Expedited Partner Therapy and the HIV Prevention Cascade: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Expedited Partner Therapy and the HIV Prevention Cascade (NCT04553211), a randomized na study. The primary outcome is Number of Participants Who Reported Any Partner Notification.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group trial with no masking. Its title is “Expedited Partner Therapy and the HIV Prevention Cascade,” and the official title specifies MSM in Peru. The listed sponsor is the University of California, Los Angeles. The record lists enrollment as 663 and the study status as completed. The start date is 2022-04-25, and primary completion is listed as 2024-04-30. Phase is recorded as NA.

The intervention was behavioral. In the EPT arm, participants were offered up to five partner antibiotic treatment packets to deliver to recent sexual partners after a diagnosis of gonorrhea and/or chlamydia; the intervention description says it was repeated after subsequent episodes. The control arm received standard-of-care counseling on partner notification after diagnosis, repeated during the 12-month follow-up period. The registry does not report further detail about how counseling or packet delivery was implemented.

For the primary result, the posted endpoint counts are 233.0 of 272.0 participants in the EPT arm and 189.0 of 271.0 participants in the control arm. These are the denominators used for the primary endpoint, rather than the overall enrollment figure. Participant flow explaining the endpoint denominators is not reported in the registry record. Random allocation supports a comparative design, but allocation procedures, stratification, concealment, and analysis populations 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.

Before assignment: No significant events that occurred between the enrollment and assignment of participants to an arm or group.

Overall Study

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: Data on Baseline characteristics not collected for sexual partners (n=107).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Reported Any Partner Notification, measured over 21 Days.

The primary endpoint counts participants who self-reported notifying one or more sexual partners at 21 Days. It is a participant-level binary outcome: a participant is counted if they report any partner notification, regardless of the number of partners notified. The registry defines the measure as the number of participants reporting notification at follow-up.

This endpoint is relevant to the intervention’s immediate partner-management goal. EPT provides treatment packets for participants to pass to recent partners, while control participants receive partner-notification counseling. A measure of whether participants report notifying any partner therefore captures a behavior the intervention is intended to address. It does not, by itself, establish whether a partner received a notification, took treatment, or completed HIV/STI testing. Those distinctions matter because participant report and partner confirmation are separate outcomes in the registry.

The short follow-up specified for this endpoint also defines what the result can address: reported notification at 21 Days. It is not a direct measure of later reinfection, sustained partner treatment, or HIV prevention. Whether the registry planned additional validation of self-reports is not reported in the registry record.

7. Results Posted in the Registry

• Expedited Partner Therapy: 85.7% (233/272) versus 69.7% (189/271) on control; risk difference 15.9 percentage points (95% CI 9.0 to 22.8), risk ratio 1.23 (1.12–1.35); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants Reporting Any Partner Treatment

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Expedited Partner Therapy (EPT): 49.3% (134/272) versus 29.5% (80/271) on control; risk difference 19.7 percentage points (95% CI 11.7 to 27.8), risk ratio 1.67 (1.34–2.08); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Expedited Partner Therapy (EPT) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Reporting Any Partner HIV/STI Testing

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Expedited Partner Therapy (EPT): 51.1% (139/272) versus 43.9% (119/271) on control; risk difference 7.2 percentage points (95% CI -1.2 to 15.6), risk ratio 1.16 (0.97–1.39); unadjusted two-proportion z-test p = 0.093.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Expedited Partner Therapy (EPT) and the control. The interval gives the range of effects that remain compatible with the data.

Number of Partners Who Confirmed Treatment

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Partners of Expedited Partner Therapy (EPT) Participants: 9.5% (6/63) versus 9.1% (4/44) on control; risk difference 0.4 percentage points (95% CI -10.7 to 11.6), risk ratio 1.05 (0.31–3.50); unadjusted two-proportion z-test p = 0.940.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Partners of Expedited Partner Therapy (EPT) Participants and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes span participant reports and partner confirmation, so they describe related but distinct parts of partner management. Taken together, the pattern is more supportive of separation between groups for participant-reported partner treatment than for partner testing or partner-confirmed treatment. This is broadly consistent with the primary endpoint’s focus on participants’ reported partner communication, but it does not make the secondary measures interchangeable with notification.

Participant reports can capture actions that partners may not independently verify, while partner-confirmed outcomes rely on confirmation being available and recorded. The confirmed-treatment comparison is based on a smaller set of partner observations than the participant-level outcomes and is correspondingly imprecise. A weak or uncertain comparison in partner confirmation does not negate the primary self-report result; it does mean the registry results do not establish that the reported behavior translated into confirmed partner actions.

