Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria (NCT03663855), a na phase 2 study. The primary outcome is Change in Cystine Capacity From Baseline.

2. Clinical Question

The study summary frames the question around finding a dose that may affect cystine capacity while avoiding unnecessarily large doses. It also describes a broader aim of informing treatment and reducing the burden associated with high pill counts and potential side effects. These are stated aims, not findings. Without a reported outcome estimate, dose-specific results, or a comparator, the record cannot establish the size or direction of any change, identify a minimum effective dose, or show how the findings relate to those broader aims.

3. Trial Design

The registry identifies this as a completed Phase 2 study with a single-group model. Tiopronin is the listed intervention, and the study summary describes evaluating escalating doses in patients with cystinuria. Allocation is recorded as not applicable and masking as none. Accordingly, the design does not include a randomized allocation or a masked comparison group in the registry description.

The record lists enrollment as 10 and names patients with cystinuria as the group. The listed timeframe for the primary outcome is baseline and Day 7. The record does not say whether every enrolled participant contributed a measurement at both time points, or how any missing measurement was handled. It also does not report the dose levels, how long each dose was given, the escalation criteria, or the timing of measurements relative to dose changes.

The study is marked completed. Its recorded start date is 2018-11-01, and its primary completion date is 2019-09-10. Those dates describe the registry entry; they do not provide additional outcome information.

A single-group design can describe measurements collected in the treated group, but it does not separate changes associated with the intervention from changes that could occur over time or for other reasons. That is a general limitation of interpretation, not evidence that any particular alternative explanation occurred in this study. The registry lists one primary outcome measure and no analyses. It does not report a protocol-level statistical analysis plan, sample-size justification, interim-analysis plan, or a detailed account of the analysis population.

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: Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per sequence data are not available to be reported for this assessment.

Overall Study

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: Multiple efforts to contact the PI/study team for the relevant data have failed. Therefore, per intervention data are not available to be reported for this assessment.

6. Primary Endpoint

The registry lists the primary outcome as Change in Cystine Capacity From Baseline, measured over Baseline; Day 7.

The primary outcome is titled “Change in Cystine Capacity From Baseline.” It is a continuous measure, reported in mg/L, with the mean identified as the summary measure and standard deviation as the dispersion measure. The timeframe is baseline and Day 7. The description says cystine capacity reflects the ability of urine to take up more cystine; the study summary also characterizes it as a measure of cystine solubility in urine.

Change from baseline is used to describe how a measurement differs between the stated starting point and a later time point. In general, this can focus attention on within-participant movement rather than only on the Day 7 measurement. However, the registry does not state how the change was calculated, whether paired measurements were available for all participants, or which dose-period measurements contributed to the endpoint.

Capacity is relevant to the study question because the stated purpose is to assess the effect of tiopronin dosing on urine cystine capacity. The measure is a laboratory characteristic, not a direct count of clinical events. The registry record does not report a mean change, a standard deviation value, or any other numerical primary-outcome result. It therefore does not show the direction, magnitude, or precision of the measured change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is sparse. It identifies a continuous primary measure, a mean summary, standard deviation as the dispersion measure, and a baseline-to-Day 7 timeframe. It does not report a numerical analysis of that outcome or a detailed analysis plan. General explanations of these methods can clarify what a reported result would mean, but they cannot substitute for an unreported estimate.

What does a mean change describe?

In general, a mean change combines the changes recorded for the participants included in an analysis into an average. Its meaning depends on how the change is defined, which observations are included, and how missing measurements are treated. For a baseline-to-Day 7 outcome, a paired analysis may use measurements from the same participant at both times, but the registry does not say whether that is the method used. It does not report a calculation rule or describe which dose periods are included.

A mean can offer a compact description of the group, but it does not show the individual pattern of responses. Different participant-level patterns can yield the same average. The registry's identification of the mean as the parameter does not give the actual mean change, nor does it reveal the distribution of individual changes.

What does standard deviation add?

In general, standard deviation describes the spread of observations around their mean. It is not the same as the uncertainty of the mean, and it does not by itself indicate whether an estimate is precise. Precision also depends on features such as the amount of information available and the analysis method. The registry names standard deviation as the dispersion measure but does not give its numerical value for the primary outcome. As a result, the amount of observed variability cannot be assessed.

A continuous outcome may be analyzed with methods that rely on assumptions about the distribution of observations or errors. If data depart substantially from a method's assumptions, estimates or uncertainty assessments may be affected; in general, over-dispersion means variability is greater than a model expects. The registry does not report a model, diagnostic checks, or evidence of over-dispersion in this study. It would be inappropriate to claim that any such issue was present or absent.

