This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Clinical Assessment of a Closed-loop System With Glucagon, Exercise and Mixed Meals (NCT02397265), a randomized na study. The primary outcome is Percentage of Time in Target Range Over 24 Hour.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02397265 |
| Phase | NA |
| Condition | Type 1 Diabetes |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
The study concerns people with type 1 diabetes. The registry lists enrollment of 24 participants, while the posted primary-outcome summaries report six participants for each of the three listed treatment groups. Details about participant eligibility, baseline characteristics, and the population included in each outcome analysis are not reported in the registry record.
Intervention
The registered interventions include a bihormonal closed-loop pump and an insulin-only closed-loop approach. The arm descriptions state that the bihormonal closed-loop pump was used in the exercise and mixed-meal substudies, and that insulin-only closed loop was another study condition. The record does not provide enough detail to reconstruct the delivery algorithm or the specific conditions experienced by each participant.
Comparator
Standard open-loop pump therapy is the comparator named in the study summary. The registry describes the study as randomized and crossover, with no masking. The posted primary-outcome results include a standard open-loop pump group as well as both closed-loop groups.
Primary question
The primary question is how much time participants spent with glucose concentrations in the target range of 3.9-10.0mmol/l over 24 hours under the registered study conditions. The outcome is reported as a median for each group. The registry record does not report a treatment-effect estimate, confidence interval, or statistical test comparing the approaches, so the posted summaries do not establish the size or precision of a between-treatment difference.
3. Trial Design
The registry identifies this as a randomized, unmasked crossover study sponsored by Imperial College London. Its title refers to a closed-loop system used with glucagon, exercise, and mixed meals. The study status is completed, and the listed enrollment is 24. The registry lists the study phase as not applicable.
A crossover design means that participants receive more than one study condition over time, so comparisons may be made within the same participants rather than only between separate groups. In general, this can account for some stable differences between participants. Interpreting a crossover study also depends on details such as treatment order, the duration of each period, and any washout between periods. Those details are not reported in the registry record, so the sequence and timing of treatment exposure cannot be reconstructed from the posted information.
The arm descriptions distinguish bihormonal closed loop, standard open-loop pump, and insulin-only closed loop. The brief study description refers to comparing closed-loop delivery with standard insulin pump therapy, while the registered interventions and arm descriptions include more than one closed-loop condition. The registry says the bihormonal closed-loop and standard open-loop pumps were used in exercise and mixed-meal substudies. It does not report how participants were assigned to those substudies, how the insulin-only condition relates to them, or whether the posted primary-outcome summaries combine or separate those circumstances.
The primary endpoint is described over 24 hours. Although the registered enrollment is 24, the outcome summaries list six participants in each arm. The relationship between those counts and overall enrollment, including whether they represent all relevant outcome observations, is not explained in the registry record. Dates for study start and primary completion are 2014-12-03 and 2015-07-22, respectively.
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.
First Intervention of Three
| Stage | First Bihormonal Closed Loop | First Standard Opened Loop Pump | First Insulin Only |
|---|---|---|---|
| STARTED | 2 | 2 | 2 |
| COMPLETED | 2 | 2 | 2 |
| NOT COMPLETED | 0 | 0 | 0 |
Second Intervention of Three
| Stage | First Bihormonal Closed Loop | First Standard Opened Loop Pump | First Insulin Only |
|---|---|---|---|
| STARTED | 2 | 2 | 2 |
| COMPLETED | 2 | 2 | 2 |
| NOT COMPLETED | 0 | 0 | 0 |
Third Intervention of Three
| Stage | First Bihormonal Closed Loop | First Standard Opened Loop Pump | First Insulin Only |
|---|---|---|---|
| STARTED | 2 | 2 | 2 |
| COMPLETED | 2 | 2 | 2 |
| NOT COMPLETED | 0 | 0 | 0 |
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.
| Characteristic | Unit | All Participant |
|---|---|---|
| Participants analysed | 6 | |
| Age, Continuous | years | 55 (50 to 60) |
| Sex: Female, Male: Female | Participants | 4 |
| Sex: Female, Male: Male | Participants | 2 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: United Kingdom | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Time in Target Range Over 24 Hour, measured over 24 hours.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | percentage of time |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is percentage of time in the glucose target range over 24 hours. The target range is specified as 3.9-10.0mmol/l. The measure represents the proportion of the observation period during which glucose concentrations fall within that range; it is reported in the registry as a percentage of time and summarized using a median.
