This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
SALSA was a randomized, open-label, phase 3, parallel-group trial evaluating whether switching virologically suppressed adults with HIV-1 infection to once-daily dolutegravir/lamivudine fixed-dose combination (DTG/3TC FDC) maintained antiviral activity compared with continuing a current antiretroviral regimen (CAR).
| Feature | SALSA |
|---|---|
| Trial name | SALSA |
| NCT identifier | NCT04021290 |
| Phase | Phase 3 |
| Condition | HIV Infections |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 493 |
| Interventions | DTG/3TC FDC; CAR |
| Lead sponsor | ViiV Healthcare |
| Sponsor type | Industry |
| Status | Completed |
The trial started on November 11, 2019, and the primary completion date was April 23, 2021. ClinicalTrials.gov reports 27 outcome measures and 6 statistical analyses for the posted results.
2. Clinical Question
The primary statistical question was whether switching from a current antiretroviral regimen to once-daily DTG/3TC FDC maintained non-inferior antiviral activity over 48 weeks. The registered primary endpoint counted participants with plasma HIV-1 RNA ≥50 copies/mL using the FDA Snapshot category at Week 48.
Population
HIV-1 infected and virologically suppressed adults enrolled in the SALSA trial.
Intervention
DTG/3TC fixed-dose combination, identified in the registry as DTG/3TC FDC.
Comparator
Continuation of the current antiretroviral regimen (CAR).
Primary question
Does switching to DTG/3TC FDC have non-inferior antiviral activity compared with continuing CAR over 48 weeks?
3. Trial Design
DTG/3TC FDC
- Intervention identified in the registry as DTG/3TC FDC.
- Compared with continuation of the current antiretroviral regimen.
- Primary comparison evaluated the FDA Snapshot category at Week 48.
CAR
- Comparator identified in the registry as CAR.
- Participants continued their current antiretroviral regimen.
- Primary comparison used a stratified analysis adjusting for baseline third-agent class.
The registry also reports a continuation phase. The posted serious-adverse-event data include a continuation-phase group with 1 affected participant among 96 participants at risk.
4. Endpoints
| Endpoint role | Registered endpoint | Time frame | Type |
|---|---|---|---|
| Primary | Number of Participants With Plasma HIV-1 RNA ≥50 Copies/Milliliter (c/mL) as Per FDA Snapshot Category at Week 48 | Week 48 | Binary |
| Secondary | Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48 | Week 48 | Binary |
| Secondary | Change From Baseline in Health Status by HIV Treatment Satisfaction Questionnaire (TSQ) at Week 24 | Baseline (Day 1) and Week 24 | Continuous |
| Secondary | Change From Baseline in Health Status by HIV TSQ at Week 48 | Baseline (Day 1) and Week 48 | Continuous |
| Secondary | Change From Baseline in Health Status by Symptom Distress Module (SDM) at Week 24 | Baseline (Day 1) and Week 24 | Continuous |
| Secondary | Change From Baseline in Health Status by SDM at Week 48 | Baseline (Day 1) and Week 48 | Continuous |
The registry's primary endpoint definition states that participants with plasma HIV-1 RNA ≥50 c/mL were evaluated using the FDA Snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared with continuation of CAR over 48 weeks.
5. Statistical Methodology
Cochran-Mantel-Haenszel analysis
The primary endpoint was analyzed using a Cochran-Mantel-Haenszel (CMH) test. The reported adjusted difference in percent (ADP) was based on a CMH stratified analysis adjusting for the baseline third-agent class: protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and integrase inhibitor (INI).
This approach is appropriate for a binary outcome when the comparison is intended to account for a prespecified categorical stratification factor. Rather than treating all participants as belonging to a single unstratified population, the analysis incorporates the baseline third-agent class into the treatment comparison.
The registry reports the primary effect measure as an adjusted difference in percent. A negative value therefore corresponds to a lower adjusted proportion meeting the ≥50 c/mL endpoint in the DTG/3TC FDC group.
