Subcutaneous vs. Intramuscular Testosterone: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subcutaneous vs. Intramuscular Testosterone (NCT03091348), a randomized phase 4 study. The primary outcome is Change in Levels of Serum Total Testosterone Concentration.

2. Clinical Question

The central statistical question is therefore a within-participant comparison: does the measured total testosterone concentration change differently when the same participant receives subcutaneous rather than intramuscular testosterone? A crossover structure can support this kind of comparison because each participant is intended to receive both treatments, so comparisons may account for characteristics that remain stable within a person. That potential advantage depends on the measurements, treatment sequence, timing, and analysis being reported and handled appropriately.

The brief summary also names calculated free testosterone and a questionnaire about overall patient experience as endpoints. The registry record lists several secondary outcomes, including hormone measures, PSA, hematocrit, questionnaire responses, and symptom scores. These stated aims do not establish that results were collected, analyzed, or favorable. The record does not report numerical findings for the primary outcome or the listed secondary outcomes, so it cannot establish the size or direction of any route-related difference.

3. Trial Design

The registry describes NCT03091348 as a phase 4, randomized, unmasked crossover study of subcutaneous and intramuscular testosterone therapy. The listed status is completed. The start date is 2017-08-29, and the primary completion date is 2017-11-21. Men's Health Boston is listed as the sponsor.

Randomization assigned participants to an order of treatments rather than to a single route for the entire study. The SQ - IM sequence is described as a subcutaneous injection followed by an intramuscular injection. The IM - SQ sequence reverses that order. The brief summary says participants would receive both routes. In a crossover study, the intended comparison is within the same participant across treatment periods, while randomizing order can help avoid systematically assigning one route first to everyone.

The study is listed as unmasked, meaning the registry does not indicate masking of participants or study personnel. Details about how treatment periods were separated, the interval between injections, the timing of blood draws relative to injections, and how possible carryover effects were addressed are not reported in the registry record. Those details matter for interpreting measurements across periods, but their absence does not establish how the study was conducted.

The listed enrollment is 4, whereas the brief summary describes 20 subjects. The registry record does not explain why these figures differ or which figure corresponds to enrollment for the completed study. It also does not report the randomization method, sequence-group counts for the primary outcome, or a flow of participants through the study. The primary outcome is specified at Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7, but the record does not explain how these visits map to treatment periods or which visits contribute to a particular route comparison.

The registered primary outcome concerns change in serum total testosterone concentration. No primary outcome results or analyses are posted in the record. Consequently, the design description identifies the intended comparison but does not supply evidence about the observed difference between routes.

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: loss to follow up

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: Participants analyzed is 0 and 1 due to loss to follow up

6. Primary Endpoint

The registry lists the primary outcome as Change in Levels of Serum Total Testosterone Concentration, measured over "Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7".

The primary endpoint is titled “Change in Levels of Serum Total Testosterone Concentration,” with units of ng/dl. The registry describes blood samples measured using Beckman assays and equipment. The listed timeframe is Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7. The stated objective is to measure testosterone concentrations after the two administration routes and assess whether they differ.

As a general statistical concept, a concentration measurement can represent a biological response at a specified sampling time. Comparing changes can focus attention on how measurements vary across treatment periods rather than only on a single value. In a crossover design, interpretation depends on knowing the relation between each measurement and the route, sequence, and timing of treatment. The registry record does not provide a detailed definition of the change calculation, the exact sampling schedule, or the specific visit-to-route mapping.

The record labels the primary outcome population as “loss to follow up,” but does not explain what that label means for the endpoint or analysis population. It gives no concentration values, change estimates, measure of variability, confidence interval, or test result. It also indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Therefore, the endpoint description establishes what was intended to be measured, not what the study found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies randomization, no masking, and a crossover model. These terms describe features of the design, but do not supply the full statistical analysis plan. The record reports zero analyses and does not provide an analysis method for the primary outcome. The explanations below describe general statistical concepts relevant to this design; they are not claims about methods used in this trial.

What does randomization contribute?

In general, randomization uses an assignment process to reduce systematic differences between groups or treatment sequences. In a crossover study, the randomized assignment is to treatment order. The record lists the SQ - IM and IM - SQ sequences. Randomization can make sequence assignment less dependent on participant characteristics, but it does not guarantee balance in a very small study, and it does not by itself address missing measurements, treatment carryover, or the choice of statistical model. The specific randomization procedure is not reported in the registry record.

How does a crossover comparison differ?

In general, a crossover study allows participants to receive more than one treatment, with measurements made across treatment periods. Since a participant can serve as their own comparator, a within-participant analysis can account for stable characteristics that might otherwise contribute to between-person variation. However, measurements from the same participant are related and should not ordinarily be treated as independent observations. The registry record does not identify the model or test used to account for this relationship.

