Feasibility Study of a Modular Control to Range System in Type 1 Diabetes Mellitus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Feasibility Study of a Modular Control to Range System in Type 1 Diabetes Mellitus (NCT01418703), a randomized na study. The primary outcome is Hypoglycemic Events.

2. Clinical Question

The clinical question is about the feasibility of a modular insulin management system under study conditions, rather than a reported estimate of its effect. The brief description says the system was intended to address hypoglycemic events and prolonged hyperglycemia using continuous glucose monitoring, past insulin injections, and information about meals. The study was also designed to challenge insulin management with meals and mild exercise. These descriptions give the rationale for evaluating glucose management across changing conditions; they do not establish what happened to participants’ glucose or event counts.

The registry describes random allocation and a crossover model. In a crossover design, participants receive more than one treatment condition at different times, so comparisons can use measurements from the same participants. The sequence of treatment conditions, any washout arrangements, and the details of the intended comparison are not reported in the registry record. The record does not report an estimate of the difference in hypoglycemic events, its uncertainty, or a statistical test. Consequently, it does not answer whether event frequency differed between the treatment conditions.

3. Trial Design

The registry identifies this as a randomized, unmasked crossover study of a modular control-to-range system in type 1 diabetes mellitus. The listed interventions are Closed Loop Control (CLC) and Open Loop. In the CLC description, a computer made recommendations for insulin treatment; in the Open Loop description, the participant was in charge of insulin treatment. The registry reports no masking. It does not report the randomization sequence, allocation procedure, or whether treatment order was balanced.

The study description says the protocol planned six admissions per subject: screening, effort test, CGM insertion 1, inpatient 1, CGM insertion 2, and inpatient 2. It describes four outpatient and two inpatient admissions, with the inpatient admissions including 30 minutes of mild exercise and three meals. The primary outcome timeframe is described as throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR. Details of the actual conduct of each admission are not reported in the registry record.

The study status is completed. The recorded enrollment is 38. This differs from the brief description, which says the investigators planned to enroll 12 adult participants and expected retention of 10/12. The registry record does not explain the difference between the planned enrollment in that description and the recorded enrollment, or how many participants completed each treatment condition.

There are two named secondary outcomes: Percent Time Spent in Near Normoglycemia and Mean Glucose. The registry lists three outcome measures overall, but does not report results for the primary or secondary outcomes. The phase is listed as NA. The registry record does not describe a control-group protocol beyond the Open Loop arm description, nor does it state details such as treatment duration outside the specified admission timeframe.

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

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 Hypoglycemic Events, measured over Throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR.

The primary endpoint is titled “Hypoglycemic Events.” It measures the number of hypoglycemic events below 70 mg/dL per patient per day. The stated unit is events/admission per patient, and the timeframe is throughout each 22-hour closed-loop and open-loop admission for sCTR and eCTR. The registry specifies that the outcome is expressed as a mean with standard deviation.

Counting events describes how often threshold-defined episodes occurred during the admissions. This is relevant to a system intended to manage glucose and avoid hypoglycemic events. The outcome definition gives the threshold and observation context, but does not specify additional event rules, such as how separate readings are grouped into an event. Those rules are not reported in the registry record.

Because the endpoint is a count, its distribution may be skewed or include many low values. A mean can summarize the average event count, while the standard deviation describes variation in counts around that mean. General statistical point: a mean and standard deviation alone do not show the distribution of individual observations, and they do not establish whether a treatment comparison is precise or statistically compatible with no difference. No endpoint means, standard deviations, confidence intervals, or comparison results are reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can help readers distinguish a treatment contrast from the uncertainty around that contrast. In general, an estimate describes the observed difference or relationship in a study, while a confidence interval describes a range of values compatible with the data under the method’s assumptions. A p-value summarizes how unusual data at least as extreme as the observed data would be under a specified null hypothesis and statistical model. Neither a p-value nor a confidence interval is a substitute for the size and clinical interpretation of an effect. For this trial, the primary outcome results, confidence intervals, and p-values are not reported in the registry record.

Why the crossover structure matters

The registry identifies a randomized crossover model. In general, a crossover comparison can use within-participant information because participants receive more than one condition. Measurements from the same person are usually related, so an analysis should represent that dependence. Treating repeated observations as independent can misstate uncertainty. The registry record does not report the treatment sequence, any washout period, the analysis method, or whether period and sequence effects were assessed. It is therefore not possible to tell how the crossover structure was handled statistically.

Random allocation can reduce systematic differences in treatment assignment, on average, when implemented as intended. It does not by itself resolve problems such as missing observations, unbalanced completion, or analysis that does not match the design. The registry reports random allocation but does not describe the allocation method or provide information needed to assess these other issues.

Understanding the endpoint summary

The primary outcome is a count of hypoglycemic events, summarized as a mean and standard deviation. A mean is the arithmetic average across the observations included in an analysis. A standard deviation describes how spread out those observations are around their mean. For count outcomes, the distribution may have a long upper tail or greater variability than a simple model assumes. General statistical point: over-dispersion occurs when observed variation exceeds what a chosen count model expects; ignoring it can make uncertainty estimates too small. The registry record does not report a count model, a distributional assessment, or an analysis method.