The secondary comparisons are unadjusted, and the registry record does not report a multiplicity plan. When several outcomes are examined, the chance of at least one apparently notable result can increase if each is interpreted without accounting for the full set of tests. This makes secondary findings less definitive than a single prespecified primary outcome, particularly when analysis details are absent. They are best read as supporting context and as prompts for further study rather than as independent confirmation of the primary result. The secondary results also do not include a posted comparison for every secondary outcome named in the registry; partner-confirmed HIV/STI testing is not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants Reporting Any Partner Treatment
• Number of Participants Reporting Any Partner HIV/STI Testing
• Number of Partners Who Confirmed Treatment
• Number of Partners Who Confirmed HIV/STI Testing

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

A risk difference compares the proportion with an outcome in one group with the proportion in another group. For the primary endpoint, the groups are EPT and control, and the outcome is reporting any partner notification at 21 Days. The estimate of 0.159 is an absolute difference on the proportion scale. It is not a relative measure such as a risk ratio, and it does not indicate how many partners were notified. The endpoint counts are participant counts, with each participant classified according to whether they reported any notification.

How should the confidence interval be understood?

A confidence interval expresses uncertainty around an estimated effect. The primary interval runs from 0.090 to 0.228. Values within the interval are compatible with the posted estimate under the assumptions of the calculation; the interval is not a guarantee that the true effect lies within those endpoints. Because the interval does not include zero, the unadjusted comparison is consistent with a positive risk difference. The interval does not account for any analysis choices or sources of bias that are not included in the calculation.

What does the p-value indicate?

The primary unadjusted p-value is < 0.001. In general, a p-value describes how unusual an observed result, or a result more extreme, would be under a specified null model. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry does not report the test or model used in a sponsor analysis; no sponsor analysis is listed. The stated p-value should therefore be understood as an unadjusted comparison accompanying the posted summary data, not as a reported adjusted analysis.

Why distinguish unadjusted results from reported analyses?

An unadjusted comparison uses the group summaries without accounting for other variables. It can describe the observed difference between the reported groups, but it cannot show whether the estimate changes after accounting for baseline factors, site, or other covariates. Whether such factors were included in the trial’s planned analysis is not reported in the registry record. The posted comparison is useful as a direct summary of the arm-level counts, while details needed to assess any adjusted analysis are unavailable.

Why are the endpoints not interchangeable?

The primary outcome measures participants’ reports of notifying any partner. Other outcomes ask whether participants reported partner treatment or testing, and whether partners confirmed treatment or testing. These measures represent different steps and sources of information. A report of notification is not confirmation of treatment, and participant-reported partner behavior is not the same as a partner’s own confirmation. A difference in one outcome therefore does not automatically imply a similar difference in another.

What does over-dispersion mean, and does it apply?

In general, over-dispersion describes count data that vary more than a statistical model expects. It can matter when counts are analyzed using models that assume a particular relationship between their mean and variance; failure to account for extra variability can affect uncertainty estimates. The posted outcomes are counts of participants with an event, and the registry record does not report an over-dispersion assessment or model for them. No claim about over-dispersion is needed to interpret the posted binary endpoint counts.

What analysis details are missing?

The registry record lists no reported analyses. The statistical test, adjustment strategy, missing-data handling, and analysis population are not reported in the registry record. Randomization is recorded, but the available results do not explain whether the primary comparison followed an intention-to-treat approach or another population definition. These missing details limit assessment of how the posted comparison relates to the trial’s original statistical plan.

11. Confidence Intervals and Precision

The primary risk-difference estimate is 0.159, with a 95% confidence interval from 0.090 to 0.228. The interval indicates that the posted estimate is not exact: values across that range remain compatible with the unadjusted comparison. Its endpoints are both above zero, which aligns with the observed difference in the direction of more participants reporting notification in the EPT arm. The interval does not resolve possible bias, missingness, or analysis choices that are not described in the registry record.

Precision differs across outcomes. The partner HIV/STI testing risk-difference interval, from -0.012 to 0.156, includes zero. The partner-confirmed treatment interval, from -0.107 to 0.116, is also broad relative to its estimate. Those intervals indicate substantial uncertainty about the corresponding comparisons; they do not establish that the groups are equivalent. The outcomes also have different endpoint denominators, so their precision should be considered in the context of the specific measure and available observations.