Non-inferiority framework
The primary analysis was explicitly a non-inferiority comparison. The registry states that non-inferiority would be concluded if the upper bound of the two-sided 95% confidence interval for the CMH-adjusted difference in the proportion of participants with plasma HIV-1 RNA ≥50 c/mL between DTG/3TC FDC and CAR was less than 5%.
This is a particularly important statistical distinction. The question is not simply whether a conventional superiority test produces a small p-value. Instead, the confidence interval is compared with a prespecified non-inferiority margin.
MMRM for longitudinal health-status outcomes
The secondary health-status outcomes were analyzed with mixed model repeated measures (MMRM). The registry reports that the model adjusted for treatment, visit, baseline third-agent class, age as a continuous variable, sex, race, baseline value as a continuous variable, treatment-by-visit interaction, and baseline-value-by-visit interaction, with visit as the repeated factor.
MMRM allows measurements collected at multiple visits to be analyzed jointly rather than treating each visit as an unrelated analysis. The model can estimate adjusted treatment differences at specified visits while accounting for the longitudinal structure of the observations.
The expression is conceptual rather than a reconstruction of the complete covariance specification, which is not provided in the ClinicalTrials.gov record.
Analysis populations
The primary analysis population was the Intent To Treat-Exposed (ITT-E) population, defined as all randomized participants who received at least one dose of study medication, either DTG/3TC or CAR.
The secondary TSQ and SDM analyses were also conducted in the ITT-E population, with the registry specifying that only participants with data available at the specified time points were analyzed for those outcomes.
6. Primary Endpoint Result
The primary endpoint was the number of participants with plasma HIV-1 RNA ≥50 copies/mL according to the FDA Snapshot category at Week 48. The posted analysis compared DTG/3TC FDC with CAR using a CMH-adjusted difference in percent.
Adjusted difference in percent
95% CI: −2.4% to 0.8% · Two-sided 95% CI
Analysis: Cochran-Mantel-Haenszel test
Population: ITT-E
The reported adjusted difference was −0.8 percentage points, comparing DTG/3TC FDC with CAR for the proportion of participants classified with plasma HIV-1 RNA ≥50 c/mL at Week 48. Because the difference is DTG/3TC FDC minus CAR, the negative estimate points toward a lower adjusted proportion meeting the endpoint in the DTG/3TC FDC group.
The estimate does not mean that the probability of virologic failure was exactly 0.8% lower for every individual participant. It is a population-level adjusted treatment comparison produced by the CMH analysis.
The two-sided 95% confidence interval extends from −2.4% to 0.8%. This interval describes the statistical uncertainty around the adjusted treatment difference under the analysis framework. It is not a range containing the individual effects experienced by patients.
For a non-inferiority question, the critical comparison is with the prespecified margin. The registry states that non-inferiority would be concluded when the upper bound of the two-sided 95% CI is below 5%. Here, the upper bound is 0.8%, which is below the stated 5% margin.
The non-inferiority conclusion therefore comes from the relationship between the confidence interval and the margin, rather than from a p-value. The posted primary analysis does not provide a p-value for this endpoint in the ClinicalTrials.gov record.
Understanding the non-inferiority logic
| Quantity | Reported value | Role in interpretation |
|---|---|---|
| Adjusted difference in percent | −0.8 | Estimated DTG/3TC FDC minus CAR difference |
| 95% CI lower bound | −2.4 | Lower end of statistical uncertainty interval |
| 95% CI upper bound | 0.8 | Upper end used for the non-inferiority decision |
| Non-inferiority margin | 5% | Upper-bound criterion specified by the registry |
In this setting, the null concern is that switching could result in an unacceptably larger proportion of participants meeting the ≥50 c/mL endpoint. The non-inferiority margin defines how large that adverse difference could be while still being considered compatible with the prespecified non-inferiority objective.
