A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study (NCT00128830), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The registry also lists virologic response and CD4 cell-count outcomes at several follow-up points. Their titles indicate that viral load thresholds and changes in CD4 count were of interest, but their numerical results are not reported in the registry record. Thus, the posted figures support a descriptive reading of adverse events, not an assessment of comparative antiviral efficacy or immune response.

3. Trial Design

This was a completed, open-label, single-group Phase 2 trial sponsored by Tibotec Pharmaceuticals, Ireland. The registry records enrollment of 211 and an individually optimized antiretroviral therapy containing etravirine. The official title describes participants as having been randomized to a TMC125 treatment arm in a sponsor-selected TMC125 study and treated for at least 48 weeks before this open-label trial. That prior study context does not make the current trial a randomized comparison: its allocation is listed as not applicable and it has one treatment group.

Participants received etravirine with two other antiretrovirals. The registry lists nucleotide reverse transcriptase inhibitors, protease inhibitors, and enfuvirtide among the interventions, but it does not report the specific combinations used by individual participants. The brief summary describes the regimen as individually optimized. The record does not report further treatment-selection details, changes in regimen, or adherence information.

Masking was none, so treatment was open-label. The primary outcome was the number of participants with adverse events, with a timeframe of up to 3 years. The primary analysis population is described as participants who received at least one dose of study medication. The registry records a start of 2005-06 and primary completion in 2008-08; status is completed.

The listed secondary outcomes concern virologic response at Week 48, Week 96, and Week 192, with response definitions involving viral load thresholds and, in some definitions, a decrease from baseline. Other listed outcomes concern median CD4 cell-count changes. These are outcome titles, not numerical findings: results for these measures are not reported in the registry record. The record also does not report a concurrent comparator, a statistical analysis plan, or details of how follow-up and outcome data were handled.

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 total, 211 participants (93 who rolled over from the etravirine arm of study TMC125-C203 (NCT00412646), 85 who rolled over from the etravirine arm of study TMC125-C223 (NCT00081978), 29 who rolled over from study TMC125-C211 (NCT00111280) and 4 who rolled over from study TMC125-C209) received treatment with etravirine.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: Participants who received at least 1 dose of study medication were included

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 With Adverse Events, measured over Up to 3 years.

The primary endpoint is the number of participants who reported at least one adverse event during follow-up of up to 3 years. The registry identifies the analysis population as participants who received at least one dose of study medication. The posted results distinguish serious adverse events from other adverse events and give the number of participants affected in each category.

This kind of endpoint is used to describe the observed safety experience during treatment and follow-up. A count of participants with an event is different from a count of all event episodes: a participant with more than one event may still contribute only once to a participant-level count, depending on the endpoint definition. The registry definition refers to participants reporting at least one event, but it does not report event-level details or clarify how recurrent events were summarized.

The endpoint is descriptive in this single-group setting. Without a concurrent control group, the counts cannot show how the observed event experience compares with another regimen under the same study conditions. Nor do the counts alone establish that treatment caused an event. Interpretation also depends on the follow-up period, event definitions, ascertainment, and completeness of reporting. Further detail on these matters is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The primary endpoint is a binary participant-level outcome: each participant is classified according to whether at least one adverse event was reported during the specified follow-up. General statistical interpretation of such an outcome focuses on the proportion of participants with an event, while also considering the number of participants observed and the completeness of follow-up. The registry posts counts and numbers at risk, but does not report a confidence interval or a model-based estimate. No additional proportion or interval is calculated.

A participant-level count is not the same as an event rate. It does not count every event episode or account for how long each participant was observed. If events recur, a participant-level endpoint may not reflect the number of recurrences. General methods for recurrent events or time-to-event outcomes address different questions and require suitable event timing and follow-up information. Such details and analyses are not reported in the registry record.

Why does the single-group design matter? A treatment effect is usually expressed as a contrast between outcomes under different treatment conditions. This trial has one group, and the registry lists allocation as not applicable. Its observed event counts describe participants treated with the study regimen, but they do not provide a concurrent control outcome. General comparisons with historical data can be affected by differences in participant selection, follow-up, event definitions, background care, and reporting. The registry does not report a historical comparison analysis.

Open-label status means masking was none. In general, knowledge of treatment can influence reporting, clinical assessment, and decisions to investigate or record events. That does not show that reporting was biased in this trial; it identifies a possible consideration when interpreting unblinded safety data. The registry record does not report methods intended to assess or adjust for such influences.

