Real-life Effectiveness of the Kaletra Adherence Support Assistance (KASA) Program: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Real-life Effectiveness of the Kaletra Adherence Support Assistance (KASA) Program (NCT01662336), a registered phase not stated study. The primary outcome is Percentage of Participants Adherent to Treatment at Month 6.

2. Clinical Question

The study's overall purpose was to describe real-life adherence, effectiveness and safety of KASA among people with HIV receiving lopinavir/ritonavir in Canada. Its primary endpoint was not a direct count of doses taken. It used a change in self-reported confidence about treatment-related activities and behaviors, with a participant classified as adherent when the score did not decline from baseline by month 6. Discontinuation or loss to follow-up was classified as non-adherence under the endpoint definition.

This question is descriptive. Because treatment and program participation were according to decisions made in routine care, the study is not described as assigning participants at random to KASA or to a control condition. The record therefore does not support interpreting a difference between groups as an effect caused by the program. The numerical primary endpoint result is not reported in the registry record, so the proportion meeting the definition and its precision cannot be assessed from the registry entry.

3. Trial Design

This was a prospective observational cohort study, titled Real-Life Effectiveness of the Kaletra Adherence Support Assistance (KASA) Program. The study concerned people with human immunodeficiency virus infection receiving lopinavir/ritonavir treatment in Canada. The registry lists an enrollment of 173 and a status of completed. The recorded study start was 2012-06, and primary completion was 2016-06.

The interventions listed were lopinavir/ritonavir and the Kaletra Adherence Support Assistance Program. The arm description states that care followed the standard of care at each study site, and that decisions about lopinavir/ritonavir treatment and KASA participation rested with the treating physician and participant. This is important to the design: the record describes observation of care decisions, not random allocation to treatments. Allocation is not stated, and the record cautions that arms are not a like-for-like control comparison.

The primary outcome was the percentage of participants adherent to treatment at month 6, assessed using the Adherence Self-Efficacy Scale. Its timeframe is baseline and 6 months. The record also lists secondary outcomes concerning adherence scores at months 6 and 12, adherence at month 12, and health-related quality-of-life domains. These entries describe intended outcome measures; the numerical results for the primary endpoint are not reported in the registry record.

The registry lists AbbVie as sponsor, with Abbott identified as prior sponsor. The study's completed status does not itself indicate that results are available in the record. No randomized treatment contrast, detailed statistical analysis plan, sample-size justification, or interim analysis information is reported in the registry record. The study design is best read as a real-world description of care and outcomes in the enrolled cohort, with the limits on causal interpretation that accompany observational treatment and participation decisions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to treat population included all enrolled participants who received at least 1 dose of lopinavir/ritonavir; participants with missing information on the absolute change in the ASES summative score who were not discontinued from the study or lost to follow-up were excluded.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Adherent to Treatment at Month 6, measured over Baseline and 6 months.

The primary endpoint is the percentage of participants considered adherent at month 6. Adherence was operationalized using the Adherence Self-Efficacy Scale (ASES), a 12 item tool addressing confidence in carrying out treatment-related activities and behaviors, including medication regimen, diet and exercise. Each item is answered on a scale from 0 (cannot do at all) to 10 (certain can do). A summative score ranges from 0 to 120, with higher scores indicating higher treatment self-efficacy.

A participant was counted as maintaining adherence if the change in the ASES summative score from baseline to month 6 was greater than or equal to zero. Participants who discontinued or were lost to follow-up were classified as non-adherent. This definition combines a score-based rule with a rule for follow-up status. It is therefore not equivalent to measuring medication possession, pill-taking behavior, or a biological marker of treatment exposure.

Self-efficacy is relevant because confidence in carrying out treatment-related behaviors may help characterize how participants experience adherence. The endpoint provides a prespecified way to convert the score change into a binary classification for reporting a percentage. However, that classification does not convey the size of an individual's score change, and a non-negative change does not establish that every dose was taken. The registry specifies a 95% confidence interval as the endpoint's dispersion measure, but the actual percentage and interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the outcome's definition, the population included in its analysis, and the way the study generated observations. Here, the main outcome is binary: a participant is categorized as adherent or non-adherent according to the ASES change rule and the follow-up rule. The reported quantity would be a percentage of participants in the endpoint population meeting that definition. Although the registry identifies a 95% confidence interval as the measure of dispersion, it does not report the percentage or interval bounds.

