This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Switch From Tenofovir to Raltegravir for Low Bone Mineral Density (NCT00939874), a na phase 4 study. The primary outcome is Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00939874 |
| Phase | Phase 4 |
| Condition | HIV, Osteopenia, Osteoporosis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 52 |
| Arms in the primary outcome | n/a |
| Lead sponsor | St Vincent's Hospital, Sydney |
| Results posted | Yes |
2. Clinical Question
Population
Adults with HIV infection and osteopenia or osteoporosis were the population of interest. The record describes the primary outcome among completed participants: Week 48 data were available for 37 completed participants and Week 96 data for 32 completed participants. It also states that 15 of the enrolled 52 participants were screen failures.
Intervention
The study examined switching HIV medication from tenofovir to raltegravir. The stated hypothesis concerned people taking antiretroviral therapy that included tenofovir disoproxil fumarate and a ritonavir-boosted protease inhibitor, switching to therapy that included raltegravir and a ritonavir-boosted protease inhibitor.
Comparator
There was no separate comparator group in this single-group study. Allocation is listed as not applicable, and the study was not masked. The record therefore does not describe a randomized, like-for-like comparison between people who switched and people who continued their previous regimen.
Primary question
The primary question was whether percent change in bone mineral density at the lumbar spine and hips differed from baseline at Weeks 48 and 96 after the medication switch. The registry record does not report the numerical changes or their confidence intervals, so the magnitude and precision of the observed change are not reported in the registry record.
In general, a before-and-after question can describe how a measure changes over time within a group. Without a concurrent control group, however, a change cannot by itself separate the effect of the switch from other influences, such as time-related changes or differences in who contributed follow-up measurements. That limitation is especially important when interpreting a clinical question as causal: the design documents change after switching, but does not establish what would have happened to the same participants without switching.
3. Trial Design
This was a completed Phase 4, single-group study sponsored by St Vincent's Hospital, Sydney. The registry record lists an enrollment of 52 and dates the study start to 2009-10 and primary completion to 2012-06. Raltegravir is listed as the intervention. The record describes the purpose as determining whether bone mineral density improves in adults with HIV infection who switch from tenofovir to raltegravir.
Allocation is recorded as not applicable, and masking is listed as none. The study model is single group. These features mean that the record does not describe random assignment, blinding, or a concurrent control arm. In general, random allocation can help balance both known and unknown factors between comparison groups, while masking can reduce some forms of bias in measurement or reporting. Those protections are not described for this study; their absence does not itself establish that the measurements are biased, but it limits what can be ruled out.
The hypothesis specifies a treatment context: antiretroviral therapy including tenofovir disoproxil fumarate and a ritonavir-boosted protease inhibitor was to be switched to therapy including raltegravir and a ritonavir-boosted protease inhibitor. The registry intervention field lists raltegravir, while the arm description is empty. More detail about the regimen, switch procedures, adherence assessment, or other protocol features is not reported in the registry record.
Week 48 data were available for 37 completed participants, and Week 96 data for 32 completed participants. The record also states that 15 of the enrolled 52 participants were screen failures. These descriptions distinguish enrollment from the available completed-participant outcome data; they should not be treated as equivalent analysis populations. The statistical plan, including any intended handling of incomplete follow-up or selection into the completed-participant group, is 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.
Overall Study
| Stage | Raltegravir |
|---|---|
| STARTED | 52 |
| Completed Week 48 | 37 |
| COMPLETED | 32 |
| NOT COMPLETED | 20 |
Analysis population for the primary outcome, as defined in the registry: Week 48 data were available for 37 completed participants and Week 96 data were available for 32 completed participants. Fifteen of the enrolled 52 participants were screen failures.
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.
| Characteristic | Unit | Raltegravir |
|---|---|---|
| Participants analysed | 37 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 35 |
| Age, Categorical: >=65 years | Participants | 2 |
| Age, Continuous | years | 50 (30 to 70) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 36 |
| Region of Enrollment: Australia | participants | 37 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change in Bone Mineral Density (BMD) of Lumbar Spine and Hips, measured over from Baseline to Weeks 48 and 96.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | percent change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent change in bone mineral density at the lumbar spine and hips, measured from baseline to Weeks 48 and 96. Bone mineral density is a measurement of how thick and strong bones are, as described in the study summary. The endpoint therefore focuses on change in a continuous measurement over time rather than on a binary event such as whether a participant did or did not experience an outcome.