7. Secondary Endpoint Results
HIV-1 RNA <50 c/mL at Week 48
The secondary virologic endpoint counted participants with plasma HIV-1 RNA <50 c/mL using the FDA Snapshot algorithm at Week 48. The posted analysis used the ITT-E population and a CMH-adjusted difference in percent.
Adjusted difference in percent
95% CI: −2.8% to 5.9% · Two-sided 95% CI
Analysis: Cochran-Mantel-Haenszel test
Non-inferiority margin: −12%
The estimated adjusted difference was 1.6 percentage points for the proportion with HIV-1 RNA <50 c/mL, comparing DTG/3TC FDC with CAR. The positive estimate points toward a higher adjusted success proportion in the DTG/3TC FDC group, although the confidence interval spans both negative and positive values.
The 95% confidence interval ranges from −2.8% to 5.9%. That interval represents uncertainty around the adjusted difference; it does not mean that individual participants have a probability somewhere between those values.
The registry specifies a non-inferiority criterion based on the lower bound of a two-sided 95% confidence interval being greater than −12%. The reported lower bound is −2.8%, which is above −12%.
No p-value is reported for this analysis in the ClinicalTrials.gov record. More importantly, the non-inferiority interpretation is driven by the prespecified margin and confidence interval rather than by treating a conventional superiority p-value as the principal decision rule.
HIV TSQ: Week 24
Adjusted mean difference
95% CI: 0.7 to 2.2 · P <0.001
MMRM analysis, ITT-E population
The reported adjusted mean difference was 1.4 score units for change from baseline in HIV Treatment Satisfaction Questionnaire status at Week 24. The confidence interval extends from 0.7 to 2.2, indicating the range of values supported by the reported model and sampling framework at the 95% confidence level.
The p-value of <0.001 is evidence against a null hypothesis of no adjusted mean difference under the model used. It does not measure the size or clinical importance of the difference. The magnitude is represented by the estimate and its confidence interval.
The result is adjusted for treatment, visit, baseline third-agent class, age, sex, race, baseline value, treatment-by-visit interaction, and baseline-value-by-visit interaction, with visit as the repeated factor.
HIV TSQ: Week 48
Adjusted mean difference
95% CI: 0.7 to 2.2 · P <0.001
MMRM analysis, ITT-E population
At Week 48, the reported adjusted mean difference was again 1.4 score units, with a 95% confidence interval from 0.7 to 2.2 and a p-value of <0.001.
The statistical interpretation is similar to the Week 24 analysis: the estimate describes an adjusted group difference, while the confidence interval describes precision and the p-value addresses evidence against a null difference. None of these quantities alone establishes how important a one-point change is to an individual participant.
Because the analysis is longitudinal and adjusted for multiple baseline and visit-related variables, the result should be understood as a model-based adjusted comparison rather than a simple difference between two unadjusted sample means.
Symptom Distress Module: Week 24
Adjusted mean difference
95% CI: −2.9 to −0.2 · P = 0.021
MMRM analysis, ITT-E population
The Week 24 SDM analysis estimated an adjusted mean difference of −1.6 score units, with a 95% confidence interval from −2.9 to −0.2.
The negative sign identifies the direction of the adjusted difference as DTG/3TC FDC minus CAR. The ClinicalTrials.gov record does not define the clinical meaning of a one-unit change on the SDM, so the statistical direction should not be converted into a clinical-benefit claim beyond what the score itself establishes.
The p-value of 0.021 indicates evidence against a null adjusted mean difference under the specified model. It is not a measure of effect magnitude and does not by itself establish clinical importance.
Symptom Distress Module: Week 48
Adjusted mean difference
95% CI: −1.8 to 0.7 · P = 0.398
MMRM analysis, ITT-E population
The Week 48 SDM analysis estimated an adjusted mean difference of −0.5 score units. The 95% confidence interval ranges from −1.8 to 0.7 and therefore includes zero.