How should uncertainty be read?

In general, a confidence interval represents uncertainty around an estimated effect under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while the interval's location and width both matter for interpretation. The registry record does not report a confidence interval for cystine capacity change. It also does not report a p-value or test result. Consequently, neither statistical compatibility with a null value nor the precision of an estimated change can be assessed from the recorded primary outcome information.

A p-value, in general, measures how unusual data at least as incompatible with a specified null model would be if that model and the analysis assumptions were correct. It does not quantify the probability that a treatment works, nor does it express the size or importance of an effect. There is no p-value reported for the primary measure in the registry record, so no claim about statistical significance can be made.

What does the planning illustration represent?

The record describes sample-size calculations as planning illustrations rather than as the trial's own design. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is described as a stated fraction of an observed effect. For non-time-to-event outcomes, the illustration is defined in participants per arm. These assumptions describe a hypothetical planning framework, not the design of this single-group study. The registry does not report a trial-specific sample-size justification, and the results of the planning calculations are not included in the available study details.

Such calculations, in general, explore how much information a future comparison might need under chosen assumptions. Their outputs depend on the assumed effect and variability, among other design choices. They are planning illustrations, not observed power and not evidence that a study had a particular probability of detecting an effect. Since no numerical planning outputs or observed primary effect are reported, no numerical sample-size conclusion can be drawn.

What can be concluded from the analysis record?

The registry lists one outcome measure and no analyses. That distinction is important: naming an outcome establishes what the study intended to measure, but it does not supply an analyzed result. The record does not specify the statistical test or model, treatment of repeated observations, handling of missing values, covariate adjustment, or analysis population. These methods are not reported in the registry record. No inference should be made about which method would have been appropriate or which was actually used.

The sponsor's own analysis takes precedence if a recalculated summary conflicts with it; however, no sponsor analysis or recalculated result is included in the study details for this record. There is therefore no numerical recalculation to compare with a sponsor result. The general methods above explain how statistical summaries are commonly interpreted, while the study-specific result and analysis remain unreported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, change in cystine capacity from baseline, and lists no analyses. A count of listed outcomes does not tell readers how many statistical tests were planned or performed. The record does not report a multiplicity strategy, such as how it would handle interpretation across multiple dose levels, time points, or analyses. It also does not report whether any secondary outcomes were analyzed. These details are not reported in the registry record.

In general, multiplicity arises when several statistical questions are considered. Repeated testing can increase the chance of a result that appears unusual under a null model, so a study may specify a strategy for controlling or interpreting that issue. The registry entry does not state whether such a strategy was needed or used. No adjustment or unadjusted test result is reported for the primary outcome.

Missing-data methods are also not described. The registry does not state how many participants had baseline and Day 7 measurements, whether data were incomplete, or how incomplete observations were handled. The enrollment listing cannot determine the number of observations in an outcome analysis. The primary-outcome population field contains no description, and no analysis population is otherwise specified.

In general, the handling of missing measurements can affect which participants contribute to an estimate and the assumptions behind the result. Without a report of completeness and analysis methods, it is not possible to assess the potential impact of missing data in this study. The record also does not report an interim-analysis plan or a statistical analysis plan. Their presence or absence should not be inferred from the lack of detail in the registry entry.

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's safety figures are recorded for the Cystinuria Patients group. Serious adverse events are reported for 10 at risk and 0 affected. Other adverse events are reported for 10 at risk and 0 affected. Deaths are recorded as 0. These are the figures in the registry record; they are not estimates of event risk beyond the group and reporting period represented by that record.

A count of 0 affected means no affected participants are recorded for that category in this entry. It does not establish that an event is impossible, nor does it describe how completely events were collected or adjudicated. The record does not report the safety observation period, detailed adverse-event terms, severity definitions, or participant-level follow-up for these figures. No serious adverse-event terms are listed.

In general, safety counts should be read alongside the group at risk, duration of observation, and completeness of reporting. The registry does not provide the details needed to assess those features fully. The safety figures are descriptive and should not be treated as a comparative estimate, because the study is single-group and no control group is listed.

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

The record identifies a clinical research question: whether cystine capacity in urine changes from baseline to Day 7 in a study of escalating tiopronin doses among patients with cystinuria. It describes cystine capacity as reflecting urine's ability to take up more cystine and names it as the primary outcome. These details establish the topic and intended measurement, but they do not reveal what the measurements showed.

