Effectiveness of Modafinil 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 Modafinil for Treating Fatigue in Adults With HIV/AIDS (NCT00118378), a randomized phase 4 study. The primary outcome is Fatigue Severity Scale (FSS).

2. Clinical Question

This is a question about a patient-reported measure of fatigue-related impairment, not a direct measure of HIV disease status. The registry also lists CD4 cell count and HIV RNA viral load as secondary outcomes. Those measures address different aspects of the clinical context and do not substitute for the stated fatigue endpoint.

The outcome description says the FSS was measured at baseline and Week 4. It does not identify a single comparison of baseline-to-Week 4 change, nor does it say whether the Week 4 analysis adjusted for baseline scores. The analysis method for the primary outcome is therefore not reported in the registry record. The clinical question can be stated, but the posted record does not provide the outcome estimates needed to judge the size or precision of any difference.

3. Trial Design

This was a randomized, double-masked, parallel-group phase 4 study sponsored by the New York State Psychiatric Institute. The registry lists enrollment of 115 and describes two groups: modafinil and placebo. Participants in each group were to take their assigned intervention for 4 weeks. The record is marked completed.

The parallel design means participants were assigned to one of the two interventions rather than receiving both in sequence. Randomization is intended, in general, to make the assigned groups comparable at the start of a study, including with respect to factors that are measured and factors that are not measured. It does not ensure that the groups will be identical in a particular trial. The registry does not report the allocation ratio, the method used to generate the random assignments, or the process used to conceal assignments before enrollment.

Double masking indicates that the study used a double-masked design, but the registry record does not specify which people were masked or how masking was maintained. Details such as the appearance of the study treatments, the procedures for breaking the mask, and any checks of masking are not reported in the registry record.

The study start is recorded as 2004-12, and primary completion as 2010-06. These dates describe the registry record’s study timeline; they do not establish how long each participant was followed beyond the stated four-week treatment period. Other follow-up schedules, eligibility criteria, site information, and procedures for treatment adherence are not reported in the registry record.

The registry identifies the primary measure as the Fatigue Severity Scale and lists CD4 cell count and HIV RNA viral load as secondary outcomes. It records four outcome measures and four analyses, but does not supply a consolidated primary-outcome result. The design features can therefore be described, while the treatment contrast itself cannot be quantified from the posted results.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The WEEK 4 outcome analyses are based on an intention to treat sample which includes the 10 dropouts (2 on Modafinil and 8 on Placebo), using the last data point brought forward.

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), measured over Measured at baseline and Week 4.

The stated primary endpoint is the Fatigue Severity Scale (FSS), reported as a mean with standard deviation and measured in units on a scale. The registry describes the FSS as a 9-item self-report scale about the impact of fatigue on everyday functioning. Each item is rated from 1 to 7, and total scores range from 9 to 63. Higher values indicate greater impairment due to fatigue.

A patient-reported measure can capture how a symptom affects daily functioning from the participant’s perspective. That is relevant to a trial asking whether an intervention is associated with a change in fatigue-related impairment. The scale’s direction matters when interpreting a result: higher FSS scores represent greater impairment, not improvement. The registry identifies the measure but does not report a result that would establish the direction or size of a between-group difference.

The FSS was measured at baseline and Week 4. The posted description identifies the Week 4 outcome analyses as intention to treat, including the 10 dropouts by carrying the last data point forward. It does not specify whether the primary analysis compared Week 4 means, changes from baseline, or another summary. That analysis detail is not reported in the registry record.

The endpoint is a continuous score, so means describe the groups’ average scores and standard deviations describe variation among individual scores. Neither summary, on its own, says how precisely the treatment contrast is estimated. A confidence interval or other uncertainty measure would help convey that precision, but a primary-outcome estimate and its uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a continuous scale score summarized using a mean and standard deviation. These summaries answer different questions. A mean describes the average score in a group, while a standard deviation describes how much individual scores vary around that average. A standard deviation is not the same as the uncertainty around the mean or around a between-group difference. For inference about a treatment contrast, an estimate with an uncertainty interval is generally more informative than group summaries alone. No single primary-outcome contrast or uncertainty interval is reported in the registry record.

