Optimizing Protein Intake in Older Americans With Mobility Limitations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Optimizing Protein Intake in Older Americans With Mobility Limitations (NCT01275365), a randomized phase 3 study. The primary outcome is Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA).

2. Clinical Question

The trial was designed to examine dietary protein intake and testosterone separately and together, according to the registry’s brief description. The posted primary outcome is a continuous measure in kilograms. The record reports arm-specific means and standard errors, with the number of participants contributing to each arm’s outcome result. Those outcome counts need not represent everyone enrolled or randomized, because the primary population is restricted to participants with data at the time point.

3. Trial Design

The registry describes a Phase 3 randomized, placebo-controlled, parallel-group trial with quadruple masking and a factorial model. The factorial arrangement crossed two protein-intake targets with testosterone or placebo injections, creating four treatment combinations. The trial record lists enrollment as 92. That enrollment figure is distinct from the arm-specific numbers with primary-outcome data.

The four groups were placebo with 0.8 g/kg/day protein, placebo with 1.3 g/kg/day protein, testosterone enanthate 100 mg intramuscularly weekly with 0.8 g/kg/day protein, and the same testosterone regimen with 1.3 g/kg/day protein. The registry’s brief summary identifies older community-dwelling men with mobility limitation and low protein intake as the intended population. The listed condition is Mobility Limitation.

The trial is marked completed. The registry records a start date of 2011-05 and primary completion on 2017-01-19. Brigham and Women's Hospital is listed as sponsor. The primary outcome was change in DXA-measured lean body mass at 6 months from baseline. The posted outcome population is all randomized and treated participants with data available at that time point.

The record does not report the allocation ratio, the detailed masking procedures, or how the factorial components were handled in the original statistical analysis. The sponsor’s original sample-size justification, planned primary analysis, interim analyses, and analysis population beyond the stated outcome definition are not reported in the registry record. The four arm descriptions establish the treatment combinations, but do not reveal whether the original analysis emphasized factorial main effects, individual arm contrasts, or both.

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: All randomized and treated participants with data available at the given time-point.

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 Change in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DXA), measured over 6 months from baseline.

Lean body mass is the amount of body mass attributed to lean tissue rather than fat. The registry specifies dual-energy X-ray absorptiometry (DXA) as the measurement method and defines the primary endpoint as change from baseline, in kilograms, at 6 months. Change scores describe how the measured quantity shifted over the study period, rather than simply comparing final measurements without reference to baseline.

Lean body mass is relevant to a trial involving mobility limitation because it provides a body-composition measure that can be considered alongside physical performance outcomes. It is not itself a direct measure of walking, strength, or day-to-day function. The registry lists several physical-function and well-being outcomes as secondary measures, but the primary endpoint remains DXA-measured lean body mass.

The posted statistic is the mean change for each treatment group, accompanied by a standard error. A group mean describes the average observed change among participants contributing data in that group. The standard error describes the precision of that estimated mean; it is not the spread of individual participant measurements. The registry does not provide arm-level confidence limits for these means.

The record identifies the endpoint and measurement time, but does not report details such as DXA acquisition procedures, quality-control procedures, or how missing baseline or follow-up measurements were handled. Those details should not be inferred from the choice of endpoint or instrument.

7. Results Posted in the Registry

• Placebo/High Protein: mean 0.74 versus 0.14 on control; difference 0.60 (95% CI -0.29 to 1.49), standardized effect d = 0.41; z-test p = 0.185.
• Testosterone/Low Protein: mean 4.43 versus 0.14 on control; difference 4.29 (95% CI 3.17 to 5.41), standardized effect d = 2.54; z-test p = <0.001.
• Testosterone/High Protein: mean 4.13 versus 0.14 on control; difference 3.99 (95% CI 2.97 to 5.01), standardized effect d = 2.45; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change of Leg Press Power

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Testosterone/Low Protein: mean 61.50 versus 26.90 on control; difference 34.60 (95% CI -20.20 to 89.40), standardized effect d = 0.46; z-test p = 0.216.
  • Testosterone/High Protein: mean 81.70 versus 26.90 on control; difference 54.80 (95% CI 8.91 to 100.69), standardized effect d = 0.96; z-test p = 0.019.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Testosterone/Low Protein and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Testosterone/High Protein than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Change of 6-minute Walking Distance

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Placebo/High Protein: mean 49.90 versus 44.20 on control; difference 5.70 (95% CI -39.08 to 50.48), standardized effect d = 0.09; z-test p = 0.803.
  • Testosterone/Low Protein: mean 38.20 versus 44.20 on control; difference -6.00 (95% CI -61.44 to 49.44), standardized effect d = -0.07; z-test p = 0.832.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo/High Protein and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Testosterone/Low Protein and the control. The interval gives the range of effects that remain compatible with the data.