Bone mineral density is used in this study because the enrolled population is described as having osteopenia or osteoporosis, and the stated hypothesis concerns improvement in bone mineral density following the medication switch. Measuring both the lumbar spine and hips captures the two specified skeletal locations; the registry record does not report further details about measurement procedures or how site-specific findings were to be combined or interpreted.
The outcome is specified as a mean with a 95% confidence interval. In general, the mean describes the average change in the analyzed group, while a confidence interval conveys uncertainty around that estimate under the analysis assumptions. A narrower interval indicates greater precision, and a wider interval indicates less precision. The registry record does not report the actual mean percent changes or their confidence intervals for either time point or location. Consequently, the size and precision of the primary endpoint findings are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines the primary outcome and the available follow-up counts, but does not report numerical results for percent change in bone mineral density. No mean change or 95% confidence interval is reported in the registry record for the lumbar spine or hips at Week 48 or Week 96. Thus, the direction, magnitude, and precision of the primary outcome cannot be characterized from the record's posted results.
The available outcome counts also differ by follow-up time: Week 48 data were available for 37 completed participants, and Week 96 data for 32 completed participants. The record states that 15 of the enrolled 52 participants were screen failures. These counts describe who was enrolled, who was identified as a screen failure, and who had completed-participant data at the specified time points. They do not, by themselves, explain why outcome data were unavailable for other participants, or whether the participants with measurements differed from those without them.
In general, interpreting an estimate requires both its value and its uncertainty. A confidence interval helps readers judge how precisely the average change has been estimated, but it does not remove the limitations of the study design or prove that the intervention caused the change. Since the numerical estimates and intervals are not reported in the registry record, no conclusion about the size or statistical uncertainty of the bone mineral density change can be drawn from the posted information.
The single-group design further limits causal interpretation. A within-group change over time, if reported, would not provide a direct estimate of the difference between switching and not switching. Without a concurrent comparator, natural changes over time, other care, adherence, or differences in follow-up could contribute to observed changes. These are general possibilities, not documented explanations for this study's results.
The record lists a secondary outcome, the percentage of participants with HIV viral load <50 copies/mL, but does not report its numerical result. It lists two outcome measures and one analysis; the relationship between those entries, the specific analysis populations, and any adjustment for multiple outcome tests are not reported in the registry record. Overall, the registry record gives design and endpoint information but does not provide the numerical findings needed to assess either the primary endpoint or the listed secondary outcome.
9. Statistical Methods Explained
The primary endpoint is a continuous outcome: percent change in bone mineral density. The registry specifies a mean and a 95% confidence interval. In general, a mean summarizes the central tendency of continuous measurements, while a confidence interval describes uncertainty about the estimated mean under the model and sampling assumptions. Neither measure substitutes for the underlying study design. A precise estimate from a single group would still not establish what would have happened under a different treatment strategy.
What does a confidence interval communicate?
In general, a confidence interval is a range of values compatible with the observed data and the assumptions of the analysis. Its width reflects precision: wider intervals indicate more uncertainty in the estimated quantity, and narrower intervals indicate less. A confidence interval is not a guarantee that the true value lies in the particular interval, and it does not by itself address bias, missing data, or causal attribution. The registry record identifies 95% confidence intervals as the planned form of dispersion but does not report their numerical limits for the primary outcome.
What does a single-group design allow?
In general, a single-group before-and-after analysis describes change among participants with measurements at more than one time point. A comparison of each participant's follow-up measurement with their baseline measurement can account for stable characteristics of that participant, but it cannot control for time-varying influences or show the counterfactual outcome without the intervention. A concurrent control group can help distinguish changes associated with an intervention from changes that may also occur without it. No comparator group is described in this record, so a between-group treatment effect is not available from its design.
