Salsalate for Insulin Resistance in Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Salsalate for Insulin Resistance in Schizophrenia (NCT01182727), a na na study. The primary outcome is Side Effects of Salsalate.

2. Clinical Question

3. Trial Design

The registry identifies this as a completed, single-group study of salsalate for insulin resistance in people with schizophrenia. It lists the phase as NA, allocation as NA, and masking as none. Enrollment was 13. The study start is recorded as 2010-08 and primary completion as 2011-11. The sponsor is University of Maryland, Baltimore.

Because the study has one group and no comparator, its design can describe what was recorded among participants receiving salsalate, but it cannot directly compare their outcomes with a group receiving another intervention or no study drug. The absence of masking is also relevant when interpreting outcomes assessed through a checklist: participants and those assessing them may have known the intervention. The registry does not report additional procedures to reduce potential assessment or reporting effects.

The intervention description specifies salsalate for 6 weeks, with a target of two divided doses and stepwise reductions for participants unable to tolerate the target dose. The description is incomplete after its account of dose reduction, and the actual dose received, adherence, and dose changes for individual participants are not reported in the registry record.

The record gives one primary outcome measure and reports no analyses. It does not report a statistical analysis plan, a sample-size justification, planned interim analyses, or a detailed account of how outcomes were to be summarized. A sample-size calculation based on a posted effect, if displayed as a planning illustration, should not be read as a design justification or as observed power. With no control group, the central design limitation is the lack of a direct comparative estimate.

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.

Before assignment: Participants were withdrawn from the trial if they had abnormal lab values or were found to have a diagnosis of diabetes.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All subjects who completed the study were analyzed.

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 Side Effects of Salsalate, measured over 6 weeks.

The primary endpoint is the number of participants with side effects over 6 weeks. The registry says side effects were to be identified using a Side Effect Checklist intended to monitor common medication side effects. It also states that all subjects who completed the study were analyzed. The registry does not report a numerical result for this endpoint, the number of participants who completed the study, or the checklist threshold used to classify a participant as having a side effect.

Counting participants with an event is a binary-outcome approach: each participant is classified according to whether the outcome occurred, and the result can be summarized as a count. This is distinct from counting how many separate symptoms or episodes each participant experienced. The endpoint description supports interpretation as a participant-level side-effect measure, but does not clarify whether multiple checklist items were combined into one overall classification or analyzed separately.

This outcome is relevant to tolerability because it concerns reported side effects during treatment. It is not, by itself, a measure of insulin resistance, inflammation, blood sugar, or diabetes risk. The registry record does not report a primary efficacy endpoint or a numerical measure of change in those physiological outcomes. Without the primary endpoint result and its analysis details, the registry does not establish how frequently participants experienced checklist-recorded side effects in the analyzed population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is recorded as single-group, with allocation listed as NA and masking listed as none. These design features determine what kinds of statistical conclusions are supported. There is no randomized contrast in the record, and no like-for-like control comparison. Statistical methods can describe outcomes within the treated group, but a within-group result is not an estimate of the difference between treatment and control.

What does a participant count represent?

The primary endpoint is expressed as the number of participants with side effects. For a binary outcome, each participant is classified as having or not having the defined event during the assessment period. A count is the number classified as having the event. A rate or proportion would also require a clearly identified denominator. The primary description identifies completed subjects as the analysis population, but the number of completers and the endpoint count are not reported in the registry record. Without them, neither the count nor the corresponding participant-level frequency can be interpreted numerically.

The endpoint wording also matters. The checklist is described as monitoring common medication side effects, but the record does not state how checklist responses were combined into an overall endpoint, how missing checklist responses were treated, or whether the primary endpoint counted any listed symptom or used a specified severity threshold. Those details affect what a participant-level count means and are not reported in the registry record.

Why does the absence of a control group matter?

A controlled comparison asks how outcomes differ between groups that receive different assigned interventions. In a randomized trial, random assignment is intended to make the groups comparable, on average, for measured and unmeasured factors. This study has no comparator arm, so that between-group estimate cannot be calculated from the design. A change from a participant’s starting value, if it had been reported, would still not by itself identify what caused the change. Natural fluctuation, changes over time, co-interventions, and measurement effects could also contribute. The registry does not report a numerical change outcome for insulin resistance or another physiological measure.

