Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects (NCT00071760), a non-randomized phase 2 study. The primary outcome is Plasma Amprenavir (APV) AUC (0-tau[τ]).

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, multicenter, parallel study with non-randomized allocation. The registry describes a 48-week study in two age-based cohorts: children aged 4 weeks to <6 months, and children aged 6 months to <2 years. Within each age cohort, the record describes an FPV-plus-RTV regimen and an FPV-only regimen. Both regimens were administered twice daily. The registry lists enrollment as 59.

Because allocation was not randomized and masking was absent, treatment assignment may be associated with participant characteristics, clinical circumstances, or other differences. The registry itself cautions that the arms are not a like-for-like control comparison. The design therefore supports descriptive reporting of the treatment groups, but does not by itself establish that any difference between them was caused by the regimen. The record does not report the allocation process or explain how participants were assigned to regimens.

The study's stated aims included pharmacokinetics, safety, tolerability, and antiviral activity. Its primary outcome was a pharmacokinetic measure at Week 48, rather than a direct comparison of clinical outcomes. The registry lists secondary outcomes including HIV-1 RNA measures, CD4+ cell counts, plasma FPV concentrations, and treatment-emergent viral mutations or changes in drug susceptibility. It lists 46 outcome measures but no analysis entries. Numerical results for the primary endpoint are not reported in the registry record.

The registry gives a start date of 2003-10-23, a primary completion date of 2011-07-05, and a completed status. The protocol's sample-size justification, allocation details, and any planned interim analyses 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: 59 participants were enrolled in the study and received at least one dose of Fosamprenavir (FPV)/Ritonavir (RTV) (Safety Population). Five participants out of 59 only received single dose before discontinuing the study. 54 participants who received both single and multiple doses of FPV/RTV were included in Intent to Treat-Exposed (ITT-E) population.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Pharmacokinetic (PK) Population: all participants for whom serial plasma PK samples were analyzed. Only those participants contributing data were analyzed.

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: Participants who received both single and multiple doses of FPV/RTV were included in Intent to Treat-Exposed (ITT-E) population.

6. Primary Endpoint

The registry lists the primary outcome as Plasma Amprenavir (APV) AUC (0-tau[τ]), measured over Week 48.

The primary endpoint was plasma amprenavir (APV) AUC over the dosing interval at steady state, measured at Week 48. AUC describes drug exposure over time across a dosing interval; it is calculated from concentration measurements rather than representing a single concentration at one moment. In pharmacokinetic work, this measure can characterize overall exposure to a drug during the interval between doses.

The registry says plasma samples were assayed for APV concentrations using a validated assay. A model-independent analysis used the linear up/log down trapezoidal method to calculate AUC from the concentration-time data. The dosing interval is represented by τ in the endpoint description. The primary outcome was summarized as a geometric mean with a 95% confidence interval, and the analysis population included participants for whom serial plasma pharmacokinetic samples were analyzed and who contributed data.

These details describe the endpoint and its planned summary, not the observed result. The registry record does not report the geometric mean, its confidence interval, the number of participants contributing to the analysis, or a numerical comparison between regimens. Consequently, the amount and precision of APV exposure observed at Week 48 cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a pharmacokinetic quantity: AUC over the dosing interval at steady state. Concentration measurements taken across time are used to represent exposure during the interval. The registry describes a model-independent calculation using the linear up/log down trapezoidal method. In general, a trapezoidal method approximates the area under a curve by joining observed points and calculating the area of the resulting segments. The linear up/log down approach uses different interpolation conventions depending on whether measured concentrations rise or fall between observations. This general description explains the method; the registry does not report the underlying concentration-time data or calculated AUC values.

The endpoint summary is specified as a geometric mean with a 95% confidence interval. A geometric mean is appropriate for quantities that are positive and may have a multiplicative, rather than additive, pattern of variation. In general, it is obtained by working on the logarithmic scale and transforming the summary back to the original scale. A confidence interval describes statistical uncertainty around an estimate under the assumptions of the analysis. It is not a range containing a known proportion of individual participants' values. Since neither the estimate nor interval is reported, the precision of the Week 48 endpoint cannot be evaluated.

The pharmacokinetic population was defined by availability of serial plasma samples that were analyzed: only participants contributing data were included. This is a data-contributor definition, not necessarily the same as every participant enrolled or assigned to a regimen. The record does not report the number contributing to this endpoint, how missing samples were handled, or whether participants with incomplete concentration profiles were excluded under prespecified rules. Those details matter because availability of usable samples can affect which participants are represented in a pharmacokinetic summary.

