Telephone Support to Improve Adherence to Anti-HIV Medications: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Telephone Support to Improve Adherence to Anti-HIV Medications (NCT00988442), a randomized phase 2 study. The primary outcome is Number of Participants With Virologic Suppression.

2. Clinical Question

The trial’s broader aim was to test whether a nursing telephone-support system improved adherence among at-risk, treatment-experienced people. The posted primary endpoint is a virologic outcome, not a direct measure of adherence. Other listed outcomes included additional virologic assessments, CD4 cell-count change, treatment-regimen discontinuation, illness events or mortality, and intervention costs. Those outcomes address different aspects of treatment experience and should not be treated as interchangeable evidence about the primary question.

3. Trial Design

This was a phase 2, randomized, parallel-group trial of behavioral interventions. The registry lists an enrollment of 59 and describes the trial as terminated. The study started in 2010-10, and primary completion was recorded as 2013-02. The reason for termination and the timing or circumstances of early closure are not reported in the registry record.

One group received enhanced nursing telephone support plus care as usual; the other received care as usual. The registry identifies the trial as single-masked, but who was masked and how masking was maintained are not reported in the registry record. Details of the randomization procedure, allocation concealment, and planned group allocation are also not reported in the registry record.

The primary outcome was the number of participants with virologic suppression at Week 48, defined as HIV-1 RNA below 200 copies/mL. The registry says that the primary analysis included enrolled participants with Week 48 HIV-1 RNA results available and labels this an intent-to-treat analysis. At early study closure, 14 participants had reached Week 48. The reported primary group counts are based on 7 participants in each arm.

The record lists 28 outcome measures and one reported analysis. It lists 27 posted secondary outcomes, including suppression assessments at other time points and outcomes concerning CD4 cell count, discontinuation, virologic failure, costs, illness events, and mortality. The registry does not report a full protocol, a statistical analysis plan, a sample-size justification for the trial, or a planned hierarchy among the outcomes. The planning calculations associated with the posted results are illustrations based on observed effects, not evidence about the trial’s original design.

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 randomized 1:1 to standard care and enhanced nursing telephone support with standard care arms.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants enrolled who had Week 48 HIV-1 RNA results available were included in this intent-to-treat-analysis. At the time of early study closure, 14 participants had reached week 48.

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: All participants enrolled in the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Virologic Suppression, measured over Week 48.

The primary endpoint counts participants who met the registry’s definition of virologic suppression at Week 48: HIV-1 RNA below 200 copies/mL. It is a binary outcome at the participant level. Each participant either meets the stated threshold at the assessment or does not; the reported outcome is the number meeting it in each group. The endpoint does not report the full distribution of viral-load values or the amount of change from an earlier measurement.

Virologic suppression is used as a clinical-trial outcome because it summarizes whether HIV-1 RNA is below a prespecified threshold at a particular follow-up time. It is distinct from medication adherence, which was the behavioral target of the telephone-support intervention. A virologic result can therefore address a downstream outcome without directly measuring the behavior the intervention was intended to influence.

The registry’s primary population description includes enrolled participants for whom Week 48 HIV-1 RNA results were available. The record notes that 14 participants had reached Week 48 when the study closed early, and the reported primary arm counts are 4 of 7 and 5 of 7. Thus, the posted primary comparison rests on a limited set of available Week 48 results. The record does not provide a primary effect estimate with a confidence interval, nor does it explain how participants without an available Week 48 result were handled beyond the stated analysis-population description.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either met the Week 48 suppression definition or did not. The registry reports counts by arm and identifies Fisher’s exact test as the sponsor’s comparison method. The posted recalculations for selected secondary outcomes express between-group comparisons as risk differences and also include relative risks, odds ratios, confidence intervals, and unadjusted p-values. These are different ways to describe the same underlying binary-outcome comparison, and they should be read in light of the small available group counts.

What does Fisher’s exact test assess?

Fisher’s exact test evaluates how compatible the observed allocation of outcome counts between groups is with a null hypothesis of no association between group and outcome, under the test’s assumptions. It is commonly used for categorical data when counts are limited. A p-value is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of a difference. The primary p-value reported by the sponsor is 1.000. The registry does not provide a primary confidence interval or a primary effect estimate alongside that test.

How should a risk difference be read?

A risk difference contrasts the proportions meeting the outcome definition in two groups. In the recalculations, the comparison is standard care relative to enhanced support. A positive estimate indicates a higher observed proportion in standard care; a negative estimate indicates a lower observed proportion in standard care. The estimate is a sample-based contrast, not a causal conclusion by itself. Its confidence interval describes the range of values compatible with the data under the calculation’s assumptions. When an interval includes zero, the data do not rule out no risk difference at the stated confidence level. A wide interval indicates substantial uncertainty about the size and direction of the contrast.

What do relative risks and odds ratios add?