Crossover interpretation also depends on period effects and carryover. A period effect is a change associated with the time or study period rather than the treatment route itself. Carryover occurs when an earlier treatment may continue to influence measurements in a later period. General methods may account for these concerns through design choices or analysis, but the record does not report the period structure, any washout interval, or an approach to period or carryover effects. It is not possible to determine from the registry entry whether or how these issues were addressed.

Why do multiple visits matter?

The primary outcome timeframe includes Visit 2, Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7. Repeated measurements can provide a view of changes over time, but they also raise questions about which measurements define the main comparison and how their dependence is handled. A model for repeated observations may estimate an average treatment effect while accounting for correlations within participants. Alternatively, a prespecified visit-specific contrast could target a particular point in the study. These are general possibilities, not methods identified in the record. The record indicates that the primary outcome has several categories or time points and was not reduced to one comparison.

What would an effect estimate and confidence interval say?

In general, an effect estimate expresses the size and direction of a contrast, while a confidence interval describes the uncertainty around that estimate under the model and assumptions used. The interval is not a guarantee that the true effect lies within its bounds. Its width depends on factors including the variability of measurements, the amount of usable information, and the analysis structure. No effect estimate or confidence interval for the primary outcome is reported in the registry record, so neither magnitude nor precision can be assessed.

A p-value, when reported, measures how unusual data at least as incompatible with a specified null model would be under that model's assumptions. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. No primary-outcome p-value is reported. The lack of a reported p-value cannot be interpreted as evidence for no difference.

What do the sample-size illustrations represent?

Any sample-size illustrations associated with the posted results are planning calculations based on the observed effect, not the trial's own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the target effect is expressed as a fraction of the observed effect. Such calculations ask what sample size might be needed under those assumptions for a future planning scenario. They are not observed power, do not show that the study was adequately powered, and do not replace a prospective sample-size justification. The registry record does not report the trial's sample-size justification or the basis for its enrollment target.

For a crossover study, a planning calculation based on an arm-based comparison may not capture the information structure of a within-participant analysis. The relevant variability may depend on within-participant differences and the correlation between repeated measurements. The record does not give the inputs needed to assess how the illustrations relate to the crossover design. They should therefore be read only as conditional planning scenarios, not as evidence about the reliability of the trial's result.

What analysis details are absent?

The statistical plan, model specification, handling of missing data, and analysis population are not reported in the registry record. The record labels the primary outcome population “loss to follow up,” without explaining the label. It also does not report how many participants contributed measurements at each visit or how missing observations were handled. These details affect how an estimate should be interpreted and how representative it may be of all randomized participants. Because no primary analysis is posted, recalculation from summary statistics is not possible, and no recalculated result should be substituted for the sponsor's analysis.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome is associated with multiple visits, and the registry record says it was not reduced to one comparison. The brief summary also names calculated free testosterone and patient experience, while the record lists secondary outcomes involving serum estradiol, LH, FSH, SHBG, PSA, hematocrit, questionnaire responses, and symptom scores. Considering several outcomes, visits, or contrasts can create a multiplicity issue: the chance of at least one apparently notable result can increase when many tests are conducted. General approaches include identifying a primary contrast in advance, adjusting for multiple comparisons, or interpreting secondary findings as exploratory. The registry record does not report a multiplicity strategy, a prespecified primary contrast across visits, or analyses of the listed secondary outcomes.

Missing data are also important because the primary outcome population is labeled “loss to follow up.” The record does not explain whether this describes participants who were missing, the population definition, or something else. It does not report the amount or pattern of missing outcome data, reasons for missingness, or a method for handling missing values. In general, missingness can affect estimates if the availability of a measurement is related to the participant's outcome or treatment experience. Without these details, the direction or size of any such effect cannot be assessed.

The analysis population is not defined in the registry record. It does not say whether the primary analysis included all randomized participants, only those who completed both treatment periods, or another group. Nor does it report deviations from assigned sequence or how incomplete crossover data were handled. These omissions prevent readers from judging how the analysis population relates to the randomized study population. The record reports zero analyses, so no primary-outcome inference or missing-data sensitivity analysis is available.

11. 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 0% reporting threshold.

The registry record lists serious adverse events, other adverse events, and deaths separately for SQ Testosterone and IM Testosterone. For SQ Testosterone, 2 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. For IM Testosterone, 2 participants are listed as at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. No serious adverse event terms are listed.

These are counts recorded for the listed groups, not estimates of the chance of an event in a broader population. A zero count means no events of that type were recorded among the participants listed as at risk; it does not establish that the risk is absent. The record does not provide additional detail about the duration of safety observation, event definitions, or how crossover exposure was attributed to each group. It also does not explain how the listed at-risk counts relate to the enrollment information, which lists 4 while the brief summary describes 20 subjects.

The adverse-event entries do not provide evidence about the primary serum testosterone outcome. They should be interpreted as limited descriptive safety information rather than as a comparative safety analysis.