A confidence interval is an estimate of sampling uncertainty under the method used to construct it, not a complete account of uncertainty. In particular, the registry record does not report how missing data, clustering of partners, or any planned adjustment was handled. The primary endpoint depends on participant self-report, and its interval does not measure the reliability of that reporting process. The displayed intervals therefore help quantify uncertainty in the simple posted comparisons, while leaving other sources of uncertainty unresolved.

12. 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.

The sample-size display gives planning illustrations in participants per arm for 80% and 90% power; it does not report total events. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The planning effect is set to the stated fraction of the observed effect: 100%, 75%, or 50%. These are planning calculations based on the observed effect, not the original trial’s design justification, which is not reported in the registry record.

In plain terms, the 80% power column gives an illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding illustration for a 90% chance. For example, planning for 100% of the observed primary effect gives 107 participants per arm for 80% power and 142 participants per arm for 90% power. Planning for 75% gives 202 and 269 participants per arm, respectively; planning for 50% gives 479 and 641 participants per arm.

Smaller effects are harder to distinguish from random variation, so the illustrations require more participants per arm as the planning effect becomes smaller. The curve visualizes this relationship under the same assumptions; it does not add evidence about the trial’s actual outcomes. These figures are not observed power. They are hypothetical planning illustrations and should not be read as a retrospective score of whether the completed trial had adequate power.

13. 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 z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.697; treatment proportion p₁ = 0.857; average p̄ = 0.777.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5887 = 1.1538.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5778 = 0.4863.
4. n = (1.1538 + 0.4863)² / (0.1592)² = 106.1, rounded up to 107 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
p0 <- 0.697416974169742                          # control proportion
p1 <- 0.856617647058823                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4553211)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 107 (80% power), 142 (90% power)
 75% of observed effect: n per arm = 202 (80% power), 269 (90% power)
 50% of observed effect: n per arm = 479 (80% power), 641 (90% power)
power.prop.test: 106.1 
Simulated power at n = 107 per arm: 0.812 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures overall, including the primary partner-notification endpoint and secondary outcomes concerning partner treatment and HIV/STI testing. Examining several outcomes creates a multiplicity issue: even if there were no underlying group differences, repeated statistical comparisons can make a nominally notable result more likely to appear by chance. In general, a prespecified strategy may control or otherwise address this issue, but the registry record does not report a multiplicity adjustment or a hierarchy for interpreting secondary outcomes. The posted secondary comparisons should therefore be treated as exploratory context rather than as a set of independently confirmatory findings.

The record does not report how missing data were handled, the number of participants with missing outcome information, or whether any imputation or sensitivity analysis was used. The primary endpoint denominators are 272.0 in EPT and 271.0 in control, while overall enrollment is listed as 663. Participant flow explaining these denominators is not reported in the registry record. It is therefore not possible to determine from the posted information why the endpoint denominators differ from the overall enrollment figure, or how missing observations may affect the estimates.

Although allocation is recorded as randomized, the analysis population is not reported in the registry record. It is not clear whether the results follow an intention-to-treat population, a per-protocol population, or another definition. The statistical model, any covariate adjustment, and handling of repeated episodes are also not reported. These omissions matter for interpreting the scope of the comparisons, especially because the intervention description refers to repeated episodes of gonorrhea and/or chlamydia while the primary outcome is a participant-level report at 21 Days.

15. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry reports serious adverse event counts of 0 among 299 at-risk participants in the EPT group and 0 among 287 at-risk participants in the control group. It also reports other adverse event counts of 0 in the same respective at-risk groups, and deaths are listed as 0 in each group. These figures describe what was recorded in the registry; they do not establish that no adverse events occurred outside the scope of reporting or observation.

The at-risk counts for the safety summaries differ from the primary endpoint denominators. The registry record does not explain the relationship between these populations or provide further detail on adverse-event collection, event definitions, or observation periods. No serious adverse event terms are listed. The zero counts should therefore be read as the posted safety results, with the limits of the registry’s reporting in mind, rather than as a complete characterization of all possible harms.

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

The posted primary result shows that a greater proportion of participants assigned to EPT reported notifying one or more partners at 21 Days than participants assigned to control. The unadjusted risk difference is 0.159, and its 95% confidence interval ranges from 0.090 to 0.228. This is a comparison of reported participant behavior within the trial and at the specified follow-up point.

That result does not establish that partners received the notification, completed treatment, or obtained HIV/STI testing. Nor does it measure subsequent infection or demonstrate an effect on HIV transmission. Those are different outcomes from the primary endpoint, and the registry’s partner-confirmation results are uncertain. The primary result also cannot by itself show why the groups differed or whether the same estimate would apply in other populations or settings.

