This page separates reported trial results from statistical interpretation. Numerical results are taken only from the ClinicalTrials.gov record. The registry provides the official trial record.
1. Trial at a Glance
VOICE was a randomized, parallel phase 2 prevention trial in women with HIV infections as the condition of interest. The trial enrolled 5029 participants and evaluated five intervention arms involving tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate, emtricitabine/tenofovir disoproxil fumarate, and corresponding placebo interventions.
| Feature | VOICE |
|---|---|
| Trial name | VOICE |
| ClinicalTrials.gov identifier | NCT00705679 |
| Phase | Phase 2 |
| Status | Completed |
| Therapeutic area | Infectious Disease |
| Condition | HIV Infections |
| Primary purpose | Prevention |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Enrollment | 5029 |
| Lead sponsor | National Institute of Allergy and Infectious Diseases (NIAID) |
| Sponsor type | NIH |
| Start | August 2009 |
| Primary completion | August 2012 |
2. Clinical Question
The trial evaluated the safety and effectiveness of three active prevention approaches involving tenofovir-based products in women at risk for sexually transmitted HIV infection. The registered primary comparisons examined HIV-1 infection incidence between active products and their corresponding placebo groups.
Population
Women participating in a phase 2 randomized prevention trial for HIV infection. The registered analyses excluded randomized participants with no follow-up HIV testing or participants determined to be HIV-positive at randomization by PCR testing of stored enrollment plasma samples.
Interventions
Tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF), and oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), with corresponding placebo interventions.
Comparator
The registered primary efficacy comparisons were TFV gel versus placebo gel, oral TDF versus oral placebo, and oral TDF-FTC versus oral placebo.
Primary question
How do the HIV-1 infection incidence rates compare between each active prevention product and its corresponding placebo arm during follow-up?
3. Trial Design
Registered interventions
Three prevention approaches
- Emtricitabine/tenofovir disoproxil fumarate
- Tenofovir disoproxil fumarate
- Tenofovir 1% vaginal gel
Corresponding placebo products
- Emtricitabine/tenofovir disoproxil fumarate placebo
- Tenofovir disoproxil fumarate placebo
- Tenofovir placebo
4. Endpoints
The registry lists 10 primary endpoints. The efficacy endpoints use both person-years of follow-up and HIV-1 infection counts, with incidence rate as the formal time-to-event analysis. A separate primary safety endpoint evaluates Grade 2, 3, and 4 adverse events.
| Registered primary endpoint | Time frame | Type |
|---|---|---|
| Person-years of Follow-up of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | For up to 30 months of follow-up | Binary |
| Number of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | For up to 30 months of follow-up | Binary |
| Incidence Rate of HIV-1 Infections of Tenofovir 1% Gel and Vaginal Placebo Gel Arms | For up to 30 months of follow-up | Time-to-event |
| Person-years of Follow-up of Oral TDF and Oral Placebo Arms | For up to 30 months of follow-up | Binary |
| Number of HIV-1 Infections of Oral TDF and Oral Placebo Arms | For up to 30 months of follow-up | Binary |
| Incidence Rate of HIV-1 Infections of Oral TDF and Oral Placebo Arms | For up to 30 months of follow-up | Time-to-event |
| Person-years of Follow-up of Oral TDF-FTC and Oral Placebo Arms | For up to 30 months of follow-up | Binary |
| Number of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | For up to 30 months of follow-up | Binary |
| Incidence Rate of HIV-1 Infections of Oral TDF-FTC and Oral Placebo Arms | For up to 30 months of follow-up | Time-to-event |
| Extended Safety of Daily Tenofovir 1% Gel, Oral TDF, and Oral FTC/TDF in Women at Risk for Sexually Transmitted HIV Infection Based on Occurrence of Grade 2, 3, and 4 Adverse Events | Throughout study, up to 2.5 years | Binary |
How the HIV endpoint was defined
Participants were followed for up to 30 months. Person-years measured the amount of follow-up time for each participant, from enrollment to the first HIV-positive test result if HIV infection occurred, or to the last HIV-negative follow-up test if HIV infection did not occur.
Participants were tested monthly for HIV-1. Positive rapid test results were confirmed by enzyme-linked immunosorbent assay (EIA) and subsequent Western blotting (WB).
5. Statistical Methodology
Cox proportional-hazards model
The three formal HIV incidence-rate comparisons were analyzed using regression with a Cox proportional-hazards model. The registry specifies that the Cox model was stratified by site.
