Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US) (NCT04001803), a na phase 3 study. The primary outcome is Change From Baseline in the Acceptability of Intervention Measure (AIM) Total Score in Staff Study Participants at Month 4.

2. Clinical Question

3. Trial Design

NCT04001803 is a completed, Phase 3, single-group, open-label, multicenter study in the United States. The registry lists enrollment of 115. The study began on 2019-07-08 and its primary completion date was 2020-10-05. The brief summary describes an approximate study duration of 52-weeks and says approximately 135 subjects would be enrolled; that planned approximate enrollment differs from the registry’s recorded enrollment. The record does not explain the difference.

The study was designed as a qualitative Hybrid III implementation study to identify and evaluate strategies for implementing cabotegravir plus rilpivirine long-acting injections. The brief summary characterizes it as a short-term facilitation study. Its stated focus includes acceptability, appropriateness, feasibility, fidelity, and sustainability of clinical practices, along with subject satisfaction and visit-related measures. The listed intervention is CAB LA+RPV LA. The registry describes one arm of HIV-infected subjects receiving that regimen.

Allocation is listed as not applicable, masking as none, and the model as single group. These features mean the record does not support a randomized comparison between separate treatment groups. The primary outcome is not a measure of comparative clinical efficacy: it is staff participants’ change from baseline in AIM total score at Month 4. The registry identifies the staff population as HIV care providers, nurses or staff performing injections, and administrators or clinic managers at investigational sites.

Although the record marks the study completed, completion status alone does not establish that every planned measure has a posted result. No numerical primary endpoint result or analysis details are reported in the registry record. The record also does not report the planned sample-size justification, the detailed implementation strategy, or whether any interim analyses occurred.

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: Study staff participants only provided input through the completion of surveys, semi-structured interviews and facilitation calls. Participant flow, Baseline characteristics or adverse events for study staff participants were not collected because it was not required per study design.

Intervention Phase (Up to Month 12)

Reasons for not completing this period:

Extension Phase (From Months 13 to 30)

Reasons for not completing this period:

Long-term Follow-up Phase(Up to Week 52)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Staff study participants Population comprised of HIV care providers (HCPs), nurses/staff performing CAB+RPV LA injections and administrators/clinic managers at each investigational site.

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: Baseline characteristics were reported for Safety Population(comprised of all participants enrolled,who received atleast 1 dose of CAB LA+RPV LA).Study staff participants only provided input through completion of surveys,semi-structured interviews,facilitation calls and didn't have to complete the informed consent process and did not receive oral lead-in medication or CAB+RPV LA injections. Demographics for study staff participants were not collected because it was not required per study design

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the Acceptability of Intervention Measure (AIM) Total Score in Staff Study Participants at Month 4, measured over Baseline and Month 4.

The primary endpoint is change from baseline in staff study participants’ AIM total score at Month 4. AIM is a four-item survey about the acceptability of an implementation process. Staff participants indicated agreement or disagreement with each item on a five point rating scale, ranging from 1 for completely disagree to 5 for completely agree. The total score ranges from 1 to 5, with higher values indicating greater acceptability.

The endpoint is calculated as the post-dose value minus the baseline value. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including an assessment at an unscheduled visit. Thus, the endpoint is intended to describe change in staff-reported acceptability during implementation, not change in HIV status, symptoms, or another clinical outcome. A positive change would represent a higher score after baseline on this scale, while a negative change would represent a lower score; the registry record does not report the observed change.

Implementation research uses measures such as acceptability to characterize how a practice is experienced by the people responsible for delivering it. Such a measure can complement clinical outcomes, but it answers a different question: staff ratings do not by themselves establish whether an implementation strategy was feasible, sustained, or effective, nor whether the regimen improved clinical outcomes. The registry record does not report the primary endpoint’s numerical estimate or its uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean, with standard deviation as its dispersion measure. For a continuous measure such as AIM total score, a mean summarizes the average score or average change in a group. A standard deviation describes how spread out individual scores or changes are around that mean. It does not, by itself, describe how precisely the mean has been estimated. A confidence interval is commonly used to express uncertainty around an estimate; no confidence interval for the primary endpoint is reported in the registry record.

What does the change score represent?

The change score is defined as the post-dose score minus baseline. Because the endpoint is expressed as a difference between two measurements, its interpretation depends on the direction of subtraction and the scale meaning. Here, a higher AIM score represents greater acceptability, so an increase in the score corresponds to higher reported acceptability relative to baseline. The scale ranges from 1 to 5. No average change or distribution of individual changes is reported, so that interpretation remains a guide to reading the measure rather than a description of observed findings.

The baseline rule uses the latest pre-treatment assessment with a non-missing value, including unscheduled visits. That rule specifies which measurement counts as baseline when more than one pre-treatment assessment may be available. It does not tell readers how many participants had a usable baseline and Month 4 score, how missing follow-up measurements were handled, or what analysis population was used. Those details are not reported in the registry record.

