Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM).: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM). (NCT01769469), a registered phase not stated study. The primary outcome is Magnitude of Change (Fold Change) in Parathyroid Hormone (PTH) From Baseline to Week 48.

2. Clinical Question

3. Trial Design

This is a prospective observational cohort sub-study associated with ATN 110 and ATN 113. The registry describes those parent studies as prospective interventional trials, while stating that this sub-study itself has no treatment or intervention. Participants in the sub-study were to be taking daily coformulated emtricitabine and tenofovir (FTC/TDF) through their parent-study participation. This distinction matters: the record is examining measurements during that treatment context, not describing random assignment of a treatment within the sub-study.

The study title and official title identify HIV-uninfected young men who have sex with men as the population of interest. The arm description says that a subset of participants enrolled in ATN 110 or ATN 113 would be recruited. Enrollment for the record is listed as 101; the arm description refers to a subset of 100 participants. These are separate registry statements, and the record does not explain the difference. The primary endpoint population is narrower in definition: participants with PTH data at baseline and Week 48.

The primary endpoint timeframe is baseline and Week 48. The record also lists secondary outcomes concerning FGF23 and 1,25 OHD, including changes, fold-change magnitude, most extreme fold change, and timing of the most extreme fold change. It lists 125 outcome measures and 43 analyses, indicating that the registry record contains a broad set of outcome and analysis entries. Those counts do not identify which results are available for interpretation in this description.

The study status is COMPLETED. The start is recorded as 2012-11 and primary completion as 2015-11. The registry record does not report a separate control group, a randomized allocation for this sub-study, or numerical results for the primary endpoint. As an observational, within-participant baseline-to-follow-up assessment, it can describe change over time, but the design does not by itself isolate the effects of FTC/TDF from other changes over the same period.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Subjects with PTH data at baseline and Week 48

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 Magnitude of Change (Fold Change) in Parathyroid Hormone (PTH) From Baseline to Week 48, measured over Baseline and Week (wk) 48.

The primary endpoint is the magnitude of change in parathyroid hormone (PTH) from baseline to Week 48, expressed as fold change. The registry identifies the summary measure as the median and the dispersion as the full range. The endpoint population consists of subjects with PTH data at baseline and Week 48. Thus, the primary measure concerns participants with observations at both specified time points rather than necessarily every person enrolled in the cohort.

In general, a fold change expresses a later measurement relative to a baseline measurement. A value of one conventionally represents no relative change; values above or below one represent relative increases or decreases, respectively. This is a general interpretation of fold-change measures, not a statement about the observed PTH values in this study. The registry’s endpoint description says the magnitude of change is the fold change compared with baseline and states that multiplying it by 100 would give percent change from baseline. The numerical PTH fold changes are not reported in the registry record, so neither the direction nor size of the observed change can be stated.

A median describes the midpoint of the observed values and is less influenced by extreme values than a mean. The full range describes the lowest and highest observed values, giving a sense of the spread while remaining sensitive to extremes. Used together, these summaries can communicate a typical fold change and the observed extent of variation. They do not, on their own, quantify uncertainty around the median or establish a causal treatment effect. The registry record does not report a confidence interval or a numerical primary result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint uses fold change, a relative measure comparing a follow-up value with a baseline value. In general, this kind of measure puts change on a ratio scale rather than reporting the raw difference between measurements. A fold-change value near one indicates little relative movement, while a value farther from one indicates a larger relative movement. This is a general explanation only; no observed PTH fold-change value is reported in the registry record. The registry’s description specifies baseline and Week 48 as the comparison times and defines the primary population as participants with PTH data at both.

Why report a median?

The median is the middle value after observations are ordered. It is often useful when data are skewed or contain extreme observations, because a small number of unusually high or low values have less influence on the median than on the mean. That general property does not establish that PTH fold changes in this cohort were skewed. The registry labels the endpoint summary as a median but does not report the distribution of observed values, a mean, or other information that would permit a distributional assessment.

The full range complements the median by describing the lowest and highest observed values. It communicates the observed span, but it is sensitive to extreme values and does not indicate how densely observations are distributed between the endpoints. A range also does not quantify the uncertainty of the median. In general, a confidence interval can convey uncertainty around an estimated quantity under a specified analysis; no confidence interval for this primary endpoint is reported in the registry record.

What can a baseline-to-follow-up contrast establish?

A change from baseline to follow-up describes how a measured outcome differs across the specified time points. Repeated measurements can account for each participant’s starting measurement when defining that participant’s change. This is different from comparing separate treatment groups. In this study record, the stated endpoint is a change during a period when participants were taking FTC/TDF through parent studies, but the sub-study itself is observational and has no intervention. A before-and-after pattern alone cannot separate a treatment effect from time trends, co-occurring events, or other factors.

