feature of binary outcomes derived from a cutoff, not an additional result from this trial.

Why is an uncertainty estimate useful?

General statistical explanation: an estimate from a sample is subject to sampling variation. A confidence interval gives a range of values that reflects this uncertainty under the assumptions of the method used. For an arm percentage, an interval would help readers judge how precisely the observed percentage estimates the corresponding population proportion. For a comparison, an interval around an effect estimate would show the uncertainty in the contrast between arms. Neither kind of interval is reported for the primary endpoint in the registry record.

The record also reports no comparative test or p-value for adherence. A p-value, when calculated under a specified statistical model, describes how compatible the observed data are with a particular null hypothesis. It does not measure the probability that the null hypothesis is true, nor does it indicate whether an effect is important. Since the registry record gives no test result or model for the adherence comparison, no such inference can be made from the posted percentages.

What does randomization contribute?

General statistical explanation: random allocation is intended to make comparison groups similar, on average, with respect to factors present before treatment assignment. It reduces the risk that investigators deliberately or systematically assign participants according to prognosis. Randomization does not guarantee identical groups, and it does not resolve bias introduced after assignment, such as outcome missingness or differential analysis exclusions. The record says the study was randomized but does not report the sequence-generation method or whether allocation was concealed.

The study was open-label, meaning masking was listed as none. For an outcome based on dosing behavior, knowledge of the assigned regimen could potentially influence participants’ behavior. Device-recorded timing may make the endpoint less dependent on a participant’s retrospective report, but the registry does not describe device validation, data processing, or safeguards against differential measurement. These are general considerations about unmasked behavioral outcomes, not claims about what occurred in this study.

How should planning calculations be read?

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrations are not the trial’s own design justification and are not observed power. A planning calculation asks how many participants per arm might be needed under specified assumptions to detect an effect of a chosen size. Because such calculations use assumptions and an effect estimate, they do not show that a study had a particular probability of finding a result after the data were observed. No sample-size justification for the original trial is reported in the registry record.

The registry record reports no comparative analysis for this endpoint. The percentages can be described as observed per-protocol summaries, but the lack of a reported model, uncertainty interval, or test means that statistical precision and inferential strength cannot be assessed from the record. General statistical concepts explain what additional analyses could convey; they do not supply missing trial results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no secondary outcomes. It reports no comparative analyses for the posted outcome. The record does not report a multiplicity plan, such as whether any adjustment for multiple outcomes or comparisons was intended. With no secondary outcome analyses posted, there is no reported set of results from which to assess how multiplicity was handled. This does not establish what the original protocol planned; that information is not reported in the registry record.

The primary endpoint is described for the per-protocol population. The record does not report the criteria used to define that population, the number of randomized participants excluded from it, or reasons for any exclusions. Although total enrollment is 102 and the arm-specific primary outcome denominators are 43.0 and 42.0, participant flow and the relationship between these numbers are not reported. The record also does not describe withdrawals, loss to follow-up, protocol deviations, or whether any participants had incomplete device data.

Missing-data procedures are not reported in the registry record. It is not stated whether missing instillation records were treated as nonadherence, excluded from calculation, imputed, or handled in another way. These choices can affect a threshold-based percentage, particularly if missingness differs across groups. The record also does not report sensitivity analyses that might show whether conclusions change under alternative assumptions about missing data.

The adverse-event denominators differ from the primary endpoint denominators, but the registry does not explain the populations used for these summaries or reconcile them with enrollment. Without participant-flow details and analysis-population definitions, readers cannot determine how fully the outcome summaries represent the randomized participants.

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: brachycardia (2.0%), heart failure (1.9%).

The registry reports serious adverse events among 52 participants at risk in the fixed-combination group and 50 in the separate-medication group. One participant is reported as affected in each group. For other, non-serious adverse events, the record reports zero participants affected in each group, with the same respective at-risk denominators of 52 and 50. These are descriptive counts; the registry record does not report a comparative safety analysis or uncertainty estimates.

The record lists “Brachycardia” at 2.0% and “Heart Failure” at 1.9% among the top serious-event terms. It does not identify an arm for either listed term or explain how the term percentages relate to the arm-level counts. The registry record does not report death counts. It also does not provide details in the posted summary about event timing, duration, severity criteria, attribution to study treatment, or how the event terms were coded.

Serious adverse-event counts and adherence percentages describe different outcomes and may use different analysis populations. The safety denominators should not be treated as the primary endpoint denominators. These figures describe what the registry reports; they do not establish whether an event was caused by a study medication or device.

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

The posted primary result describes the proportion of per-protocol participants who met the study’s adherence threshold during six months. That proportion was 63.0% with Travalert and the fixed travoprost/timolol combination, and 43.0% with Travalert and separate travoprost and timolol. The comparison concerns the regimens as implemented in this trial, including their different dosing schedules and use of devices.

