This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Clinical Trial of CNS-targeted HAART (CIT2) (NCT00624195), a randomized phase 2, phase 3 study. The primary outcome is Neuropsychological Performance Change.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00624195 |
| Phase | Phase 2, Phase 3 |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 59 |
| Arms in the primary outcome | 2 |
| Lead sponsor | University of California, San Diego |
| Results posted | Yes |
2. Clinical Question
Population
People with HIV-associated neurocognitive impairment were the intended study population. The registry record lists HIV infections as the condition and records enrollment of 59 participants. The outcome summaries include 26 participants in the CNS-targeted arm and 23 in the non-CNS-targeted arm. Eligibility criteria and further description of the population are not reported in the registry record.
Intervention
The intervention strategy was CNS-targeted highly active antiretroviral therapy, abbreviated CNS-T in the registry record. The strategy was described as selecting agents to optimize CNS penetration and potentially modifying the regimen based on an interim pharmacokinetic assessment of plasma antiretroviral exposure.
Comparator
The comparison strategy was non-CNS-targeted antiretroviral therapy, intended to suppress plasma viral load without targeting CNS penetration. Specific complete regimen details are not reported in the registry record.
Primary question
Did the CNS-targeted strategy produce a different mean change in global deficit score from baseline to 16 weeks than the non-CNS-targeted strategy? The record also describes secondary questions about CNS and systemic HIV suppression, but secondary outcome results are not reported in the registry record.
The study focused on neurocognitive performance in people with HIV-associated neurocognitive impairment. Its primary outcome was change in the global deficit score, a composite measure derived from neurocognitive tests. Because higher global deficit scores indicate poorer cognitive functioning, a negative change represents improvement in the score. The registry record states the hypothesis that participants assigned to CNS-T would have greater neurocognitive improvement than those assigned to non-CNS-T.
The comparison addresses a treatment strategy rather than a single named drug. The CNS-targeted strategy was designed to select therapy for CNS penetration and could involve regimen modification based on pharmacokinetic assessment. The comparator was intended to suppress plasma viral load without specifically targeting CNS penetration. The registry record describes viral suppression as a secondary goal and states hypotheses about CSF and plasma suppression. Results for those secondary questions are not reported in the registry record.
3. Trial Design
The record describes a randomized, parallel-group clinical trial with single masking. It lists Phase 2 and Phase 3 and an enrollment of 59. The study was sponsored by the University of California, San Diego. The recorded start was 2007-03, primary completion was 2012-02, and status is completed. The identity of the masked party, the randomization method, and the allocation ratio are not reported in the registry record.
Participants were assigned to either a CNS-targeted or a non-CNS-targeted antiretroviral therapy strategy. The CNS-T strategy was described as selecting agents to optimize CNS penetration and modifying the regimen if an interim pharmacokinetic assessment found plasma antiretroviral exposure inappropriate. The non-CNS-T strategy was described as aiming to suppress plasma viral load without targeted CNS penetration. The complete lists of regimens and detailed treatment procedures are not reported in the registry record.
The primary outcome was neuropsychological performance change measured by the global deficit score between baseline and 16 weeks. The outcome summaries report 26 participants in the CNS-targeted arm and 23 in the non-CNS-targeted arm. These outcome counts do not account for all 59 enrolled participants, and the reasons for the difference are not reported in the registry record. This prevents the posted summaries alone from establishing exactly which participants were included in the primary outcome analysis or why some enrolled participants are not represented in the arm-level results.
The record lists one outcome measure and no posted analyses. It describes secondary aims concerning CNS and systemic viral suppression, but no secondary results are posted. Details of follow-up beyond the primary endpoint, analysis populations, handling of protocol deviations, and the original statistical plan 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.