What does the study design imply for comparisons?

Allocation was non-randomized, the study was open-label, and the design was parallel. In a randomized study, assignment by chance is intended to balance measured and unmeasured participant characteristics across groups, on average. Non-randomized assignment does not provide that protection. Differences between regimens may reflect characteristics of the participants or circumstances associated with assignment, as well as any regimen-related differences. Open-label conduct also means masking was absent, although the registry record does not describe how that may have influenced measurement or reporting. The registry specifically cautions against treating the arms as a like-for-like control comparison. No statistical adjustment strategy is reported.

What can be inferred from the analysis record?

The registry lists 46 outcome measures and no analysis entries. This means the registry record does not present statistical analysis entries for those measures; it does not establish that no analyses were conducted. The primary outcome description names a summary statistic, confidence interval, assay, analysis population, and AUC calculation approach. It does not give a full statistical analysis plan. Details such as model specifications, handling of incomplete data, subgroup analysis plans, and any multiplicity strategy are not reported in the registry record.

Multiplicity is relevant when a study assesses many outcomes, visits, or contrasts. In general, the more statistical questions examined, the greater the chance that some results may appear noteworthy by chance if no adjustment or interpretation plan is used. The record lists multiple secondary outcomes and repeated study visits for some measures, but does not report how the family of analyses was handled. No p-values or adjusted estimates are posted, so the statistical impact of multiplicity cannot be assessed.

How should planning calculations be read?

Any sample-size planning illustrations associated with the study are not observed trial results and should not be read as observed power. The described illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event calculations, the stated output is a total event count; other calculations are expressed as participants per arm. The registry record does not report the trial's own sample-size justification. Such illustrations are hypothetical planning aids and cannot replace the missing endpoint estimate or analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 46 outcome measures, including multiple measures of viral RNA, CD4+ cell counts, plasma drug concentrations, and treatment-emergent viral changes. Some outcomes are specified at each study visit, and others name particular visits through Week 48. When many outcomes, time points, or contrasts are examined, multiplicity can make isolated findings more likely to arise by chance. In general, a prespecified testing strategy or suitable adjustment can help control that risk. The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or a statistical analysis plan describing which comparisons were confirmatory.

The record lists no analysis entries. Numerical results, p-values, and confidence intervals for the listed primary and secondary outcomes are not reported in the registry record. This prevents assessment of how results were analyzed or whether any multiplicity adjustment was applied in analyses not represented in the registry.

The primary endpoint population includes participants with serial plasma pharmacokinetic samples that were analyzed and who contributed data. The number in that population is not reported. Rules for missing samples, incomplete concentration profiles, withdrawals, or other missing outcome data are also not reported in the registry record. No imputation method or sensitivity analysis for missing data is described. These omissions leave uncertainty about the amount and handling of missing information and how representative the analyzed pharmacokinetic population was of those enrolled.

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% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis (17.2%), pneumonia (17.2%), hypertension (6.9%), neutropenia (6.7%), seizure (6.7%).

The registry reports serious adverse event counts for two Arm A age cohorts. For Cohort 2, Arm A, aged 4 weeks to <6 months, 29 participants were listed as at risk for serious adverse events and 13 as affected. For Cohort 1, Arm A, aged 6 months to <2 years, 30 were listed as at risk and 12 as affected. These are cohort-specific registry counts; they should not be treated as a randomized comparison. The record does not provide corresponding serious adverse event counts for Arm B in these entries.

For other adverse events, the record lists 24 affected among 29 at risk in Cohort 2, Arm A, and 28 affected among 30 at risk in Cohort 1, Arm A. Deaths are listed as 1 and 2, respectively. These counts alone do not establish cause, timing, severity beyond the category recorded, or whether an event was related to study treatment. The record does not provide the context needed to attribute deaths or events to a regimen.

The registry lists gastroenteritis and pneumonia at 17.2% each, hypertension at 6.9%, neutropenia and seizure at 6.7% each, and hydrocele at 3.4% among the top serious-event terms. The record does not specify further detail in this summary about the term-level denominators or causal attribution. These percentages describe registry-reported terms; they should not be interpreted as comparative treatment effects.

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

The record establishes that the study evaluated pharmacokinetics, safety, tolerability, and antiviral activity of regimens containing FPV, with or without RTV, in young children with HIV. It identifies APV AUC at steady state at Week 48 as the primary endpoint and describes how that quantity was intended to be calculated and summarized. These design details clarify the question the study set out to address.

