Evaluation of the Safety and Efficacy of Long-term Use of Omega-3 Fatty Acid Ethyl Esters: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of the Safety and Efficacy of Long-term Use of Omega-3 Fatty Acid Ethyl Esters (NCT02153073), a registered phase not stated study. The primary outcome is Number of Participants Who Had One or More Adverse Events (AE) and Serious Adverse Events (SAE).

2. Clinical Question

In statistical terms, the study aims to describe the occurrence of adverse events during long-term use in routine medical practice. The secondary outcomes listed concern percent change from baseline in lipid measures, including triglycerides, LDL cholesterol, VLDL cholesterol, Apo-B, Apo-CIII, lipoprotein, remnant-like particles-cholesterol, and total cholesterol. The registry record lists these outcomes, but does not report corresponding analyses in the information. The question that can be answered from the posted primary results is therefore narrower: what participant counts were recorded for adverse events and serious adverse events, and what context is needed to interpret those counts?

3. Trial Design

This is a completed special drug use surveillance study of omega-3 fatty acid ethyl esters, with the official title identifying Lotriga granular capsules and long-term use. The stated purpose was to evaluate safety and efficacy among patients with hyperlipidemia in daily medical practice. The study lists one intervention: omega-3 fatty acid ethyl esters. The described dose was 2 g orally once or twice daily after meals.

The record gives an enrollment of 3084 and describes the primary outcome timeframe as up to Month 12. The recorded study start was 2013-05-29, and primary completion was 2017-05-31. The study status is completed. These dates describe the registry record; they do not, by themselves, show how long any particular participant was followed.

No randomized control group is listed, and the allocation method is not stated. Consequently, the arm should be read as a treated group rather than one side of a randomized comparison. The record does not report a comparator against which to estimate relative safety or efficacy. The adverse-event summary lists 2786 participants at risk. Separately, the primary outcome description defines the safety analysis set as all participants who completed the study. The registry record does not clarify the relationship between that definition and the at-risk count in the event summary.

The registry lists lipid outcomes as secondary measures, but the number of analyses reported is zero. Thus, the available results do not support conclusions about changes in those lipid measures. The registry record also does not report the detailed protocol, how participants entered surveillance, the intended follow-up schedule for each participant, or how the dose choice was determined. These absences matter because a surveillance study in daily practice describes events under the recorded conditions, but does not provide the controlled comparison that would isolate an intervention effect from other influences.

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: Participants with a historical diagnosis of hyperlipidemia were enrolled. Participants received interventions as part of routine medical care.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

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: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Had One or More Adverse Events (AE) and Serious Adverse Events (SAE), measured over Up to Month 12.

The primary outcome is the number of participants who had one or more adverse events and serious adverse events, with a timeframe of up to Month 12. Its unit is participants. In practical terms, this outcome counts people meeting the event criteria rather than counting every event occurrence. A participant with repeated events may still contribute to a participant count as a person with an event; the registry record does not provide further rules about how repeated events were handled.

Counting participants with an event is useful for describing how commonly events were observed within a monitored group. It gives a direct account of the number of people affected in the recorded safety population. Serious adverse events are an important safety category because their seriousness makes them relevant to safety monitoring. The posted results also distinguish serious events from other adverse events.

These counts are descriptive. Without a control group, they cannot show whether the event occurrence is higher or lower than it would have been without the intervention, nor can they establish causation. The endpoint title includes both adverse events and serious adverse events, but the available summary reports separate serious and other event counts; it does not provide a detailed case-level account or an adjusted estimate. The registry record does not report confidence intervals or a comparative statistical analysis for the primary outcome.