Overall Study
| Stage | CNS-targeted | Non-CNS-targeted |
|---|---|---|
| STARTED | 29 | 30 |
| COMPLETED | 26 | 23 |
| NOT COMPLETED | 3 | 7 |
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.
| Characteristic | Unit | CNS-targeted | Non-CNS-targeted | Total |
|---|---|---|---|---|
| Participants analysed | 29 | 30 | 59 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 29 | 30 | 59 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 45.5 (SD 8.8) | 43.6 (SD 11.1) | 44.5 (SD 9.9) |
| Sex: Female, Male: Female | Participants | 5 | 6 | 11 |
| Sex: Female, Male: Male | Participants | 24 | 24 | 48 |
| Region of Enrollment: United States | participants | 29 | 30 | 59 |
6. Primary Endpoint
The registry lists the primary outcome as Neuropsychological Performance Change, measured over Baseline and 16 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome was change in neuropsychological performance from baseline to 16 weeks, measured using the global deficit score, or GDS. The GDS is calculated by averaging individual deficit scores from neurocognitive tests. The registry record says the test scores were adjusted for age, education, gender, and ethnicity, with a scoring approach intended to capture unexpectedly poor performance while not counting better-than-expected performance in the same way.
The GDS ranges from 0 to 5, and higher scores indicate poorer cognitive functioning. The record states that scores greater than or equal to 0.5 are considered evidence of cognitive impairment. Since the outcome is a change score, a negative value means the score fell between baseline and follow-up; in this context, that direction is consistent with improvement in the measured score. A positive value would indicate an increase in the score.
A global composite can summarize performance across several neurocognitive tests rather than relying on one task. That may be useful when the clinical question concerns overall functioning, while potentially obscuring differences among specific cognitive domains. The registry record says the study aimed to assess global performance and different domains, but the posted primary result is for the global deficit score. Domain-specific primary results are not reported in the registry record.
The outcome description identifies a baseline and 16-week assessment. It does not report the score distributions, the individual tests included, or how missing measurements were handled. Those details matter for understanding how the composite was formed and how many participants contributed to the change summaries.
7. Results Posted in the Registry
- Non-CNS-targeted: mean -0.17 versus -0.27 on control; difference 0.10 (95% CI -0.16 to 0.36), standardized effect d = 0.21; z-test p = 0.452.
Mean difference: Non-CNS-targeted
95% CI: -0.16 to 0.36
Recalculated from the posted summary statistics
8. Statistical Interpretation
The mean change was -0.27 units in the CNS-targeted arm and -0.17 units in the non-CNS-targeted arm. Since lower GDS scores indicate better cognitive functioning, both arm means describe decreases in the score over the stated assessment period. The estimated mean difference, expressed as non-CNS-targeted minus CNS-targeted, was 0.1 units. That direction corresponds to a somewhat larger average decrease in the CNS-targeted group, but the estimated difference is small relative to the uncertainty reported around it.
The confidence interval for the mean difference extends from a negative value to a positive value, so it includes zero. The unadjusted recalculation from the posted summary statistics gives p = 0.452. These results do not establish a clear difference between the strategies on the primary outcome. They also do not establish that the strategies are equivalent: an interval spanning zero can be compatible with effects in either direction, and the record does not report an equivalence or non-inferiority design.
The observed arm means are not themselves the treatment comparison. Each mean describes change in one arm, while the between-arm estimate addresses the difference in average change. The distinction matters because improvement within both groups does not show that one assigned strategy caused greater improvement than the other. The trial's randomized comparison is intended to address the relative strategies, but interpretation also depends on the analysis population and follow-up data, details that are not reported in the registry record.
The arm-level standard deviations were 0.52 in the CNS-targeted arm and 0.41 in the non-CNS-targeted arm. These describe participant-to-participant variability in observed change, not the uncertainty in the mean difference. The posted comparison uses a pooled standard deviation of 0.472 and reports a standardized difference of 0.212. A standardized difference expresses the estimated difference relative to the pooled variability; it is a descriptive scale and does not by itself determine clinical importance.
The registry record reports a single primary outcome measure and no posted analyses. The comparison statistics available for the primary result are therefore best read as a summary-based unadjusted recalculation rather than a fully documented account of the trial's prespecified analysis. The original statistical plan, covariate adjustment, missing-data approach, and analysis population are not reported in the registry record. Consequently, the posted estimate and its uncertainty are informative about the displayed summaries, but cannot answer questions about analysis choices that are not documented.
The posted results also do not resolve the registry's secondary questions about CSF and plasma viral suppression. The record describes these as goals and states hypotheses, but secondary outcome results are not reported in the registry record. The primary GDS result should not be treated as evidence about those virologic outcomes or about specific cognitive domains.