The endpoint is also tied to admission and patient. If participants contributed repeated admissions or multiple treatment conditions, those observations may be correlated. The stated unit and timeframe indicate the intended measurement context, but do not provide the number of observations contributing to each group summary. That information is not reported in the registry record. A mean and standard deviation would not, by themselves, reveal how events were distributed across participants or admissions.

Effect estimates and precision

An effect estimate should identify the comparison being made and the scale on which it is expressed. A confidence interval can show how much uncertainty surrounds that estimate, under the statistical assumptions used. Without a reported estimate and interval, readers cannot assess whether the data are compatible with a small or large difference in either direction. The registry record does not report an adjusted or unadjusted comparison, a confidence interval, or a hypothesis test for the primary outcome.

The study record includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a stated fraction of the observed effect. It also distinguishes participant-per-arm quantities from total event counts for time-to-event outcomes. These are described as planning assumptions, not as the study’s own design justification. The record does not report an observed primary effect or calculated planning quantities, so no resulting sample-size requirement can be interpreted from the registry record. Any sample-size illustration based on an observed effect would be a planning calculation, not observed power.

Why missing analysis details matter

A statistical analysis plan ordinarily clarifies which outcome contrast is primary, how repeated measures are handled, what population is analyzed, how missing observations are addressed, and whether adjustments are made for multiple outcomes or comparisons. These choices affect interpretation and precision. The registry record reports no analyses for the outcomes, and details of the statistical plan are not reported in the registry record. There is no basis to infer an analysis model from the outcome’s mean-and-standard-deviation summary alone.

The registry lists Percent Time Spent in Near Normoglycemia and Mean Glucose as secondary outcomes, in addition to the primary endpoint. If multiple outcomes or comparisons are examined, multiplicity can increase the chance of a nominally unusual result arising by chance. General statistical methods for addressing this include prespecifying a hierarchy or adjusting inference across comparisons. Whether any such approach was used is not reported in the registry record. Since outcome analyses are not reported, there is no set of effect estimates or tests to evaluate for multiplicity.

Missing data can also affect a crossover study when participants do not complete all conditions or when some measurements are unavailable. General approaches depend on why observations are missing and on the data structure; no single approach is suitable in every setting. The record’s expected retention of 10/12 is part of the brief study description, but actual retention and missing-outcome handling are not reported in the registry record. The record also does not specify an analysis population, such as whether all randomized participants or only participants with observations under both conditions were included.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures overall. The primary outcome is Hypoglycemic Events; the named secondary outcomes are Percent Time Spent in Near Normoglycemia and Mean Glucose. The record does not describe a hierarchy among these outcomes, identify additional planned comparisons, or state whether any adjustment for multiple testing was used. A multiplicity strategy is not reported in the registry record.

Multiplicity matters because evaluating multiple outcomes, time points, or comparisons can increase the chance of finding an apparently unusual result when no underlying effect exists. General approaches include defining a primary comparison in advance, using a testing hierarchy, or adjusting inference across comparisons. The registry record does not provide enough information to establish which approach, if any, was used. It also states that the primary outcome has several categories or time points and is not reduced to one comparison. The outcome results and analysis details are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The brief description says expected retention was 10/12, but the record does not give actual completion by treatment condition, the number of participants contributing to each outcome, reasons for missing data, or methods for handling incomplete observations. These details are important in a crossover study because an incomplete record may leave a participant without measurements under every condition.

The analysis populations are not reported in the registry record. It is therefore unclear whether analyses were intended to include all randomized participants, only participants who completed specified admissions, or another defined group. The record reports 0 analyses. Without results, analysis-population details, and missing-data methods, readers cannot assess how exclusions or incomplete observations may have influenced the estimates.

11. 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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists safety counts for Open-Loop, sCTR Closed-Loop Control, and eCTR Closed-Loop Control. The number at risk for serious adverse events is recorded as 38, 26, and 12, respectively, and the number affected by serious adverse events is recorded as 0 in each group. The record lists no serious adverse event terms.

For other adverse events, the number at risk is recorded as 38 for Open-Loop, 26 for sCTR Closed-Loop Control, and 12 for eCTR Closed-Loop Control. The numbers affected are 2, 2, and 0, respectively. The registry does not provide descriptions of these other events in the record summarized by these counts. Death values are null; death counts are not reported in the registry record and should not be read as zero.

These figures are descriptive entries, not a comparison of risk. The groups have different recorded numbers at risk, and the registry does not report a statistical safety analysis, event timing, severity details for other events, or exposure-adjusted comparisons. Because the study is crossover, the group counts should not be assumed to represent mutually exclusive sets of participants without additional information about how the registry assigned participants to these safety groups. The counts alone do not establish whether a treatment condition is safer or risk-free.

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

The registry record establishes that a randomized, unmasked crossover study was completed and describes a comparison of computer-assisted CLC recommendations with Open Loop insulin treatment. It identifies hypoglycemic events below 70 mg/dL per patient per day as the primary endpoint, with a stated admission timeframe. It also names two secondary outcomes and records some adverse-event counts. These details clarify the question the study was intended to address.

