A Study To Assess GW433908 (Fosamprenavir) Containing Regimens In HIV-1 Infected Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Assess GW433908 (Fosamprenavir) Containing Regimens In HIV-1 Infected Subjects (NCT00296504), a non-randomized phase 3 study. The primary outcome is Number of Participants With Any Adverse Event (AE): Interim Analysis.

2. Clinical Question

The clinical question is therefore primarily descriptive and safety-focused. The registry record identifies a long-term safety study of fosamprenavir-containing regimens among participants with prior fosamprenavir study experience. It does not describe a randomized test of fosamprenavir against a concurrent control group. Although ritonavir is listed as an intervention and the adverse-event results distinguish several source populations, those groupings should not be read as randomized treatment arms.

The primary outcome covers any adverse event from baseline on Day 1 through 31 January 2006, up to Week 264. An adverse event is defined in the record as an untoward medical occurrence after administration of a pharmaceutical product, whether or not it is considered causally related to treatment. The result for this primary outcome is not reported in the registry record. Secondary outcomes include HIV-1 RNA and CD4+ cell measurements at specified visits, but their numerical results are not included in the record details available for interpretation.

3. Trial Design

This is a Phase III study listed as completed, with non-randomized allocation, no masking, and a single-group model. The registry lists enrollment of 753 participants. Its official title describes an open-label study intended to assess the long-term safety profile of regimens containing GW433908, also known as fosamprenavir. The stated study purpose is to add information on long-term safety and tolerability among people who had received fosamprenavir in earlier GlaxoSmithKline studies.

The record lists a start date of 2001-11 and primary completion in 2010-10. These dates establish the broad study timeline, but they do not specify each participant's follow-up duration. The primary outcome uses a separate interim observation window: baseline on Day 1 through 31 January 2006, up to Week 264. The record does not explain how that interim population relates to all enrolled participants beyond identifying the primary outcome population as those receiving at least one dose of fosamprenavir or fosamprenavir/ritonavir in Study APV30005.

Fosamprenavir and ritonavir are listed as drug interventions. The registry also separates adverse-event summaries by cohorts associated with earlier study populations and a final analysis population. Because allocation is non-randomized, these cohorts cannot be presumed exchangeable or interpreted as treatment arms with a controlled baseline balance. The record itself cautions that they are not a like-for-like control comparison.

The enrollment figure describes the study record as a whole; it should not be substituted for the denominator of any particular outcome or cohort. The primary outcome population and the adverse-event groups have their own stated denominators. Details of recruitment, follow-up completeness, treatment changes, the planned statistical approach, and the rationale for the enrollment target are not reported in the registry record.

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 are divided into arms depending on the regimen they received in Studies APV30001, APV30002, and APV30003 or whether they were PI-naïve or PI-experienced at the time they enrolled into other studies. For the final analysis, 111 participants are included who continued in APV30005 after 31 January 2006 until study completion.

Only the first 6 of 9 groups are shown.

Interim Analysis

Reasons for not completing this period:

Final Analysis

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants receiving at least one dose of FPV or FPV/RTV in Study APV30005.

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.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Any Adverse Event (AE): Interim Analysis, measured over Baseline (Day 1) up to 31 January 2006 (up to Week 264).

The primary endpoint is the number of participants with any adverse event during the interim observation period. An adverse event, as defined in the registry record, is any untoward medical occurrence in a participant administered a pharmaceutical product; it does not have to be judged causally related to that product. The outcome therefore records whether an event occurred, rather than establishing whether treatment caused it or measuring its severity.

Counts of participants with any event are useful for describing the safety experience observed in a study population. They can give a broad account of how many participants had at least one recorded event during the specified period. They do not by themselves describe the number of events per participant, the timing or duration of events, or the likelihood that a particular event was caused by treatment. Those questions require other outcome details and an appropriate analytic approach.

The registry identifies this as an interim analysis and specifies its observation window as baseline on Day 1 through 31 January 2006, up to Week 264. The numerical result for the primary endpoint is not reported in the registry record, so the count and its precision cannot be assessed from that endpoint entry. The record says that a list of adverse events is reported in the other non-serious adverse events material, but the primary outcome description does not itself provide the count of participants with any adverse event.