The p-value of 0.398 does not provide evidence against a null adjusted mean difference at conventional significance thresholds. This should not be interpreted as proof that the two groups are identical: a nonsignificant p-value can reflect uncertainty, and the confidence interval describes the range of adjusted differences supported by the data.
8. Secondary Results at a Glance
| Endpoint | Estimate | 95% CI | P-value | Method |
|---|---|---|---|---|
| HIV-1 RNA <50 c/mL at Week 48 | 1.6% | −2.8% to 5.9% | Not reported | CMH |
| HIV TSQ change at Week 24 | 1.4 | 0.7 to 2.2 | <0.001 | MMRM |
| HIV TSQ change at Week 48 | 1.4 | 0.7 to 2.2 | <0.001 | MMRM |
| SDM change at Week 24 | −1.6 | −2.9 to −0.2 | 0.021 | MMRM |
| SDM change at Week 48 | −0.5 | −1.8 to 0.7 | 0.398 | MMRM |
The ClinicalTrials.gov record contains six posted statistical analyses: one primary endpoint analysis and five secondary endpoint analyses. The table above summarizes all six.
9. Safety Results
The registry provides serious adverse-event counts by study phase and arm. These data are reported as affected participants divided by participants at risk.
| Phase / group | Serious adverse events |
|---|---|
| Randomized phase — first reported group | 7/246 |
| Randomized phase — second reported group | 16/247 |
| Continuation phase | 1/96 |
The ClinicalTrials.gov record identifies the randomized-phase denominators as 246 and 247, but the serious-adverse-event field does not associate the two randomized-phase entries with DTG/3TC FDC versus CAR in a way that can be safely reconstructed from the registry-reported text. Accordingly, the counts are presented in the registry's reported order rather than assigning them to treatment labels.
10. Statistical Methods Explained
Why was a Cochran-Mantel-Haenszel test used?
The primary endpoint was binary: participants were classified according to the FDA Snapshot category at Week 48. The CMH approach provides a way to compare the treatment groups while adjusting for the baseline third-agent class used for stratification.
In this trial, the baseline third-agent class consisted of PI, NNRTI, and INI categories. The adjusted difference therefore incorporates the prespecified stratification factor rather than relying solely on an unadjusted comparison of the two randomized groups.
Why is the confidence interval central to the non-inferiority analysis?
Non-inferiority asks whether the data exclude an unacceptable loss of efficacy. A point estimate alone cannot answer that question because the estimate is uncertain. The confidence interval supplies an upper bound on the adverse treatment difference that can be compared directly with the non-inferiority margin.
For the primary endpoint, the reported upper bound was 0.8%, while the registry specifies a 5% non-inferiority margin. The relevant comparison is therefore between 0.8% and 5%, not between a p-value and an arbitrary significance threshold.
What does an adjusted difference of −0.8% mean?
The estimate is the reported CMH-adjusted difference in percent between DTG/3TC FDC and CAR for the proportion of participants with plasma HIV-1 RNA ≥50 c/mL at Week 48. Because the comparison is DTG/3TC FDC minus CAR, a negative number indicates a lower adjusted proportion in the DTG/3TC FDC group.
It is not a relative risk, odds ratio, hazard ratio, or individual-level probability. It is an adjusted absolute difference between group proportions.
Why was MMRM used for the TSQ and SDM outcomes?
The TSQ and SDM endpoints involve measurements at multiple time points, including baseline and later visits. MMRM is designed for longitudinal data and can estimate adjusted treatment differences while accounting for the repeated nature of measurements within participants.
The SALSA registry analysis adjusted for treatment, visit, baseline third-agent class, age, sex, race, baseline value, treatment-by-visit interaction, and baseline-value-by-visit interaction. This makes the reported adjusted mean different from a simple arithmetic difference in observed means.
What does a p-value of <0.001 mean for the TSQ result?
Under the statistical model and null hypothesis used for that analysis, a p-value <0.001 indicates strong evidence against a null adjusted mean difference. It does not mean that there is a <0.1% probability that the treatment effect is real, nor does it measure clinical importance.