How should uncertainty be understood? A confidence interval is a statistical range intended to convey uncertainty around an estimate under specified assumptions. General interpretation considers both the estimate and the width of its interval; the interval is not a guarantee about an individual participant or a probability statement about the true value. The registry record does not report confidence intervals for the posted adverse-event counts, so their statistical precision cannot be evaluated from the record. The counts should not be treated as exact estimates of event frequency beyond the observed participants and follow-up.

Binary outcomes are often analyzed with methods that model event counts relative to the number observed. Such methods depend on assumptions about the population, outcome ascertainment, and sampling. In a comparative analysis, a model might estimate a difference or ratio between groups, but this record does not contain a randomized control group or a reported comparative model. No comparative estimate should be inferred from the count data.

What does the sample-size illustration mean? The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; it also describes planning for fractions of the observed effect. Such an illustration is a hypothetical design calculation, not an observed result and not observed power. The record notes that time-to-event illustrations use a total number of events, while other illustrations use participants per arm. These assumptions do not change the actual single-group design, and no planning illustration can supply a missing control-group result. The registry record does not report that these assumptions were the trial's design rationale or statistical plan.

What analyses are available? The registry lists no analyses. It does not report the statistical model for the primary endpoint, a prespecified analysis plan, uncertainty intervals, subgroup analyses, or sensitivity analyses. The posted values therefore support simple descriptive statements only. General statistical methods can explain how an analysis might be structured, but they cannot replace an unreported analysis or justify reconstructing one from the counts.

Over-dispersion is a general concern when count data vary more than a chosen model expects. It is especially relevant to some event-count models, where repeated events and variation in underlying event rates may violate simple distributional assumptions. The primary endpoint is a count of participants with at least one event, rather than a reported recurrent-event rate. The record does not provide data or a fitted model with which to assess over-dispersion, so it is not possible to conclude that it occurred or affected results.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Etravirine")
n      <- c(211)
events <- c(195)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Etravirine  211  195  92.4  88.0  95.6  88.0  95.3  88.0  95.3

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including virologic response at Week 48, Week 96, and Week 192, as well as CD4 cell-count changes at several time points. Multiple outcomes and time points create a general multiplicity issue: examining many results can increase the chance of finding an apparently notable result by chance if each is tested separately. Whether and how to control that risk depends on the prespecified analysis plan and the role assigned to each outcome. Such a plan, including any multiplicity adjustment or testing hierarchy, is not reported in the registry record.

Numerical results for the listed secondary outcomes are not reported in the registry record. No conclusions about those outcomes, or their statistical significance, can be drawn from outcome titles alone. The record also does not report p-values, confidence intervals, or a description of any interim analyses.

The primary analysis population is described as participants who received at least one dose of study medication. The record does not describe the handling of missing outcome data, withdrawals, incomplete follow-up, or participants with unavailable adverse-event information. It therefore does not establish whether missingness was present or how it may have affected the posted counts. Imputation procedures, sensitivity analyses, and reasons for missing data are not reported in the registry record.

Because the analysis population is defined by receipt of at least one dose, it should be described using the registry's wording rather than assumed to be an analysis population with other specific properties. The record does not provide additional population definitions or a flow of participants through follow-up.

12. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.4%), cellulitis (1.4%), myocardial infarction (0.9%), adrenal insufficiency (0.9%), gastritis (0.9%).

The registry reports 46 participants affected by serious adverse events among 211 at risk, and 147 participants affected by other adverse events among 211 at risk. These are participant counts for the registry-defined population, not counts of every event episode. The timeframe for the primary adverse-event outcome is up to 3 years. The record does not provide a breakdown by individual follow-up duration or event timing.

The serious-event terms listed by percentage are pneumonia at 2.4%, cellulitis at 1.4%, myocardial infarction at 0.9%, adrenal insufficiency at 0.9%, gastritis at 0.9%, and pancreatitis at 0.9%. These listed percentages do not show how many participants had each event, and the registry does not specify in this record whether a participant could appear under multiple terms. The percentages should be read as reported term frequencies, not as comparative treatment effects.

Seriousness is a classification of adverse events, not a statement of causation. The record does not show whether events were judged related to treatment, nor does it provide a control group for comparison. The counts describe what was reported during this study and do not, by themselves, identify the source of an event or establish comparative safety.

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

The registry record documents a completed, open-label study of etravirine as part of individually optimized antiretroviral therapy in participants with HIV-1. Its posted primary outcome concerns participants who experienced at least one adverse event, with follow-up described as up to 3 years. The record reports participant counts for serious and other adverse events and lists selected serious-event terms by percentage. These observations describe the safety experience recorded in the study population.

