A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir (NCT03198884), a registered phase not stated study. The primary outcome is Number of Participants With RNA <50 Copies/mL at 48 Weeks.

2. Clinical Question

3. Trial Design

This completed study is identified as a retrospective chart review of a nucleoside-sparing regimen containing darunavir, ritonavir, and dolutegravir. The listed condition is HIV-1 infection, and the sponsor is Southern Illinois Healthcare Foundation. The record lists the study start as 2017-01-01 and primary completion as 2018-04-18.

The enrollment field reports 20 participants. In contrast, the primary endpoint population description states that 19 patients meeting inclusion criteria were analyzed. These entries describe different aspects of the record, and the reason for the difference is not reported. The registry does not provide further details about how charts were selected, how eligibility was assessed, or how follow-up information was collected.

The record lists a retrospective chart review group and one drug intervention. It does not describe a concurrent comparator or random allocation. The record's own caution notes that this is not a randomized comparison and that the arms are not a like-for-like control comparison. Accordingly, the listed data are descriptive of the reviewed group; they do not, on their own, support a controlled treatment contrast.

The primary outcome is the number of participants with RNA <50 copies/mL at 48 weeks. Listed secondary outcomes concern mean CD4+ cell count change, adverse events, Grade 1 adverse events, RNA results at 24, 36, and 48 weeks, and creatinine clearance at 24, 36, and 48 weeks. The record reports 7 outcome measures and 2 analyses, but does not identify the analyses in further detail. The results for the named efficacy and laboratory outcomes 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: Subjects included were at least 18 years of age, receiving DRV/r + DTG QD for at least 24 weeks and had laboratory data through 48 weeks of follow up. Those excluded were not taking the study regimen, missed more than five doses of medication over two weeks prior to study visit or if there was missing lab data for 2 or more study time points.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 19 patients meeting the inclusion criteria were analyzed for this study. We evaluated the percentage of study subjects with an HIV RNA \< 50 copies at 48 weeks after initiation of the once daily two-drug regimen.

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 Number of Participants With RNA <50 Copies/mL at 48 Weeks, measured over 48 weeks.

The primary endpoint is the number of participants with HIV RNA <50 copies/mL at 48 weeks. This threshold-based outcome classifies participants according to whether their RNA measurement is below the stated level at the specified follow-up point. The registry's endpoint description instead phrases the objective as evaluating the percentage of study subjects meeting that threshold. The record does not explain the difference between the count wording in the outcome title and the percentage wording in the description.

In general, a threshold endpoint can make a clinical outcome easier to interpret as the share or count of participants meeting a prespecified criterion at a particular time. It does not show how far measurements lie below or above the threshold, and it may not convey changes at other time points. Those distinctions matter when reading a binary outcome: participants are classified by whether the criterion is met, rather than represented by the full range of their RNA measurements.

The registry names the threshold and timeframe, but does not report the observed count, the percentage, or an uncertainty interval for the primary endpoint. It also does not describe the handling of participants without a measurement at 48 weeks. As a result, the endpoint's definition is available, but its observed value and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint represent?

The primary measure is a count of participants meeting a threshold: RNA <50 copies/mL at 48 weeks. In general, a binary endpoint places each assessed participant into a category, such as meeting or not meeting a stated criterion. The count is then meaningful only in relation to the population assessed and the rules used for participants whose outcome is unavailable. The registry names the endpoint and describes the analyzed population as 19 patients, but does not report the endpoint count, the number with an available measurement, or the missing-data rules.

The endpoint description refers to a percentage, while the outcome title specifies a number of participants. A percentage ordinarily expresses a count in relation to a denominator, but the registry does not post that percentage or clarify which denominator would apply. No count or percentage should be reconstructed when the necessary observed endpoint data are absent.

How should precision be assessed?

In general, a confidence interval describes a range of values compatible with the observed data under the assumptions of the statistical method. It helps readers distinguish an estimate that is precise from one that remains uncertain. The registry record does not report a confidence interval for the primary endpoint, nor does it report a standard error, test statistic, or p-value for that outcome. Consequently, the precision and statistical evidence for the primary result cannot be evaluated from the posted record.

A p-value, in general, addresses how compatible observed data are with a specified statistical model or null hypothesis; it is not a measure of clinical importance or the probability that a hypothesis is true. No primary p-value or hypothesis test is described in the record. No significance threshold for the trial's own analysis is reported. The significance level 0.05 appears only in the stated assumptions for a planning illustration, not as evidence of the analysis plan used for this retrospective study.

What do the planning assumptions mean?

The record describes a sample-size planning illustration based on the observed effect, not the trial's own design. Its stated assumptions are a two-sided significance level 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions; they do not establish that the study was prospectively designed with those assumptions or that it had a particular achieved power.