Change of 50-meter Loaded Walking Test

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Placebo/High Protein: mean 0.11 versus 0.15 on control; difference -0.04 (95% CI -0.17 to 0.09), standardized effect d = -0.25; z-test p = 0.532.
  • Testosterone/Low Protein: mean 0.06 versus 0.15 on control; difference -0.09 (95% CI -0.22 to 0.04), standardized effect d = -0.53; z-test p = 0.160.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Placebo/High Protein and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Testosterone/Low Protein and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes spanning strength, power, walking performance, stair climbing, self-reported physical function, psychological well-being, and fatigue. The posted secondary results cover measures of leg press power, six-minute walking distance, and the 50-meter loaded walking test. These outcomes address aspects of function and well-being that are related to, but not interchangeable with, lean body mass.

Across the posted secondary comparisons, the pattern is not uniform. Some recalculated contrasts have intervals that include zero, while one leg press power contrast has an interval excluding zero and an unadjusted p-value of 0.019. The posted walking comparisons have intervals that include zero. These secondary findings do not form a consistent demonstration of change across all functional measures, and the registry does not report a coherent adjusted analysis across outcomes.

The secondary outcomes provide context for the primary body-composition endpoint, but they do not validate or explain it automatically. A difference in lean body mass does not necessarily imply a difference in walking or self-reported function. Likewise, a secondary measure can show a different pattern without contradicting the primary result, because each measures a different construct and has its own uncertainty.

Unadjusted secondary results carry less weight when many outcomes and comparisons are examined. With multiple opportunities to observe a low p-value, some results may appear notable by chance. The registry does not report a multiplicity adjustment, a hierarchy for secondary hypotheses, or sponsor inferential analyses for the secondary outcomes. The secondary results are therefore best treated as exploratory signals rather than definitive evidence across functional domains. Results for other listed outcomes are not reported in the registry record.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change of Maximal Voluntary Strength
• Change of Leg Press Power
• Change of 6-minute Walking Distance
• Change of Stair Climbing Tests
• Change of 50-meter Loaded Walking Test
• Change of Self-reported Physical Function Domain of Short Form Health Survey (SF-36)
• Change of Psychological Well Being Index (PGWBI)
• Change of Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale

9. Statistical Interpretation

10. Statistical Methods Explained

What does an arm mean describe?

The primary outcome is continuous, and the registry reports a mean change for each treatment group. A mean is an average over the participants whose outcome data contribute to that group’s result. The reported sample counts differ by arm, and the registry’s outcome definition restricts the population to randomized and treated participants with data available at the time point. The arm means therefore describe observed data in those outcome populations; they are not automatically estimates for every participant enrolled.

The standard error (SE) measures the sampling precision of an estimated mean. It is different from a standard deviation, which describes variability among individual observations. A smaller SE generally corresponds to a more precisely estimated mean, all else being equal. The record reports SEs rather than standard deviations for the primary endpoint. Arm-level confidence intervals are not reported.

What is a mean difference?

A mean difference compares the estimated average change in one group with the average change in a reference group. For the recalculated primary contrasts, placebo/low protein is the reference. The difference is expressed in the endpoint’s units, kilograms. The contrast between two groups answers a narrower question than the factorial design’s broader questions about the average effect of protein assignment, the average effect of testosterone assignment, and whether the effect of one factor depends on the other.

The registry presents four treatment combinations, but does not report a factorial model or its estimates. The recalculated pairwise comparisons should therefore not be described as factorial main effects or as evidence about interaction. A formal interaction analysis would assess whether the contrast associated with one factor changes across levels of the other factor. Such an analysis is not reported in the registry record.

How should confidence intervals and p-values be understood?