The estimate of 1.4 and its 95% confidence interval of 0.7 to 2.2 provide the effect-size and precision information. The p-value answers a different question.
Why can a nonsignificant p-value still leave uncertainty?
The Week 48 SDM analysis had an estimate of −0.5, a 95% CI of −1.8 to 0.7, and a p-value of 0.398. Because the confidence interval includes zero, the analysis does not distinguish clearly between a negative, near-zero, or modest positive adjusted difference within that interval.
A nonsignificant result therefore should not be translated into a claim that the treatments have exactly the same effect. It indicates that the analysis did not provide sufficient statistical evidence against the specified null hypothesis.
Why is the analysis population called ITT-E?
The registry defines ITT-E as all randomized participants who received at least one dose of study medication, either DTG/3TC or CAR. This preserves the randomized treatment comparison among participants who were actually exposed to study medication, while distinguishing the analysis population from a broader set that might include randomized participants who never received treatment.
11. Covariate Adjustment and Stratification
The primary analysis adjusted for the baseline third-agent class. The registry identifies three categories: protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and integrase inhibitor (INI).
| Statistical element | SALSA implementation |
|---|---|
| Primary endpoint | Binary FDA Snapshot category at Week 48 |
| Primary method | Cochran-Mantel-Haenszel test |
| Stratification variable | Baseline third-agent class |
| Third-agent categories | PI, NNRTI, INI |
| Primary effect measure | Adjusted Difference in Percent |
Stratification is useful when a baseline categorical variable is considered relevant to the treatment comparison. Instead of ignoring that variable, the CMH framework combines information across its strata to produce an adjusted comparison.
The registry's analysis text specifically identifies baseline third-agent class as the adjustment factor. The ClinicalTrials.gov record does not provide the stratum-specific participant counts or cell counts, so the page does not reconstruct the underlying CMH calculation.
12. Intention-to-Treat Analysis in SALSA
The ITT-E population is central to interpreting the posted efficacy results. Participants were randomized before treatment exposure, and the registry defines ITT-E as all randomized participants who received at least one dose of DTG/3TC or CAR.
Why randomization matters
Randomization creates the basis for a treatment-group comparison in which baseline differences are not intentionally selected by investigators.
Why exposure matters here
The registry's ITT-E definition requires at least one dose of study medication, distinguishing the analysis population from all randomized participants regardless of exposure.
Why this is not per-protocol
The ClinicalTrials.gov record explicitly identify the primary analysis population as ITT-E rather than a per-protocol population.
Interpretation
The primary result should therefore be understood as the treatment comparison specified for the ITT-E population, not as an analysis restricted to participants who completed every assessment.
13. Missing Data and Repeated Measures
The registry explicitly states that the TSQ and SDM secondary analyses were conducted in the ITT-E population and that only participants with data available at the specified time points were analyzed.
For these outcomes, MMRM was used with visit as the repeated factor. This is different from simply analyzing only the final observed score for every randomized participant. A repeated-measures model uses the longitudinal data structure and the covariates specified in the analysis.
14. Multiplicity and Multiple Endpoints
The posted registry results include one primary endpoint analysis and five secondary endpoint analyses. The ClinicalTrials.gov record identifies the hypothesis type for the primary endpoint as non-inferiority and identify the secondary health-status analyses as "Other / not stated."
| Endpoint family | Number of posted analyses | Reported inferential framework |
|---|---|---|
| Primary virologic endpoint | 1 | Non-inferiority |
| Secondary virologic endpoint | 1 | Non-inferiority |
| HIV TSQ | 2 | Other / not stated |
| SDM | 2 | Other / not stated |
The ClinicalTrials.gov record does not provide a multiplicity-adjustment strategy across the secondary endpoints. Consequently, the reported secondary p-values should be interpreted as the p-values associated with their respective posted analyses, without assuming an unreported familywise error-control procedure.