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

The posted record supports a description of the intended study question: compare serum total testosterone concentration after subcutaneous and intramuscular administration in men receiving testosterone therapy. It also identifies a randomized crossover design, treatment sequences, a primary outcome timeframe, and a limited set of safety counts. Those details help readers understand what the study aimed to evaluate.

The record does not report the primary outcome measurements, an estimate comparing routes, a confidence interval, or a test result. It therefore does not show whether concentrations were higher or lower after either route, how large a difference might have been, or how precisely a difference was estimated. The absence of a posted result is not evidence that the routes produced the same concentrations. It is also not evidence that one route produced a difference.

Equivalence is a specific statistical claim that requires a defined margin and an analysis precise enough to rule out differences outside that margin. The registry record does not report an equivalence margin or an analysis supporting such a claim. Likewise, statistical significance alone, if it were reported, would not establish that an effect was clinically meaningful; interpretation would require the estimate, its uncertainty, and relevant context.

The crossover structure may allow within-participant comparisons in general, but the registry record does not report the analysis method, treatment-period details, or handling of carryover and missing observations. The enrollment field and brief summary also give inconsistent study-size descriptions, without an explanation. These gaps limit what can be concluded about the information available for the intended comparison.

The zero adverse-event counts in the listed groups are descriptive observations, not proof that adverse events cannot occur. Overall, the record documents an intended comparison and limited safety counts, but does not provide results that establish the size, direction, precision, or clinical meaning of a difference between routes.

13. Why This Trial Matters Statistically

This trial is statistically notable because its randomized crossover structure targets a within-participant comparison. In general, measuring both treatments in the same person can reduce the influence of stable differences between people. That feature can be valuable when the scientific question concerns how an outcome varies with treatment route. It also makes careful reporting of treatment sequence, measurement timing, and repeated-measures analysis especially important.

The registry record specifies a primary outcome measured across multiple visits, but does not identify a single comparison or report an analysis. This illustrates why defining the estimand—the precise treatment contrast the analysis is intended to estimate—matters. An outcome title alone does not tell readers which visits, changes, or treatment periods determine the main estimate. Without a clear contrast, it is difficult to connect the stated research question to a statistical result.

The record also illustrates the distinction between a completed trial and a reported result. The study status is completed, but no primary outcome estimate or analysis is posted. Completion status does not itself communicate the findings, their uncertainty, or whether the planned question was answered.

Finally, the enrollment field and brief summary describe different study sizes, and the record does not explain the difference. This is a reporting limitation that complicates interpretation of the study population and the available information. The safety entries offer counts, but not a comparative estimate of the primary endpoint. Together, these features show why design details, consistent participant accounting, prespecified analysis choices, and outcome reporting are necessary for readers to evaluate evidence statistically.

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 primary limitation for interpreting this study is that the registry record does not report results or an analysis for the primary serum total testosterone outcome. Without measurements, an estimate, or a confidence interval, the route comparison cannot be evaluated for direction, size, or precision. The record indicates multiple visits but does not specify a single primary contrast across them.

Enrollment is described inconsistently: the enrollment field lists 4, while the brief summary describes 20 subjects. The registry record does not explain the discrepancy. It also does not provide participant flow, sequence-group counts for the primary outcome, or the number with measurements at each visit. The listed safety-group counts do not resolve these omissions.

Important design and analysis details are absent. The record does not report the randomization procedure, treatment-period timing, washout interval, mapping of visits to treatment routes, or approach to period and carryover effects. It does not describe the statistical model, analysis population, missing-data handling, or multiplicity strategy. The primary outcome population label “loss to follow up” is not explained.

The record lists an unmasked design and several secondary outcomes, but supplies no results for them. The safety entries are limited counts and do not include detail about observation duration or event definitions. These limitations are specific to the information recorded; they do not establish that a particular design or analysis decision was made incorrectly. They mean that the posted information is insufficient for a full statistical appraisal of the completed crossover comparison.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Subcutaneous vs. Intramuscular Testosterone — NCT03091348.
• Registry record last updated 2019-10-08; status last verified 2019-09.
• Results first posted 2019-09-25.
• 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

NCT03091348 is listed as a completed phase 4 randomized, unmasked crossover study sponsored by Men's Health Boston. It compares subcutaneous with intramuscular testosterone therapy in men. The record lists a start date of 2017-08-29 and a primary completion date of 2017-11-21.

The primary outcome is change in serum total testosterone concentration, measured from blood samples using Beckman assays and equipment, with visits listed from Visit 2 through Visit 7. The record does not report primary outcome results or analyses. It lists 4 as enrollment, while the brief summary describes 20 subjects, without explaining the difference.

Safety entries list 2 participants at risk in each treatment group, with 0 serious adverse events, 0 other adverse events, and 0 deaths in each. These counts do not establish the primary outcome or broader safety risk.