A confidence interval gives a range of values compatible with the observed estimate under the method’s assumptions. A wider interval indicates less precision than a narrower interval. For a mean difference, an interval that includes zero is compatible with no difference as well as with differences in either direction. An interval that excludes zero indicates that zero is not among the values in that interval, but does not establish clinical importance or eliminate bias and design limitations.

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null model. It is not the probability that the null hypothesis is true, nor a measure of the size or importance of a difference. The posted primary p-values are unadjusted recalculations, not reported sponsor analyses. The registry record does not specify a sponsor p-value method or multiplicity procedure for the primary outcome.

For the primary comparisons, the recalculated confidence intervals for the testosterone groups versus placebo/low protein exclude zero, while the interval for placebo/high protein versus placebo/low protein includes zero. The corresponding unadjusted p-values are < 0.001, < 0.001, and 0.185. These are pairwise results and should be interpreted as such, rather than as a complete analysis of the factorial questions.

What does the recalculation represent?

The recalculated contrasts use the posted means, SEs, and group counts. They are simple unadjusted comparisons of group summaries. The registry does not report adjusted estimates, covariates, model diagnostics, or the sponsor’s inferential analyses. Since no discrepancy is flagged between these recalculations and a sponsor analysis, there is no reported difference to reconcile; however, the absence of a discrepancy does not turn these calculations into the trial’s prespecified analysis.

General statistical context: analyses based on group summaries may not account for baseline values, stratification, repeated measurements, or other design features. Whether any such features were used in the trial’s own analysis is not reported in the registry record. The recalculations should not be interpreted as proof that the original analysis used the same assumptions.

Why can over-dispersion matter?

General statistical context: over-dispersion occurs when observed variability is greater than a model assumes. If a model underestimates variability, standard errors can be too small and intervals too narrow; if it accounts for the variability appropriately, uncertainty is represented more realistically. This concept is especially important for outcomes whose variation is not well described by a simple distributional model. The posted primary endpoint is continuous, and the registry does not report evidence of over-dispersion, diagnostic checks, or a model that would require a particular correction. No conclusion about this issue can be drawn from the summary statistics alone.

How do planning illustrations differ from trial power?

The planning illustrations use an observed contrast as a basis for hypothetical future sample sizes. They state the assumed significance level, allocation, and normal approximation, and show results for specified fractions of the observed effect. These are planning calculations, not the trial’s original design justification. The registry’s own sample-size assumptions and justification are not reported in the registry record. The illustrations do not say what probability this completed trial had of detecting an effect before it began.

11. Confidence Intervals and Precision

The precision of the primary arm means is reflected in their standard errors: 0.31 kg for placebo/low protein, 0.33 kg for placebo/high protein, 0.48 kg for testosterone/low protein, and 0.42 kg for testosterone/high protein. These standard errors quantify uncertainty in estimated group means, not the range of changes among individual participants. The registry does not report confidence intervals for the arm means themselves.

The recalculated mean difference for placebo/high protein versus placebo/low protein is 0.6 kg, and its confidence interval includes zero. This interval is compatible with no difference as well as with a range of positive or negative differences. The recalculated contrasts of testosterone/low protein and testosterone/high protein against placebo/low protein have intervals that exclude zero. Their unadjusted p-values are both < 0.001. The interval limits are not repeated because the posted limits include more than three decimal places.

Precision and statistical significance are related but are not interchangeable. An interval may be narrow enough to exclude zero yet still cover effects with different practical importance. Conversely, an interval that includes zero may also include effects that could matter. The registry does not specify a threshold for a clinically important change in lean body mass, so the clinical relevance of the estimates cannot be determined from statistical precision alone.

The available outcome counts are modest within each arm, and the standard errors reflect the uncertainty associated with the posted data. The registry does not report missing-data methods or sensitivity analyses, so the intervals and recalculations do not address potential bias from unavailable outcome measurements. They quantify uncertainty under the calculation assumptions, not all sources of uncertainty in the trial.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are for continuous outcomes and express participants per arm, not total events. They are planning calculations based on the observed effect, not the sample-size assumptions used to design this trial. The registry record does not report the trial’s original design assumptions or sample-size justification.

The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. For each such assumed effect, the 80% power column gives the number of participants per arm for a design with an 80% chance of detecting that effect under the calculation assumptions. The 90% power column gives the corresponding per-arm number for a 90% chance. These are hypothetical planning targets, not evidence about what happened in the completed trial.