What does a binary percentage describe?

A binary endpoint reduces each participant's information to one of two categories. This can make the result straightforward to communicate, but it discards detail about the magnitude of score change. A participant whose ASES score increased and a participant whose score stayed the same both satisfy the non-negative-change criterion. The percentage would describe the frequency of that classification in the analyzed population; it would not describe the distribution of score changes or prove that medication was taken as directed.

For a proportion, a confidence interval is an uncertainty range calculated from the observed data under a statistical method and its assumptions. It is not a range containing a known fraction of individual participant outcomes, nor does it account automatically for every possible source of bias. The registry specifies a 95% confidence interval but does not state its reported bounds or the exact method used to calculate it. Without the estimate and interval, readers cannot evaluate sampling precision from the record.

Why does the cohort design matter?

In a randomized trial, random assignment is intended to balance measured and unmeasured participant characteristics across treatment groups on average. This record describes a prospective observational cohort. Decisions about lopinavir/ritonavir and KASA participation were made by the treating physician and participant, and allocation is not stated. People who do and do not participate in a support program may differ in ways related to adherence or outcomes. General statistical reasoning therefore cautions against treating an unadjusted association in an observational study as a causal effect.

Prospective observation can still describe outcomes as they occur in routine care and can document the population and outcome definitions used. But a causal comparison requires an appropriate design and analysis that address how treatment groups came to differ. The registry record does not report a detailed statistical plan or an adjusted analysis for this endpoint. It also explicitly cautions that the arms are not a like-for-like control comparison.

How should the ASES endpoint be understood?

The ASES measures confidence in undertaking treatment-related activities and behaviors. Its 12 items contribute to a summative score from 0 to 120; higher scores indicate higher treatment self-efficacy. The month 6 endpoint considers the change from baseline, with a change greater than or equal to zero counted as maintaining adherence. This is a choice of threshold that turns a continuous score change into a yes-or-no outcome. It is useful for expressing a proportion under a rule, but the threshold does not by itself validate self-efficacy as a complete measure of medication-taking behavior.

The endpoint also treats participants who discontinued or were lost to follow-up as non-adherent. This is a conservative classification in the sense that those participants do not count as adherent, but the registry entry does not describe the reasons for discontinuation or loss to follow-up. The consequences of this rule depend on how many participants had each follow-up status and how their outcomes might otherwise have been distributed. Those details are not reported in the registry record.

What do planning calculations mean?

Sample-size calculations are planning illustrations, not summaries of observed outcomes. The registry describes an illustration based on a stated fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For a time-to-event setting, the stated planning convention is the total number of events; for other settings, it is participants per arm. These assumptions do not establish that the cohort was designed using that calculation, and the registry record does not report the study's own sample-size justification.

When an illustration uses an observed effect as a planning reference, the resulting sample size is conditional on that effect and the other assumptions. It should not be called observed power or treated as evidence that a study had adequate power for its actual analyses. In this registry entry, the primary numerical endpoint result is not reported. There is therefore no reported primary estimate on which to base a reader's independent assessment of such an illustration. The registry record also does not report interim analyses or a complete statistical plan.

What is multiplicity and over-dispersion?

Multiplicity arises when multiple outcomes or comparisons are examined. If many statistical tests are performed, the chance of at least one apparently unusual result can rise unless the analysis plan accounts for the number and purpose of the tests. The registry lists 20 outcome measures, including several secondary measures of adherence and health-related quality of life. The record does not report a multiplicity adjustment or a hierarchy specifying which secondary outcomes were confirmatory. The listing alone does not show that every outcome was analyzed or tested.

Over-dispersion is a general concern when the variability in observed data exceeds what a chosen statistical model expects. In count or clustered data, failing to allow for extra variation can make standard errors too small and confidence intervals too narrow. It is not possible to assess over-dispersion for the primary binary endpoint from this entry, which does not provide the observed estimate, participant-level data, or analysis method. It should not be assumed to be present or absent.