For causal interpretation, a suitable comparison group and an analysis plan addressing differences between groups would generally be important. The registry record does not describe such a comparison for this sub-study. It also does not report an allocation method for the sub-study. The parent studies are described as interventional, but their design details should not be assumed to define the methods of this observational sub-study. Accordingly, the record supports describing the intended longitudinal measurement, not attributing a change to treatment.

How should uncertainty and variability be distinguished?

In general, variability describes differences among observed participants, whereas statistical uncertainty describes how precisely a population quantity has been estimated from the observations. The full range is a measure of observed spread; it is not a confidence interval. A median can be accompanied by an interval estimate to convey uncertainty, but the registry record does not report one for the primary endpoint. Without numerical outcome data and an uncertainty estimate, the magnitude and precision of the PTH result cannot be evaluated.

Repeated biological measurements may also vary within participants and across time. In general, measurement error and natural variability can affect observed change. Statistical methods may account for repeated observations, distributional features, or other covariates, depending on the study design. The registry does not report the analysis model, transformations beyond the fold-change endpoint definition, covariate adjustment, or handling of within-participant correlation. Those methods must not be inferred from the endpoint label alone.

What do the planning assumptions mean?

The registry’s planning illustration is described as a calculation from an observed effect, not as the trial’s own design. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such calculations ask what sample size might be needed under specified assumptions to detect a target effect at a chosen significance level and power. They are planning illustrations, not evidence that the study was designed or conducted with those assumptions.

The record’s sample-size description distinguishes participants per arm for non-time-to-event calculations from the total number of events for time-to-event calculations. These are different units and should not be conflated. In either case, a planning calculation is not observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty; the illustration cannot establish that the study was adequately powered for its primary endpoint. The registry does not report the study’s own sample-size justification or statistical plan.

The planning assumptions refer to two arms even though the sub-study record does not describe a randomized, like-for-like two-arm comparison. That planning setup should therefore be understood as a hypothetical calculation framework, not as evidence of the actual cohort structure or allocation. No numerical planning estimates or observed primary effect are reported in the registry information available for this analysis.

What cannot be reconstructed?

The registry identifies the endpoint and its summary format, but does not provide the numerical PTH result, a confidence interval, a test statistic, a p-value, or the analysis model. It also does not report the number of participants with complete PTH measurements, missing-data procedures, or adjustment for multiple outcomes. No unadjusted recalculation can be made without posted summary statistics. The record’s description of 125 outcome measures and 43 analyses does not fill those gaps or establish which analyses were prespecified.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a broad set of outcomes, including PTH as the primary endpoint and secondary measures involving FGF23 and 1,25 OHD. It records 125 outcome measures and 43 analyses. When many outcomes or analyses are considered, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can address that issue by adjusting inference or by defining a hierarchy of outcomes. The registry record does not report whether any multiplicity adjustment, outcome hierarchy, or prespecified analysis plan was used. It is therefore not possible to assess how the listed outcomes were handled statistically.

The primary endpoint applies to participants with PTH data at baseline and Week 48. This means the endpoint population is defined by availability of measurements at both time points. The record does not state how many participants met that definition, whether missingness occurred, why any measurements were missing, or whether the analysis used imputation or another missing-data method. It also does not describe sensitivity analyses for missing data. These omissions limit assessment of whether the analyzed participants might differ from those without complete measurements.

The registry lists enrollment as 101 and describes a subset of 100 participants in the arm description, but does not explain the relationship between those entries. Neither entry identifies the number contributing to the primary PTH analysis. The reported adverse-event fields also do not provide an interpretable at-risk denominator. Analysis populations for the primary outcome and adverse events therefore cannot be reconstructed from the record.

The record does not report an intention-to-treat population, a per-protocol population, or rules for inclusion in analyses beyond the PTH endpoint’s requirement for measurements at both time points. These terms should not be assigned to the cohort without a stated analysis definition.

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

The study addresses a relevant statistical question: how renal, endocrine, and bone-related measurements, including PTH, change over time among HIV-uninfected young men who have sex with men taking FTC/TDF through parent studies. Its observational cohort structure and baseline-to-Week-48 endpoint are suited to describing measured change in the participants who have the required observations. The registry record does not report the numerical primary result, so the direction, size, and spread of PTH change cannot be described.

Even if a change were reported, a before-and-after difference in an observational cohort would not by itself show that FTC/TDF caused it. Without a separate comparison group and a design or analysis that addresses competing explanations, changes over time may reflect multiple influences. The parent studies are described as interventional, but this sub-study’s record says it has no intervention. The parent studies’ methods cannot be assumed to resolve the causal limitations of this sub-study.