What randomization contributes

In general, random assignment aims to reduce systematic differences between treatment groups at the start of a trial. When allocation is implemented as planned, it supports a comparison based on assigned intervention rather than on participants’ choices or clinical characteristics. Chance differences can still occur, especially in any one realized trial. Details of the randomization sequence and allocation concealment are not reported in the registry record, so the particular implementation cannot be assessed from this description.

A double-masked design can reduce the potential for expectations to influence participant reports, care, or assessment. This is especially relevant when the endpoint is self-reported. Masking does not guarantee that reporting or assessment is free of bias, and the record does not identify which parties were masked or describe any assessment of masking. Those design details are not reported in the registry record.

Means, variation, and uncertainty

For a continuous outcome, a mean difference can express how far apart two group averages are, in the scale’s units. A confidence interval is a general statistical tool for showing the range of values compatible with the observed data and the analysis assumptions. A narrow interval indicates greater precision than a wide interval, although interpretation also depends on the outcome and context. The registry identifies a mean and standard deviation as the outcome summary, but does not give the one primary comparison or its interval. It is therefore not possible to discuss the trial’s estimated effect or precision.

A p-value, when reported, addresses how compatible data are with a specified null model under the analysis assumptions; it is not the probability that a treatment works or that the null hypothesis is true. A p-value alone also does not express the magnitude or clinical importance of an estimate. No single primary-outcome p-value is reported in the registry record, so there is no basis to characterize statistical significance for the primary question.

Analysis population and imputation

The record describes the Week 4 analyses as intention to treat and says they include 10 dropouts by using the last data point carried forward. In general, an intention-to-treat approach analyzes participants according to their randomized assignment, preserving the comparison created by randomization as far as possible. The registry’s description indicates that the dropouts were retained in the stated Week 4 analysis population through an imputation procedure.

Last observation carried forward fills a missing later measurement with an earlier available measurement. This can retain participants in an analysis, but it relies on an assumption about what their unobserved later scores would have been. Their outcomes may in reality have changed after the last recorded measurement. If the amount or pattern of change differs between groups, the imputed values can influence the estimated contrast. This is a general limitation of the method, not evidence that it biased this trial’s result. Reasons for dropout, timing of last observations, alternative missing-data analyses, and sensitivity analyses are not reported in the registry record.

Planning calculations and over-dispersion

The stated planning illustration uses a two-sided significance level of 0.05, equal allocation, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. Such calculations are planning illustrations, not observed trial outcomes and not evidence that a trial had a particular probability of detecting an effect after it was completed. The actual planning values, the effect estimate used, and the trial’s own sample-size justification are not reported in the registry record.

In general, planning calculations for a continuous outcome depend on assumptions about the effect to detect and the variability of the outcome, as well as the chosen error rate and allocation. Over-dispersion means that the observed variability is greater than assumed by a model; when that happens, a calculation based on the smaller assumed variability can overstate the precision expected from a given sample size. This is a general statistical consideration, not a reported feature of this trial. The record does not provide enough information to assess whether over-dispersion was considered.

Multiplicity and the primary comparison

Multiplicity arises when several outcomes, time points, categories, or analyses are examined. The more opportunities there are to identify a result, the more important it can be to prespecify a primary comparison and describe how multiple testing is handled. The registry notes that the primary outcome includes several categories or time points and was not reduced to one comparison. A multiplicity adjustment or hierarchy of tests is not reported in the registry record. Without a single primary contrast and a stated analysis plan, the inferential status of any individual result cannot be evaluated from this record alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary outcome measured at baseline and Week 4, and notes that the primary outcome has several categories or time points and was not reduced to one comparison. It lists four outcome measures and four analyses. These registry entries indicate that the posted record does not present one consolidated primary comparison. The precise set of comparisons, any prespecified hierarchy, and any adjustment for multiplicity are not reported in the registry record.

