Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS (NCT00737204), a randomized phase 4 study. The primary outcome is Fatigue Severity Scale(FSS) Outcome.

2. Clinical Question

The study is titled “Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS,” and its brief description states that it was designed to determine whether armodafinil reduces fatigue in adults with HIV/AIDS. That wording describes the research question, not the finding. The posted results identify the primary measure and its assessment period, but do not provide the values needed to determine the direction or magnitude of the observed comparison.

CD4 cell count and HIV viral load are listed as secondary outcomes. The registry record does not report their results. It also does not provide further detail about eligibility criteria, such as how HIV/AIDS or fatigue was defined for enrollment, beyond the population description. The clinical question should therefore be read narrowly: it concerns a short-term comparison of FSS scores in the randomized study population, rather than every aspect of fatigue or HIV-related health.

3. Trial Design

This was a Phase 4, randomized, triple-masked, parallel-group study. Its status is completed. The registry record gives an enrollment of 70 and identifies armodafinil and placebo as the two interventions. In a parallel-group design, participants are assigned to one intervention group rather than crossing between interventions; randomization is intended to make the groups comparable on average, although the record does not describe the sequence-generation procedure or allocation concealment.

The record identifies the study as triple masked but does not specify which groups of people were masked. It also does not report how masking was maintained or assessed. The description therefore supports reporting the stated masking level, but not naming the masked roles or assuming that masking was successful throughout the study.

The armodafinil arm is described as taking treatment for 4 weeks, with a daily dose titrated from 50mg to 250mg as clinically indicated. Participants who responded were to be offered 12 additional weeks of armodafinil. The placebo arm was described as receiving matching placebo pills during the 4-week period, with the number of tablets titrated in parallel with the active-arm strategy. Its description ends with an unfinished statement about non-responders, so what was planned for those participants is not reported in the registry record.

The study began in 2008-06, with primary completion in 2010-04. The primary outcome was measured at baseline and Weeks 4. The record does not describe the randomization ratio, the recruitment process, or whether follow-up beyond the primary 4-week assessment was included in the reported outcome analysis. These omissions limit how fully the conduct and timing of the trial can be reconstructed from the registry record alone.

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: A total of 114 patients were screened for eligibility, 25 had medical or psychiatric exclusion criteria, 7 were active substance users, 4 were taking stimulants, 3 were not clinically fatigued, 5 declined participation, and 70 were randomized. Of the 70, 64 completed the 4-week trial.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Of the 70 patients randomized, 64 completed the 4-week trial. Data presented are for the 70, using the last data point carried forward (intention to treat).

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 Fatigue Severity Scale(FSS) Outcome, measured over Measured at baseline and Weeks 4.

The primary endpoint is the Fatigue Severity Scale (FSS) outcome, reported as a mean in units on a scale. The FSS is described as a 9-item self-report measure of the impact of fatigue on everyday functioning. Each item is rated from 1 to 7, and the total score ranges from 9-63. A higher score indicates greater impairment due to fatigue.

A self-report scale can capture the participant’s experience of fatigue and its effect on daily life, which may not be represented fully by a laboratory measure. The FSS offers a structured way to collect those reports across participants and compare scores over time. The planned assessment points were baseline and Weeks 4, making the Week 4 measure the stated short-term endpoint. The registry record does not explain whether the primary comparison used change from baseline, the Week 4 score adjusted for baseline, or another model.

The measure’s interpretation depends on the actual score distributions and the contrast between groups. The registry record does not report arm-specific means or standard deviations, nor a between-arm estimate, confidence interval, or p-value for the primary outcome. It is therefore possible to describe what the FSS measures and how its scores are oriented, but not the size or precision of the trial’s observed effect from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the primary measure as a continuous outcome summarized by a mean and standard deviation. It does not give the statistical model used to compare groups. The concepts below are general explanations of how such measures and common inferential statistics are interpreted; they should not be taken as a description of analyses that the registry record does not report.

What does a mean describe?

For a continuous measure such as the FSS total score, the mean describes the arithmetic center of the observed scores in a group. It can provide a concise summary, but it does not show the full distribution. Participants may have similar scores or widely differing scores while producing the same mean. Here, the scale’s stated direction matters: a higher FSS score indicates greater impairment due to fatigue.

Comparing group means can be useful when the measure is collected in the same way in both groups and the analysis accounts appropriately for the study design. A difference in means is an estimate, not a direct statement about every individual participant. The registry record does not report the group means or say whether the primary comparison was based on Week 4 values, changes from baseline, or an adjusted model.

What does a standard deviation describe?