For these analyses, the hazard ratio compares the estimated instantaneous rate of HIV-1 infection between the active product and corresponding placebo group. A hazard ratio of 1 represents equal estimated hazards; values below 1 indicate a lower estimated hazard in the active-product group, while values above 1 indicate a higher estimated hazard.
Stratified analysis
The Cox model was stratified by site. Stratification allows the baseline hazard to vary across sites while estimating the treatment comparison within the overall Cox framework. This is particularly relevant when randomized participants are recruited across multiple sites with potentially different underlying event rates.
Incidence rate and person-years
The registered incidence-rate endpoint was defined as the number of HIV-1 infections divided by the amount of person-years of follow-up to HIV-1 infection status, multiplied by 100. The resulting unit was cases per 100 person-years.
This construction accounts for differences in the amount of follow-up contributed by participants. It is therefore different from simply dividing the number of infections by the number of randomized participants.
Fisher exact test
The primary safety analysis used a two-sided Fisher exact test. The analysis population was all randomized participants under an intention-to-treat definition, and the registered comparison was oral TDF-FTC versus oral placebo.
Intention-to-treat analysis
For the primary safety analysis, the registry explicitly identifies an intention-to-treat population consisting of all randomized participants. For the HIV incidence analyses, the registry defines the analysis population as all randomized participants except those with no follow-up HIV testing or those determined to be HIV-positive at randomization by PCR testing of stored enrollment plasma.
6. Planned Statistical Framework
The registry's formal analyses show a coherent time-to-event framework for the HIV incidence endpoints: participants contribute follow-up time until HIV infection or their last HIV-negative follow-up assessment, and the active-versus-placebo comparisons are estimated using site-stratified Cox proportional-hazards models.
Why use person-years?
Participants can contribute different amounts of observation time. Person-years incorporate the time actually contributed before HIV infection or the end of observed HIV-negative follow-up.
Why use a Cox model?
The endpoint is inherently time-dependent: the analysis uses not only whether HIV infection occurred but also when infection occurred relative to follow-up.
Why stratify by site?
The registered model was stratified by site, allowing the underlying hazard structure to differ by site without requiring a single common baseline hazard.
Why Fisher exact?
The registry specifies a two-sided Fisher exact test for the binary safety comparison. Fisher's exact test evaluates the association between treatment group and the observed categorical safety outcome without relying on the large-sample approximation used by a conventional chi-square test.
7. Primary Results: Tenofovir 1% Gel
The primary incidence-rate comparison for tenofovir 1% vaginal gel versus placebo gel used a site-stratified Cox proportional-hazards model. The reported effect measure was a hazard ratio.
HIV-1 infection incidence: TFV Gel vs Placebo Gel
95% CI: 0.61–1.21 · P = 0.37
Outcome unit: cases per 100 person-years · Follow-up: for up to 30 months
The estimated hazard ratio of 0.85 means that, under the fitted Cox model, the estimated instantaneous rate of HIV-1 infection in the TFV gel group was 85% of that in the placebo-gel group. Expressed as a relative quantity, HR 0.85 corresponds to an estimated hazard that is 15% lower than the comparator hazard.
This does not mean that 15% of participants were protected, that HIV infection was reduced by exactly 15% for every individual, or that the absolute number of infections was 15% lower. The hazard ratio is a model-based relative measure of the event rate over follow-up.
The 95% confidence interval, 0.61–1.21, spans 1.00. Thus the data are compatible with a range of relative effects that includes both a lower and a higher estimated hazard than placebo. The interval describes statistical uncertainty around the estimated hazard ratio; it is not a range within which individual treatment effects must fall.
The P = 0.37 value measures the strength of evidence against the specified null hypothesis under the statistical testing framework. It does not measure the magnitude of the effect, the probability that the treatment works, or the clinical importance of HR 0.85.
The registry states that the null hypothesis was that the active product would be no more than 25% effective. The Cox model was stratified by site. Interpretation also depends on the model's proportional-hazards assumption and on censoring and the defined analysis population.
8. Primary Results: Oral TDF
The oral TDF versus oral placebo comparison was also analyzed using a site-stratified Cox proportional-hazards model.