Allocation is listed as not applicable, and masking as none. The record does not report a randomized allocation process or a masking procedure. In general, randomization is intended to reduce systematic differences between groups, and masking can reduce the influence of expectations on outcome assessment or reporting. These concepts explain why those design features matter; they do not establish that any particular bias occurred in this study.
How should follow-up counts be understood?
The record reports Week 48 data for 37 completed participants and Week 96 data for 32 completed participants. It also reports 15 screen failures among the enrolled 52 participants. In general, outcome counts can differ across time points because participants may not contribute measurements at every visit. The reasons for unavailable follow-up, the timing of any withdrawals, and the methods used to handle missing measurements are not reported in the registry record. Without those details, the potential for missing-data bias cannot be evaluated from the record.
An analysis restricted to participants with completed measurements can describe those observed participants, but it may not represent everyone enrolled if measurement availability is related to outcome or participant characteristics. This is a general concern, not evidence that the available participants in this trial differed in a particular way. The record does not state whether the analysis followed an intention-to-treat principle, used a per-protocol population, or used another defined population.
What can the registry's analysis description establish?
The record lists two outcome measures and one analysis. It identifies the primary endpoint as percent change in bone mineral density at the lumbar spine and hips from baseline to Weeks 48 and 96, and lists the percentage of participants with HIV viral load <50 copies/mL as a secondary outcome. The exact model, covariate adjustment, handling of repeated measurements, and prespecified testing hierarchy are not reported in the registry record. It is therefore not possible to determine from the record whether the two time points and anatomical sites were analyzed separately or jointly.
In general, measurements from the same participant across time are related rather than independent. Statistical methods for repeated measurements account for that dependence, but the registry record does not identify a specific method. Likewise, clinical measurements can show greater variability than a simple model anticipates. In general, over-dispersion means that observed variability exceeds what a model assumes; accounting for it can affect standard errors and confidence intervals. There is no information in the registry record to establish whether over-dispersion was assessed or whether it was relevant to these data.
What is the role of planning calculations?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, significance level, and analysis. It is not an observed result and is not observed power. The registry record does not report the trial's own sample-size justification or detailed planning assumptions. Any planning illustration based on an observed effect is distinct from the original design justification, and its assumptions should not be mistaken for trial findings. The numerical primary effect required for such an illustration is not reported in the registry record.
The record's endpoint specification identifies a mean and 95% confidence interval, but does not supply the numerical estimate, interval, or full analysis procedure. These omissions prevent assessment of statistical precision, model fit, or the robustness of the result. General explanations of these methods clarify what the analysis could mean, but they cannot replace unreported trial results or analysis details.
10. Multiplicity, Missing Data and Analysis Populations
The record lists two outcome measures: percent change in bone mineral density at the lumbar spine and hips from baseline to Weeks 48 and 96, and the percentage of participants with HIV viral load <50 copies/mL. It also lists one analysis. The record does not explain how those entries map to the analyses performed, whether each anatomical site and follow-up time was tested separately, or whether a particular outcome was designated as the sole primary statistical test.
In general, testing multiple outcomes, sites, or time points can increase the chance of at least one apparently notable result arising by chance. Statistical plans may address this through a prespecified hierarchy or an adjustment for multiple testing. Whether any such strategy was planned or used is not reported in the registry record. Numerical outcome results and p-values are also not reported in the registry record, so the consequences of multiplicity cannot be assessed from the posted information.
Missing-data information is limited to the completed-participant counts: Week 48 data were available for 37 participants and Week 96 data for 32. The record says that 15 of the enrolled 52 participants were screen failures. It does not report why other participants lacked measurements at each time point, how missing measurements were handled, or whether sensitivity analyses were conducted. In general, missingness can affect estimates when the availability of data is related to participant characteristics or outcomes; the record does not permit determining whether that concern applies.
