Quality of Life of HIV-infected Participants Switched to Raltegravir Versus Other Antiretroviral Regimens (MK-0518-266): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Quality of Life of HIV-infected Participants Switched to Raltegravir Versus Other Antiretroviral Regimens (MK-0518-266) (NCT01814722), a registered phase not stated study. The primary outcome is Medical Outcomes Study-HIV (MOS-HIV) Health Survey Scores.

2. Clinical Question

The clinical question is about patient-reported health and quality of life after a treatment switch, rather than a randomized assignment to therapy. The record describes a longitudinal observational study: participants were followed over time while switching regimens in clinical practice. It does not report a random allocation procedure, and the listed groups are not a like-for-like controlled comparison. Differences between groups, if they had been estimated, could reflect pre-existing differences in participants or clinical decisions as well as regimen group.

The primary outcome was MOS-HIV health survey scores at Week 4 follow-up. The record also names changes from baseline in depression, anxiety and stress; HIV symptoms; and dermatology-related quality of life as secondary outcomes. It does not report numerical outcome estimates or statistical comparisons for these measures. The central question therefore remains unanswered by the posted results: the record does not establish whether the quality-of-life scores differed across regimen groups, or how large or precise any difference might have been.

3. Trial Design

This was a multicenter, longitudinal observational study of adults with HIV switching from first-line to second-line therapy in academic and community-based practices in the United States. The registry lists 63 participants enrolled. The study is identified as terminated, with a start date of 2012-11-09 and a primary completion date of 2013-10-31. The reason for termination is not reported in the registry record.

The three regimen groups were raltegravir plus two NRTIs, an NNRTI plus two NRTIs, and a PI plus two NRTIs. The listed NNRTIs could include delavirdine, efavirenz, etravirine, rilpivirine, or nevirapine. The listed PIs could include nelfinavir, lopinavir, saquinavir, tipranavir, atazanavir, or darunavir. The registry does not identify which individual drugs participants received within those categories.

Because this was observational, the groups reflect the regimens participants switched to rather than a stated random assignment. Allocation procedures are not stated. The record does not report the clinical or participant characteristics used to choose a regimen, nor does it describe adjustment for differences among groups. The groups should therefore not be interpreted as randomized treatment arms or as a like-for-like controlled comparison.

The primary endpoint timeframe was Week 4 follow-up. The registry names three secondary outcomes, each described as a change from baseline: the Depression, Anxiety, and Stress Scale (DASS-21), the HIV Symptom Index (HIV-SI), and the Dermatology Life Quality Index (DLQI). Although the record lists four outcome measures in total, it says that analyses of the primary MOS-HIV outcome were not performed because there were too few participants. A detailed schedule of visits and the timing of secondary outcome assessments are not reported in the registry record.

The record does not state the planned sample-size justification, a statistical analysis plan, interim analyses, or an analysis population definition. It also does not explain why the study was terminated. These omissions limit what can be inferred about the intended analysis and the reasons that no primary outcome comparison was posted.

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

Analysis population for the primary outcome, as defined in the registry: Analyses were not performed due to too few participants.

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: Gender and Age data for one participant from the Raltegravir, and two participants from the NNRTI groups were missing, resulting in a n = 60.

6. Primary Endpoint

The registry lists the primary outcome as Medical Outcomes Study-HIV (MOS-HIV) Health Survey Scores, measured over Week 4 Follow-up.

The primary endpoint was MOS-HIV Health Survey scores at Week 4 follow-up. The MOS-HIV is a 35-item questionnaire about health-related quality of life. It assesses 10 dimensions: general health perceptions, pain, physical functioning, role functioning, social functioning, mental health, energy or fatigue, cognitive function, health distress, and quality of life. It also includes a single item about perceived health transition.

The subscales are scored as summed rating scales from 0 to 100, with higher scores indicating better health. The record also describes a Physical Health Summary score and a Mental Health Summary score. These summary scores are transformed to a standardized scale with a norm of 50 and a standard deviation of 10 in the sample in which they were developed. The record does not give participant-level or group-level MOS-HIV values for this study.

A quality-of-life questionnaire is used to capture aspects of health that may not be represented by clinical measures alone. The MOS-HIV covers physical, mental, social, and symptom-related dimensions, allowing the study question to focus on participants' reported experience after switching regimens. That purpose does not make the score a direct measure of treatment effect: interpretation depends on the observed scores, the comparison method, and the study design.

Here, the registry says the primary analysis was not performed because there were too few participants. It reports no group means, changes from baseline, contrasts, confidence intervals, or p-values for MOS-HIV. Accordingly, the endpoint description explains what the survey measures, but the posted results do not show how scores changed or differed between regimen groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a longitudinal observational comparison, not a randomized trial. In a randomized study, assignment is determined by a random process, which can help balance measured and unmeasured participant characteristics between groups. Here, the record does not state an allocation method, and the regimen groups are described as groups participants switched to in practice. This means any observed group contrast would need cautious interpretation: differences in quality-of-life scores could be associated with regimen group, but could also reflect differences among the participants receiving each regimen.