Why does the single-group design matter?

A single-group study can describe outcomes among participants receiving the studied regimen and participating in the implementation approach. It does not create a randomized contrast with another group. In general, a within-group change can reflect the intervention, changes in practice over time, participant or staff characteristics, or other conditions that coincide with follow-up. A randomized comparison can help distinguish an intervention contrast from such influences; this record lists no randomized allocation and no separate control arm. The study’s implementation focus is distinct from estimating a comparative clinical treatment effect.

The study is open-label. In general, when participants and staff know the intervention being delivered, reports about its acceptability may reflect their experience of the intervention and the implementation process, but also expectations or context. This does not invalidate a staff-reported implementation measure; it defines the kind of outcome being measured and the limits on causal interpretation.

What do precision and over-dispersion mean?

Precision concerns how much uncertainty surrounds an estimate. A mean based on observations that vary widely may be less precisely estimated than a mean based on observations that are more alike, all else being equal. A confidence interval conveys a range of values compatible with the estimate and its statistical uncertainty under the analysis assumptions. A standard deviation describes observed variability, whereas a confidence interval describes uncertainty in an estimated quantity. Neither a primary estimate nor its interval is reported for this outcome.

Over-dispersion is a general concern when a statistical model expects less variability than the data actually contain. In that setting, standard errors may be too small and uncertainty may be understated unless the analysis accounts for the extra variation. This concern can arise in analyses of counts or clustered data, for example, but the registry record does not report a model for the primary outcome, a dispersion assessment, or an adjustment for over-dispersion. It would therefore be inappropriate to infer that such an approach was used.

How should planning calculations be read?

Sample-size calculations are planning illustrations, not observed study results. The registry’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated convention concerns total events; for other outcomes, it concerns participants per arm. These are generic assumptions for the planning illustration and do not describe this study’s single-group design as a two-arm randomized trial.

The record does not report the study’s own sample-size justification. Any planning illustration based on an observed effect should not be read as evidence that the study had a particular probability of detecting an effect, nor as a substitute for a reported result and its uncertainty. Sample-size planning addresses the design assumptions used to size a study; it does not reveal what the study found.

The registry also does not report the statistical model, estimator details, confidence-interval method, hypothesis test, or handling of site-level clustering for the primary endpoint. Since staff participants were associated with investigational sites, analyses could in general need to consider whether observations within a site are correlated. The record does not say whether that issue was assessed or how it was addressed. No statistical method beyond the outcome’s mean and standard deviation description should be inferred.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Staff Study Participants")
n   <- c(24)
m   <- c(0)
sp  <- c(0.42)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Staff Study Participants  24  0.000  0.420  -0.177  0.177

11. Multiplicity, Missing Data and Analysis Populations

The record lists 94 outcome measures and records 0 analyses. It does not report a multiplicity strategy, such as whether the primary outcome was tested separately from secondary outcomes, whether the secondary analyses were exploratory, or whether any adjustment was made for multiple comparisons. When many outcomes are examined, the chance of at least one apparently unusual result can increase; methods for addressing this depend on the analysis plan and aims. The registry record does not say which approach was used.

Missing-data handling is also not reported. The primary endpoint definition specifies how baseline is selected when a non-missing pre-treatment assessment is available, but it does not describe what happens when baseline or Month 4 is missing. There is no reported account of imputation, complete-case analysis, sensitivity analyses, or the number of staff participants with paired measurements. The analyzed population and any exclusions from the analysis are not reported in the registry record.

The registry identifies staff as the primary endpoint population and describes their roles, but does not state whether the primary analysis included all enrolled staff, only staff with complete measurements, or another defined group. No interim analysis plan is reported. These omissions limit evaluation of the analysis population, vulnerability to missing data, and how multiplicity may have affected interpretation. They do not establish that any particular method was or was not used outside what the record reports.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: mental status changes (1.7%), chest pain (1.7%), abscess limb (0.9%), acute respiratory failure (0.9%), diabetic ketoacidosis (0.9%).

For participants with HIV infection, the registry records 9 participants with serious adverse events among 115 at risk, 101 participants with other adverse events among 115 at risk, and 1 death. These are descriptive counts for the study group. They are not comparative risk estimates because the record describes a single group and no like-for-like control arm.

The listed serious-event terms and percentages are mental status changes, 1.7%; chest pain, 1.7%; abscess limb, 0.9%; acute respiratory failure, 0.9%; diabetic ketoacidosis, 0.9%; and drug abuse, 0.9%. The registry record does not provide a causal attribution for these terms. The percentages should not be interpreted as proof that the regimen caused an event, and the term list alone does not describe the clinical context or severity beyond the serious-event classification.

Safety counts and the primary implementation outcome answer different questions. The serious-event figures concern reported adverse events among participants with HIV infection, whereas the primary endpoint concerns staff ratings of implementation acceptability. The record does not provide a comparative safety analysis or detailed event-level narratives, so the counts should be read as descriptive reporting rather than evidence of comparative safety.