Multiplicity matters because examining several time points, outcomes, or analytic choices can increase the chance that at least one result appears notable by chance. This is a general concern, not a claim about what happened in this trial. The record does not identify which comparisons were planned in advance or whether any results were selected for reporting. Without those details, it is not possible to determine how a particular result should be interpreted across the full set of analyses.

The Week 4 analyses are described as intention to treat and include 10 dropouts using last data point carried forward. The group counts are stated as 2 on modafinil and 8 on placebo. This provides a limited description of missing-outcome handling, but does not state why participants dropped out, when their last observations occurred, or whether missingness was related to their observed or unobserved fatigue scores. Other analysis populations are not reported in the registry record.

Last observation carried forward can be useful as a simple way to retain participants, but it treats a prior value as a stand-in for a later unobserved outcome. In general, that assumption may be implausible if participants’ scores would have changed. Sensitivity analyses using other assumptions could help show how dependent a result is on the missing-data method. Such analyses are not reported in the registry record, and the absence of a single primary-outcome estimate prevents assessment of the impact of missingness on the treatment contrast.

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 registry lists 62 participants at risk in the modafinil group and 53 in the placebo group for serious adverse events. The reported number affected is 0 in each group. For other adverse events, it likewise lists 62 and 53 participants at risk, with 0 affected in each group. These are the counts recorded; they are not estimates of the probability of future events or a complete assessment of safety.

A count of zero affected means no participants were recorded as having an event in that category in the posted figures. It does not prove that the risk is absent. Counts can also be difficult to interpret without details such as event definitions, observation time, event collection procedures, and completeness of reporting. Those details are not reported in the registry record.

The death figures are not reported in the registry record. No serious adverse-event terms are listed. The record does not provide an adverse-event comparison with uncertainty estimates, nor does it describe event severity beyond the serious and other categories. These safety counts should be read separately from the primary fatigue outcome: they do not indicate whether the FSS differed between groups, and they do not resolve the missing primary-outcome comparison.

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

The record establishes that a randomized, double-masked, parallel trial compared four weeks of modafinil with four weeks of placebo in adults with HIV/AIDS, with fatigue assessed using the FSS. It also describes the Week 4 analysis population as intention to treat, including 10 dropouts through last data point carried forward. These are useful details about the question and the way the outcome population was defined.

What the posted results do not establish is the direction, size, or precision of a difference in fatigue severity. The registry does not report one primary-outcome comparison, nor does it provide the group scores, treatment contrast, confidence interval, or p-value needed to interpret such a comparison. The registry’s explanation that the outcome has several categories or time points and was not reduced to one comparison is an important limit on interpretation.

This reporting gap should not be translated into a claim that modafinil and placebo had identical outcomes. It also should not be translated into a claim that modafinil reduced fatigue or that it did not. Without a reported estimate, the data available in the registry record cannot distinguish among those possibilities. The scale’s scoring direction only tells readers what higher or lower scores would mean if a result were available: higher scores indicate greater impairment.

The listed secondary outcomes, CD4 cell count and HIV RNA viral load, concern other measures and cannot answer the primary fatigue question. The adverse-event counts are also separate from efficacy. The record lists zero affected for the serious and other adverse-event categories in both groups, while death counts are not reported in the registry record. These entries do not fill the gap in the primary endpoint results.

Thus, the defensible interpretation is bounded. The study’s design and outcome measure are identifiable, but the primary result is not reported as one interpretable group comparison. Any claim about the magnitude, clinical importance, statistical significance, or certainty of a fatigue effect would require information not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly defined outcome and a clearly reported comparison are both necessary for statistical interpretation. The FSS is described in enough detail to identify what was measured and which direction represents greater impairment. The record also names the intervention, comparator, treatment period, and analysis population. But without a single primary-outcome contrast, readers cannot move from the study question to an estimate of how the groups differed.