HIV-1 infection incidence: Oral TDF vs Oral Placebo
95% CI: 0.97–2.29 · P = 0.07
Outcome unit: cases per 100 person-years · Follow-up: for up to 30 months
The estimated hazard ratio of 1.49 means that, under the fitted Cox model, the estimated instantaneous rate of HIV-1 infection in the oral TDF group was 1.49 times the estimated rate in the oral placebo group. In relative terms, this corresponds to a 49% higher estimated hazard.
That estimate should not be read as a 49% increase in the number of participants who became infected, because the hazard ratio is not a simple risk ratio. It incorporates the time-to-event structure and the censoring framework of the analysis.
The 95% confidence interval is 0.97–2.29. Because the interval includes 1, the estimated effect is statistically compatible with equal hazards as well as with a range of lower or higher hazards. The width of the interval also shows that the estimate is not highly precise.
The P = 0.07 value does not quantify the size or clinical importance of HR 1.49. It is a measure of evidence against the registered null hypothesis under the specified test. It should not be interpreted as a 7% probability that the null hypothesis is true.
The registry states that the oral TDF arm was discontinued for futility in September 2011. That design history is important when interpreting the final posted analysis because follow-up did not proceed identically across all trial arms.
9. Primary Results: Oral TDF-FTC
The oral TDF-FTC versus oral placebo incidence-rate comparison was analyzed using the same site-stratified Cox proportional-hazards framework.
HIV-1 infection incidence: Oral TDF-FTC vs Oral Placebo
95% CI: 0.73–1.49 · P = 0.81
Outcome unit: cases per 100 person-years · Follow-up: for up to 30 months
The estimated hazard ratio of 1.04 means that the estimated instantaneous rate of HIV-1 infection in the oral TDF-FTC group was 1.04 times the estimated rate in the oral placebo group under the fitted Cox model. This is close to 1 on the relative-hazard scale.
HR 1.04 does not mean that the two groups had identical individual outcomes. It is a summary estimate of the relative event rate produced by the specified survival model.
The 95% confidence interval of 0.73–1.49 includes 1 and extends on both sides of equal estimated hazard. Consequently, the interval allows for both a lower and a higher hazard relative to placebo. The interval is also sufficiently broad that the point estimate alone should not be treated as a precise description of the underlying treatment effect.
The P = 0.81 value is evidence from the specified statistical test, not a measure of effect size. A high P-value does not establish that the treatment and placebo are biologically identical; it indicates that the observed data do not provide strong evidence against the specified null hypothesis within this analysis.
The registry states that the TDF-FTC and oral placebo arms continued follow-up until the end of study in August 2012. As with the other Cox analyses, interpretation requires attention to censoring, the analysis population, site stratification, and the proportional-hazards assumption.
10. Primary Safety Result
The registered extended-safety endpoint evaluated the occurrence of Grade 2, 3, and 4 adverse events throughout the study, up to 2.5 years. The registry describes elevated serum creatinine levels as the only safety outcome of concern where a significant difference was detected between an active arm and its corresponding placebo arm.
Extended safety: Oral TDF-FTC vs Oral Placebo
Two-sided Fisher exact test · Intention-to-treat population
Time frame: throughout study, up to 2.5 years
The registry reports a two-sided Fisher exact test P-value of 0.004 for the registered safety comparison. Fisher's exact test evaluates the evidence for an association between randomized treatment group and the categorical safety outcome under the specified analysis.
The P-value does not tell us how large the safety difference was. No effect estimate or confidence interval for this safety comparison is provided in the ClinicalTrials.gov record, so the magnitude and precision of the difference should not be inferred from P = 0.004 alone.
The analysis population was all randomized participants under an intention-to-treat definition. The endpoint was defined around Grade 2, 3, and 4 adverse events, with elevated serum creatinine identified by the registry as the safety outcome of concern for which a significant difference was detected.
11. Serious Adverse Events by Arm
The ClinicalTrials.gov record reports serious adverse events as affected participants divided by participants at risk for each arm. These are descriptive safety counts and should not be substituted for the formal Fisher exact analysis of the registered extended-safety endpoint.
| Arm | Serious adverse events | Affected / at risk |
|---|---|---|
| Oral TDF | Serious adverse events | 17 / 1007 |
| Oral TDF-FTC | Serious adverse events | 42 / 1003 |
| Oral Placebo | Serious adverse events | 57 / 1009 |
| TFV Gel | Serious adverse events | 39 / 1007 |
| Gel Placebo | Serious adverse events | 26 / 1003 |
The denominators shown above are the registry-reported affected/at-risk values. The registry data do not provide a separate effect estimate or confidence interval for these serious-adverse-event counts. They therefore provide a descriptive view of safety rather than a complete inferential comparison.