For time-to-event tables, the stated planning convention is to give the total number of events; for other tables, it is to give participants per arm for 80% power or 90% power. These are planning illustrations, not observed characteristics of the retrospective chart review. They must not be read as observed power, as a record of the actual enrollment plan, or as evidence that the study had a comparator. Although the assumptions describe equal allocation between two arms for planning, the trial record itself does not describe a randomized comparison or a like-for-like control group. Numerical outputs for the planning illustration are not reported in the registry record.

What analysis details are absent?

The registry lists 7 outcome measures and 2 analyses. It does not specify the methods used for the primary endpoint, identify the two analyses in detail, or state whether estimates were adjusted for any covariates. It also does not report a statistical analysis plan, the handling of repeated measurements, or the criteria for including chart records in each endpoint analysis. No recalculated analysis from posted summary statistics is available because the primary efficacy result is not posted.

In general, an unadjusted analysis describes the observed data without accounting for other variables, while an adjusted analysis attempts to account for specified variables. These methods answer different questions and can produce different estimates. Since the record does not describe a model or adjusted estimates, readers should not assume that adjustment was or was not performed. Likewise, no inference about the suitability of a particular model can be made without details of the observations and analysis.

Why do the design and endpoint definitions matter?

A retrospective chart review relies on information recorded during care rather than on outcome collection described as part of a randomized comparison. In general, this can make the completeness and timing of measurements dependent on the available records. The registry does not explain how outcome measurements were chosen, how missing values were treated, or whether outcome assessment followed a common schedule for all participants. The primary endpoint has a specified 48-week timeframe, but the measurement and missingness procedures are not reported.

The record lists a primary endpoint and several secondary outcome topics. In general, examining multiple outcomes can raise questions about how chance findings are interpreted and whether a multiplicity adjustment was planned. The registry record does not report a multiplicity procedure or explain how the primary outcome was distinguished analytically from secondary outcomes. These omissions limit evaluation of the statistical plan, but they do not establish that any particular method was or was not used.

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("Retrospective Chart Review")
n      <- c(19)
events <- c(19)
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  Retrospective Chart Review  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary RNA threshold outcome and lists secondary outcomes for CD4+ cell count change, adverse events, Grade 1 adverse events, RNA results at 24, 36, and 48 weeks, and creatinine clearance at 24, 36, and 48 weeks. It reports 7 outcome measures and 2 analyses, without explaining how the listed outcomes correspond to those counts or describing the analyses in detail. A multiplicity adjustment or other approach to interpreting findings across outcomes is not reported in the registry record.

Missing-data handling is also not described. The enrollment field reports 20 participants, while the primary population description says that 19 patients meeting inclusion criteria were analyzed. The record does not state why those counts differ, whether any primary endpoint measurements were unavailable, or how participants with incomplete follow-up were treated. This does not establish that the difference is due to missing data; its explanation is not reported in the registry record.

The safety entries list 20 at risk for both serious and other adverse events, while the primary population description reports 19 analyzed. The registry does not clarify whether the safety and efficacy populations were defined differently. It also does not describe imputation, exclusions, or sensitivity analyses. In general, these details matter because the analyzed population and the handling of unavailable outcomes affect the interpretation of an estimate. Without the corresponding methods and endpoint results, the extent of any such effect cannot be assessed.

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 non-serious adverse event terms

The registry lists 0 participants affected by serious adverse events among 20 at risk, and 10 participants affected by other adverse events among 20 at risk. It also lists 0 deaths. These are the reported counts, not calculated rates. The record does not provide the event terms for the serious-event category; no serious-event terms are listed.

These entries should not be read as evidence that no adverse events of any kind occurred: the record separately reports 10 participants affected by other adverse events. Nor does the serious-event count establish that the risk is absent. In general, an observed count depends on the population and the period and methods used to identify events. The record does not describe the duration or completeness of adverse-event monitoring, or how the chart review classified events.

Incidence of adverse events and the number of Grade 1 adverse events are listed as secondary outcomes, but their detailed results are not reported in the registry record. The adverse-event entries therefore provide limited descriptive information, without event-level detail or a control group for comparison.

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

The record establishes that a retrospective chart review was completed and that its primary endpoint concerned RNA <50 copies/mL at 48 weeks. It also records the regimen under study, the participant enrollment field, the stated analyzed population, and a small set of safety counts. Those details describe the study record; they do not supply a posted efficacy estimate.

Because the primary endpoint count and percentage are not reported, the registry record cannot show how many analyzed participants met the threshold or how precisely that result was estimated. Results for the named secondary outcomes are also not reported. It is therefore not possible to describe the direction or size of change in CD4+ cell count, creatinine clearance, or RNA outcomes at other time points from this record.