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("Lopinavir/Ritonavir + KASA")
n      <- c(157)
events <- c(68)
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  Lopinavir/Ritonavir + KASA  157  68  43.3  35.4  51.4  35.8  51.1  35.8  51.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 20 outcome measures. Secondary outcomes include changes in the ASES summative score and its integration and perseverance subscales at months 6 and 12, adherence at month 12, and changes in several health-related quality-of-life domains. Multiple outcomes can describe different aspects of a study, but examining many results raises a multiplicity question: whether the analyses were planned as a hierarchy, whether some were exploratory, and whether any statistical adjustment was used. Those details are not reported in the registry record.

The primary endpoint population is defined as enrolled participants who received at least 1 dose of lopinavir/ritonavir. Participants with missing information on the absolute change in the ASES summative score were excluded if they had not discontinued or been lost to follow-up. By contrast, participants who discontinued or were lost to follow-up were considered non-adherent. Thus, missing score information and missing follow-up do not receive the same treatment in the endpoint definition.

The registry does not report how many participants had missing score data, discontinued, or were lost to follow-up, nor does it report sensitivity analyses showing how alternative missing-data assumptions would affect the endpoint. Missingness can matter when the probability of having an observed outcome is related to adherence or other participant characteristics. General statistical practice distinguishes assumptions about why data are missing and tests whether conclusions are robust to plausible alternatives. The registry entry does not describe those assumptions or analyses.

The record lists no reported analysis for the primary endpoint, and its numerical result is not reported. It also does not report an interim analysis plan, a detailed statistical analysis plan, or a multiplicity strategy. Consequently, readers can identify the endpoint definition and intended outcome set but cannot assess how the listed outcomes were analyzed or how missing information affected reported estimates.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: cardiac disorder (0.6%), death (0.6%), depression (0.6%).

The registry reports 3 participants with serious adverse events among 173 at risk in the lopinavir/ritonavir plus KASA group. It reports 0 participants with other adverse events among 173 at risk. These figures describe the safety entries recorded for this group; they do not establish whether events were caused by the medication, the program, the underlying condition, or other circumstances. The registry record does not provide a comparison group that would support a direct comparative safety interpretation.

The most frequently listed serious adverse event terms are cardiac disorder, death, and depression, each shown as 0.6%. These are registry-reported percentages for the listed terms; the entry does not provide term-specific counts alongside them. The death figure among serious event terms should not be mistaken for a reported total death count for the study. The deaths field is not reported in the registry record.

Serious adverse events and other adverse events are separate categories in the posted safety information. A count of participants with an event is not necessarily the same as a count of all event occurrences, since one participant may experience more than one event. The registry entry does not provide enough detail to determine event timing, duration, relatedness assessment, severity beyond the serious classification, or how events were handled analytically. These safety figures are descriptive registry entries rather than evidence of a causal safety comparison.

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

The study addresses a practical question: how adherence-related outcomes and safety were described in a prospective cohort receiving lopinavir/ritonavir, with participation in KASA occurring through routine care decisions. Its endpoint definition and study context are useful for understanding what the investigators intended to measure. The registry identifies an ASES-based adherence classification at month 6 and specifies how discontinuation and loss to follow-up were categorized.

However, the registry record does not report the primary endpoint's observed percentage or confidence interval. Readers therefore cannot determine from the entry how common the defined adherence outcome was, how precise an estimate might be, or how the outcome varied across participants. The outcome's absence from the registry record is not evidence that the endpoint had no effect, that adherence was low, or that the program had no benefit.

The endpoint also has a specific meaning. It reflects whether self-efficacy score change was non-negative from baseline to month 6, with particular follow-up statuses classified as non-adherent. It is not a direct observation of medication-taking, nor a measure of viral suppression or another clinical endpoint. The record's broad purpose includes effectiveness and safety, but the interpretation of any such outcome depends on its definition and the results actually reported.

The observational design means that this study can describe experience in the cohort but does not, on the registry information alone, isolate a causal effect of KASA. Physician and participant decisions shaped treatment and program participation, and the record warns against treating arms as a like-for-like control comparison. Associations in such a setting may reflect differences between participants or care circumstances as well as any contribution from the program.

Accordingly, the registry supports statements about the study's design, population, endpoint definition, and recorded safety entries. It does not support a conclusion about the size or direction of the primary adherence result, a causal treatment effect, or a comparison of risks between randomized groups. Those conclusions would require reported outcome data and methods that are not present in the registry record.