The outcome is also limited by its stated timeframe and population definition. “Up to Month 12” identifies the maximum stated period, but the record does not describe individual follow-up duration or how incomplete follow-up was handled. The safety analysis set is defined as participants who completed the study, which makes the handling of non-completers important to interpretation; those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is expressed as a count of participants, not as a continuous measurement. A participant-level count asks whether people experienced at least one event within the outcome definition. This differs from counting all event episodes, since one person could experience more than one event. The primary outcome title refers to participants with one or more adverse events and serious adverse events; the summary separately gives counts for serious events and other adverse events. Further event-counting rules are not reported in the registry record.

What does a participant count tell the reader?

A count is a direct description of the observed group, but its meaning depends on the population being counted and the time during which events could be observed. The event summary reports 26 participants with serious adverse events and 38 with other adverse events among 2786 at risk. These should be read as group-specific counts, not as an estimate of the intervention’s effect. Without an appropriate comparison, there is no basis for separating events associated with treatment from events that might occur as part of underlying illness, background risk, or other care.

In general, a proportion pairs an event count with a denominator to describe the fraction of a defined population affected. A rate can additionally account for the time each person was observed. The registry record gives an at-risk denominator but does not report individual follow-up time or a person-time analysis. It would therefore be inappropriate to infer a time-adjusted rate. No new proportion is calculated in this explanation.

Why does the comparison design matter?

Random allocation, when used and properly implemented, can make groups more comparable on average and support a causal comparison. This record does not report randomization or a control group; allocation is not stated, and the study is not a randomized comparison. As a result, the observed counts cannot be contrasted with a like-for-like untreated or alternative-treatment group. Even if another source reported a different event count, differences in participant characteristics, follow-up, event definitions, or surveillance could explain a contrast rather than the intervention itself.

General statistical interpretation also distinguishes precision from causality. A confidence interval describes the uncertainty around an estimate under a specified statistical model. It does not remove bias caused by a non-comparative design or incomplete observation. The registry record does not report confidence intervals for the primary event counts, so their statistical precision is not quantified in the posted results.

What is known about the analysis population?

The primary outcome description defines the safety analysis set as all participants who completed the study. The event summary separately gives 2786 participants at risk, while enrollment is listed as 3084. Those figures should not be treated as interchangeable. The registry record does not explain the relationship between the completion-based definition and the at-risk denominator, nor does it describe the characteristics of participants excluded from the safety analysis set.

In general, restricting an analysis to participants who complete follow-up can affect interpretation if completion is related to health status, treatment exposure, or event occurrence. This is a potential concern to assess, not a claim that such bias occurred in this study. The registry record does not report how withdrawal, loss to follow-up, or missing event information was handled.

How should the sample-size illustrations be understood?

The planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, such illustrations are described as participants per arm; time-to-event illustrations use a total number of events. These are hypothetical planning calculations, not observations from this surveillance study and not its reported design. They do not constitute observed power. The record does not report the study’s own sample-size justification or planned statistical design. Because this study has no reported randomized two-arm comparison, the illustration assumptions should not be mistaken for the actual surveillance arrangement.

What analyses are available?

The registry lists secondary outcomes for percent change from baseline in triglycerides, LDL cholesterol, VLDL cholesterol, Apo-B, Apo-CIII, lipoprotein, remnant-like particles-cholesterol, and total cholesterol. The number of reported analyses is zero. Accordingly, no estimate of change, uncertainty interval, or significance test for these outcomes is reported in the registry record. A list of planned or named measures is not itself evidence of a measured result.

In general, count outcomes can be analyzed using methods suited to binary participant status or event counts, depending on how the outcome is defined and what question is asked. More complex event-count models may need to account for over-dispersion, which occurs when variation in counts is greater than a simple model expects. Time-to-event methods can incorporate differing follow-up, but require event timing and censoring information. The registry record does not report which such methods, if any, were used for the posted primary results. These concepts describe possible statistical approaches generally and should not be read as a claim that any one method was applied.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary lipid outcomes, including percent change from baseline in triglycerides, LDL cholesterol, VLDL cholesterol, Apo-B, Apo-CIII, lipoprotein, remnant-like particles-cholesterol, and total cholesterol. It reports no analyses. Therefore, there are no posted results across these outcomes for which to assess statistical significance or the impact of multiple testing. The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment to control the chance of false-positive findings across multiple tests.

