Pregnancy Intervention With a Closed-Loop System (PICLS) Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pregnancy Intervention With a Closed-Loop System (PICLS) Study (NCT03774186), a randomized na study. The primary outcome is Number of Episodes of Severe Hypoglycemia.

2. Clinical Question

The registry frames the study as an exploratory pilot feasibility randomized clinical trial. Its aims extend beyond the primary safety outcome to glycemic variability, fear of hypoglycemia, quality of life, device satisfaction, and exploratory maternal and fetal outcomes. The primary outcome therefore addresses a specific safety event, while the wider set of measures describes additional clinical and participant-reported aspects of the two approaches.

3. Trial Design

The Pregnancy Intervention With a Closed-Loop System (PICLS) Study, NCT03774186, is recorded as a randomized, single-masked, parallel-group trial. The phase is listed as NA. The registry reports enrollment of 24, with 12 participants in the sensor-augmented pump therapy arm and 11 in the hybrid closed-loop therapy arm for the primary outcome. The difference between the enrollment total and the listed arm counts is not explained in the registry record.

Participants were assigned to one of two device strategies. In the hybrid closed-loop group, the pump and continuous glucose monitor communicated to support automated insulin adjustments, while meal boluses remained the participant’s responsibility. In the sensor-augmented pump group, participants used an insulin pump and continuous glucose monitor without automated system adjustments. The registry describes follow-up from the 2nd trimester through pregnancy and 4-6 weeks post-partum; the primary outcome timeframe is stated as through study completion, an average of 9 months.

The study is listed as completed. The registry records a start date of 2019-03-21 and a primary completion date of 2022-03-08. The sponsor is University of Colorado, Denver. The registry record does not report who was masked, how randomization was generated or concealed, or whether participants could be masked to their device strategy. These design details should not be inferred from the single-masked designation.

The pilot feasibility designation is important when reading the results: this trial reports outcomes from a small randomized comparison, and the registry does not report a prespecified statistical analysis plan or a sample-size justification. The posted planning illustrations are based on observed effects and are not the trial’s original design calculations.

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 Number of Episodes of Severe Hypoglycemia, measured over through study completion, an average of 9 months.

The primary endpoint is the number of episodes of severe hypoglycemia requiring third-party assistance. It is a count of events, not a count of participants who experienced at least one event. The registry specifies that the outcome assesses safety of hybrid closed-loop therapy compared with sensor-augmented pump therapy during gestation and the early post-partum period, through study completion, an average of 9 months.

Counting episodes can capture repeated events in the same participant, so an event total and a participant total are not interchangeable. The posted value is zero in each arm: 12 participants are listed for sensor-augmented pump therapy and 11 for hybrid closed-loop therapy. No spread, confidence interval, or comparison estimate is posted for this endpoint. The reason is described as values missing or not estimable for a two-arm comparison for a count-other endpoint.

As a general statistical point, this outcome is used to describe a specific serious safety event rather than overall glucose control. A zero posted count describes the events recorded in this trial; it does not establish that the underlying event rate is zero or that the two strategies have identical safety profiles. The precision of a comparison cannot be assessed from an event count alone, and the registry does not provide a comparative interval estimate for this endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What do the effect estimates describe?

For outcomes recorded as participants with an event, the recalculated risk difference compares the proportion with the event in the hybrid closed-loop group with the proportion in the sensor-augmented pump group. A positive value means the recorded proportion is higher in the hybrid closed-loop group; a negative value means it is lower. The confidence interval gives a range of values compatible with the posted data and the calculation method. It is not a guarantee that the true value lies within that particular interval.

The record also gives risk ratios and odds ratios for the binary outcomes. A risk ratio compares the event proportions directly. An odds ratio compares event odds rather than event proportions. These measures use different scales, so their numerical values should not be read as interchangeable. In small groups, all such estimates can be sensitive to a small number of participants changing event status.