The rows for 100%, 75%, and 50% of the observed effect illustrate how the required sample size changes as the assumed target changes. Smaller effects need more participants to detect, all else being equal. The calculations can therefore be useful for understanding the scale of a future study under specified assumptions, but their estimates depend strongly on the observed effect used as the starting point.

These values are not observed power. Observed power is not a substitute for interpreting the estimated effect and its uncertainty. The planning figures do not establish that the trial was adequately powered for its original aims, because its original assumptions are not reported in the registry record. They also do not account for any multiplicity, missingness, or factorial-model considerations unless explicitly included in the stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.600; pooled standard deviation σ = 1.467.
2. n = 2 × (1.96 + 0.842)² × 1.467² / 0.600² = 93.9, rounded up to 94 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.6                      # observed difference in means
sigma <- 1.46714007511212                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1275365)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 94 (80% power), 126 (90% power)
 75% of observed effect: n per arm = 167 (80% power), 224 (90% power)
 50% of observed effect: n per arm = 376 (80% power), 503 (90% power)
power.t.test: 94.8 
Simulated power at n = 94 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The trial has a factorial arrangement and multiple listed outcomes. The registry does not report how the original analysis addressed multiple treatment contrasts, multiple outcomes, or the factorial structure. In particular, no multiplicity adjustment, testing hierarchy, or distinction between confirmatory and exploratory hypotheses is reported in the registry record.

The recalculated p-values are unadjusted pairwise comparisons against placebo/low protein. They do not account for the number of comparisons being considered. As a result, the p-values should not be read as if they were adjusted evidence from a prespecified family of tests. The registry also does not report factorial main-effect or interaction estimates, so the pairwise contrasts do not answer whether protein intake modifies the testosterone-associated contrast.

The primary outcome population is described as all randomized and treated participants with data available at the given time point. This definition does not include participants without outcome data at that time point. The registry does not report how many participants lacked measurements, reasons for missingness, imputation procedures, or sensitivity analyses. It is therefore not possible to assess from the record whether missing outcome data could have influenced the posted means.

The original analysis population and handling of departures from assigned treatment are not reported beyond the stated primary outcome definition. The registry does not report whether analyses followed an intention-to-treat approach, whether participants were analyzed according to treatment received, or whether per-protocol analyses were conducted. Interim analyses, stopping rules, and the sponsor’s planned statistical methods are also not reported in the registry record.

These omissions limit assessment of the results’ robustness and confirmatory status. They do not establish that the trial lacked such procedures; they mean those details cannot be evaluated from the registry record.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chronic obstructive pulmonary disease (4.5%), fall (4.2%), dizziness (4.2%), ischaemic stroke (4.2%), dyspnoea (4.2%).

The registry lists serious adverse events by treatment group, with the number at risk and the number affected. Serious events were recorded for 2 of 24 at risk in placebo/low protein, 2 of 24 in placebo/high protein, 0 of 22 in testosterone/low protein, and 1 of 22 in testosterone/high protein. Deaths were recorded as 0 in each group. These are registry counts and should be read in the context of the stated at-risk groups.

The record also lists serious adverse event terms including chronic obstructive pulmonary disease at 4.5%, and fall, dizziness, ischaemic stroke, dyspnoea, and hypotension at 4.2% each. The record does not establish that an event was caused by an assigned treatment. These counts and terms alone do not permit a comparative safety conclusion; the registry does not provide adjusted analyses or detailed event timing in the information.

Serious adverse events are not the same as all adverse events. The other adverse-event counts were 20 of 24, 21 of 24, 21 of 22, and 15 of 22 across the four groups in the order. The registry’s categories and counts should be kept distinct, and no additional rates or totals are inferred from them.

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

The posted results describe the average six-month change in DXA-measured lean body mass for each treatment combination among participants with available outcome data. The means were higher in the testosterone groups than in the placebo/low-protein group, and the unadjusted recalculated pairwise contrasts against that reference had confidence intervals excluding zero. The placebo/high-protein contrast against the reference had a confidence interval that included zero.

Those observations are not a complete answer to the trial’s stated factorial aim. Pairwise contrasts against one group do not estimate the average contribution of protein assignment across testosterone groups, the average contribution of testosterone assignment across protein groups, or their interaction. The registry does not report those factorial estimates. It also does not report a sponsor analysis of the primary outcome, so the recalculated comparisons should not be mistaken for the trial’s original inferential result.