In general, multiplicity matters when several statistical hypotheses are tested: the more opportunities to find a nominally unusual result, the greater the chance that at least one such result occurs by chance. A prespecified strategy can clarify which results are confirmatory and how uncertainty should be interpreted. No such strategy is reported in the registry record, so none should be inferred.

For missing data, the primary outcome description says the safety analysis set included participants who completed the study. The adverse-event summary lists 2786 at risk, and enrollment is 3084. The record does not explain the relationship between these figures, report the amount or pattern of missing outcome data, or describe an approach to missingness. It also does not report whether incomplete follow-up, withdrawal, or unrecorded event status was addressed through any statistical procedure.

In general, missing information can affect estimates when the likelihood of being observed is related to participant characteristics or outcomes. Complete-case summaries can be informative, but their interpretation depends on who completed follow-up and why. Without details on non-completers and missing event status, the extent and direction of any resulting bias cannot be determined. The completion-based safety-set definition should therefore be kept in view when reading the observed counts.

11. 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 0.2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myocardial infarction (0.1%), angina pectoris (0.1%), atrial fibrillation (0.1%), sinusitis (0.0%), gastric cancer (0.0%).

The adverse-event summary lists 26 participants with serious adverse events and 38 with other adverse events among 2786 at risk in the omega-3 fatty acid ethyl esters 2 g group. It also records 10 deaths. These are descriptive figures; the registry record does not report a control group or an analysis that determines whether the intervention caused any event or death. The record does not state whether the death count overlaps with participants counted among those with serious or other adverse events.

The listed serious-event terms include myocardial infarction, angina pectoris, and atrial fibrillation, each reported at 0.1%; sinusitis, gastric cancer, and oesophageal carcinoma are each reported at 0.0%. These percentages are rounded, and event counts by individual term are not reported in the registry record. In general, a rounded percentage of 0.0% may reflect a small observed proportion; it should not be interpreted as a statement that no event occurred. The list also does not establish whether events were judged related to treatment.

Interpretation depends on the population and observation period. The primary outcome is described as covering up to Month 12, and the safety analysis set is defined by study completion. The record does not explain individual follow-up duration or how participants with incomplete follow-up were handled. These summaries are therefore best read as reported event counts in the recorded surveillance group, not as a comparative safety estimate.

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

The results provide a descriptive account of adverse events recorded in a long-term surveillance study of omega-3 fatty acid ethyl esters among patients with hyperlipidemia in daily medical practice. The posted summary reports counts for serious and other adverse events, the number at risk, deaths, and rounded percentages for selected serious-event terms. Such information can help readers understand what the registry recorded for the intervention group during follow-up up to Month 12.

However, the figures do not show that the intervention caused the listed events, nor do they establish that it prevented or increased events. The record reports no randomized comparison and no control group. Events can occur in people receiving treatment for reasons unrelated to that treatment, and a single-group summary cannot distinguish those explanations. Without a comparable group and a suitable analysis, relative risks, risk differences, or causal effects are not reported.

The counts also do not provide a complete picture of uncertainty. The registry record does not report confidence intervals for the primary results, event-level details, or a time-adjusted analysis. The safety population is defined as participants who completed the study, while the event summary gives 2786 at risk; the relationship between these details is not explained. As a result, the possible influence of incomplete follow-up cannot be assessed from the registry information described.

The record lists lipid measures as secondary outcomes, but reports zero analyses. No conclusion about changes in triglycerides, cholesterol measures, or the other listed lipid parameters can be drawn from those outcome names alone. The study’s stated aim included efficacy, but the available posted results do not quantify efficacy.