15. Non-Inferiority Trial Design
SALSA provides a useful example of why non-inferiority trials require a different statistical reading from conventional superiority trials.
| Feature | Primary SALSA analysis |
|---|---|
| Endpoint | Participants with plasma HIV-1 RNA ≥50 c/mL at Week 48 |
| Effect measure | CMH adjusted difference in percent |
| Comparison | DTG/3TC FDC − CAR |
| Confidence interval | Two-sided 95% |
| Non-inferiority margin | 5% |
| Criterion | Upper confidence-limit <5% |
| Observed upper confidence limit | 0.8% |
For the primary endpoint, the reported upper confidence limit of 0.8% is below the prespecified 5% margin. Statistically, this means the uncertainty interval excludes an adjusted increase as large as the stated non-inferiority margin.
This framework does not require the point estimate to be exactly zero. A non-inferiority analysis can produce an estimate favoring either treatment while still meeting its predefined criterion, provided the confidence interval remains on the acceptable side of the margin.
16. Crossover, Factorial Design, and Interim Analysis
The ClinicalTrials.gov record does not report a crossover design or a factorial design. The registered design model is parallel, with two arms.
The registry-reported statistical-analyses data also do not identify an interim analysis or an alpha-spending procedure. Therefore, this page does not infer one from the phase 3 designation or from the presence of a non-inferiority hypothesis.
| Design topic | What the ClinicalTrials.gov record supports |
|---|---|
| Parallel design | Yes — registered design model is parallel |
| Randomization | Yes |
| Masking | None |
| Factorial design | Not reported in the ClinicalTrials.gov record |
| Crossover | Not reported in the ClinicalTrials.gov record |
| Interim analysis | Not reported in the ClinicalTrials.gov record |
| Bayesian analysis | Not reported in the ClinicalTrials.gov record |
17. What the Primary Effect Measure Does — and Does Not — Mean
The primary adjusted difference of −0.8% is an absolute difference in the percentage of participants meeting the plasma HIV-1 RNA ≥50 c/mL endpoint, adjusted using the CMH framework for baseline third-agent class.
The 95% confidence interval of −2.4% to 0.8% describes uncertainty around the adjusted treatment difference. It does not give a range of outcomes for individual participants.
The registry's criterion focuses on the upper bound of the two-sided 95% confidence interval. Because the upper bound is 0.8%, the reported interval remains below the 5% non-inferiority margin.
The primary estimate is not a hazard ratio, odds ratio, relative risk, or percentage reduction in an individual participant's risk. It is an adjusted difference in percentages.
18. Interpreting the MMRM Estimates
The secondary health-status outcomes illustrate a different statistical language from the primary binary endpoint. The MMRM estimates are adjusted mean differences rather than risk differences.
| Outcome | Time point | Estimate | 95% CI | P-value |
|---|---|---|---|---|
| HIV TSQ | Week 24 | 1.4 | 0.7 to 2.2 | <0.001 |
| HIV TSQ | Week 48 | 1.4 | 0.7 to 2.2 | <0.001 |
| SDM | Week 24 | −1.6 | −2.9 to −0.2 | 0.021 |
| SDM | Week 48 | −0.5 | −1.8 to 0.7 | 0.398 |
The signs of the estimates should be interpreted using the direction of the underlying questionnaire score. The ClinicalTrials.gov record identifies the instruments and statistical estimates but do not provide a clinical threshold for what constitutes a meaningful change on either scale. Statistical significance therefore should not be substituted for a clinical-importance threshold that is not provided here.
19. Limitations
- Registry-level information: this analysis is constrained to the ClinicalTrials.gov record and does not add unreported baseline tables, subgroup estimates, median outcomes, or other publication-derived results.
- Open-label design: the registry reports masking as none. This is relevant when interpreting outcomes that involve participant-reported health status, including TSQ and SDM.
- ITT-E definition: the primary analysis population includes randomized participants who received at least one dose, rather than every randomized participant regardless of exposure.