No numerical primary-outcome result is reported in the registry record. The average change, its variability, and its uncertainty are not available in the study details. Therefore, the direction and size of any observed change cannot be described. Nor can the precision of an estimate or the compatibility of the data with a range of possible effects be assessed.

The study summary states aims related to determining a minimum effective dose, guiding treatment, and limiting unnecessary side effects or pill burden. A stated aim is not a demonstrated outcome. The registry does not provide dose-specific results or the dose schedule, so it cannot identify a minimum effective dose from the information recorded. The summary's goals should not be interpreted as findings about efficacy, side effects, adherence, or clinical benefit.

The single-group design also limits causal interpretation. In general, a measurement change within a group is not equivalent to a comparison against what would have happened over the same period without the intervention. Because no separate comparator is listed, the record cannot provide a randomized between-group estimate. This does not determine whether tiopronin caused a change; it means the registry design description does not furnish that kind of comparison.

The record marks the study completed and lists safety counts, including zero affected in the serious-event and other-event categories. Those descriptive counts do not answer the primary efficacy question, and the safety-reporting details are limited. Overall, the registry entry documents the study's aims, design, and endpoint definition, but does not report the outcome evidence required to judge the observed change or its clinical meaning.

13. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a clearly stated research aim and a reported result. The registry describes an escalating-dose question and defines a continuous primary outcome at baseline and Day 7. Yet it lists no analyses and provides no numerical endpoint result. For statistical interpretation, an endpoint definition alone cannot establish the effect's direction, size, variability, or precision.

The single-group structure is also important. A within-group change can be useful descriptively, but it is not the same estimand as a contrast between treatment and control. Without a separate comparator, any change cannot be separated statistically from changes that might occur over time or under other conditions. This general design consideration is particularly relevant when the stated aim is to evaluate the effect of an intervention.

The registry's sample-size assumptions are described as planning illustrations, not as the trial's own design. Keeping that distinction clear prevents hypothetical planning calculations from being mistaken for observed power or a justification for the enrolled study. The record does not include numerical planning outputs or a trial-specific sample-size rationale.

Finally, the study asks about a laboratory measure that is characterized as cystine solubility in urine, while the summary connects that measure to broader goals involving dose choice and treatment burden. Statistical evidence for the measured endpoint would not by itself answer every broader clinical question. With no reported endpoint values, even the measured effect cannot be characterized from this record. The case therefore illustrates why interpretation depends on both design and complete outcome reporting, not solely on a stated objective or completed status.

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 registry entry is that no numerical primary-outcome result is reported. Without the mean change and its variability, the observed effect and its precision cannot be assessed. The entry also lists no analyses, leaving the method used to produce a result unspecified.

The single-group design has no separate comparator in the registry description. This prevents a direct randomized comparison and limits causal interpretation of any within-group change. The record also describes no masking. Dose levels, escalation procedures, treatment duration at each level, and dose-specific outcome results are not reported, so the planned dose-response question cannot be evaluated from the available details.

The primary-outcome timeframe is baseline and Day 7, but the record does not describe measurement timing relative to dose escalation or explain how change was calculated. It does not report the number of participants contributing paired measurements, an analysis population, missing-data methods, or participant characteristics. These omissions limit assessment of who contributed to the endpoint and how the measurement was analyzed.

The record does not report a statistical analysis plan, sample-size justification, multiplicity approach, or interim-analysis plan. It also does not provide enough safety-reporting detail to establish the observation period or completeness of event ascertainment. These are limitations of what is reported in the registry record; they do not establish that the information was absent from all study documents.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria — NCT03663855.
• Registry record last updated 2021-12-17; status last verified 2021-11.
• Results first posted 2021-12-17.
• 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

The registry record describes a completed Phase 2, single-group study of tiopronin in patients with cystinuria. It lists enrollment as 10, allocation as not applicable, and masking as none. The study summary describes escalating doses and an aim of examining urine cystine capacity.

The primary outcome is change in cystine capacity from baseline, with measurements framed at baseline and Day 7. It is a continuous measure in mg/L, summarized by a mean with standard deviation as the dispersion measure. The record lists one outcome measure and no analyses.

No numerical primary-outcome result, dose-specific estimate, confidence interval, or p-value is reported in the registry record. Safety entries record 0 serious adverse events affected, 0 other adverse events affected, and 0 deaths. The study aims and design are described, but the numerical findings needed to assess the primary question are not reported.