In short, the results document observed safety counts in the recorded group; they are not proof of a causal safety effect, a comparison with another treatment, or a demonstration of efficacy. The rounded term percentages should be read with their limited precision, and the absence of reported analyses, comparator data, and missing-data details constrains what can be concluded.

13. Why This Trial Matters Statistically

This study is statistically notable because it illustrates the difference between surveillance and comparative evaluation. A long-term record of events in daily medical practice can describe the experience of a treated group. The counts of serious and other adverse events and the listed event terms give a concrete account of what was recorded. But an event count alone does not answer whether the intervention changes risk: that question requires a meaningful comparison and an analysis that accounts for how groups were formed and followed.

The distinction matters especially for safety interpretation. Serious events may be important to monitor, but a list of event terms and rounded percentages does not establish a causal relationship. The absence of a reported control group leaves no like-for-like benchmark. The record also defines the safety population by study completion, while giving an at-risk count separately; without clarity about follow-up and missing information, readers cannot assess how completely the observed experience represents all enrolled participants.

There is also a useful lesson in the gap between listed outcomes and analyzed results. The registry names several lipid measures as secondary outcomes, yet reports no analyses. Naming an outcome does not establish that a result was available, that a change occurred, or that an inferential test supported a conclusion. Statistical interpretation depends on reported estimates and their uncertainty, not on an outcome list by itself.

Finally, planning calculations should be kept separate from the study’s actual design. The record’s stated planning assumptions describe hypothetical two-arm illustrations, whereas this surveillance record lists one intervention group and no randomized comparison. Such illustrations are not observed power and do not convert a descriptive study into a comparative trial. Keeping these distinctions clear helps readers use registry evidence appropriately without overstating what its design or results can establish.

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 main design limitation is the absence of a reported control group and the lack of a stated allocation method. The study is not a randomized comparison, so the observed adverse-event counts cannot be used to estimate a comparative treatment effect. The record does not provide a like-for-like benchmark for interpreting whether event occurrence differs from another care option or from no exposure.

The primary safety analysis set is defined as participants who completed the study, while the event summary lists 2786 at risk and enrollment is 3084. The registry record does not explain the relationship between these figures, describe the characteristics of non-completers, or state how missing event information was handled. It also does not provide individual follow-up duration, despite a primary outcome timeframe of up to Month 12. These omissions limit assessment of completeness and the opportunity to observe events.

Event reporting is limited to participant counts and selected serious-event terms with rounded percentages. Counts by individual term, details of event timing, and judgments about relatedness to the intervention are not reported in the registry record. The record lists 10 deaths but does not describe their relationship to adverse-event categories. No confidence intervals or other measures of uncertainty are reported for the primary safety results.

The registry lists secondary lipid outcomes but reports no analyses. Accordingly, the available record does not quantify efficacy or changes in lipid parameters. It also does not report the protocol details, a statistical analysis plan, sample-size justification, interim analyses, or a multiplicity approach. These limitations are specific to what is documented in the registry record and should not be filled in by assumption.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluation of the Safety and Efficacy of Long-term Use of Omega-3 Fatty Acid Ethyl Esters — NCT02153073.
• Registry record last updated 2019-07-18; status last verified 2019-07.
• Results first posted 2019-07-05.
• 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

NCT02153073 is a completed special drug use surveillance study titled as an evaluation of the safety and efficacy of long-term use of omega-3 fatty acid ethyl esters. It concerns patients with hyperlipidemia in daily medical practice and lists a 2 g oral regimen taken once or twice daily after meals. Enrollment was 3084. The study start was 2013-05-29, and primary completion was 2017-05-31.

The primary outcome was the number of participants with one or more adverse events and serious adverse events up to Month 12. The primary safety population is described as participants who completed the study. The event summary lists 2786 at risk, with 26 participants with serious adverse events, 38 with other adverse events, and 10 deaths. No randomized control comparison is reported. Secondary lipid outcomes are listed, but the registry record reports no analyses. The counts are descriptive and do not establish causation or comparative safety.