The record does not report the primary outcome data or the secondary outcome results. It therefore does not show the observed number of hypoglycemic events under each condition, the difference between conditions, or how precise any difference was. No statistical test or confidence interval for the primary comparison is reported in the registry record. The study’s completed status and recorded enrollment are not substitutes for those results.

The study description says the system was designed to use continuous glucose monitoring and insulin-treatment information, and describes meals and mild exercise as challenges to insulin management. This describes the system’s intended functions and the planned study context. It does not establish that the system reduced hypoglycemia, prevented prolonged hyperglycemia, or improved glucose management. Such claims would require reported outcome estimates and appropriate analysis.

Likewise, the serious adverse-event counts listed as 0 in each group are descriptive registry entries. They do not prove an absence of risk, especially without information about event ascertainment, follow-up, and analysis. The death counts are not reported in the registry record. The other adverse-event counts are also insufficient to establish a comparative safety profile.

The record’s planned enrollment and expected retention differ from the recorded enrollment, and the reason is not reported. Actual retention, analysis populations, missing-data handling, and statistical methods are also not reported in the registry record. These omissions limit assessment of the strength and generalizability of any study findings. The appropriate interpretation is therefore that the registry documents a feasibility study design and selected safety entries, while its clinical outcome findings cannot be determined from the posted results.

13. Why This Trial Matters Statistically

This trial matters statistically because its crossover design makes the relationship between observations central to valid inference. Participants in a crossover study can contribute information under more than one treatment condition. General statistical principle: methods that account for within-participant correlation can use the paired structure, while methods that treat all observations as independent may misrepresent uncertainty. The registry record identifies the design but does not report how the analysis accounted for it.

The primary endpoint also illustrates why outcome definition and analysis are separate. The registry specifies a count of events below 70 mg/dL, expressed as a mean with standard deviation. That provides a measurement target, but a count can have a distribution that is not well represented by a normal model. General methods may use count-based models or other approaches suited to the observed data. The statistical method, distributional checks, and results are not reported in the registry record, so the suitability of any analysis cannot be assessed.

The study is described as a feasibility investigation, and its planned challenge conditions included meals and mild exercise. For such a study, transparent reporting of completion, outcome distributions, and uncertainty is important: feasibility aims and comparative effectiveness questions are related but not identical. The registry provides the recorded enrollment and a planned retention expectation, but does not report actual retention or primary outcome analyses.

Finally, the registry names multiple outcomes and does not provide analysis details. Prespecification of primary comparisons, multiplicity handling, and missing-data methods helps readers judge whether the reported inference follows the study’s aims. These details are not reported in the registry record. The trial’s design and endpoint are informative, but the absence of posted outcome analyses prevents a statistical assessment of the system’s observed performance.

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 main limitation for interpretation is that primary and secondary outcome results are not reported in the registry record. No group summaries, treatment contrasts, confidence intervals, or p-values are available. The direction and precision of a difference in hypoglycemic events cannot be determined.

The planned and recorded enrollment information is not reconciled. The brief description says the investigators planned to enroll 12 adult participants and expected retention of 10/12, while the registry records enrollment of 38. The reason for the discrepancy, actual retention, and numbers contributing to each treatment condition are not reported. This prevents a clear account of the analyzed population and the completeness of outcome data.

Several design and analysis details are also absent. The sequence of randomized treatment conditions, any washout arrangements, the method for analyzing repeated observations, and handling of period or sequence effects are not reported in the registry record. The record does not specify rules for defining separate hypoglycemic events beyond the threshold, nor does it report the statistical model or missing-data approach.

The primary outcome timeframe refers to 22-hour admissions and identifies sCTR and eCTR, but the registry record does not provide the outcome results for those conditions. It also notes that the primary outcome has several categories or time points and is not reduced to one comparison. Without a clearly reported comparison and results, readers cannot assess whether all relevant outcome dimensions were considered.

The safety record has limited detail: serious adverse-event terms are not listed, other adverse events are not described, and deaths are not reported. The counts do not establish comparative safety. These limitations reflect information absent from the registry record and should not be interpreted as evidence that the study did not collect additional information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Feasibility Study of a Modular Control to Range System in Type 1 Diabetes Mellitus — NCT01418703.
• Registry record last updated 2014-11-13; status last verified 2014-11.
• Results first posted 2014-11-13.
• 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

NCT01418703 is a completed, randomized, unmasked crossover study of a modular control-to-range system in type 1 diabetes mellitus, sponsored by the University of Virginia. The registry records enrollment of 38. The intervention descriptions compare computer-recommended Closed Loop Control insulin treatment with Open Loop treatment managed by the participant.

The primary outcome is hypoglycemic events below 70 mg/dL per patient per day during the specified admission periods, summarized as a mean with standard deviation. The named secondary outcomes are Percent Time Spent in Near Normoglycemia and Mean Glucose. The registry record does not report analyses or outcome results. It lists no participants affected by serious adverse events in the three safety groups, records other adverse events for 2, 2, and 0 participants across those groups, and does not report death counts. The record does not provide enough outcome or analysis information to assess treatment differences or their precision.