In general, a standard deviation describes how spread out individual observations are around their group mean. It is not the same as the uncertainty in the mean or in a between-group estimate. A large spread means that individual scores vary more within the group; the uncertainty of a comparison also depends on the amount of information available and the analysis method. No primary-outcome standard deviations are reported in the registry record, so the variability of the FSS scores cannot be assessed from it.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the data and the model used to estimate an effect. Its width is an indicator of precision, and its location helps show the direction and range of plausible differences. A confidence interval should be interpreted alongside the outcome scale and the design, not as a guarantee that the true effect lies within a particular range. The registry record does not report a confidence interval for the primary comparison.

What does a p-value address?

In general, a p-value measures how unusual data at least as incompatible with a stated null hypothesis would be if that null model and its assumptions held. It does not measure the probability that the null hypothesis is true, the probability that a result is due to chance, or the size or clinical importance of an effect. The registry record does not report a primary-outcome p-value or identify the test used. A p-value alone would also be insufficient to describe the magnitude or precision of the comparison.

Why does the analysis model matter?

When repeated measurements are available, an analysis may use the baseline and follow-up scores together, or it may compare follow-up scores while accounting for baseline. These approaches answer closely related but not identical statistical questions and can have different assumptions. The record gives the assessment times but does not report which approach was used. It likewise does not state whether covariates were included, how model assumptions were assessed, or how any deviations from assumptions were handled.

As a general matter, a model for a continuous outcome should reflect the scale, study design, and distribution of the data. If observations are strongly skewed or otherwise depart from model assumptions, the adequacy of a simple mean-based analysis may need examination. The registry record does not report distributional diagnostics or an alternative analysis plan. It is therefore not possible to evaluate those choices for this study.

What do the planning assumptions mean?

The registry record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. In general, such illustrations ask how many participants per arm might be needed under specified assumptions; they are not observed power and are not evidence that the trial was designed with those assumptions. The record does not report its own sample-size justification, so the illustrations should not be treated as the trial’s original design rationale.

These planning calculations also depend on the effect used as their reference and on assumptions about variability, allocation, and analysis. A planning estimate based on an observed effect is conditional on that estimate and may not match a future study’s true effect or variability. The registry record does not provide the information needed to evaluate the trial’s original sample-size calculation. No specific planning requirement is stated in this explanation because the corresponding numerical outputs are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description states that data for all 70 randomized patients were presented using last data point carried forward (LOCF), with the analysis described as intention to treat. LOCF is a method for filling in a missing follow-up value by carrying forward a participant’s last observed value. In general, this approach can be problematic if the participant’s outcome would have changed after the last observation: the carried-forward value may then misrepresent the unobserved value and may understate uncertainty. Its performance depends on why data are missing and how outcomes evolve over time.

The registry record says that 64 patients completed the 4-week trial, but does not report missingness by arm, the reasons participants did not complete, or the timing of their last available measurements. It also does not provide sensitivity analyses comparing LOCF with other missing-data approaches. Consequently, the effect of the missing-data method on the FSS comparison cannot be assessed from the posted information.

Four outcome measures and three analyses are recorded, and the listed secondary outcomes include CD4 cell count and HIV viral load. The registry record does not explain how the analyses map to the outcomes, which outcomes were included in each analysis, or whether any multiplicity adjustment was planned or applied. In general, testing multiple outcomes or contrasts can increase the chance of at least one false-positive result if each is interpreted without accounting for the broader testing context. Whether that concern affected this study cannot be determined from the record.

The record does not report a detailed statistical analysis plan, analysis-set definitions beyond the primary outcome description, or how participants with incomplete data were handled for secondary outcomes. Those aspects are not reported in the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The posted adverse-event fields list 36 participants at risk in the armodafinil arm and 34 in the placebo arm. For serious adverse events, the number of affected participants is recorded as 0 in each arm. For other adverse events, the number of affected participants is also recorded as 0 in each arm. The death counts are not reported in the registry record, and no top serious adverse-event terms are listed.

These entries should be read as registry counts, not as a detailed safety analysis. The record does not provide event descriptions, observation periods, severity grades, attribution assessments, or information about whether one participant could experience more than one event. The fields also do not explain how adverse events were collected or coded. A count of affected participants is not interchangeable with a count of all event episodes.

Zero recorded affected participants does not by itself establish that no events occurred outside the recorded definitions or reporting period. Nor does it quantify uncertainty around uncommon events. With no event terms or further safety details reported, the registry record supports only a description of the entries shown: zero affected participants are recorded for both serious and other adverse events in each arm, while deaths are not reported.

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

The trial addresses a focused statistical question: how FSS scores at the 4-week assessment compared between randomized groups assigned to armodafinil or placebo. Its registry record identifies the population, interventions, outcome scale, assessment timing, and stated approach to missing primary outcome data. This information helps define what the trial set out to measure.