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

The study’s primary question concerns implementation: whether staff participants’ ratings of the acceptability of the injectable regimen’s implementation process changed from baseline to Month 4. That is a relevant implementation outcome because staff experience can inform how a clinical practice is received by people involved in delivering it. The score is not a measure of virologic response, resistance, adherence, or treatment satisfaction among participants with HIV.

The registry record does not report the numerical primary outcome result. It therefore cannot establish whether staff acceptability changed, the size of any change, or the uncertainty around an estimate. It also does not provide numerical results for the listed secondary implementation and participant experience measures. A completed study record and an outcome definition are not evidence of a particular result.

The single-group design also limits what a change over time could mean. If a within-group change had been reported, it would not alone identify the effect of the implementation strategy compared with another approach. The record includes no randomized control group. The study can be understood as an evaluation of implementation experience in participating settings, not as a randomized estimate of comparative clinical effectiveness.

The safety counts offer descriptive information for the study group, including reported serious and other adverse events and a death. Without a control group, event attribution, or a comparative analysis, those counts do not establish whether the regimen increased or decreased risk relative to another option. Likewise, the study’s stated motivations and potential advantages in the brief summary are background rationale, not results demonstrated by this record.

In short, the record explains what the study sought to assess and how the primary scale was defined. It does not report the outcome data needed to judge the observed change or its precision. Claims about acceptability, implementation success, clinical benefit, or comparative safety would go beyond the results recorded.

14. Why This Trial Matters Statistically

This study illustrates why implementation outcomes should be distinguished from clinical endpoints. A regimen may be examined not only for clinical outcomes but also for whether the practices needed to deliver it are acceptable, appropriate, feasible, faithful to the intended approach, and sustainable. The registry identifies these implementation domains and sets the primary endpoint around staff-rated acceptability. That endpoint addresses a question about the delivery process and staff experience rather than a direct clinical effect.

The design also matters for statistical interpretation. With a single group and no randomized allocation, the study does not estimate a randomized contrast between implementation strategies or treatment regimens. Its central focus is implementation in participating settings. Readers should therefore look for a clear description of the population assessed, the outcome definition, missing-data handling, and the analysis approach when interpreting any reported change.

The registry’s primary outcome definition is informative: it specifies a four-item scale, its direction, its range, the assessment time point, and the baseline rule. Yet the record does not report the numerical primary result or its uncertainty. Without those elements, the definition alone cannot establish whether acceptability changed or how precisely it was estimated.

The record further shows the importance of separating planned outcomes from analyzed findings. It lists numerous outcome measures but records no analyses, and it does not include numerical results for the primary endpoint. This distinction helps prevent intended measurements, study completion, or background expectations from being mistaken for evidence about observed outcomes.

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 record constrain interpretation. The most important is that the numerical result for the primary endpoint is not reported in the registry record. There is no mean change, standard deviation, confidence interval, or test result with which to assess direction, magnitude, or precision. Numerical results for the listed secondary implementation measures are likewise not reported in the record.

The design is single-group, open-label, and has no randomized comparison. As a result, the record does not provide a concurrent comparator for interpreting change over time. It also cannot separate a change associated with the implementation strategy from other influences that may have occurred during the study. The study’s stated implementation aims should not be treated as evidence of comparative treatment efficacy.

The primary endpoint is staff-reported acceptability, and the registry does not report the number of staff participants with usable measurements at baseline and Month 4. The analysis population, missing-data approach, statistical model, and handling of potential site-level correlation are not reported in the registry record. The multiplicity approach and any interim analysis plan are also not reported.

The brief summary describes approximate planned enrollment of 135 subjects, while the registry lists enrollment of 115. The record does not explain the difference. Although the study is marked completed, that status does not resolve missing outcome or analysis details. Safety reporting is descriptive and lacks a comparator and causal attribution in the record. These limitations should shape conclusions drawn from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Identify and Determine Best Implementation Practices for Injectable Cabotegravir+Rilpivirine in the United States (US) — NCT04001803.
• Registry record last updated 2023-04-14; status last verified 2023-03.
• Results first posted 2022-01-10.
• 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

NCT04001803 is a completed, Phase 3, multicenter, single-group, open-label implementation study in the United States of long-acting cabotegravir plus rilpivirine. The registry records enrollment of 115, with a primary completion date of 2020-10-05. The primary endpoint is change from baseline to Month 4 in staff participants’ AIM total score, a measure of implementation acceptability ranging from 1 to 5.

The study also lists secondary measures concerning toolkit helpfulness, implementation barriers and facilitators, and participant experience. The registry record does not report a numerical primary endpoint result, the statistical analysis details, or a missing-data strategy. Safety figures include 9 participants with serious adverse events, 101 with other adverse events, and 1 death among 115 participants with HIV infection. These are descriptive counts from a single-group study, not comparative estimates.