12. Why the Hazard Ratio Is the Central Efficacy Measure
For VOICE's formal HIV incidence comparisons, the registry reports a hazard ratio rather than a simple proportion infected. This reflects the fact that participants were followed over time and could contribute different amounts of person-years before HIV infection or the end of observed HIV-negative follow-up.
| Comparison | Hazard ratio | 95% CI | P-value |
|---|---|---|---|
| TFV Gel vs Placebo Gel | 0.85 | 0.61–1.21 | 0.37 |
| Oral TDF vs Oral Placebo | 1.49 | 0.97–2.29 | 0.07 |
| Oral TDF-FTC vs Oral Placebo | 1.04 | 0.73–1.49 | 0.81 |
The three estimates illustrate why the confidence interval is essential. The point estimates range from below 1 to above 1, while every registry-reported 95% confidence interval includes 1. A point estimate alone therefore provides an incomplete description of the evidence.
13. Statistical Methods Explained
Why was a Cox proportional-hazards model used?
The primary HIV incidence endpoint is time-to-event in structure. Participants were observed from enrollment until HIV infection or their last HIV-negative follow-up assessment. A Cox model is designed to compare event hazards while accommodating censored follow-up.
What does a hazard ratio of 0.85 mean?
For the TFV gel comparison, HR 0.85 means the fitted model estimated the instantaneous HIV-1 infection rate in the TFV gel group at 85% of the estimated rate in the placebo-gel group. It is a relative hazard measure, not an absolute risk reduction and not a statement about the outcome of every participant.
Why is a hazard ratio above 1 possible in a prevention trial?
A hazard ratio is estimated from observed event timing. An estimate above 1 means that the observed data produced a higher estimated event hazard in the active-product group than in the comparator group. For oral TDF, the registry-reported estimate was HR 1.49. This point estimate must be considered together with its 95% confidence interval of 0.97–2.29.
Why was the Cox model stratified by site?
The registry specifies site stratification. A stratified Cox model permits different baseline hazard functions across the strata while estimating the treatment comparison using the available within-stratum information. The result is a treatment-effect model that does not require all sites to share exactly the same underlying baseline hazard.
Why does person-years matter?
Two groups can have the same number of participants but different total amounts of observed follow-up. Person-years captures the amount of observation time contributed by participants. The registry's incidence rate uses infections divided by person-years and expresses the result per 100 person-years.
Why does P = 0.37 not mean that the treatment has a 37% chance of working?
A P-value is calculated under a specified null hypothesis and testing framework. It quantifies how unusual the observed data, or more extreme data, would be under that framework. It is not the probability that the treatment works, the probability that the null hypothesis is true, or a measure of the magnitude of the hazard ratio.
Why is the safety analysis different from the HIV incidence analysis?
The registry reports a Cox proportional-hazards model for the formal HIV incidence-rate comparisons but a two-sided Fisher exact test for the registered extended-safety comparison. The former uses time-to-event information; the latter evaluates a categorical safety outcome using the observed treatment-group counts.
14. Non-Inferiority, Superiority, and the Registered Null Hypothesis
The statistical-analysis records classify the primary HIV comparisons as superiority hypotheses. The registry analysis notes specify that the null hypothesis was that the active product would be no more than 25% effective.
The registry analysis notes state that the trial was designed so that 94 events per pairwise comparison were needed to detect 55% effectiveness while ruling out a lower effectiveness of 25% with 90% power and a false-positive error rate of 0.0025.
These are design assumptions and targets, not descriptions of the observed treatment effects. A power calculation specifies what the trial was designed to detect under stated assumptions; it does not establish that the assumed effect occurred.
15. Futility Discontinuations and Their Statistical Importance
Oral TDF arm discontinued
The registry states that the oral TDF arm was discontinued for futility.
TFV gel and gel placebo discontinued
The registry states that the TFV gel and gel placebo arms were discontinued for futility.
Study completion
The TDF-FTC and oral placebo arms continued follow-up until the end of study in August 2012.
Futility discontinuation is statistically important because follow-up duration and information accumulation are not necessarily the same across all randomized comparisons. It also means that a final posted estimate should be interpreted in the context of the actual observation period and the prespecified or registry-described stopping framework.