The numbers do not establish a statistically reliable difference because no comparative estimate, confidence interval, or p-value is reported. Without uncertainty estimates, the degree of precision around either percentage and around their contrast is not known from the registry record. Nor do the posted values establish that the regimens would produce the same adherence patterns in other settings or populations.

The endpoint is a measure of medication-taking behavior based on timing and a threshold. It does not measure intraocular pressure, visual function, disease progression, or quality of life. No such clinical outcomes are reported as secondary results in the registry. The adherence percentages therefore cannot be used to infer a clinical benefit or lack of benefit.

The per-protocol analysis population further limits interpretation. Overall enrollment is 102, whereas the primary outcome groups are reported as 43.0 and 42.0. The registry does not explain participant flow or the criteria that determined inclusion in the per-protocol analysis. The findings should be understood as summaries of the reported analysis groups, not necessarily as outcomes for all randomized participants.

Finally, the record is open-label and does not provide details on allocation concealment, missing-data handling, or endpoint data processing. Those omissions make it harder to judge potential bias and reproducibility. The result is informative as a posted descriptive comparison of adherence under two dosing arrangements, but the registry record alone does not support broader conclusions about comparative clinical outcomes.

13. Why This Trial Matters Statistically

This study addresses a statistical question about a behavior that can be recorded over time and then summarized at the patient level. The endpoint does not simply count whether a medication was ever used. It applies a threshold to the proportion of instillations occurring within a specified time window, then reports the percentage of patients who satisfy that rule. That structure makes clear why the endpoint definition and the handling of incomplete device records are central to interpretation.

The randomized parallel design gives the comparison a framework for evaluating two medication schedules. However, the primary result is reported only as arm-specific percentages, with no inferential comparison or uncertainty interval. This illustrates a key distinction in clinical research: descriptive estimates tell readers what was observed in the analysis groups, while comparative analyses quantify how uncertain a group contrast is under a stated method. The latter is not reported for adherence in this registry record.

The trial also highlights the importance of defining analysis populations. The record gives overall enrollment, per-protocol outcome denominators, and different safety denominators, but does not explain participant flow or reconcile those groups. Readers need those details to understand which participants contribute to each result and how missingness or exclusions may affect the summaries.

Finally, the regimens differ in both medication arrangement and schedule, so adherence is a relevant behavioral endpoint for this comparison. Yet it remains distinct from clinical outcomes. Separating adherence from efficacy and safety prevents a behavioral result from being interpreted as evidence about disease control. The registry’s concentration inconsistency for timolol also shows why precise intervention descriptions matter: the official title lists 0.5%, while the intervention list gives 0.05%, and the discrepancy is unresolved in the record.

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 leaves important details about the primary analysis unspecified. It identifies the endpoint as a percentage of adherent patients and gives the threshold definition, but does not report the underlying number of patients meeting the criterion in each arm or the method used to derive the percentages. It does not report confidence intervals, a comparative effect estimate, or a statistical test. These omissions prevent assessment of precision and formal comparison.

The per-protocol population is not described in enough detail to determine which participants qualified or why others may not have been included. Overall enrollment is 102, while the primary endpoint denominators are 43.0 and 42.0; participant disposition and reasons for the difference are not reported in the registry record. The record does not explain missing device data, withdrawals, adherence-data quality checks, or sensitivity analyses. These details are especially relevant when the endpoint depends on recorded instillation times.

The study was unmasked, but the registry does not report whether outcome processing was blinded or how device data were reviewed. Details of random-sequence generation and allocation concealment are also not reported. These omissions do not establish that bias occurred, but limit the ability to evaluate its possibility.

There is an intervention-description inconsistency: the official title states timolol 0.5%, whereas the intervention list states timolol 0.05%; the arm descriptions do not specify a concentration. The registry record does not resolve which concentration was used. It also does not report a sample-size justification for the original trial or a multiplicity plan. Finally, the posted primary outcome concerns adherence only, and no secondary outcome analyses are listed.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Adherence Assessment With Travalert Dosing Aid — NCT00508469.
• Registry record last updated 2012-07-12; status last verified 2012-06.
• Results first posted 2012-07-12.
• 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 describes a completed Phase 4 randomized, parallel, open-label study of Travalert use with a fixed travoprost/timolol combination versus separate travoprost and timolol. The stated conditions are open-angle glaucoma and ocular hypertension. Participants were assigned to six-month dosing regimens, and the primary endpoint was the percentage meeting an adherence definition based on at least 80% of instillations occurring within ±2 hours of schedule.

For the per-protocol population, the registry reports adherence percentages of 63.0% with the fixed combination and 43.0% with separate medications. No comparative analysis or uncertainty estimate is reported. The registry gives overall enrollment of 102 and outcome denominators of 43.0 and 42.0, without participant-flow details. Safety summaries report one serious-event-affected participant in each group and zero participants affected by other adverse events. Death counts are not reported in the registry record. The timolol concentration differs between the official title and intervention list, and the record does not resolve the inconsistency.