The median and full range would describe the center and observed span of fold changes, but they would not alone show the precision of the estimate. A confidence interval, participant-level information, and a clearly described analysis would help evaluate uncertainty. Those details are not reported for the primary endpoint in the registry record. Nor does the endpoint definition establish a clinical threshold or the importance of a particular magnitude of change.

The outcome list indicates that the record encompasses measures beyond PTH, but listing an outcome is not the same as reporting its result. The reported counts of outcome measures and analyses do not show which findings were statistically persuasive, whether analyses were adjusted for multiplicity, or how missing measurements were addressed. Likewise, the adverse-event fields cannot establish an absence of events because their at-risk values are zero and deaths are null.

Accordingly, the record supports a description of the study’s question, design, endpoint definition, and reporting gaps. It does not support a conclusion about the observed PTH change, the effects of treatment, safety, or clinical benefit. Those conclusions would require interpretable outcome results and methods details not reported in the registry record.

12. Why This Trial Matters Statistically

This study is statistically notable for focusing on repeated renal, endocrine, and bone-related measurements in a population described as HIV-uninfected young men who have sex with men. Its primary endpoint expresses PTH change relative to baseline and uses a median with a full range. That combination makes the endpoint’s scale and summary choices important: a typical relative change and the observed spread are different features of the data, and neither is a measure of uncertainty by itself.

The distinction between the parent trials and this sub-study is also important. FTC/TDF exposure is part of the participants’ parent-study context, while this record describes an observational cohort with no treatment or intervention of its own. Recognizing that distinction prevents a descriptive longitudinal analysis from being mistaken for a randomized treatment comparison. It also clarifies what the study can address: measurements over time in the cohort, rather than an isolated causal treatment contrast.

The record lists a wide outcome and analysis scope, with 125 outcome measures and 43 analyses. Such breadth makes transparency about prespecification, multiplicity, missing data, and analysis populations especially useful. These methods are not reported in the registry record. Their absence prevents readers from determining how to interpret a collection of outcomes or how robust the analyses may be.

Finally, this record illustrates why endpoint definitions and results must be considered separately. The primary endpoint is clearly described as a fold change from baseline to Week 48, but its numerical estimate and uncertainty are not reported in the registry information. Without those results, statistical interpretation remains limited to the study’s intended measurement and design rather than the magnitude or precision of any observed finding.

13. 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 for interpreting the study’s findings is that the numerical primary endpoint result is not reported in the registry record. No PTH fold-change estimate, range, confidence interval, test statistic, or p-value is available in the information. As a result, the observed direction, magnitude, and precision of change cannot be assessed.

The design is observational, with participants taking FTC/TDF through ATN 110 or ATN 113 and no treatment or intervention assigned within this sub-study. The registry does not describe a separate control group or a like-for-like treatment comparison. Any observed change over time would therefore be descriptive and would not, on its own, establish that treatment caused the change.

The primary endpoint population is limited to participants with PTH data at baseline and Week 48. The registry does not report the number meeting this requirement, missing-data reasons, or missing-data methods. The enrollment entry and the arm description give different counts, 101 and 100, without explanation. The record does not identify how many participants contributed to the primary analysis.

Although the registry lists 125 outcome measures and 43 analyses, it does not report a statistical analysis plan, multiplicity procedures, adjustment variables, or analysis-population rules. Adverse-event fields show zero at-risk values and list deaths as null, which does not permit a meaningful assessment of event occurrence. These reporting limitations are specific to the information available in this trial record and constrain both outcome interpretation and appraisal of analysis methods.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Renal, Endocrine, and Bone Changes in Response to FTC/TDF in Uninfected Young Men Who Have Sex With Men (YMSM). — NCT01769469.
• Registry record last updated 2019-03-27; status last verified 2018-11.
• Results first posted 2019-03-11.
• 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.

17. Record Summary

The registry record concerns a completed prospective observational cohort sub-study linked to ATN 110 or ATN 113. Its title identifies HIV-uninfected young men who have sex with men, and its primary endpoint is the median fold change in PTH from baseline to Week 48, with the full range as the dispersion measure. The sub-study itself has no treatment or intervention; participants were taking daily FTC/TDF through their parent studies.

Enrollment is listed as 101, while the arm description refers to a subset of 100 participants. The primary endpoint population is defined by availability of PTH data at both specified time points. Secondary outcomes include FGF23 and 1,25 OHD measures. The record lists 125 outcome measures and 43 analyses.

The numerical primary result, its uncertainty, the analysis plan, missing-data methods, and multiplicity procedures are not reported in the registry record. The observational design does not provide a stated treatment comparison for this sub-study, so the record describes an intended longitudinal assessment rather than an isolated causal treatment effect.