The study summary describes this outcome as a principal measure of efficacy for closed-loop insulin delivery and says that it incorporates safety by reflecting time outside both low and high glucose levels. In general, a time-in-range outcome can convey how glucose control varies across an observation period rather than relying only on a single measurement. It can also make the duration of excursions relevant to the summary, not just whether an out-of-range value occurred.
The registry identifies inter-quartile range as the dispersion measure, and the arm summaries include lower and upper values alongside the medians. The endpoint is specifically a 24-hour outcome; the record does not report how that observation period was selected or whether it represents a particular meal or exercise challenge. Nor does it explain how missing glucose measurements, if any, were handled. Those omissions limit interpretation of the endpoint summaries and their comparability across study conditions.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary-outcome summaries are medians of percentage time in the target range. For bihormonal closed loop, the median is 2.0, with registry-listed lower and upper values of 0.4 and 3.0. For standard open-loop pump therapy, the median is 4.7, with lower and upper values of 1.8 and 12.0. For insulin-only closed loop, the median is 1.3, with lower and upper values of 0.4 and 7.2. The registry identifies the dispersion as an inter-quartile range.
These summaries describe the observed outcome values in the recorded groups; they are not an adjusted comparison of treatments. No treatment contrast, confidence interval, or inferential test is posted. The registry also reports zero analyses. Consequently, the results do not quantify the uncertainty around a difference between conditions or establish whether the observed summaries are compatible with no difference. The posted values alone should not be used to claim that one approach performed better or worse.
The reported arm counts are six for each condition. Because this is a crossover study, the arm counts do not by themselves explain how many distinct participants contributed, how the treatment periods were organized, or how within-participant observations were handled. The registry lists overall enrollment of 24, but does not describe why the primary outcome has these arm counts or whether any observations were excluded. That information is important when interpreting how representative the summaries are of the enrolled participants.
The primary outcome is explicitly framed as percentage of time in the target range over 24 hours. Still, the record does not provide details about the distribution of individual participant outcomes, the measurement schedule, or the analysis population. A median and inter-quartile range describe the center and spread of observed values, but they do not show the full distribution or indicate how much observations from the same participant may be related.
These results should therefore be read as descriptive registry summaries, not as a complete comparative analysis. The registry does not report a statistical analysis plan, adjustment for the crossover structure, or handling of the exercise and mixed-meal conditions. It also does not report secondary outcome results. The absence of those details does not establish that no analysis was conducted outside the registry; it means that such analysis is not reported in the registry record.
9. Statistical Methods Explained
The record gives descriptive summaries for the primary endpoint but does not report a statistical comparison. Understanding what those summaries can show, and what remains unknown, requires distinguishing a group summary from an estimated treatment effect.
What does a median describe?
In general, the median is the central value when observations are ordered. It describes the center of the observed data and is less sensitive than the mean to unusually high or low observations. The posted primary outcome is identified as a median, with the dispersion described as an inter-quartile range. An inter-quartile range describes the span of the middle half of a distribution. The registry lists lower and upper values alongside each median, but it does not explain the calculation or formatting of those values beyond identifying the dispersion measure.
A median is not a treatment effect. In a randomized study, a treatment effect would ordinarily express a contrast between conditions, with its uncertainty described as well. The registry does not post such a contrast for this outcome. The arm summaries can be read as descriptions of the recorded groups, but they do not show how a formal analysis accounted for the crossover design or whether differences between participants were controlled.
Why does the crossover structure matter?
In general, crossover studies collect outcomes from the same participant under different treatment conditions. Those repeated measurements are usually related: a participant's outcomes under different conditions may be more alike than outcomes from unrelated people. A suitable analysis should reflect that dependence. Treating every period as if it came from a different participant can misstate uncertainty because it ignores the repeated-measure structure.
Crossover interpretation can also depend on period effects, treatment order, and possible carryover from an earlier condition. These are general design considerations, not claims about what happened in this study. The registry states that the design was crossover and randomized, but does not report the treatment sequence, period structure, washout details, or a model accounting for repeated observations. The analysis approach for those features is therefore not reported in the registry record.
What is the role of uncertainty?