14. Why This Trial Matters Statistically

This study is statistically important as an example of how a real-world program evaluation depends on precise outcome definitions. The primary endpoint converts change in a self-efficacy score into a binary adherence classification. That allows reporting as a percentage, but it also makes the interpretation dependent on the chosen threshold and on how discontinuation, loss to follow-up, and missing score information are handled.

The prospective observational design is also central to the statistical reading. In routine care, decisions about treatment and program participation may reflect clinical judgment and participant preferences. Those decisions can create differences between participants that complicate causal interpretation. Recognizing this distinction prevents descriptive cohort findings from being mistaken for results of randomized assignment.

The registry's missing numerical primary result illustrates another basic principle: a clearly described outcome is not the same as a reported finding. The record specifies the measure, timeframe, and confidence-interval type, but does not report the percentage or interval bounds. Without these, neither the estimated frequency nor its precision can be evaluated. The completed status and enrollment figure cannot fill that gap.

The outcome list also raises questions that commonly arise in clinical research: how multiple endpoints were prioritized, whether missing data were examined through sensitivity analyses, and whether the statistical analysis plan was documented. The registry record does not report those details. That absence limits readers' ability to assess selective reporting, analytic choices, and uncertainty beyond the endpoint definition itself.

Finally, the safety entries reinforce the difference between describing events and establishing causation. Counts and listed event terms provide a record of what was reported, while a causal comparison requires an appropriate design and analysis. Statistical literacy means reading each result according to its design, population, endpoint, and reported uncertainty, while being explicit when results or methods are not available in the registry record.

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.

A central limitation is that the registry record does not report the numerical primary endpoint result or its 95% confidence interval. Although the outcome definition is detailed, the result's magnitude and precision cannot be assessed. The same absence limits comparison with any proposed benchmark or evaluation of how the outcome changed across the cohort.

The endpoint is based on self-efficacy rather than a direct measure of medication-taking. A non-negative change in an ASES summative score is the study's operational definition of maintained adherence; it should not be treated as interchangeable with all other adherence measures. The binary rule also does not preserve the magnitude of score change. The record does not report whether alternative thresholds or continuous score analyses were used.

As an observational cohort, the study does not establish a randomized comparison. Treatment and KASA participation were according to decisions by the treating physician and participant, and the registry cautions that arms are not like-for-like controls. Differences in outcomes could therefore be associated with participant characteristics or care decisions. The record does not report an adjusted causal analysis that would clarify this concern.

The endpoint population has specific inclusion and missing-data rules, but the registry does not report the number excluded for missing score information or the number considered non-adherent because of discontinuation or loss to follow-up. Without these details, it is difficult to evaluate the influence of the rules or the likely direction of any missing-data bias. Sensitivity analyses are not reported in the registry record.

Finally, the registry does not report a detailed analysis plan, multiplicity strategy, or interim analysis information. Safety entries are descriptive and do not establish causation or a comparative risk. These limitations concern what can be inferred from the registry record; they do not imply that analyses or data are absent outside it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Real-life Effectiveness of the Kaletra Adherence Support Assistance (KASA) Program — NCT01662336.
• Registry record last updated 2018-01-29; status last verified 2017-06.
• Results first posted 2018-01-29.
• 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

The registry record describes a completed prospective observational cohort study of the Kaletra Adherence Support Assistance Program with lopinavir/ritonavir treatment among people with HIV in Canada. Enrollment was 173. The recorded study start was 2012-06, and primary completion was 2016-06. AbbVie is listed as sponsor, with Abbott identified as prior sponsor.

The primary endpoint was the percentage adherent at month 6, defined using change from baseline in the ASES summative score and a rule classifying participants who discontinued or were lost to follow-up as non-adherent. The actual primary endpoint percentage and its 95% confidence interval are not reported in the registry record. The study was observational, with treatment and program participation determined through physician and participant decisions, rather than a reported randomized control comparison.

The registry lists secondary adherence and health-related quality-of-life outcomes, along with descriptive safety information. It records 3 participants with serious adverse events and 0 with other adverse events in the lopinavir/ritonavir plus KASA group, with 173 at risk for each category. These entries should be read descriptively. The registry record does not report a detailed statistical analysis plan, a multiplicity strategy, or an adjusted causal comparison.