A relative risk compares the outcome probabilities as a ratio, while an odds ratio compares the odds. A value at the null corresponds to no relative contrast; values on either side represent directions of association. These measures use different scales from a risk difference, so their numerical magnitudes should not be compared directly. The registry’s secondary recalculations include these measures as well as risk differences. They remain unadjusted summaries of the posted counts and do not resolve the uncertainty arising from limited observations.

Why are the secondary p-values unadjusted?

The posted secondary recalculations give an unadjusted p-value for each comparison. An unadjusted p-value assesses one comparison without correcting for the fact that multiple outcomes or time points may be examined. When many comparisons are considered, the chance of seeing at least one small p-value by chance can increase. The registry does not report a multiplicity-adjustment plan or identify a prespecified hierarchy for secondary outcomes. Therefore, these p-values should be treated as exploratory evidence, not as confirmatory tests that stand independently of the broader set of outcomes.

What do the planning calculations mean?

The associated sample-size calculations are planning illustrations based on the observed effects, not the trial’s design justification and not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and detection of a stated fraction of the observed effect. The sample-size values describe participants per arm for 80% or 90% power under those assumptions. They should not be interpreted as a retrospective measure of whether the completed trial had enough power, nor as evidence that the observed effects are true or reproducible. The registry’s original sample-size assumptions and justification are not reported in the registry record.

For binary outcomes, estimates and tests depend on both the number meeting the definition and the number with outcome data in each group. Missing outcome data can affect the composition of the analyzed groups and the interpretation of the comparison. The primary population description specifies availability of Week 48 results, but the registry does not report a missing-data method, a sensitivity analysis, or sufficient detail to determine the impact of unavailable outcomes. These limitations should accompany interpretation of both p-values and effect estimates.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Enhanced Nursing Telephone Support With Standard C", "Standard Care")
n      <- c(7, 7)
events <- c(4, 5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Enhanced Nursing Telephone Support With Standard C  7  4  57.1  18.4  90.1  25.0  84.2  24.5  84.3
ARM  Standard Care  7  5  71.4  29.0  96.3  35.9  91.8  34.9  91.5

11. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis compares the Week 48 suppression counts with Fisher’s exact test and reports p = 1.000. No primary effect estimate or confidence interval is reported in the registry record. The posted recalculation fields for secondary outcomes are separate, unadjusted reconstructions from the arm-level summary counts; they do not provide a recalculated primary result or replace the sponsor’s stated primary analysis.

There is no reported discrepancy between the posted secondary summaries and their recalculations. That does not make the secondary recalculations equivalent to a sponsor analysis: the registry lists no sponsor-reported analysis for those secondary comparisons. They are useful for describing approximate contrasts and their uncertainty, but they do not incorporate any adjustment or modeling detail that may have been used in an unreported analysis. In the absence of a reported sponsor analysis for those endpoints, the recalculated results should be understood as descriptive, unadjusted comparisons rather than as the trial’s official inferential conclusions.

The primary sponsor result and the secondary recalculations also answer different comparisons at different outcome time points. They should not be collapsed into a single conclusion. The primary test pertains to Week 48 and the available primary results; the recalculations pertain to the listed secondary assessments. Neither the primary p-value nor the secondary calculations establish that the groups are equivalent, and none directly demonstrates whether the telephone intervention changed adherence.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 28 outcome measures, including the primary outcome and a wide range of secondary outcomes. It reports one analysis for the primary comparison, while the posted secondary outcome records include several calculated comparisons. The registry does not report a statistical analysis plan, a multiplicity-adjustment method, or a prespecified hierarchy that would identify which secondary outcomes were intended to support confirmatory claims. This absence matters because interpreting many unadjusted comparisons as if each were a standalone test can overstate the strength of evidence. The secondary p-values should therefore be viewed cautiously and in context, rather than selected individually as definitive findings.

Missing outcome data are also important. For the primary endpoint, the registry describes an analysis of enrolled participants with Week 48 HIV-1 RNA results available and notes that 14 participants had reached Week 48 when early closure occurred. The posted primary counts include 7 participants per arm. The record does not report the outcomes of participants without an available Week 48 result, why results were unavailable, or a method for addressing missing outcomes. It does not provide a sensitivity analysis showing how conclusions might change under alternative assumptions about those outcomes.

The term intent-to-treat appears in the registry’s primary population description, but the same description restricts inclusion to participants with available Week 48 results. The record does not explain how this restriction was reconciled with the intent-to-treat label. It is therefore not possible to determine from the registry record whether all randomized participants were analyzed as assigned or how unavailable outcomes were handled in the analysis.

The record also does not report the randomization method, allocation concealment, who was masked, the planned statistical model beyond the reported Fisher exact test, or a rationale for the sample size. These omissions do not establish that such procedures were absent; they mean that their details are not reported in the registry record. Together with early closure, limited Week 48 availability, and multiple outcomes, they constrain assessment of precision, bias, and the confirmatory status of findings.