16. Censoring and Time-to-Event Interpretation
For the HIV endpoints, participants contributed person-time until the first HIV-positive test result if infected or until the last HIV-negative follow-up test if not infected. This creates a natural right-censoring structure for participants who remained HIV-negative through their last observed assessment.
Event
The event was HIV-1 infection, assessed through monthly testing with confirmatory EIA and Western blotting after positive rapid-test results.
Censoring
Participants who remained HIV-negative contributed follow-up through their last HIV-negative test rather than being treated as if they had experienced an HIV event.
Person-time
Follow-up time was accumulated from enrollment to HIV infection or the last HIV-negative follow-up result.
Model
The formal incidence-rate comparison used a Cox proportional-hazards model stratified by site.
17. Interpreting the Confidence Intervals
Confidence intervals are particularly informative for this trial because the three primary HIV hazard-ratio estimates have different point estimates but all have intervals that include 1.
| Comparison | Estimate | 95% CI | What the interval communicates |
|---|---|---|---|
| TFV Gel vs Placebo Gel | 0.85 | 0.61–1.21 | Uncertainty includes both lower and higher estimated hazards than placebo. |
| Oral TDF vs Oral Placebo | 1.49 | 0.97–2.29 | Uncertainty includes equal hazard and extends toward higher estimated hazard. |
| Oral TDF-FTC vs Oral Placebo | 1.04 | 0.73–1.49 | Uncertainty includes equal hazard and both lower and higher estimated hazards. |
The interval is not a prediction interval for individual participants. It describes uncertainty around the estimated population-level treatment effect under the specified statistical model and confidence-interval construction.
18. Multiplicity and Multiple Primary Comparisons
The registry lists three formal HIV incidence-rate comparisons: TFV gel versus placebo gel, oral TDF versus oral placebo, and oral TDF-FTC versus oral placebo. The registry-reported design notes state a false-positive error rate of 0.0025 for the event-based pairwise comparison design.
Because multiple active-product comparisons were part of the trial, interpretation of individual P-values requires attention to the trial's prespecified error-control framework rather than treating each P-value as if it arose from an isolated experiment. The ClinicalTrials.gov record does not provide a complete multiplicity-adjustment table or a separate alpha allocation for every posted endpoint.
19. Safety Analysis and Fisher Exact Testing
The extended-safety endpoint was defined as the occurrence of Grade 2, 3, and 4 adverse events throughout the study, up to 2.5 years. The registry states that this measure describes the number of participants with elevated serum creatinine levels, identified as the only safety outcome of concern where a significant difference was detected between an active arm and its corresponding placebo arm.
Fisher's exact test evaluates the observed categorical treatment-by-outcome table without requiring the same large-sample approximation as a chi-square procedure. In this trial, the registry specifies a two-sided test for the oral TDF-FTC versus oral placebo comparison.
The reported P = 0.004 indicates statistical evidence against the null hypothesis used for that Fisher exact test. It does not provide the size of the difference. Because the registry-reported statistical analysis does not report a risk ratio, odds ratio, risk difference, or confidence interval for this safety result, no magnitude of effect should be inferred from the P-value alone.
20. Analysis Populations
| Analysis | Population specified in the registry |
|---|---|
| TFV Gel vs Placebo Gel incidence rate | All randomized participants except those with no follow-up HIV testing or those determined HIV-positive at randomization by PCR testing of stored enrollment plasma. |
| Oral TDF vs Oral Placebo incidence rate | All randomized participants except those with no follow-up HIV testing or those determined HIV-positive at randomization by PCR testing of stored enrollment plasma. |
| Oral TDF-FTC vs Oral Placebo incidence rate | All randomized participants except those with no follow-up HIV testing or those determined HIV-positive at randomization by PCR testing of stored enrollment plasma. |
| Extended safety | All randomized participants; intention-to-treat analysis. |
The distinction is important. The registry explicitly calls the safety population intention-to-treat, while the HIV incidence analyses apply specific exclusions related to follow-up HIV testing and HIV status at randomization.
21. What These Results Do — and Do Not — Establish
What the hazard ratio describes
A relative comparison of the estimated instantaneous HIV-1 infection rate between an active product and its corresponding placebo under the Cox model.
What it does not describe
It is not an individual-level probability, an absolute risk difference, or a percentage of participants who benefited.