Any-event outcomes are broad by design: they may include events with different clinical importance and different possible causes. They are most informative when read alongside definitions, event-specific findings, population denominators, follow-up information, and any uncertainty estimates. Those additional details for the primary outcome are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants with any adverse event. That is a binary participant-level outcome in the sense that each participant can be classified as having experienced an event or not during the stated window, with the reported measure expressed as a number of participants. The record does not give a primary endpoint estimate, a confidence interval, or a model-based analysis. It lists no outcome analyses in the available record details.

What does a participant count convey?

A count tells how many participants met the outcome definition in the population being described. Interpreting a count requires its denominator, the population definition, and the observation period. Counts alone are not directly comparable when populations differ in size or follow-up. A proportion can be useful for describing the fraction of a defined group affected, but no new proportion should be inferred unless it is reported. The primary outcome entry does not give a result count, while the cohort safety summaries do give denominators and affected-participant counts for those specific groups.

The primary endpoint definition is deliberately broad: an adverse event need not be considered related to treatment. That definition supports a general account of medical occurrences during exposure, but it does not isolate events caused by the intervention. Causality requires more than observing an event after treatment; interpretation would depend on the design, comparison group, clinical assessment, and other evidence. The registry design is non-randomized and single-group, and the record cautions that the groups are not like-for-like controls.

How should uncertainty be understood?

In general, a confidence interval describes the range of values compatible with the observed data under a specified statistical method and its assumptions. It helps distinguish a relatively precise estimate from one with substantial uncertainty. No confidence interval for the primary outcome is reported in the registry record, and the numerical primary result itself is also absent. Thus, its precision cannot be assessed from the available entry. This is different from concluding that the result is zero or that no events occurred; the record simply does not report the primary result.

In general, statistical tests and p-values address compatibility between data and a specified null hypothesis under a model. They do not establish causality, clinical importance, or the absence of an effect. No primary endpoint p-value or statistical test is reported in the registry record. Given the single-group, non-randomized design, the primary safety count is descriptive rather than a randomized treatment contrast.

What is the role of the planning illustration?

The record describes a sample-size 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 says that the effect to detect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed trial results or observed power. The record does not give an observed effect value in the registry record, and it cautions that the arms are not a like-for-like control comparison. Therefore, the illustration should not be treated as evidence of the study's achieved power or as a substitute for the missing primary endpoint result. The record does not report the trial's own sample-size justification.

In general, power calculations depend on assumptions about the outcome, effect to detect, allocation, significance level, and analysis. A calculation can change when those assumptions change. A planning estimate does not establish that the study actually detected an effect, and it does not describe the uncertainty of an observed estimate. The registry record does not report a protocol-based statistical plan that would allow the planning illustration to be linked to the primary outcome analysis.

Why do design and analysis populations matter?

Analysis results depend on which participants are included and how their outcomes are handled. The primary outcome population is described as participants receiving at least one dose of fosamprenavir or fosamprenavir/ritonavir in Study APV30005. The safety summaries separately identify cohorts by source study and population. Those definitions should be retained when reading each result; one denominator cannot be assumed to apply to another outcome or group. The registry does not report a full analysis-population plan or explain how missing observations were handled.

In general, over-dispersion matters when observed outcome variability is greater than assumed by a statistical model; ignoring it can make uncertainty estimates too optimistic. This study's primary endpoint is a participant count, and no model or dispersion estimate is reported. There is therefore no basis in the registry record to claim that over-dispersion was assessed or that a particular adjustment was used. More broadly, the record does not report the statistical analysis plan, interim-analysis procedures, or methods for multiplicity and missing data.