What would a group comparison estimate?

A comparison would require a defined outcome summary for each regimen group and a contrast between those summaries. For a score measured at follow-up, the analysis might compare follow-up scores or compare changes from baseline, depending on the stated statistical plan. The registry does not say which approach was intended for the primary MOS-HIV question. It provides no group summaries or estimated contrasts, so neither the magnitude nor direction of a primary difference can be evaluated.

A confidence interval is a range of values compatible with the data and the assumptions of the analysis. It communicates precision as well as the estimated contrast: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. No confidence interval is reported for the primary outcome. Consequently, readers cannot judge the precision of a between-group estimate or whether the data would rule out differences that might be meaningful. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not by itself measure the size or practical importance of a difference. The registry does not report a primary p-value.

Why does the observational design matter?

In nonrandomized comparisons, allocation may be related to clinical or participant characteristics. If those characteristics are also related to quality of life, a simple comparison could mix differences associated with the regimen group and differences associated with the participants. Statistical adjustment can sometimes address measured differences, but it cannot guarantee removal of bias, particularly from factors not measured or not included in the model. The registry does not report a covariate set, an adjustment method, or an adjusted estimate. It is therefore not possible to determine whether any such approach was planned or used.

The study is described as longitudinal, meaning observations are intended to be collected over time. The primary timeframe is Week 4 follow-up, and several secondary outcomes are described as changes from baseline. For change-from-baseline outcomes, interpretation depends on which baseline and follow-up observations are available and how missing measurements are handled. The registry does not report those details or the outcome values.

What can be said about the sample-size illustrations?

The planning illustrations are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider detecting a stated fraction of the observed effect. For non-time-to-event outcomes, the reported unit is participants per arm; for time-to-event outcomes, the unit is total events under a Schoenfeld approach. These are planning assumptions, not a description of the study's own design justification. The planned sample size and the rationale for it are not reported in the registry record.

Sample-size calculations are conditional illustrations: they show how a target effect and analysis assumptions relate to a planning requirement. They do not tell readers what was observed, and they are not observed power. A sample-size calculation based on an observed effect is especially dependent on that effect estimate and its uncertainty. The registry does not provide the outcome estimate needed to assess that basis for this primary endpoint. The numerical planning results and the effect fractions are not reported in the registry record.

Over-dispersion is a general concern for count outcomes when observed variability is greater than a model expects; ignoring it can make uncertainty look too small. This primary endpoint is a quality-of-life score, and the registry does not report a count model or an over-dispersion analysis. This general concept should not be mistaken for a method reported for this study.

What is the status of the analysis?

The registry states that the primary analyses were not performed because there were too few participants, and it lists no analyses. It does not report an analysis population, a statistical model, a missing-data method, or interim analyses. These details cannot be reconstructed from the outcome descriptions or the group counts. The most defensible statistical reading is therefore descriptive: the registry defines the question and measures, but does not provide an inferential comparison of the primary endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary MOS-HIV outcome and three secondary outcomes: change from baseline in DASS-21, HIV-SI, and DLQI. Considering several outcomes can raise a multiplicity issue: the more hypotheses assessed, the greater the chance that at least one result appears unusual by chance if each is tested separately. A statistical plan may address this through a prespecified hierarchy, adjustment, or another approach. No multiplicity procedure or hierarchy beyond the designation of a primary outcome is reported in the registry record.

The record says the primary analysis was not performed because there were too few participants. It does not provide numerical results for the secondary outcomes either. It is therefore not possible to assess whether the secondary measures were analyzed, whether any results were selected for reporting, or how multiplicity was handled. The number of listed outcomes alone does not establish that all were tested.

Missing-data handling is not reported in the registry record. This matters for longitudinal outcomes because participants may not have a recorded baseline or follow-up score. The record does not say how much outcome data were missing, whether all enrolled participants contributed to each measure, or whether any method was used to address missing measurements. No assumptions about missingness or imputation can be inferred from the outcome descriptions.

The analysis populations are also not reported in the registry record. There is no stated definition of which participants would be included in the primary or secondary analyses, and the reason for the low participant count is not described beyond the statement that there were too few participants for the primary analysis. These omissions limit assessment of the analysis set, missingness, and the consistency between the planned question and any analyzed participants.

11. 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.

The registry lists three groups for adverse-event reporting: raltegravir plus two NRTIs, NNRTI plus two NRTIs, and PI plus two NRTIs. The serious adverse-event risk sets are 36, 21, and 6, respectively, and the serious adverse-event counts are 0 in each group. The other adverse-event risk sets are also 36, 21, and 6, with 0 affected in each group.

These are descriptive counts in the registry, not a statistical comparison of safety between groups. The record does not provide comparative estimates, confidence intervals, or a defined analysis method for these counts. Because this is an observational study and the groups are not described as randomized, differences in the groups would not automatically be attributable to the regimen. In this record, the zero affected counts do not establish that adverse events cannot occur or that the groups have equivalent safety.