The registry record does not report a numerical value for the primary endpoint, its 95% confidence interval, or the number of participants contributing to that analysis. It also does not report numerical antiviral activity results. Therefore, the record does not support a statement about the observed magnitude or precision of APV exposure, or about the size of any change in HIV-1 RNA. Absence of posted estimates is not evidence that an effect was absent; it means the relevant numerical results are not reported in the registry record.

The trial's non-randomized allocation and open-label conduct matter when interpreting comparisons. The record cautions that the treatment arms are not a like-for-like control comparison. Differences between groups, if reported in another source, could reflect factors associated with assignment as well as treatment. The available information does not establish a causal effect of one regimen relative to the other.

The safety counts describe events in the reported Arm A age cohorts and do not establish that events were treatment-related. The registry's listed serious-event terms and percentages likewise do not provide a causal comparison. Taken together, the posted information describes the study's aims, design, endpoint methods, and some safety counts, but it is insufficient to assess the primary endpoint's numerical result or draw comparative efficacy conclusions.

13. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is pharmacokinetic rather than a direct clinical outcome. AUC represents drug exposure over a dosing interval and is derived from measured concentrations across time. Understanding the endpoint requires attention to the sampling schedule, assay, method of calculating exposure, and the population with usable samples. The registry describes some of these components, including the assay, trapezoidal approach, and contributor-based pharmacokinetic population.

The study also illustrates why design features shape interpretation. Two regimens were evaluated in parallel, but allocation was non-randomized and the study was open-label. As the registry cautions, the arms are not a like-for-like control comparison. Statistical descriptions of group differences cannot, by themselves, remove the potential for differences associated with how participants entered each regimen.

Finally, the registry record separates endpoint definition from endpoint evidence: it details the Week 48 summary method but does not report the numerical primary result. It also lists multiple secondary outcomes without analysis entries. This makes clear that a detailed outcome description is not equivalent to a posted estimate, and that design and analysis information are both needed to judge precision and comparative meaning. The safety counts offer descriptive information, but not a causal treatment comparison.

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 principal limitation for interpreting the primary endpoint is that the registry record does not report its numerical estimate, confidence interval, or analysis population size. The record describes the pharmacokinetic method but does not provide the concentration-time observations or the resulting AUC summary. The amount and precision of observed APV exposure at Week 48 therefore cannot be assessed from this record.

Allocation was non-randomized, and the registry explicitly states that the arms are not a like-for-like control comparison. The record does not report the assignment process or an adjustment method for differences between groups. Open-label conduct is also listed, but the record does not describe its potential influence on measurement or reporting. These features constrain interpretation of any between-regimen contrast.

The registry lists many outcome measures but no analysis entries. It does not report a statistical analysis plan, multiplicity handling, or rules for missing data. The primary endpoint population includes participants contributing analyzed serial samples, but the number contributing and the handling of incomplete sampling are not reported. These gaps make it difficult to determine which participants informed each outcome or how robust the results would be to missing information.

Safety information is reported for the two Arm A age cohorts, while the registry summary does not provide matching safety counts for Arm B. Event counts and listed terms do not establish treatment attribution, and the record does not provide enough context to infer comparative safety. The registry's total enrollment is 59, but it does not report group-specific enrollment or the endpoint-specific denominators needed to interpret the primary estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Of An Investigational Regimen Including FDA Approved HIV Drugs In HIV-Infected Pediatric Subjects — NCT00071760.
• Registry record last updated 2023-10-10; status last verified 2023-10.
• Results first posted 2012-08-23.
• 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 NCT00071760 as a completed Phase II, open-label, multicenter, parallel study with non-randomized allocation. It enrolled 59 participants and evaluated twice-daily FPV with RTV or FPV alone in children aged 4 weeks to <2 years. The stated study duration was 48 weeks.

The primary endpoint was plasma APV AUC over the dosing interval at steady state at Week 48, summarized as a geometric mean with a 95% confidence interval. The registry describes the pharmacokinetic assay and calculation method but does not report the numerical primary result. It lists secondary virologic, immunologic, pharmacokinetic, and resistance-related outcomes, with no analysis entries.

Serious and other adverse event counts are reported for the two Arm A age cohorts, along with deaths and selected serious-event terms. The registry cautions that the non-randomized arms are not a like-for-like control comparison. Its record gives a start date of 2003-10-23 and a primary completion date of 2011-07-05.