The absence of masking may be relevant to checklist-based assessment. General statistical and measurement principle: when participants or assessors know which intervention is being given, expectations can influence symptom reporting or assessment. This possibility does not show that reporting was biased in this study. The record does not describe procedures that would allow its extent to be evaluated.

How should uncertainty be considered?

General statistical explanation: an estimate describes the observed data, while an uncertainty interval conveys how imprecisely the underlying quantity may be estimated under a statistical model. A p-value, when used, evaluates compatibility between data and a specified null hypothesis under assumptions; it does not measure the probability that a treatment works. Neither a primary-outcome estimate nor an uncertainty interval or p-value is reported in the registry record. There is therefore no inferential result to interpret for the stated primary endpoint.

The adverse-event listing gives counts among participants at risk, but does not include uncertainty intervals. A zero count is a description of the recorded observations, not proof that an event cannot occur. Over-dispersion is a general concern for count outcomes when variability exceeds what a chosen model expects; however, the primary endpoint is presented as a participant count rather than a reported repeated-event analysis. The registry does not report a model or dispersion assessment, so no such method can be attributed to this study.

What can planning calculations say?

General statistical explanation: a sample-size calculation asks how many participants a future or planned study might require under stated assumptions about the effect to detect, statistical significance level, allocation, and analysis method. Such a calculation is a planning illustration, not evidence that a study had a particular probability of finding an effect after it was completed. The record’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. Those assumptions do not match the recorded single-group design. Any corresponding participant counts should therefore be read as hypothetical planning illustrations, not as the trial’s observed power or its actual enrollment rationale. The trial’s own sample-size justification is not reported in the registry record.

The record reports no analyses and does not describe a statistical analysis plan. It does not report whether analyses were adjusted, how repeated or multiple checklist items were handled, or whether analyses were prespecified. These omissions limit evaluation of the analytical choices and their effect on the reported result; in this case, the primary numerical result itself is also not reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Salsalate")
n      <- c(10)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Salsalate  10  3  30.0  6.7  65.2  10.8  60.3  10.9  61.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but the measure description refers to a checklist of common side effects. It does not explain whether individual checklist items were treated as separate outcomes, whether they were combined into a single endpoint, or whether any secondary outcomes were analyzed. The number of statistical tests and any multiplicity adjustment are not reported in the registry record. Without those details, the risk of selective emphasis among multiple outcomes cannot be assessed.

The primary endpoint population is described as all subjects who completed the study. The number of completers, the number with available checklist data, and the handling of participants who did not complete the study are not reported. The record does not say whether missing data were imputed, excluded, or handled using another method. It also does not report reasons for noncompletion or missing assessments. The difference between enrollment of 13 and the adverse-event at-risk count of 10 is present in the record, but its explanation is not reported.

The record does not identify an intention-to-treat population or another formal analysis population beyond the statement that completed subjects were analyzed for the primary measure. It reports no analyses. As a result, the analysis denominator and the treatment of incomplete observations cannot be reconstructed from the registry record. These gaps are important because the estimate for a participant-level endpoint depends on who was included and how missing outcomes were handled.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

The adverse-event entry lists 0 serious adverse events among 10 participants at risk and 0 other adverse events among 10 participants at risk in the salsalate group. These are counts of recorded events in the listed group, not estimates that the event risk is zero. The registry does not provide uncertainty intervals for either count or describe the event-reporting procedures in further detail.

The primary endpoint separately concerns participants with side effects on a checklist over 6 weeks. Its numerical result is not reported in the registry record. The zero other-adverse-event count should therefore not be assumed to be the checklist endpoint result: the record does not explicitly identify the two measures as equivalent. It also does not report the number completing the primary endpoint, while the safety entry lists 10 at risk and the study enrollment is 13. The reason for the different counts is not stated.

The deaths field is not reported in the registry record. The absence of a listed serious adverse-event term does not establish that no particular event was assessed or that all possible events were absent. These figures describe what is entered in the registry and should be interpreted within those limits.

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

The record establishes that a completed, single-group study of salsalate was registered for people with schizophrenia and insulin resistance, with enrollment of 13 and a six-week primary side-effect assessment. It also records zero serious adverse events and zero other adverse events among 10 participants at risk. These registry entries describe the registered study and its posted safety counts.