The registry record does not identify an intention-to-treat, per-protocol, or other named analysis population. Nor does it report the statistical plan, interim analyses, or a sample-size justification. These details should not be inferred from the completed-participant counts or from the stated endpoint.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Raltegravir | 5 | 37 | 13.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Raltegravir | 23 of 37 |
Most frequent serious adverse event terms
| Event term | Organ system | Raltegravir |
|---|---|---|
| PARTNER PREGNANCY | Pregnancy, puerperium and perinatal conditions | 1 of 37 |
| RIGHT FLANK/QUADRANT PAIN | Musculoskeletal and connective tissue disorders | 1 of 37 |
| CEREBRAL ANEURYSM | Blood and lymphatic system disorders | 1 of 37 |
| LEFT KIDNEY STONES | Renal and urinary disorders | 1 of 37 |
| PROBABLE LUMBAR RADICULOPATHY | Musculoskeletal and connective tissue disorders | 1 of 37 |
| HOSPITAL ADMISSION FOR MALENA AND FEVERS | Gastrointestinal disorders | 1 of 37 |
| LOWER REPIRATORY TRACT INFECTION | Respiratory, thoracic and mediastinal disorders | 1 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Raltegravir |
|---|---|---|
| Upper Respiratory Tract Infection | Respiratory, thoracic and mediastinal disorders | 7 of 37 |
| Diarrhoea | Gastrointestinal disorders | 4 of 37 |
| Abdominal Cramps | Gastrointestinal disorders | 2 of 37 |
| Cold | Respiratory, thoracic and mediastinal disorders | 2 of 37 |
| Conjunctivitis | Eye disorders | 2 of 37 |
| Reflux | Gastrointestinal disorders | 2 of 37 |
| Sleep Apnoea | Respiratory, thoracic and mediastinal disorders | 2 of 37 |
| Viral Upper Respiratory Tract Infection | Respiratory, thoracic and mediastinal disorders | 2 of 37 |
Serious events with the highest arm-level rate: partner pregnancy (2.7%), right flank/quadrant pain (2.7%), cerebral aneurysm (2.7%), left kidney stones (2.7%), probable lumbar radiculopathy (2.7%).
For the raltegravir group, the registry lists 37 participants at risk for serious adverse events and 5 affected. For other adverse events, it lists 37 at risk and 23 affected. These are distinct registry categories; the figures do not identify the specific event count per participant, severity distribution within the other-adverse-event category, or the timing of events. Deaths are not reported in the registry record.
The listed serious adverse event terms are PARTNER PREGNANCY, RIGHT FLANK/QUADRANT PAIN, CEREBRAL ANEURYSM, LEFT KIDNEY STONES, PROBABLE LUMBAR RADICULOPATHY, and HOSPITAL ADMISSION FOR MALENA AND FEVERS. Each term is listed as 2.7%. The record does not provide further detail about the event narratives, their relationship to the study intervention, or the denominator and method underlying each displayed percentage. These terms should be read as registry event labels, not as evidence that the events were caused by raltegravir.
In general, adverse-event summaries describe events recorded during a study; they do not by themselves establish causality. Interpretation also depends on definitions, follow-up duration, ascertainment, and comparison with an appropriate control group. A single-group record cannot provide a like-for-like comparative safety estimate.
12. What the Result Does, and Does Not, Mean
The registry record identifies a clinical question about bone mineral density following a switch from tenofovir to raltegravir in adults with HIV and osteopenia or osteoporosis. It specifies the lumbar spine and hips, percent change from baseline, and assessments at Weeks 48 and 96. It also reports how many completed participants had data at those time points. These features establish what the primary endpoint was intended to measure and provide context for the available follow-up.
The record does not report numerical primary endpoint estimates or confidence intervals. Therefore, it does not allow readers to judge the observed direction or magnitude of change, or how precisely that change was estimated. The listed secondary outcome is the percentage of participants with HIV viral load <50 copies/mL, but its numerical result is also not reported in the registry record. The design and endpoint description alone are not evidence of a particular outcome.
Even if a within-group change were available, the single-group design would not directly show the difference between switching and continuing another regimen. In general, changes over time can reflect the intervention as well as other influences. Without a concurrent comparator, those influences cannot be separated using a between-group contrast. The design also does not establish that any recorded adverse event was caused by the intervention.
The available counts should be interpreted as counts of completed participants with data at specified follow-up times, alongside the record's screen-failure information. They do not describe all reasons for unavailable data or resolve whether the observed participants represent everyone enrolled. The analysis population and missing-data methods are not reported in the registry record.