For gestational weight gain, the mean difference compares the group averages. The posted standard deviations describe how spread out individual values are around each group’s mean. A mean difference does not show the full distribution of individual outcomes, and the registry does not report an adjusted analysis for this outcome.

How should confidence intervals be read?

As a general statistical explanation, a confidence interval expresses uncertainty in an estimate under the assumptions of the method used. A wider interval indicates less precision than a narrower interval. For a difference, an interval including zero is compatible with no difference as well as with differences in either direction. The intervals for the three recalculated secondary comparisons include zero, so the posted data do not provide a precise estimate that rules out no difference. This is not proof of equivalence or proof that no meaningful difference exists.

The primary count outcome has no posted comparative interval. Its observed count is zero in both arms, but a comparison cannot be interpreted using an interval or p-value that the registry does not report. A zero count in a small trial can occur even when the underlying event probability is not zero. The record does not provide the information needed to quantify uncertainty around the primary count comparison.

What do the p-values mean?

The p-values for the secondary comparisons are unadjusted. As a general explanation, a p-value measures how unusual data at least as inconsistent with a specified no-difference model would be, if that model and the analysis assumptions were correct. It is not the probability that the no-difference model is true, and it does not measure the size or clinical importance of an effect. The p-values should be interpreted alongside the estimates and confidence intervals, not as standalone conclusions.

The registry record does not report sponsor analyses for the three secondary outcomes. The effect estimates and p-values are recalculated from the posted summary statistics without adjustment. They should not be represented as the trial investigators’ prespecified or adjusted results. No discrepancy is flagged between these recalculations and a sponsor analysis; sponsor analyses are not listed.

What are the planning illustrations?

The planning illustrations use the observed effect as their starting point. They show participant counts per arm under the stated assumptions: a two-sided significance level of 0.05, equal allocation, a normal approximation, and a target effect set to a stated fraction of the observed effect. They are planning illustrations, not observed power, and do not establish that the study had a particular probability of detecting an effect. Because the starting estimates come from a small trial, the observed effect used for planning may be unstable.

As a general statistical point, over-dispersion matters when count outcomes vary more than a model assumes. A model that underestimates such variability can produce intervals that are too narrow and tests that appear more decisive than warranted. The registry does not report a count-model specification, an over-dispersion assessment, or a model-based analysis for the primary endpoint. The posted primary counts therefore should not be treated as evidence that any particular count model was used.

What is not documented?

The statistical analysis plan, covariate adjustment, handling of repeated measures, analysis populations, and missing-data methods are not reported in the registry record. Nor is it reported whether secondary outcomes were prespecified for formal hypothesis testing or whether any interim analyses were planned or conducted. Without those details, the recalculated comparisons remain descriptive, unadjusted readings of posted summary statistics.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled across the many outcomes. It lists multiple safety, glucose-control, maternal, fetal, quality-of-life, fear-of-hypoglycemia, and device-satisfaction measures. The three available recalculated secondary comparisons have unadjusted p-values. No family-wise error procedure, false-discovery procedure, hierarchy of hypotheses, or distinction between confirmatory and exploratory testing is reported. As a general statistical point, the chance of at least one apparently unusual result can rise when many outcomes are examined, so isolated unadjusted findings deserve caution.

Missing-data methods are not reported in the registry record. The analysis populations are also not described: it is not clear whether outcomes were analyzed according to randomized assignment, according to device use, or using another rule. Although enrollment is listed as 24, the primary endpoint arms list 12 and 11 participants, and the adverse-event groups list 12 participants in each arm. The registry does not explain these differences or provide a participant flow accounting for exclusions, withdrawals, or outcome availability.

The record does not describe imputation, complete-case analysis, or sensitivity analyses for missing outcomes. It also does not state whether missingness was assessed by arm or whether the reasons for missing data were recorded. These omissions matter because a comparison can be biased if outcome availability is related to treatment assignment or to the outcome itself.