What the confidence interval describes
Uncertainty around the estimated treatment effect under the statistical model and confidence-interval framework.
What the P-value describes
Evidence against the specified null hypothesis under the testing framework; it is not an effect-size measure.
22. Important Limitations and Interpretation Issues
- Futility discontinuations: the oral TDF arm was discontinued in September 2011, while the TFV gel and gel placebo arms were discontinued in November 2011. The TDF-FTC and oral placebo arms continued until August 2012.
- Unequal follow-up histories: discontinuation of individual arms affects the amount and timing of information available for their corresponding comparisons.
- Confidence-interval width: each reported primary HIV hazard-ratio interval includes 1, so the point estimate should not be interpreted without the accompanying uncertainty interval.
- Proportional-hazards assumption: the Cox model summarizes relative hazard under its model assumptions. A single HR is most naturally interpreted when the proportional-hazards structure is a reasonable representation of the data.
- Censoring: HIV-negative participants contribute information only through their last observed HIV-negative follow-up, making the handling and assumptions surrounding censoring part of the time-to-event interpretation.
- Analysis-population exclusions: the formal HIV analyses exclude randomized participants with no follow-up HIV testing and participants determined to be HIV-positive at randomization by the specified PCR testing.
- Multiplicity: the trial included multiple pairwise HIV incidence comparisons. The registry-reported design notes specify a false-positive error rate of 0.0025 for the pairwise event target, but the complete endpoint-level multiplicity framework is not provided in the ClinicalTrials.gov record.
- Safety magnitude: the Fisher exact safety analysis reports P = 0.004 but no corresponding effect estimate or confidence interval in the ClinicalTrials.gov record.
- Descriptive serious adverse events: serious adverse-event counts by arm are provided as affected/at-risk values, but these counts do not by themselves constitute the formal registered safety comparison.
23. Why This Trial Matters Statistically
VOICE is a useful statistical teaching case because it combines randomized prevention research, multiple active-versus-placebo comparisons, person-time measurement, time-to-event modeling, site stratification, exact categorical testing, and futility discontinuations within one trial.
| Concept | How it appears in VOICE |
|---|---|
| Randomization | Participants were randomized in a five-arm parallel phase 2 prevention trial. |
| Time-to-event endpoint | HIV-1 infection was evaluated over follow-up of up to 30 months. |
| Person-years | Follow-up time was accumulated to HIV infection or the last HIV-negative test. |
| Hazard ratio | Used for the three formal HIV incidence-rate comparisons. |
| Cox model | The registry reports regression using a Cox proportional-hazards model. |
| Stratified analysis | The Cox model was stratified by site. |
| Confidence interval | Each of the three reported HIV hazard ratios has a two-sided 95% confidence interval. |
| P-value | Reported for all four posted statistical analyses. |
| Fisher exact test | Used for the two-sided primary safety comparison. |
| Intention-to-treat | Explicitly specified for the extended-safety analysis. |
| Futility | Individual study arms were discontinued for futility during follow-up. |
| Multiple comparisons | Three active-product versus placebo HIV incidence comparisons were formally analyzed. |
24. Related Tutorials
Learn more about the methods used in this trial:
25. Related Statistical Calculators
26. Sources
- ClinicalTrials.gov: NCT00705679.
- Linked publication record: PubMed PMID 28178109.
- Linked publication record: PubMed PMID 27146827.
- Linked publication record: PubMed PMID 26850270.
- Linked publication record: PubMed PMID 26155597.
- Linked publication record: PubMed PMID 26123563.
Continue through the Clinical Biostats statistical library
Explore the statistical concepts behind randomized prevention trials, time-to-event endpoints, categorical safety analyses, and treatment-effect estimation.
27. Record Summary
VOICE provides a useful example of how a randomized prevention trial can combine person-years of follow-up, time-to-event analysis, site-stratified Cox regression, hazard ratios, confidence intervals, and Fisher exact testing. The three reported HIV incidence comparisons produced hazard ratios of 0.85, 1.49, and 1.04, respectively, with two-sided 95% confidence intervals of 0.61–1.21, 0.97–2.29, and 0.73–1.49. The extended-safety analysis reported a two-sided Fisher exact P-value of 0.004. Interpretation of these results requires attention to the confidence intervals, the registered hypotheses, the analysis populations, the site-stratified Cox model, censoring, multiple comparisons, and the futility discontinuations that occurred during the trial.