- Secondary endpoint multiplicity: the ClinicalTrials.gov record does not report a multiplicity-adjustment procedure across the secondary analyses.
- Non-inferiority margin: the primary conclusion depends on the prespecified 5% margin. A margin is a design assumption and should be considered separately from the observed point estimate.
- Health-status interpretation: the ClinicalTrials.gov record provides adjusted mean differences and confidence intervals but do not provide a minimal clinically important difference for TSQ or SDM.
- Missing-data detail: the registry states that only participants with available data at specified time points were analyzed for the TSQ and SDM endpoints, but the ClinicalTrials.gov record does not specify a particular imputation strategy.
- Safety attribution: the serious-adverse-event field gives randomized-phase counts in two reported groups but does not label those two entries by treatment in the registry-reported text.
- Unreported design details: the ClinicalTrials.gov record does not establish crossover, factorial structure, Bayesian methodology, or interim-analysis procedures.
- Clinical importance: statistical significance and non-inferiority criteria do not by themselves establish the clinical importance of a particular score difference or virologic effect.
20. Why This Trial Matters Statistically
SALSA is a useful teaching case because its primary endpoint and secondary outcomes require several different statistical ideas within the same randomized trial. The primary analysis is a stratified non-inferiority comparison of a binary virologic endpoint, while the health-status outcomes use longitudinal mixed models with extensive covariate adjustment.
| Concept | How it appears in SALSA |
|---|---|
| Randomization | Randomized phase 3 parallel-group design |
| Binary endpoint | Plasma HIV-1 RNA ≥50 c/mL at Week 48 |
| Non-inferiority | Primary endpoint evaluated against a 5% margin |
| Cochran-Mantel-Haenszel test | Primary stratified analysis |
| Risk difference | Normalized form of the reported adjusted difference in percent |
| Confidence interval | Two-sided 95% interval used directly in the non-inferiority criterion |
| Stratification | Baseline third-agent class: PI, NNRTI, INI |
| ITT-E analysis | Primary analysis population |
| MMRM | TSQ and SDM longitudinal health-status outcomes |
| Covariate adjustment | Age, sex, race, baseline value and other prespecified factors in MMRM |
| Repeated measures | Visit used as the repeated factor in MMRM |
| Multiplicity | Multiple secondary analyses are posted; adjustment strategy not reported |
21. Related Tutorials
Learn more about the methods used in this trial:
22. Related Statistical Calculators
23. Sources
- ClinicalTrials.gov: SALSA — NCT04021290.
- PubMed: PMID 39225890.
- PubMed: PMID 39015350.
- PubMed: PMID 38515183.
- PubMed: PMID 34358493.
Continue through the Clinical Biostats statistical pathway
Use the trial's methods as a starting point for deeper study of stratified categorical analysis, non-inferiority designs, confidence intervals, risk differences, and longitudinal mixed models.
24. Record Summary
SALSA provides a compact example of several important clinical-trial statistical principles. The primary endpoint was binary and evaluated at Week 48 using a CMH-adjusted difference in percent, with baseline third-agent class as the stratification factor. The trial specified a non-inferiority margin of 5%, and the reported primary estimate was −0.8% with a two-sided 95% confidence interval of −2.4% to 0.8%.
The secondary analyses demonstrate a different class of methods. Virologic suppression below 50 c/mL was analyzed using the same general CMH framework, while TSQ and SDM outcomes were evaluated using MMRM with treatment, visit, baseline third-agent class, age, sex, race, baseline value, treatment-by-visit interaction, and baseline-value-by-visit interaction included in the reported model structure.
The most important statistical lesson is that the different endpoints require different interpretations. The primary non-inferiority result is governed by the relationship between its confidence interval and the prespecified margin. The MMRM outcomes are adjusted mean differences, where confidence intervals and p-values describe statistical uncertainty but do not automatically establish clinical importance. Safety results should be interpreted separately from efficacy, and secondary p-values should not be treated as though an unreported multiplicity procedure had been performed.