The results do not establish whether changes in lean body mass corresponded to meaningful changes in mobility, strength, or daily functioning. Those are distinct outcomes, and the secondary results are limited and unadjusted. The record does not specify a threshold for a clinically important change in lean body mass, nor does it provide evidence on persistence beyond 6 months.

The findings apply to the recorded trial population: community-dwelling older men with mobility limitation and low protein intake. They should not be assumed to apply to other populations or settings. The available registry information also does not establish treatment causality for the adverse events or resolve the effect of missing outcome data.

Statistical evidence is not the same as a treatment recommendation. These results characterize estimates and their uncertainty; they do not by themselves determine an individual’s care or establish a broad clinical conclusion.

17. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a factorial design with a continuous primary endpoint and several related secondary outcomes. The four treatment combinations make it possible in principle to ask about protein, testosterone, and whether their effects depend on one another. Yet the posted pairwise comparisons use one combination as a reference and do not report the factorial estimates. This distinction matters: a set of arm contrasts does not automatically answer the design’s full scientific questions.

The record also illustrates why an estimate should be read with its uncertainty. The primary group means show different observed changes, while the standard errors and confidence intervals indicate how precisely those changes and contrasts are estimated. A small p-value does not express the magnitude’s practical importance, and a non-significant result does not prove that groups are equivalent.

Planning figures based on observed effects are another useful teaching point. They show how the required per-arm size depends on the assumed effect and target power, but they are not the trial’s original design justification and are not observed power. The original sample-size assumptions are not reported in the registry record.

Finally, registry reporting is part of statistical interpretation. Missing details about multiplicity, missing data, factorial analysis, and sponsor inferential methods constrain what can be concluded from posted summaries. Recognizing those boundaries is as important as reading the numerical estimates.

18. Limitations

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

Several limitations are specific to the available record. Although the trial is described as factorial, the posted primary comparisons are pairwise contrasts against placebo/low protein. Main effects for testosterone and protein, and an interaction estimate, are not reported in the registry record. The design’s central separate-and-combined questions therefore cannot be fully assessed from these results.

The primary endpoint population includes randomized and treated participants with data at the time point, but the registry does not report missing-data counts, reasons, or methods. The number contributing to the outcome differs across arms. Without information about missingness or sensitivity analyses, the potential effect of unavailable measurements cannot be assessed.

The registry lists multiple secondary outcomes, while only some secondary outcome results are reported in the available results. Multiplicity handling, prespecified outcome hierarchy, and sponsor analyses are not reported. The secondary contrasts should therefore be interpreted cautiously, particularly when an isolated unadjusted result appears notable.

The original sample-size justification and statistical plan are not reported. The planning illustrations based on observed effects do not resolve whether the trial was designed with adequate precision for its original hypotheses. The registry also does not provide arm-level confidence intervals for the primary means, a clinically important-change threshold, or longer-term primary-outcome results.

Generalizability is bounded by the described population: community-dwelling men aged 65 years or older with mobility limitation and low protein intake. The registry information does not establish applicability to other populations. These limitations concern what can be evaluated from the reported record; they do not show that unreported procedures were absent.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Optimizing Protein Intake in Older Americans With Mobility Limitations — NCT01275365.
• Registry record last updated 2021-07-29; status last verified 2021-07.
• Results first posted 2018-02-19.
• 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.

22. Record Summary

The registry record describes a completed randomized Phase 3 factorial trial of testosterone and protein-intake targets in community-dwelling older men with mobility limitation and low protein intake. It lists quadruple masking, placebo injections, and four treatment combinations crossing testosterone enanthate 100 mg intramuscularly weekly or placebo with 0.8 g/kg/day or 1.3 g/kg/day protein.

The primary outcome was mean change in DXA-measured lean body mass at 6 months from baseline. Posted arm means and standard errors are available, along with recalculated unadjusted pairwise comparisons against placebo/low protein. The registry does not report the sponsor’s primary inferential analysis or factorial main-effect and interaction estimates.

Secondary outcomes include physical performance and self-reported measures. Safety counts and serious adverse event terms are also recorded. Multiplicity procedures, missing-data methods, and the trial’s original sample-size justification are not reported in the registry record.