Randomization is a design feature, not a result. It supports a fair comparison in principle, but the value of that design for decision-making depends on reporting the outcome estimates and their uncertainty. A statement that a trial was randomized cannot substitute for the mean scores, contrast, and precision needed to understand what the observed data show.

The record also highlights how missing-data choices intersect with an intention-to-treat analysis. Including dropouts by carrying the last observation forward makes the handling method visible, but does not demonstrate that the imputed values represent what participants would have reported at Week 4. Describing the method and reporting sensitivity analyses are both important to understanding how missing outcomes may affect conclusions.

Finally, an outcome measured at multiple time points or across several categories needs a transparent plan for identifying the primary comparison and handling multiplicity. The registry itself says the primary outcome was not reduced to one comparison. Without that definition, readers cannot tell which result should anchor the interpretation or how to assess the implications of multiple analyses.

The statistical importance of this record therefore lies not in a demonstrated treatment effect, but in the distinction between design information and result information. A trial can have a stated clinical question, a defined measurement tool, and a randomized structure while still leaving the main effect unquantifiable in its registry results.

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 primary limitation for interpretation is that the registry does not report one primary-outcome comparison. It identifies the FSS, the Week 4 analysis population, and the reason the primary outcome was not reduced to one comparison, but does not provide a group contrast or uncertainty estimate. Consequently, the direction, magnitude, and precision of any fatigue difference are not assessable from the posted results.

The outcome description says the FSS was measured at baseline and Week 4, but does not specify whether the analysis used Week 4 values, change from baseline, or a baseline-adjusted model. Statistical model details, handling of repeated measurements, and treatment of any scale categories or time points are not reported in the registry record. The intended primary comparison and multiplicity procedure are also not reported.

The record says the Week 4 analyses used an intention-to-treat population that included 10 dropouts through last data point carried forward. It does not describe dropout reasons, timing of last observations, or results under alternative missing-data assumptions. This matters because the assumed relationship between earlier observed values and later missing outcomes can affect an analysis. It is not possible to determine the size or direction of such an influence without outcome estimates and sensitivity analyses.

Enrollment is listed as 115, but the record does not provide the group-specific number included in the primary outcome analysis beyond the stated dropout counts and adverse-event risk sets. It does not report the randomization ratio, allocation concealment, adherence, protocol deviations, or other analysis populations. Details of masking, outcome collection, and study sites are also not reported in the registry record.

The adverse-event entries give counts of affected participants but do not provide event-level descriptions, follow-up time, or uncertainty estimates. The death counts are not reported in the registry record. These limitations do not establish that the study was conducted poorly; they define what cannot be assessed from the registry information available.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Modafinil for Treating Fatigue in Adults With HIV/AIDS — NCT00118378.
• Registry record last updated 2017-05-10; status last verified 2017-03.
• Results first posted 2014-06-09.
• 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.

18. Record Summary

The registry record describes a completed randomized, double-masked, parallel phase 4 study sponsored by the New York State Psychiatric Institute, with enrollment of 115. Adults with HIV/AIDS were assigned to modafinil or placebo for 4 weeks. The study dates are recorded as starting in 2004-12, with primary completion in 2010-06.

The primary outcome was the Fatigue Severity Scale, measured at baseline and Week 4 and summarized as a mean with standard deviation. Higher scores indicate greater fatigue-related impairment. The Week 4 analysis is described as intention to treat, including the 10 dropouts through last data point carried forward.

The registry notes that the primary outcome had several categories or time points and was not reduced to one comparison. It therefore does not report a single primary-outcome result that can be interpreted as a treatment effect. CD4 cell count and HIV RNA viral load are listed as secondary outcomes. Serious and other adverse-event counts are recorded as zero affected in both groups; death counts are not reported in the registry record.