The design also matters to the scope of conclusions. A retrospective chart review without a described comparator can describe outcomes in the reviewed group, but it does not provide a randomized contrast. Any observed outcomes would not by themselves determine what would have happened under another regimen. The registry's own caution about the lack of a randomized, like-for-like comparison is relevant when considering causal interpretations.

The safety counts report no serious adverse events and no deaths in the listed risk groups, alongside 10 participants affected by other adverse events. These counts do not characterize the kinds, timing, or duration of the events, and no comparative safety estimate is reported. They should be interpreted as the chart-review entries recorded, not as a complete account of all possible harms.

In short, the record provides an outcome definition and some study descriptors but not the primary efficacy result or the detailed secondary results. It supports a description of what the study intended to assess and what safety counts were posted. It does not support a numerical estimate of efficacy, an estimate of comparative effect, or a conclusion about causation.

14. Why This Trial Matters Statistically

This study illustrates why outcome definitions and outcome results must be distinguished. The registry clearly names a threshold and a follow-up point for the primary endpoint: RNA <50 copies/mL at 48 weeks. Yet it does not report the corresponding count or percentage. A clearly specified endpoint is useful for understanding the question, but it cannot substitute for the observed estimate or information about its precision.

The record also illustrates the importance of identifying the analysis population. Enrollment is listed as 20, while the primary population description says 19 patients meeting inclusion criteria were analyzed. Safety entries use a risk count of 20. These figures are not interchangeable, and the registry does not explain their relationship. Transparent reporting of the population used for each endpoint would make the results easier to assess.

Design determines what a statistical comparison can establish. A retrospective chart review without a described control group can provide descriptive information about the reviewed records, but it does not yield a randomized treatment contrast. The record itself notes that the comparison is not randomized and that arms are not a like-for-like control comparison. This is an important boundary on causal interpretation, independent of the endpoint threshold.

Finally, the record lists several outcomes but does not report their results, missing-data procedures, analysis details, or a multiplicity approach. These details help readers judge whether estimates are complete, how uncertainty is handled, and how findings across outcomes should be interpreted. Their absence does not prove that the work was not done; it means the registry record does not allow those methods to be evaluated.

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 are specific to the information recorded for this study. First, the primary efficacy result is absent. Although the endpoint is named and the population description is given, the record does not report the number meeting the RNA threshold, the percentage, or an interval describing uncertainty. Secondary efficacy and laboratory outcomes are named but their numerical results are not reported in the registry record.

Second, the population counts are not reconciled. Enrollment is listed as 20, the primary population description says 19 patients were analyzed, and the safety entries list 20 at risk. The record does not explain eligibility exclusions, endpoint-specific populations, or whether measurements were missing. It would be speculative to assign a reason to these different counts.

Third, the design is retrospective and no randomized control group is described. The record cautions against treating the arms as a like-for-like control comparison. It does not provide further detail about chart selection, measurement schedules, or outcome ascertainment. These omissions make it difficult to assess selection and measurement processes from the registry record.

Fourth, statistical methods are incompletely described. The record reports 7 outcome measures and 2 analyses but does not identify the analyses, explain missing-data handling, report a multiplicity approach, or specify whether estimates were adjusted. The sample-size assumptions are expressly planning illustrations, not the trial's own design, and their numerical outputs are not reported in the registry record. These limitations constrain interpretation of both statistical precision and the scope of the conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Retrospective Study to Evaluate the Safety and Efficacy of a Nucleoside-Sparing Regimen of Darunavir, Ritonavir, and Dolutegravir — NCT03198884.
• Registry record last updated 2020-09-01; status last verified 2020-08.
• Results first posted 2020-07-07.
• 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

NCT03198884 is a completed retrospective chart review concerning a darunavir, ritonavir, and dolutegravir regimen for HIV-1 infection. The record lists Southern Illinois Healthcare Foundation as sponsor, enrollment of 20, a start date of 2017-01-01, and primary completion on 2018-04-18.

The primary endpoint is the number of participants with RNA <50 copies/mL at 48 weeks. The population description states that 19 patients meeting inclusion criteria were analyzed, but the primary endpoint result is not reported in the registry record. Listed secondary outcomes cover CD4+ cell count, adverse events, RNA outcomes at other time points, and creatinine clearance; their results are also not reported.

The safety record lists 0 serious adverse events among 20 at risk, 10 participants with other adverse events among 20 at risk, and 0 deaths. No randomized comparator is described. The record cautions that the study is not a randomized comparison and that the arms are not a like-for-like control comparison.