9. Statistical Methods Explained
The primary measure is continuous: each participant has a numerical change in global deficit score, and the arm summaries are means with standard deviations. For a continuous outcome, the mean difference compares the average change between the two assigned groups. Here, the reported contrast is non-CNS-targeted minus CNS-targeted, with an estimate of 0.1 units. Keeping the contrast direction explicit helps interpret its sign: negative GDS change represents a decrease in the score, and the positive difference indicates that the average change in the comparator arm was less negative than the average change in the CNS-targeted arm.
What does a mean difference describe?
In general, the mean difference retains the outcome's original measurement units. It is therefore tied to the GDS scale and can be read as a difference in average score change, rather than as a relative percentage. The estimate summarizes the contrast between group averages; it does not mean that every participant had a change of that size. Individual outcomes can vary around each arm mean, as reflected by the arm-level standard deviations.
The posted summaries list 26 participants and a mean change of -0.27 with standard deviation 0.52 for CNS-targeted therapy, and 23 participants and a mean change of -0.17 with standard deviation 0.41 for non-CNS-targeted therapy. The reported pooled standard deviation is 0.472, and the standardized difference is 0.212. These quantities describe the scale and variability of the observed contrast. They do not substitute for the original participant-level analysis, which is not reported in the registry record.
What is a confidence interval?
In general, a confidence interval is a range of values compatible with the data under the method used to calculate it. It conveys uncertainty around an estimated contrast, rather than giving a set of likely values for each participant. The interval reported for this difference spans both negative and positive values, including zero. Thus, the displayed summaries do not rule out no mean difference, nor do they rule out a difference in either direction within the interval.
The unadjusted p-value is 0.452. In general, a p-value describes how unusual data at least as incompatible with a specified no-difference model would be if that model and the test assumptions held. It is not the probability that the no-difference model is true, and it does not measure the size or clinical importance of the estimated contrast. The registry record does not report the prespecified statistical test or a full analysis plan, so the recalculated p-value should be interpreted as a summary-statistic calculation rather than as a confirmed sponsor analysis.
Why does variability matter?
General statistical interpretation: greater variability among participant outcomes makes an average difference harder to estimate precisely when other factors are comparable. Standard deviations describe spread among observations. Standard errors describe uncertainty in an estimated mean or contrast. The posted arm-level standard errors are 0.102 for CNS-targeted and 0.086 for non-CNS-targeted; they are not measures of the range of individual participant responses.
The calculation uses a pooled standard deviation of 0.472. Pooling is a way to summarize variability across groups for a standardized comparison under the calculation's assumptions. It is distinct from the original-unit mean difference. General statistical explanation: a standardized effect can help describe the size of a contrast relative to outcome variability, but it can be less directly interpretable than the mean difference in GDS units. The registry record does not report a clinical threshold for a meaningful between-arm difference, so the standardized difference alone cannot establish clinical importance.
What is not documented about the analysis?
The record does not report the original statistical plan, the primary analysis population, whether covariates were included, or how missing outcome data were handled. It also does not report whether the displayed arm counts correspond to all randomized participants with baseline data, participants with a follow-up measure, or another defined group. Without those details, it is not possible to verify from the registry record whether the displayed summaries reflect the intended primary analysis.
General statistical explanation: randomization is intended to make assigned groups comparable on average, including on characteristics that were not measured. An analysis that preserves participants according to randomized assignment generally maintains the benefit of that design, while exclusions after randomization can affect comparability. The registry record does not state how assignment and exclusions were handled for the posted outcome summaries, so no particular analysis-population approach can be attributed to this trial.
The trial was described as single-masked, but the identity of the masked party is not reported in the registry record. Masking can reduce certain sources of bias, depending on who is masked and how the outcome is assessed. Because the GDS is constructed from neurocognitive test performance and adjusted scores, details about assessor masking and testing procedures would be relevant; those details are not reported in the registry record.
The record lists only the primary outcome result, with no secondary results posted. It also does not document multiplicity procedures or interim statistical monitoring. These omissions do not demonstrate that such procedures were or were not used; they mean they are not reported in the registry record. The available result supports a cautious reading of the displayed mean changes and their comparison, not assumptions about unreported analytic choices.