The findings do not provide a comparison with another treatment. There is no concurrent control group, and the study is identified as single-group with allocation not applicable. Accordingly, the counts cannot estimate how event occurrence would differ under another regimen. They also cannot isolate the effect of etravirine from other antiretrovirals, underlying illness, background risk, or other influences. No claim of causation follows from the event counts alone.

The record lists virologic and CD4 outcomes, but their numerical results are not reported in the registry record. Their presence among the outcome titles is not evidence of a particular response. No conclusion about antiviral efficacy or changes in CD4 count should be drawn from the posted adverse-event findings.

Precision is also uncertain because confidence intervals and other uncertainty estimates are not reported. The record does not provide detailed follow-up duration, event timing, handling of missing data, or a statistical analysis plan. These omissions limit assessment of how representative the counts are and how precisely they describe the wider population.

In general, a clinical trial result is strongest for the specific population, treatment conditions, outcomes, and analysis that were studied and reported. Here, the defensible interpretation is descriptive: adverse events were reported in the treated group, with serious and other events counted separately. The evidence in the registry record does not establish comparative benefits, comparative harms, or a causal effect.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between describing an observed treatment experience and estimating a comparative treatment effect. The record provides safety counts from a single group. Such data can document what was reported during follow-up, but a treatment contrast requires information about outcomes under a suitable comparator. Without that contrast, a count alone cannot show whether event occurrence is higher or lower than it would have been under another regimen.

The study also highlights why endpoint definitions matter. The primary outcome counts participants with at least one adverse event, not every event episode. That choice offers a participant-level summary, but it does not convey recurrence, timing, duration, or person-time. Those questions require other data and methods. The registry's listed percentages for serious-event terms add descriptive detail, yet do not substitute for term-specific participant counts or a comparative analysis.

Open-label follow-up and individually optimized background therapy are important context for interpreting safety observations. In general, treatment knowledge and differences in concomitant care can affect event ascertainment and make attribution difficult. The registry record does not report analyses addressing those issues, so they remain limitations rather than demonstrated biases.

Finally, outcome titles and planning illustrations must be distinguished from trial findings. The record lists virologic and CD4 outcomes without numerical results, and its sample-size description is a planning illustration rather than evidence of observed power. Recognizing these distinctions prevents descriptive counts or design calculations from being mistaken for efficacy results or controlled safety comparisons.

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 principal limitation is the single-group design. There is no concurrent control group, so the adverse-event counts do not estimate a comparative effect. Open-label status means masking was none; the registry does not report procedures to reduce or evaluate possible effects of treatment knowledge on event reporting or assessment.

The population is described as having been treated for at least 48 weeks in a sponsor-selected TMC125 study before the open-label trial. This prior-study context may be important when considering who entered the trial, but the record does not report further eligibility details or how participants were selected from that study. The results should not automatically be generalized to people with different treatment histories.

The regimen was individually optimized, and the record lists several classes of other antiretrovirals. It does not report the specific combinations used, treatment changes, adherence, or treatment exposure by participant. These details limit interpretation of events in relation to etravirine separately from other therapy.

The primary endpoint covers up to 3 years, but individual follow-up duration, event timing, recurrent events, and person-time are not reported. The registry does not provide term-specific participant counts for the serious-event list. It also does not report confidence intervals, missing-data handling, participant flow, or sensitivity analyses. These omissions limit assessment of precision and completeness.

Finally, numerical results for the listed virologic and CD4 outcomes are not reported in the registry record. The statistical analysis plan and any multiplicity procedures are also not reported. Consequently, the record supports a limited descriptive safety interpretation, not a full evaluation of all outcomes or a comparative treatment assessment.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study With TMC125 in Human Immunodeficiency Virus (HIV) Type 1 Infected Patients, Who Were Treated With TMC125 Arm in a Sponsor-Selected TMC125 Study — NCT00128830.
• Registry record last updated 2013-06-20; status last verified 2013-06.
• Results first posted 2013-04-09.
• 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

NCT00128830 is a completed, open-label, single-group Phase 2 trial sponsored by Tibotec Pharmaceuticals, Ireland. It enrolled 211 participants with HIV-1 and evaluated etravirine as part of individually optimized antiretroviral therapy. The registry identifies the primary outcome as the number of participants with adverse events during follow-up of up to 3 years.

The posted results list 46 participants with serious adverse events and 147 with other adverse events, each among 211 at risk. Selected serious-event terms are reported as percentages. There is no concurrent comparator, and the registry does not report confidence intervals or a statistical analysis plan. Numerical results for the listed virologic and CD4 outcomes are not reported in the registry record. The findings therefore describe recorded events in the study group and do not establish comparative safety or efficacy.