The record does not report the numerical result for the primary side-effect endpoint. It does not provide an estimate of insulin resistance change, a comparison with another group, or statistical uncertainty for an outcome. As a result, readers cannot use the registry entry to quantify the frequency of checklist-recorded side effects in the stated primary analysis population or determine how precisely that frequency was estimated.

Even if a within-group change or count had been reported, the absence of a comparator would limit causal interpretation. Outcomes in a single group do not show how the same participants would have fared under a different condition. No treatment effect relative to a control group can be inferred from this design. The registry’s rationale about inflammation and insulin response is background context, not an observed trial finding.

The zero adverse-event counts also need careful interpretation. They indicate no recorded events in the listed categories among the stated at-risk group; they do not establish that the event risk is absent. The record gives no uncertainty interval and does not explain how the at-risk count relates to enrolled or completed participants.

Accordingly, the registered information is most informative about the study’s design, intended endpoint, and limited posted safety counts. It does not supply enough outcome data to judge the primary endpoint quantitatively, to estimate an intervention effect, or to assess the precision of such an effect.

14. Why This Trial Matters Statistically

This study is a useful example of why design and reporting details matter alongside a stated research question. The topic links an intervention, salsalate, with insulin resistance in people with schizophrenia, but the primary endpoint recorded in the registry is side effects. Keeping the endpoint distinct from the study rationale prevents a safety measure from being mistaken for evidence about insulin response or diabetes risk.

The single-group design is another key statistical feature. It can record experiences during treatment, but it does not provide a concurrent contrast. Without a comparator, changes over time cannot be separated from other explanations by a between-group analysis. The absence of masking is relevant to a checklist-based outcome because reporting and assessment may be influenced by knowledge of treatment, although the record does not establish that this occurred.

Reporting completeness also affects interpretation. The registry records enrollment of 13, a safety at-risk count of 10, and an analysis population described as completed subjects, but does not explain how these groups relate. It does not report the numerical primary endpoint, a statistical analysis, or the handling of missing assessments. These omissions make it difficult to assess both the outcome and the population to which it applies.

Finally, a zero event count is not the same as proof of no risk, and a planning calculation is not observed power. Reading those distinctions carefully helps keep the conclusions proportionate to the information in the registry: design and recorded counts can be described, while the missing endpoint result and lack of comparative data remain central limits.

15. 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 central limitation is that the numerical result for the primary endpoint is not reported in the registry record. The endpoint is defined as participants with side effects on a checklist, but the event count and number analyzed are absent. The registry’s statement that completed subjects were analyzed does not specify the number of completers.

The study has one group and no comparator. It therefore cannot supply a direct comparison with another intervention or a control condition. Allocation is listed as NA and masking as none. The record does not describe whether any procedures were used to reduce bias in side-effect reporting or assessment.

The registry reports enrollment of 13, while the adverse-event listing gives 10 participants at risk. It does not explain this difference. The deaths entry is not reported. The adverse-event counts do not include uncertainty estimates, and their relationship to the primary checklist endpoint is not specified.

The intervention description outlines a six-week course and dose reductions for intolerance, but does not provide participant-level exposure, adherence, or actual dose information. The record does not report details of checklist scoring, the handling of incomplete assessments, multiplicity procedures, or a statistical analysis plan. It also reports no analyses and no numerical efficacy result. These limitations mean that the registry supports a description of the study design and certain recorded safety counts, but not a quantitative evaluation of the primary outcome or a comparative treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Salsalate for Insulin Resistance in Schizophrenia — NCT01182727.
• Registry record last updated 2022-03-11; status last verified 2022-03.
• Results first posted 2013-06-14.
• 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.

19. Record Summary

NCT01182727, titled Salsalate for Insulin Resistance in Schizophrenia, is recorded as completed. The sponsor is University of Maryland, Baltimore. The study is described as single-group, with no masking and allocation listed as NA. Enrollment was 13; the start is recorded as 2010-08 and primary completion as 2011-11.

The intervention was salsalate, and the primary outcome was the number of participants with side effects on a Side Effect Checklist over 6 weeks. The record says completed subjects were analyzed, but the numerical primary result and number of completers are not reported. The adverse-event listing records zero serious and zero other adverse events among 10 participants at risk; deaths are not reported. No analyses are reported. The record therefore provides design information and limited safety counts, but not a numerical primary endpoint result or a comparative estimate.