10. Confidence Intervals and Precision
The estimate of the difference in mean change is 0.1 GDS units, with a reported confidence interval whose lower limit is -0.161 and upper limit is 0.361. This interval covers zero and includes estimates on both sides of no difference. The data therefore do not pin down the direction of the underlying average contrast with high precision. The interval is more informative than the point estimate alone because it shows a range of contrasts compatible with the calculation.
The interval's width reflects uncertainty in the difference, not the spread of individual participant scores. The arm standard deviations, 0.52 and 0.41, describe variability in participant changes, whereas the confidence interval describes uncertainty about the group contrast. These are related but distinct ideas. A confidence interval can include zero even when the point estimate is not zero, and that is the pattern in the posted result.
In general, greater precision corresponds to a narrower interval, while less precision corresponds to a wider interval. Precision depends on factors such as sample size, variability, and the calculation method. The outcome summaries include 26 and 23 participants in the respective arms, but the registry record does not explain why these counts differ from the total enrollment of 59 or identify the exact analysis population. This limits assessment of how the available outcome data relate to the randomized cohort.
The interval is based on the unadjusted recalculation from posted summary statistics, not a fully described registry analysis. The registry record does not report whether the original analysis used adjustment, a different model, or a particular missing-data method. Precision should therefore be understood as applying to the displayed summary-based comparison, with these analysis details unresolved.
11. Planning a Similar Trial: Sample Size
This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.
| Effect to detect | Participants per arm, 80% power | Participants per arm, 90% power |
|---|---|---|
| 100% of the observed effect | 350 | 468 |
| 75% of the observed effect | 621 | 832 |
| 50% of the observed effect | 1,398 | 1,871 |
The sample-size display gives planning illustrations in participants per arm, not total events. Its assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effects used for planning are stated fractions of the observed effect. The original trial design assumptions and sample-size justification are not reported in the registry record.
For planning at 100% of the observed effect, the display gives 350 participants per arm for 80% power and 468 participants per arm for 90% power. For planning at 75% of the observed effect, it gives 621 participants per arm for 80% power and 832 participants per arm for 90% power. For planning at 50% of the observed effect, it gives 1,398 participants per arm for 80% power and 1,871 participants per arm for 90% power.
In plain terms, the 80% power column describes the illustrated number of participants per group for a study designed to have an 80% chance of detecting the specified effect under the stated assumptions. The 90% column describes the corresponding planning target for a 90% chance. These are planning illustrations, not observed power. The calculations use the observed effect as their reference, so they should not be mistaken for the trial's original sample-size calculation.
As the effect being planned for becomes smaller, more participants are needed under the same general assumptions. This occurs because a smaller group difference is harder to distinguish from random variation. The values are not a recommendation for a future study; they depend on the assumptions stated and on treating the observed effect as the planning reference. The registry record does not report the original study's target sample size justification or its own design assumptions.
12. How the Sample Size Is Derived
Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z1−α/2 = 1.960) and the desired power (z1−β = 0.842 for 80% and 1.282 for 90%).
Formula
n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.
Worked calculation for this trial
- Observed difference Δ = 0.100; pooled standard deviation σ = 0.472.
- n = 2 × (1.96 + 0.842)2 × 0.4722 / 0.1002 = 349.3, rounded up to 350 participants per arm for 80% power.
The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).
R code
alpha <- 0.05
z_a <- qnorm(1 - alpha / 2) # two-sided
delta <- 0.1 # observed difference in means
sigma <- 0.471714843541118 # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))
# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")
# Simulation: exact two-sample t-test using simulated means and variances
set.seed(624195)
n <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n)) # difference in sample means
s2 <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1)) # pooled sample variance
tstat <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))
Output from running the code
100% of observed effect: n per arm = 350 (80% power), 468 (90% power)
75% of observed effect: n per arm = 621 (80% power), 832 (90% power)
50% of observed effect: n per arm = 1,398 (80% power), 1,871 (90% power)
power.t.test: 350.3
Simulated power at n = 350 per arm: 0.799 (20000 replicates)The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.
13. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome measure: change in neuropsychological performance measured by the global deficit score between baseline and 16 weeks. It also describes secondary goals involving CNS and systemic HIV suppression, but no secondary outcome results are posted. The record does not report whether additional outcomes or analyses were prespecified outside the posted registry entry.