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("FPV Population (APV30001)", "NFV Population (APV30001)", "FPV Population (APV30002)", "NFV Population (APV30002)", "FPV/RTV QD Population (APV30003)", "FPV/RTV BID Population (APV30003)")
n      <- c(119, 18, 221, 54, 73, 78)
events <- c(117, 16, 215, 52, 72, 75)
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  FPV Population (APV30001)  119  117  98.3  94.1  99.8  94.1  99.5  94.1  99.5
ARM  NFV Population (APV30001)  18  16  88.9  65.3  98.6  67.2  96.9  66.9  96.6
ARM  FPV Population (APV30002)  221  215  97.3  94.2  99.0  94.2  98.7  94.2  98.7
ARM  NFV Population (APV30002)  54  52  96.3  87.3  99.5  87.5  99.0  87.5  98.9
ARM  FPV/RTV QD Population (APV30003)  73  72  98.6  92.6  100.0  92.6  99.8  92.7  99.7
ARM  FPV/RTV BID Population (APV30003)  78  75  96.2  89.2  99.2  89.3  98.7  89.3  98.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures and a range of secondary assessments, including HIV-1 RNA thresholds at several visits, CD4+ cell counts, and median plasma HIV-1 RNA at scheduled weeks. Assessing many outcomes or time points can raise a multiplicity issue: in general, the chance of at least one apparently notable result may increase when many statistical tests are conducted. Whether and how to address that issue depends on the prespecified analysis plan. The multiplicity strategy is not reported in the registry record.

The record identifies an interim primary outcome and gives its observation window, but it does not describe interim monitoring procedures, stopping boundaries, or any adjustment related to repeated looks at accumulating data. Those details are not reported in the registry record. The existence of an interim outcome label alone does not establish what monitoring or statistical procedures were used.

Missing-data handling is also not reported in the registry record. The secondary outcome names include observed analyses and named assessment weeks, but the registry entries do not state how missing visits, withdrawals, or incomplete measurements were treated. In general, observed-case summaries describe measurements available at a visit; their interpretation can be affected if availability differs across participants or over time. The record does not provide enough information to assess whether that concern applied or how it was handled.

The primary outcome population is defined as those receiving at least one dose in Study APV30005, while safety listings distinguish several source populations. These definitions matter because the appropriate denominator depends on the specific analysis. A comprehensive statistical analysis plan, including prespecified populations, handling of missing data, and multiplicity procedures, is not reported in the registry record. The missing primary outcome result also prevents a direct assessment of its estimate or precision.

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: drug hypersensitivity (9.2%), ankle fracture (5.6%), pneumonia (2.7%), suicide attempt (2.7%), anaemia (2.3%).

The serious adverse-event summaries list, for each named cohort, the number at risk and the number affected. For example, the FPV Population (APV30001) lists 119 participants at risk and 33 affected, while the NFV Population (APV30001) lists 18 at risk and 1 affected. The FPV Population (APV30002) lists 221 at risk and 62 affected; the NFV Population (APV30002) lists 54 at risk and 7 affected. These are descriptive counts for the stated cohorts, not randomized comparisons.

Other adverse events are reported separately in the same cohort summaries. The figures include 115 of 119 for FPV Population (APV30001), 16 of 18 for NFV Population (APV30001), 209 of 221 for FPV Population (APV30002), and 53 of 54 for NFV Population (APV30002). These categories should not be conflated: the serious-event counts and other-event counts refer to distinct registry groupings. The record does not explain whether an individual could contribute to multiple event terms.

The listed serious-event terms and percentages include drug hypersensitivity at 9.2%, ankle fracture at 5.6%, pneumonia and suicide attempt at 2.7% each, and anaemia and chest pain at 2.3% each. The percentages are event-term summaries; their denominators and event-count details are not reported in the registry record. The terms do not establish that treatment caused the events. No deaths are listed in the cohort details, but the record does not supply a death count for these groups.

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

The record supports a limited descriptive reading: it identifies a long-term safety study of fosamprenavir-containing regimens, defines a primary any-adverse-event outcome, and provides cohort-level counts for serious and other adverse events. It also lists several serious adverse-event terms with percentages. These pieces of information describe what the registry records, but they are not sufficient to estimate the primary endpoint's frequency because its numerical result is not reported in the registry record.

The record does not establish that fosamprenavir caused any listed event. Its broad adverse-event definition explicitly does not require a causal relationship. In addition, the study is non-randomized, has no masking, and is described as single-group. Cohort differences may reflect different source populations or other differences; the registry cautions that the groups are not a like-for-like control comparison. Consequently, between-cohort differences cannot be interpreted as clean treatment effects.

The listed secondary outcomes indicate that viral RNA and CD4+ cell measurements were assessed at specified times. Their names alone do not show whether those measurements changed, how many participants contributed, or how precise any estimate was. Those numerical outcome results are not reported in the registry record. No conclusion about comparative efficacy or the size of a treatment effect follows from outcome titles alone.