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

The result describes the Week 48 counts among participants with available HIV-1 RNA results: 4 of 7 in the enhanced-support group and 5 of 7 in the standard-care group met the registry’s suppression definition. The sponsor’s Fisher exact test gave p = 1.000. The registry does not report a primary effect estimate or confidence interval, so the p-value does not show how large a difference might be compatible with the observed data.

These observations do not establish that enhanced telephone support improved or worsened virologic suppression, and they do not establish that the groups were equivalent. A test that does not indicate a statistically significant difference is not proof of no effect. With few available Week 48 observations, the data provide limited precision. The result also cannot be interpreted as a direct measure of adherence: virologic suppression was the endpoint, while adherence was the behavioral target described in the study summary.

The findings apply to the posted trial record and the outcomes and analysis populations described there. The registry does not report enough detail to assess the effect of missing Week 48 outcomes, the reason for early closure, or the full analysis plan. The secondary recalculations provide additional descriptive comparisons, but their unadjusted nature and the many listed outcomes make them less suitable as standalone confirmatory evidence.

Nothing in these results determines what an individual should do about treatment. They are statistical descriptions of a terminated trial with limited primary outcome availability. Broader conclusions would require evidence beyond these posted results and a fuller understanding of the trial’s methods and outcome data.

14. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition is only one part of evaluating clinical evidence. The Week 48 threshold is specific, but the primary comparison relies on available results from a small subset of the overall enrollment. A precise definition does not remove uncertainty when outcome data are limited.

It also shows why counts, effect estimates, confidence intervals, and p-values answer different questions. Counts convey what was observed. A p-value summarizes compatibility with a null hypothesis under a specified test, but does not quantify the possible effect. An effect estimate with an interval would help show the range and direction of plausible contrasts; the primary registry result does not report one. Secondary recalculations show how intervals can remain broad even when an estimate is available.

The distinction between an intervention’s intended target and its measured endpoint is also important. Nursing telephone support was intended to improve adherence and medication self-management, whereas the primary outcome measured virologic suppression. These are related questions, but the posted primary endpoint is not a direct adherence measure.

Finally, the registry lists many outcomes but does not report a multiplicity plan or a detailed analysis plan. This makes it important to distinguish the sponsor’s primary comparison from exploratory secondary calculations, and to avoid selecting individual results without considering the whole set. The record is useful for examining how early closure, outcome availability, and reporting detail shape what can be concluded statistically.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this trial restrict interpretation. The primary outcome was assessed at Week 48, but the registry reports that only participants with available Week 48 HIV-1 RNA results were included and that 14 participants had reached that time point at early closure. The posted arm counts are 7 in each group. This limited availability leaves substantial uncertainty and raises questions about how participants without an observed Week 48 result differed from those included. The reason for early closure and the handling of unavailable results are not reported in the registry record.

The primary outcome is a count at a threshold, not a continuous description of viral load, and the registry does not report a primary effect estimate or confidence interval. The reported Fisher exact p-value cannot by itself show the size or precision of a group difference. The primary population description uses an intent-to-treat label while limiting the analysis to those with available Week 48 results; how this was implemented is not reported.

The intervention and standard-care descriptions are brief. Call frequency, duration, staff procedures, and the detailed content of care as usual are not reported in the registry record, limiting assessment of intervention delivery and reproducibility. Although the trial is listed as single-masked, the masked parties and masking procedures are not specified. Randomization and allocation-concealment methods are also not described.

The registry lists numerous outcomes, but does not report a multiplicity plan or full statistical analysis plan. Secondary recalculations are unadjusted and should not be treated as confirmatory. The record also does not report the trial’s sample-size justification. These reporting gaps, alongside early termination and limited primary data, make estimates and cross-outcome comparisons difficult to interpret.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Telephone Support to Improve Adherence to Anti-HIV Medications — NCT00988442.
• Registry record last updated 2017-07-17; status last verified 2017-04.
• Results first posted 2017-07-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00988442, titled Telephone Support to Improve Adherence to Anti-HIV Medications, was a phase 2 randomized parallel-group trial of enhanced nursing telephone support plus standard care versus standard care. It enrolled 59 and is listed as terminated. The study started in 2010-10, with primary completion in 2013-02.

The primary outcome was the number of participants with HIV-1 RNA below 200 copies/mL at Week 48. The registry reports 4 of 7 participants in the enhanced-support group and 5 of 7 in standard care, with a sponsor-reported Fisher exact p-value of 1.000. The primary record notes early closure and limited availability of Week 48 results; it does not provide a primary effect estimate or confidence interval.

Secondary outcomes cover virologic, immunologic, treatment, cost, illness, and mortality measures. Recalculated secondary comparisons are unadjusted and have substantial uncertainty. The registry does not report the reason for termination, detailed missing-data methods, a multiplicity plan, or a full statistical analysis plan.