Multiplicity arises when several outcomes, time points, or comparisons are tested. In general, considering many tests can increase the chance of observing a seemingly notable result by chance, and prespecified procedures can address that issue. The record does not report a multiplicity adjustment or a detailed analysis plan. The absence of that information does not establish whether adjustment was used; it means the approach is not reported in the registry record. With only the primary result available, the secondary virologic hypotheses cannot be evaluated from the posted results.
Missing-data handling is also not reported. The arm summaries list 26 participants in the CNS-targeted group and 23 in the non-CNS-targeted group, while enrollment is 59. The registry record does not explain the difference, state how many participants had missing GDS measurements, or describe any imputation or other missing-data method. It also does not identify whether the summaries are based on all randomized participants or a subset with outcome data.
The analysis population is not reported in the registry record. In general, an analysis based on randomized assignment and an analysis limited to participants with observed outcomes can answer different questions, particularly if outcome availability is related to participant characteristics or treatment experience. Without information on assignment adherence, exclusions, withdrawals, or missing measurements, the displayed arm results cannot be confidently assigned to a specific analysis population.
The record does not report interim statistical analyses or stopping rules. It mentions an interim pharmacokinetic assessment as part of the CNS-targeted treatment strategy, but that treatment-management feature should not be confused with an interim statistical analysis of trial outcomes. The distinction is important: the registry description of a clinical assessment does not establish that trial results were examined for efficacy or safety during follow-up.
14. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| CNS-targeted | 1 | 29 | 3.4% |
| Non-CNS-targeted | 1 | 30 | 3.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| CNS-targeted | 0 of 29 |
| Non-CNS-targeted | 1 of 30 |
Most frequent serious adverse event terms
| Event term | Organ system | CNS-targeted | Non-CNS-targeted |
|---|---|---|---|
| Death | Infections and infestations | 0 of 29 | 1 of 30 |
| Psychiatric Event | Psychiatric disorders | 1 of 29 | 0 of 30 |
Most frequent non-serious adverse event terms
| Event term | Organ system | CNS-targeted | Non-CNS-targeted |
|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | 0 of 29 | 1 of 30 |
Serious events with the highest arm-level rate: psychiatric event (3.4%), death (3.3%).
The serious adverse event summaries list 29 participants at risk in the CNS-targeted arm, with 1 affected by a serious event, and 30 at risk in the non-CNS-targeted arm, also with 1 affected. The arm-level entries therefore describe one participant with a serious adverse event in each group. The record gives no death count for either arm; deaths are not reported in the registry record.
The serious-event terms listed among the most frequent include Psychiatric Event at 3.4% and Death at 3.3%. These are registry-listed terms and percentages, but the record does not provide enough detail in these entries to assign them to a particular treatment arm or to connect them to the arm-level counts. In particular, the presence of Death as a listed term alongside unreported arm death counts should not be interpreted as an arm-specific death result.
In general, adverse-event summaries depend on definitions, event collection periods, and denominators. The record identifies participants at risk for the serious and other adverse-event summaries, but it does not report detailed event descriptions, timing, relatedness assessments, or the criteria used to classify seriousness. The listed counts should be read as registry summaries, not as a complete account of safety or as proof of a causal relationship to treatment.
15. What the Result Does, and Does Not, Mean
The primary posted outcome describes average GDS change from baseline to 16 weeks. The mean change was -0.27 in the CNS-targeted arm and -0.17 in the non-CNS-targeted arm. Because higher GDS scores indicate poorer cognitive functioning, these negative arm means represent decreases in the measured score. The estimated difference between the arms was 0.1 units, and its confidence interval includes zero. The displayed results therefore do not establish a clear between-arm difference in average GDS change.
This conclusion is narrower than saying that there was no effect. The interval remains compatible with a range of possible differences in either direction, and the record does not report an equivalence margin or an equivalence design. Likewise, the arm averages do not describe every participant's response, and the record does not give individual-level distributions. The result concerns the average global deficit score change, not all aspects of cognition or HIV-related health.
The registry's description includes secondary goals regarding CSF and plasma viral suppression. Those results are not reported in the registry record, so the primary GDS comparison cannot answer whether the assigned strategies differed on those outcomes. Nor does this result establish whether particular regimens, individual antiretroviral agents, or other treatment approaches have similar effects.