The record does not report the numerical primary outcome results. It therefore does not establish whether the groups differed, which group had a higher mean, how large any difference was, or how precisely it was estimated. No claim about improvement, lack of improvement, equivalence, or clinical importance can be drawn from the registry information alone. The research question in the study description is not a result.

Even when a numerical difference is available, statistical interpretation generally requires considering the estimate, its uncertainty, the outcome’s meaning, and the analysis assumptions together. A small p-value alone would not establish that a difference is important, and a non-significant result alone would not demonstrate that groups are equivalent. Those general considerations cannot substitute for the absent estimate and uncertainty interval in this record.

The listed secondary outcomes, CD4 cell count and HIV viral load, also have no results reported in the registry record. The safety fields list zero affected participants for serious and other adverse events in both groups, but deaths are not reported and the record lacks further event details. The safety entries should not be used to infer more than the fields document.

The conclusion is therefore limited: the registry record documents a randomized, triple-masked comparison of armodafinil and placebo and describes the short-term fatigue endpoint, but it does not provide enough outcome information to quantify the primary comparison. This is a limit of the available registry record, not a claim about results that may or may not appear elsewhere.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a registry record can describe a clinical question and trial structure without furnishing the estimates required to evaluate the primary result. Randomization, masking, a defined outcome scale, and a stated assessment period are important features to identify. They do not replace an arm-level summary or a between-group estimate with uncertainty.

The endpoint also illustrates why measurement details matter. The FSS is a self-report measure of fatigue’s impact on everyday functioning, with a specified direction in which higher scores indicate greater impairment. Knowing the scale’s meaning is necessary to interpret an estimate, but it cannot reveal the estimate when results are not reported. A clear outcome definition and a complete results report serve different purposes.

Missing-data handling is another important statistical issue. The record reports 64 completers out of 70 randomized patients and describes LOCF for the primary outcome. General concerns about carrying forward a prior measurement highlight why the amount, timing, and reasons for missing data—and sensitivity analyses—matter when assessing robustness. Those details are not reported in the registry record.

Finally, the record illustrates the distinction between a trial’s design justification and a planning illustration based on an observed effect. Planning assumptions can help describe hypothetical requirements for future studies, but they are not observed power and do not establish what assumptions guided the original trial. The registry record does not report the trial’s own sample-size justification. Keeping these distinctions clear prevents design features, planning calculations, and outcome findings from being conflated.

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 most direct limitation for interpreting this trial from the registry record is the absence of numerical primary outcome results. Although the endpoint, scale direction, and timing are described, arm-specific FSS summaries and a comparative estimate with its precision are not reported. The record therefore does not support a quantitative assessment of the primary question.

Several design and analysis details are also not reported in the registry record. These include the randomization procedure, allocation concealment, the roles masked, the planned primary statistical model, whether baseline adjustment was used, and any model diagnostics. The record does not state the original sample-size justification, nor does it report the assumptions used in that justification.

Missing-data information is limited. The record describes LOCF and reports 64 completers from 70 randomized patients, but does not give missingness by arm, reasons for non-completion, or sensitivity analyses. The placebo-arm treatment description is incomplete, so the planned approach for placebo non-responders is not reported in the registry record. Details about the duration and conduct of any follow-up after the primary 4-week assessment are also not given for the reported outcome analysis.

Multiplicity is difficult to assess because the record lists four outcome measures and three analyses without explaining their mapping or reporting whether any adjustment was used. Secondary outcome results are not reported. Safety reporting is similarly limited to affected-participant counts, with no event terms listed and death counts not reported. These omissions restrict assessment of the outcome findings and the completeness of the statistical and safety reporting available in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS — NCT00737204.
• Registry record last updated 2014-06-12; status last verified 2013-03.
• Results first posted 2014-06-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT00737204 is a completed Phase 4, randomized, triple-masked, parallel-group study titled “Effectiveness of Armodafinil for Treating Fatigue in Adults With HIV/AIDS.” The registry record reports an enrollment of 70 and compares armodafinil with placebo. The primary endpoint is the FSS, measured at baseline and Weeks 4; higher scores indicate greater impairment due to fatigue.

The primary outcome description says data for all 70 patients were presented using LOCF and an intention-to-treat approach. It also reports that 64 patients completed the 4-week trial. The registry record does not report arm-specific primary outcome values or a between-arm estimate. CD4 cell count and HIV viral load are listed as secondary outcomes, with no results reported.

The adverse-event entries record zero participants affected by serious and other adverse events in each arm; deaths are not reported. The record does not provide a detailed sample-size justification or a full statistical analysis plan.