Accordingly, the record describes the study question, design, endpoint, follow-up counts, and adverse-event summaries, but leaves the primary numerical findings and several analysis details unreported. Statistical conclusions about the size, precision, or cause of any bone mineral density change cannot be drawn from the registry record alone.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a clearly stated clinical question and the evidence needed to quantify its answer. The registry identifies a continuous primary outcome, the measurement locations, the baseline reference, and the follow-up times. It also specifies that the outcome was to be summarized as a mean with a 95% confidence interval. Yet the numerical estimates and intervals are not reported in the registry record. Without them, neither effect magnitude nor precision can be evaluated.
The single-group structure is also central to interpretation. A before-and-after design can describe observed change, but does not supply a concurrent estimate of what would have happened without switching. General statistical reasoning therefore distinguishes a change within one group from a causal effect attributable to a treatment strategy. The record's allocation and masking entries reinforce that no randomized, masked comparison is described.
Follow-up counts matter because the primary endpoint is assessed at more than one time point and data availability differs between Weeks 48 and 96. In general, estimates based on participants with observed measurements may be affected if follow-up availability is related to outcomes. The registry gives some counts but does not state the reasons for missing measurements or the methods used to address them. That makes the analysis population and potential selection effects important unresolved questions.
The record also lists a secondary viral-load outcome and serious and other adverse-event summaries. These broaden the scope of the study information, but they do not replace missing primary endpoint estimates or a comparative design. Multiplicity methods and a detailed statistical plan are not reported in the registry record. The statistical importance is therefore not a claim about a particular treatment effect; it is the need to distinguish a defined endpoint from unreported results, and within-group description from controlled comparison.
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 most direct limitation of the registry information is that numerical primary outcome results are not reported. The record identifies mean percent change and 95% confidence intervals as the outcome summary, but supplies no estimates for the lumbar spine or hips at either follow-up time. Numerical results for the secondary viral-load outcome are also not reported in the registry record.
The study is single group, with allocation listed as not applicable and no masking. It has no concurrent control group in the registry description, so it cannot provide a direct randomized comparison of switching with another strategy. The record's hypothesis describes a regimen context involving tenofovir disoproxil fumarate and a ritonavir-boosted protease inhibitor before the switch, and raltegravir with a ritonavir-boosted protease inhibitor after it. The intervention arm description itself is empty, and further regimen details are not reported in the registry record.
Follow-up data were available for 37 completed participants at Week 48 and 32 at Week 96, while 15 of the enrolled 52 participants were screen failures. Reasons for unavailable outcome data beyond the screen-failure statement, missing-data methods, and the defined analysis population are not reported in the registry record. The analysis model, covariate adjustment, repeated-measures approach, and sensitivity analyses are likewise not reported.
Multiplicity handling, interim analyses, and the trial's sample-size justification are not reported in the registry record. The adverse-event summary does not report deaths, event narratives, attribution, or the denominator and method behind each listed serious-event percentage. These limitations restrict assessment of outcome precision, missing-data impact, statistical robustness, and comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Switch From Tenofovir to Raltegravir for Low Bone Mineral Density — NCT00939874.
- Registry record last updated 2015-06-12; status last verified 2015-05.
- Results first posted 2015-06-12.
- 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.
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18. Record Summary
The completed Phase 4 study, sponsored by St Vincent's Hospital, Sydney, examined switching from tenofovir to raltegravir in adults with HIV and low bone mineral density. The registry lists enrollment of 52, a study start of 2009-10, and primary completion in 2012-06. It describes a single-group design, allocation not applicable, and no masking.
The primary endpoint was percent change in lumbar spine and hip bone mineral density from baseline to Weeks 48 and 96, summarized as a mean with a 95% confidence interval. Week 48 data were available for 37 completed participants and Week 96 data for 32; 15 enrolled participants were screen failures. Numerical primary and secondary outcome results, the detailed statistical plan, missing-data methods, and analysis-population definitions are not reported in the registry record.
The record lists serious and other adverse-event counts and six serious-event terms, each recorded as 2.7%. Deaths are not reported in the registry record. The single-group design does not provide a randomized comparison.