The intervention and control descriptions concern partner management after a gonorrhea and/or chlamydia diagnosis. The posted endpoint is self-reported, and the registry record does not report validation of those reports, missing-data methods, an adjusted analysis, or a multiplicity strategy. These limitations do not change the recorded counts, but they affect how broadly the findings can be interpreted. A statistically notable unadjusted comparison should not be treated as proof of a complete prevention pathway or as a clinical recommendation.

In general, trial results are most useful when interpreted alongside the endpoint definition, study population, analysis methods, uncertainty, and safety reporting. In this trial, the primary data address reported notification among participants, while partner treatment, testing, and confirmation are separate outcomes. The conclusions supported by the posted results should remain specific to those measures and their reported follow-up periods.

17. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a behavioral step in partner management rather than a biological endpoint. The contrast between participant-reported notification and partner-confirmed treatment or testing illustrates why endpoint definitions matter: a favorable comparison for one step in a pathway does not automatically establish effects on later steps.

The randomized parallel design provides a direct framework for comparing the assigned groups, and the primary unadjusted risk-difference interval is entirely above zero. At the same time, the absence of reported analysis details makes it important to distinguish the arm-level comparison from a fully documented statistical analysis. Details about the analysis population, adjustment, missing data, and multiplicity would help readers judge the robustness and intended role of each result.

The results also show why precision should be evaluated outcome by outcome. Participant-level outcomes and partner-confirmation outcomes have different denominators and uncertainty. A point estimate alone can obscure how much uncertainty accompanies a comparison, while a nonsignificant result is not proof of equivalence. The registry’s separate reporting of partner-focused measures makes that distinction visible without collapsing the cascade into a single outcome.

Finally, the record demonstrates the value of transparent reporting alongside careful limits on interpretation. Enrollment, endpoint counts, follow-up timing, and safety figures provide useful context, while missing analysis and participant-flow details leave unresolved questions. For clinical researchers and biostatisticians, this makes the trial a useful example of reading a randomized comparison through its endpoint definition, precision, and reporting completeness rather than relying on a p-value alone.

18. 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 endpoint is self-reported partner notification, so it measures participants’ reports rather than independently verified notification. Its 21 Days timeframe captures a specific follow-up point and does not itself describe longer-term partner treatment or testing. Participant characteristics beyond the trial’s focus on MSM in Peru are not reported in the registry record, limiting assessment of how well the results apply to particular subgroups or other settings.

The registry lists enrollment as 663, while the primary endpoint counts use 272.0 participants in EPT and 271.0 in control. Participant flow and the reasons for these endpoint denominators are not reported in the registry record. The safety summaries use at-risk counts of 299 and 287, but the relationship between those counts and the endpoint populations is not explained. Missing-data handling and analysis populations are also not reported.

The trial is listed as having no masking. The registry does not describe whether outcome reporting was verified or whether assessment procedures could reduce the influence of participants’ knowledge of group assignment. No reported analysis details establish whether covariates, repeated infection episodes, or other design features were incorporated. The intervention description refers to repeated EPT after subsequent infections, while the primary outcome remains a participant-level report at 21 Days; how repeated episodes were handled analytically is not reported in the registry record.

Finally, several secondary outcomes are listed, but multiplicity procedures are not reported, and partner-confirmed HIV/STI testing is not reported in the registry record. These limitations affect confidence in broad conclusions about the full partner-management pathway, beyond the posted primary self-report comparison.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Expedited Partner Therapy and the HIV Prevention Cascade — NCT04553211.
• Registry record last updated 2026-09-01; status last verified 2026-08.
• Results first posted 2026-09-01.
• 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.

22. Record Summary

NCT04553211 is a completed randomized, parallel-group trial titled “Expedited Partner Therapy and the HIV Prevention Cascade,” with an official title specifying MSM in Peru. The registry lists enrollment of 663, no masking, and the University of California, Los Angeles as sponsor. EPT involved offering partner antibiotic treatment packets after gonorrhea and/or chlamydia diagnosis; control participants received partner-notification counseling.

The primary endpoint was the number of participants reporting any partner notification at 21 Days. The unadjusted risk difference was 0.159, with a 95% confidence interval from 0.090 to 0.228 and p < 0.001. Secondary outcomes covered partner treatment, testing, and partner confirmation, with less consistent and sometimes imprecise comparisons. The registry reports zero serious adverse events, other adverse events, and deaths in the posted safety groups. Analysis details, missing-data handling, and participant-flow explanations are not reported in the registry record.