The posted comparison is based on summary statistics, while the original analysis plan, missing-data approach, and analysis population are not reported. The arm outcome counts also do not match total enrollment, and the reason for that difference is not reported. These limits affect how confidently the summary can be connected to all randomized participants. The result is best understood as an imprecise estimate of the displayed average change contrast, rather than a definitive statement about treatment strategies or about participants beyond the reported summaries.
16. Why This Trial Matters Statistically
This trial addresses a statistical challenge that arises when a treatment strategy is intended to affect a specific biological compartment but the primary outcome is a functional measure. The CNS-targeted and non-CNS-targeted strategies were distinguished by their intended CNS penetration, while the primary comparison focused on a global neurocognitive score. The registry also identifies viral suppression as a secondary question, highlighting that clinical and virologic outcomes are related questions but are not interchangeable endpoints.
The GDS composite offers one way to summarize performance across neurocognitive testing. A composite can make an overall comparison more direct, but may conceal variation among component tests or domains. The record states that different domains were of interest, yet domain-specific results are not reported. This makes the scope of the posted result important: it concerns the global score, not every possible pattern of cognitive performance.
The comparison also illustrates why effect estimates and uncertainty should be considered together. The mean difference is 0.1 units, but its confidence interval spans zero and extends to values in either direction. A point estimate alone could make the groups appear different in one direction; the interval conveys that the data are not sufficiently precise to determine that direction clearly. The unadjusted p-value of 0.452 provides another summary, but does not replace interpretation of the estimate, interval, and underlying outcome scale.
Finally, registry reporting affects statistical interpretation. The record documents the randomized design and primary endpoint, but does not report the full analysis plan, missing-data methods, or secondary results. These omissions do not invalidate the posted numbers; they define what can be concluded from them. Distinguishing documented results from unreported methods is essential when interpreting a clinical trial.
17. 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 outcome summaries include 26 participants in the CNS-targeted arm and 23 in the non-CNS-targeted arm, while recorded enrollment is 59. The reason for this difference is not reported in the registry record. The record does not state how many participants were randomized, completed follow-up, or contributed usable baseline and 16-week GDS assessments. This limits understanding of the analysis population and the role of missing outcomes.
The primary comparison is based on an unadjusted recalculation from posted summary statistics. The registry record does not report the sponsor's original statistical analysis, any covariate adjustment, or the method used to calculate the confidence interval. It also does not report the original sample-size justification, so the planning illustrations should not be read as the study's intended enrollment target.
The treatment strategies are described at a high level, and complete regimens are not reported in the registry record. The masked party, randomization procedure, adherence measures, and details of the pharmacokinetic assessment are also not reported. These details would help readers understand implementation and potential sources of variation between groups.
The global deficit score is the only posted outcome result. Domain-specific neurocognitive results and the secondary CSF and plasma viral suppression results are not reported in the registry record. The record also does not report multiplicity procedures, interim statistical monitoring, or detailed adverse-event definitions and event timing. These limits mean the result should be interpreted specifically as the posted GDS comparison, not as a comprehensive account of cognitive, virologic, or safety outcomes.
18. Related Tutorials
19. Related Statistical Calculators
20. Sources
- ClinicalTrials.gov: Clinical Trial of CNS-targeted HAART (CIT2) — NCT00624195.
- Registry record last updated 2014-04-23; status last verified 2014-03.
- Results first posted 2014-04-23.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
21. Record Summary
NCT00624195 is the completed randomized, single-masked, parallel-group trial titled Clinical Trial of CNS-targeted HAART (CIT2). The registry lists Phase 2 and Phase 3, enrollment of 59, a recorded start of 2007-03, and primary completion in 2012-02. The sponsor is the University of California, San Diego.
The primary outcome was change in global deficit score from baseline to 16 weeks. Mean change was -0.27 among 26 participants in the CNS-targeted arm and -0.17 among 23 participants in the non-CNS-targeted arm. The estimated mean difference was 0.1 units, with a confidence interval spanning zero. Secondary viral suppression results are not reported in the registry record.
The record does not report the original statistical plan, analysis population, missing-data approach, or reasons the outcome counts differ from enrollment. These limitations should be kept in view when interpreting the posted primary comparison.