The death entries are not reported in the registry record. A blank or unreported death value is not the same as a recorded count of zero. The registry also lists no top serious-event terms. These safety fields should be read as the event information posted for this record, not as a complete account of every possible safety outcome.

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

The registry establishes that the study asked whether MOS-HIV health-related quality-of-life scores at Week 4 follow-up differed among participants switching to raltegravir-based, NNRTI-based, or PI-based regimens. It defines the groups and describes the questionnaire, including the score dimensions and the direction of its subscale scores. It also reports that the primary analyses were not performed because there were too few participants.

What the record does not establish is whether quality of life improved, worsened, or differed between groups. There are no posted primary outcome estimates, group summaries, confidence intervals, or p-values. The absence of an analysis is not a finding of no difference. It is an absence of evidence from a reported comparison, so the size and precision of any group difference remain unknown.

The record also cannot establish that any potential difference was caused by a regimen. The study was observational, allocation was not stated, and the groups are explicitly not a like-for-like controlled comparison. Even if group score estimates were available, causal interpretation would depend on participant differences and the methods used to account for them. Those methods and covariate details are not reported in the registry record.

The same caution applies to secondary outcomes and safety. The outcome names do not show that changes were analyzed, while the posted adverse-event counts are descriptive and do not establish comparative safety. Death values are not reported in the registry record, rather than reported as zero.

The sample-size illustrations, where presented, are planning exercises based on stated assumptions and are not observed power. They do not replace an outcome analysis or provide evidence about the quality-of-life question. The record's status is terminated, but it does not report the reason for termination. The appropriate conclusion is limited: the registry documents the intended observational question and the lack of a primary analysis, without establishing a comparative quality-of-life result.

13. Why This Trial Matters Statistically

This record is statistically instructive because it separates a clearly stated research question from an answer supported by outcome data. The registry specifies a patient-reported primary measure, a follow-up timeframe, and three clinically distinct regimen groups. Yet it also says the primary analysis was not performed because there were too few participants. A defined endpoint does not by itself yield an estimate, and without an estimate there is no basis for interpreting the size or precision of a group difference.

The design also illustrates why the label observational matters. Participants switched regimens in clinical practice; the record does not describe random allocation. A comparison across groups could therefore reflect both regimen group and differences among participants. Recognizing this distinction helps prevent descriptive group contrasts from being read as causal treatment effects.

The outcome instrument spans physical, mental, social, and symptom-related aspects of health. That breadth is relevant to the clinical question, but it also makes clear why readers need outcome-specific estimates and methods to interpret results. A statement that a survey was planned, or a list of its scoring properties, is not a substitute for reported scores.

Finally, the registry status and safety counts need careful reading. Termination is recorded, but its reason is not. Zero adverse-event counts are reported for the listed risk sets, while death values are not reported. Those distinctions prevent unreported information from being mistaken for a negative finding. Taken together, the record demonstrates the importance of separating study design, planned measurement, posted outcomes, and the conclusions that the available analysis can support.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation is that the registry states the primary analysis was not performed because there were too few participants. No MOS-HIV group scores, contrasts, or uncertainty estimates are posted. The primary comparative question therefore cannot be answered from the registry results.

The observational design limits causal interpretation. The allocation process is not stated, and the record identifies the groups as not a like-for-like control comparison. The registry does not report participant characteristics by group or methods for adjustment, so the extent of potential confounding cannot be assessed.

The record is marked terminated, but the reason for termination is not reported in the registry record. It lists an enrollment of 63, but does not explain how that number relates to the stated difficulty conducting the primary analysis. The planned sample-size justification is also not reported, and the planning illustrations do not establish what sample size the study was designed to achieve.

Methods needed to assess the analysis are absent: the record does not describe the model, analysis population, missing-data handling, multiplicity approach, or interim analyses. It does not report numerical results for the named secondary outcomes. Safety information is limited to the posted event counts; death values are not reported in the registry record. These limitations leave both the outcome comparison and the completeness of the intended analyses uncertain.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Quality of Life of HIV-infected Participants Switched to Raltegravir Versus Other Antiretroviral Regimens (MK-0518-266) — NCT01814722.
• Registry record last updated 2017-04-21; status last verified 2017-03.
• Results first posted 2014-10-09.
• 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.

18. Record Summary

NCT01814722 is a terminated, multicenter longitudinal observational study of adults with HIV switching from first-line to second-line therapy. The registry lists an enrollment of 63 and compares three regimen groups: raltegravir plus two NRTIs, NNRTI plus two NRTIs, and PI plus two NRTIs. The primary outcome is MOS-HIV health-related quality-of-life scores at Week 4 follow-up.

The registry states that the primary analyses were not performed because there were too few participants. It does not report primary or secondary outcome estimates, analysis methods, or a reason for termination. The posted adverse-event counts are zero affected in each listed group; death values are not reported. The record defines the intended comparison but does not provide a statistical result establishing how quality-of-life scores differed among the groups.