In general, absence of a reported result is not evidence that no events or changes occurred. It means that the relevant estimate cannot be evaluated from the registry record. Likewise, a sample-size planning illustration is not an observed result and does not show that a study achieved a particular power. The record's illustration is based on an observed effect and specified assumptions, but the registry entries do not include the effect value needed to interpret it.

The appropriate conclusion is therefore bounded: the registry describes the design and purpose and supplies some safety summaries, but it does not report the primary endpoint result or enough statistical detail to establish precision, causality, or a comparative treatment effect. These limitations are especially important when reading cohort differences and event-term percentages.

14. Why This Trial Matters Statistically

This study is statistically notable for the distinction between long-term safety surveillance and comparative treatment evaluation. Its stated purpose is to add information about safety and tolerability among participants with earlier fosamprenavir exposure. Its design, however, is listed as non-randomized, unmasked, and single-group. That design can support descriptive reporting, but it does not provide the protection against confounding that random allocation is intended to provide in a controlled comparison.

The record also illustrates why outcome definitions and populations matter. The primary outcome is a broad count of participants with any adverse event over a specified interim period. Separate safety summaries use named cohorts from earlier studies and give their own denominators. Keeping those groups distinct prevents the overall enrollment figure from being mistaken for the population at risk in each specific safety summary.

Another statistical lesson is the difference between a reported outcome and an outcome label. The record names a primary endpoint and several secondary measures, yet the numerical primary result is not reported in the registry record. Without an estimate and a measure of uncertainty, readers cannot assess the endpoint's frequency or precision. Likewise, listed secondary measures do not establish what their values were.

Finally, planning calculations and observed evidence answer different questions. The sample-size illustration uses stated assumptions, but it is not an observed result, and the record does not report the study's own sample-size justification. These distinctions matter when interpreting registry records: design, population, endpoint definition, result availability, and uncertainty all shape what can responsibly be concluded.

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 primary limitation for interpreting the stated primary question is that its result is not reported in the registry record. The record gives the definition and timeframe for the any-adverse-event outcome but no count, estimate of frequency, or uncertainty measure. It is therefore not possible to quantify the primary safety outcome from this record.

The design limits comparative inference. Allocation is non-randomized, masking is absent, and the model is single-group. The adverse-event summaries divide participants into cohorts associated with different studies and populations; the record cautions that these are not like-for-like control comparisons. Differences across such cohorts may reflect differences in population or context rather than a treatment effect.

The enrollment of 753 is a study-level figure and does not establish the denominator for a particular endpoint or cohort. The record gives distinct denominators for the listed adverse-event groups, but detailed follow-up completeness and the relationship between all enrolled participants and each analysis population are not reported in the registry record. Methods for missing observations, withdrawals, and treatment changes are also not reported.

The listed secondary outcome names do not include their numerical results in the registry entries. Statistical methods, confidence intervals, p-values, multiplicity procedures, interim monitoring methods, and the trial's sample-size justification are not reported in the registry record. The adverse-event term percentages are listed without corresponding denominator or event-count details in the record details available for interpretation. These gaps restrict assessment of precision, completeness, and causal attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study To Assess GW433908 (Fosamprenavir) Containing Regimens In HIV-1 Infected Subjects — NCT00296504.
• Registry record last updated 2013-04-19; status last verified 2012-06.
• Results first posted 2011-11-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed Phase III, open-label, non-randomized, single-group study of fosamprenavir-containing regimens in people with HIV-1 infection. Enrollment is listed as 753. The stated purpose is to add long-term safety and tolerability information for participants who had received fosamprenavir in earlier studies. Fosamprenavir and ritonavir are listed as drug interventions.

The primary outcome is the number of participants with any adverse event from baseline on Day 1 through 31 January 2006, up to Week 264. Its numerical result is not reported in the registry record. The record includes cohort-level serious and other adverse-event counts and several serious-event terms with percentages. It also names secondary HIV-1 RNA and CD4+ cell outcomes, but their numerical results are not reported in the registry record.

The non-randomized design and non-comparable cohorts limit treatment comparisons. Statistical analysis details, missing-data methods, multiplicity procedures, and the study's sample-size justification are not reported in the registry record.