In general, a confidence interval gives a range of values compatible with a statistical estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, though its interpretation depends on the design and model. No confidence interval for a treatment contrast is reported for the primary endpoint. The lower and upper values listed with the arm medians are described as dispersion, not as a confidence interval for a between-treatment effect.
A significance test, when reported, addresses a different question: how compatible the observed data are with a specified null hypothesis under the test's assumptions. No test result or p-value is reported. A lack of a posted test is not evidence that the conditions are equivalent, and it does not show that an effect is absent. The record simply does not provide inferential results for the primary outcome.
What can the sample counts tell us?
The registry lists six participants for each primary-outcome arm and overall enrollment of 24. Those figures describe recorded counts, not the precision of a treatment comparison. In a crossover design, the number of participants and the number of treatment-period observations are distinct ideas, and the registry does not explain their relationship. It does not report how many participants contributed observations to each period, whether all enrolled participants completed all conditions, or how missing measurements were handled.
In general, small samples can yield imprecise estimates, but the precision of a crossover comparison also depends on within-participant variability and the number of usable observations. Those quantities are not reported in the registry record. There is no basis in the posted information for calculating a new precision estimate or inferring the study's statistical power.
What analysis details are absent?
The record does not report the prespecified statistical model, covariate adjustment, treatment-period terms, handling of sequence effects, or any planned interim analyses. It does not provide a sample-size justification. The registry lists no posted secondary outcome results and no posted analyses. These absences limit assessment of whether the analysis followed a prespecified plan or how the primary summary was derived.
In general, a complete clinical-trial interpretation considers the endpoint definition, analysis population, missing-data approach, and the model used to compare treatments. Here, the endpoint definition and descriptive summaries are posted, but the comparative analysis details are not. The appropriate reading is therefore limited to the reported medians, their stated dispersion, and the available design description—not a conclusion about a treatment contrast.
10. Multiplicity, Missing Data and Analysis Populations
The registry reports one outcome measure and no posted secondary outcome results. It also reports zero analyses. The record does not explain whether additional outcomes were collected but not posted, or whether multiple planned comparisons were part of the study. A multiplicity strategy—such as how error rates would be addressed across multiple outcomes or contrasts—is not reported in the registry record. Without that information, it is not possible to assess whether any broader set of statistical tests was planned or how such testing would have been interpreted.
Missing-data methods are also not reported. The registry does not say whether any participants lacked usable glucose measurements, whether participants withdrew from particular conditions, or how incomplete periods were treated. It does not identify an analysis population, such as all randomized participants or only those with complete outcome data. The posted counts of six per arm do not explain whether they represent all randomized participants, completed periods, or a subset with available measurements.
These gaps matter because incomplete data can affect descriptive summaries and treatment comparisons, especially if missingness differs across study conditions or relates to glucose outcomes. In general, methods for handling missing data depend on why the data are missing and on the analysis goal. No assumptions about missingness or imputation can be inferred from the registry record. The design is described as randomized and crossover, but the population and statistical methods used for the primary analysis are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bihormonal Closed Loop | 0 | 6 | 0.0% |
| Standard Opened Loop Pump | 0 | 6 | 0.0% |
| Insulin Only | 0 | 6 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Bihormonal Closed Loop | 0 of 6 |
| Standard Opened Loop Pump | 0 of 6 |
| Insulin Only | 0 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bihormonal Closed Loop | 0 of 6 |
| Standard Opened Loop Pump | 0 of 6 |
| Insulin Only | 0 of 6 |
The adverse-event summary lists six participants at risk in each of the three groups. It records zero serious adverse events, zero other adverse events, and zero deaths for each group. No serious adverse-event terms are listed.
These figures describe the events posted for the recorded groups; they do not establish that no adverse events occurred outside the registry reporting or that an event is impossible. A zero count in a limited group can coexist with uncertainty about less common events. The registry does not report event definitions, duration of safety follow-up, the method for collecting events, or whether participants were monitored for the same length of time under each condition.
In a crossover study, safety exposure may occur during different treatment periods, but the record does not specify how adverse events were assigned to conditions or how repeated exposure was handled. The at-risk counts alone cannot answer those questions. The safety record should therefore be read narrowly: no serious or other adverse events and no deaths are listed for the stated groups, and the reporting details needed for a broader safety assessment are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was randomized, unmasked, and crossover, and that it evaluated closed-loop approaches alongside standard open-loop pump therapy. Its primary outcome was percentage of time in the target glucose range over 24 hours. It posts medians and dispersion values for three treatment groups and lists six participants per group for that outcome.
Those numbers are descriptive. They show the values recorded in the registry for each group, but they do not provide a formal estimate of the difference between treatments. No confidence interval, test result, or comparative model is reported. The posted data therefore do not quantify the precision of a treatment contrast, and they do not establish that the groups are equivalent or that one condition is superior.
The record also does not detail how the crossover observations were analyzed, how exercise and mixed-meal substudies were organized, or how missing outcomes were handled. The registered overall enrollment is 24, but the relationship between that enrollment and the outcome counts is not explained. Without those details, the context for the arm summaries remains incomplete.
In general, a trial's observed summaries are one component of evidence, and their interpretation depends on design, outcome measurement, analysis methods, and uncertainty. Here, the registry provides limited descriptive primary-outcome information and a brief safety summary. It does not report the statistical plan or comparative findings needed to draw a precise conclusion about treatment effects. These limitations concern what is available in the registry record; they do not establish what analyses may have been performed elsewhere.
13. Why This Trial Matters Statistically
This study raises statistical questions that are important for interpreting clinical technology trials. Its crossover design means that outcomes may be measured repeatedly within the same participants. In general, those observations are related, so the analysis needs to account for the within-participant structure when estimating treatment differences and uncertainty. The registry identifies the design but does not report how that structure was handled analytically.
The study also focuses on a time-in-range endpoint over 24 hours and refers to exercise and mixed meals. Such conditions make clear that an outcome's context and observation window matter: a summary only has a clear interpretation when readers know which participants, periods, and challenges contributed to it. The record does not describe how the primary outcome summaries relate to the exercise and mixed-meal substudies.
A further statistical lesson is the distinction between descriptive results and comparative evidence. The registry posts medians for three groups, but does not report a contrast, uncertainty interval, or statistical test. Group summaries alone cannot show the precision of a difference, particularly when the study has a repeated-measures design and the counts are limited.
Finally, registry completeness affects interpretability. Missing details about treatment sequence, missing data, analysis populations, and the statistical plan leave important questions unresolved. These are not merely technical omissions: they determine what the reported summaries represent and how far they can support a comparative conclusion. The record is therefore useful for identifying the endpoint and design, while also showing why transparent reporting of analysis methods is essential.
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 is the absence of a reported comparative statistical analysis. Although the record posts arm medians and dispersion values, it provides no treatment-effect estimate, confidence interval, or test result. The posted summaries cannot by themselves establish the magnitude or precision of a difference.
Important design details are also absent. The registry does not report the order or timing of crossover conditions, washout periods, or the analysis of repeated measurements. The study title and descriptions refer to exercise and mixed meals, but the record does not explain how those conditions connect to the outcome summaries or how participants were allocated across substudies.
The registry lists enrollment of 24, while the primary-outcome summaries list six participants in each group. It does not explain whether these outcome counts represent complete data, a particular substudy, or a subset of the enrolled participants. Baseline characteristics and detailed eligibility criteria are not reported in the registry record, limiting assessment of the participants represented by the summaries.
Missing-data handling, analysis populations, and a sample-size justification are not reported. Nor are secondary outcome results or details of safety-event collection. These limitations restrict interpretation of the posted summaries and prevent a full assessment of the planned and completed analyses. They describe gaps in the registry record and do not establish whether additional information is available elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Assessment of a Closed-loop System With Glucagon, Exercise and Mixed Meals — NCT02397265.
- Registry record last updated 2019-11-01; status last verified 2019-10.
- Results first posted 2019-11-01.
- 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.
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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry describes a completed randomized, unmasked crossover study sponsored by Imperial College London, with enrollment of 24 and a study population of people with type 1 diabetes. The registered conditions include bihormonal closed loop, insulin-only closed loop, and standard open-loop pump therapy.
The primary endpoint is percentage of time in the glucose target range of 3.9-10.0mmol/l over 24 hours. The record posts median summaries for three groups, with six participants listed in each group, but provides no comparative analysis, confidence interval, or test result. No secondary outcome results are posted. The safety summary lists zero serious adverse events, zero other adverse events, and zero deaths in each group. Details about crossover periods, analysis methods, missing data, and the relationship between enrollment and outcome counts are not reported in the registry record.