Interim analyses and stopping rules are not reported in the registry record. The statistical analysis plan and any prespecified adjustment strategy are also not reported. Consequently, the recalculated secondary comparisons should be interpreted as unadjusted descriptive comparisons rather than as a complete account of a prespecified inferential framework.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: preeclampsia with severe features (16.7%), fetal demise (8.3%), dka (8.3%), severe hypoglycemia (8.3%), chronic hypertension with superimpose preeclampsia with severe features (8.3%).

The primary endpoint records zero episodes of severe hypoglycemia in each arm. Separately, the serious adverse-event listing reports participants affected: 0 of 12 in the sensor-augmented pump therapy group and 6 of 12 in the hybrid closed-loop group. The registry also lists other adverse events affecting 10 of 12 and 11 of 12 participants, respectively, and no deaths in either group. These summaries represent different safety presentations; the registry does not explain how the serious adverse-event counts relate to the primary endpoint’s episode counts.

Among the listed serious adverse-event terms, the registry reports preeclampsia with severe features at 16.7%, and fetal demise, DKA, severe hypoglycemia, and chronic hypertension with superimposed preeclampsia with severe features at 8.3% each. The record does not explain the denominators or the relationship between these term percentages and the group-level affected-participant counts. The percentages should not be added together or interpreted as mutually exclusive categories.

Serious adverse-event summaries describe events recorded during the trial; they do not by themselves establish that a device strategy caused an event. With small groups and limited detail about event timing, attribution, and denominators, the figures are descriptive. The registry does not report a comparative statistical analysis for these safety summaries.

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

The posted results describe a small randomized comparison of two insulin-delivery approaches in pregnancies associated with type 1 diabetes. They show that no severe hypoglycemia episodes requiring third-party assistance were recorded for either arm in the primary outcome summary. They also provide selected maternal outcome values and adverse-event summaries. These data are useful as a record of what was observed in this trial, but the primary endpoint does not have a comparative estimate or uncertainty interval.

The secondary recalculations show uncertain estimates: their confidence intervals include no difference and extend across a range of possible group differences. The unadjusted p-values do not establish a treatment effect, and the registry does not report sponsor analyses for those comparisons. A lack of a clearly distinguished difference is not evidence that the approaches are equivalent. Equivalence or non-inferiority requires a defined margin and an analysis designed for that question, neither of which is reported in the registry record.

These results also do not establish that the recorded event patterns would occur in other populations or settings. The arm sizes are small, and the registry does not provide enough detail about missing outcomes, analysis populations, or the statistical plan to resolve important uncertainties. The planning illustrations are not evidence of observed power and should not be mistaken for a design justification.

As a general interpretation principle, statistical uncertainty and clinical importance are separate. An estimate can be imprecise even when its point estimate appears substantial, and a small p-value would not by itself establish clinical importance. Here, the posted data support a descriptive account of this trial’s outcomes, not a definitive conclusion about comparative efficacy or safety.

No medical decision should be based on these registry summaries alone. The record does not report a complete adjusted analysis or enough information to determine how all measured outcomes should be weighed together. The study’s exploratory pilot framing is consistent with treating its results as preliminary and hypothesis-generating.

13. Why This Trial Matters Statistically

This trial is statistically useful because it puts a clear safety outcome at the center of a randomized comparison while also recording a broad range of maternal, fetal, glucose-control, and participant-reported measures. The primary endpoint is clinically specific: it counts severe hypoglycemia episodes requiring third-party assistance. The distinction between event counts and participant counts is important, especially when the same participant might contribute more than one event.

The record also illustrates why observed values alone do not settle comparative questions. Zero events in both arms may appear straightforward, but without an uncertainty estimate or a reported count-analysis method, the precision of the comparison cannot be established. For the available secondary comparisons, the broad intervals show how limited samples can leave substantial uncertainty even when group estimates differ.

The pilot setting makes the planning illustrations particularly easy to misread. They are based on observed effects and stated assumptions; they are not observed power or evidence that the trial was designed around those effects. Planning a later study requires a justified target effect and a transparent analysis plan, rather than treating a small study’s observed estimate as a stable design input.

Finally, the registry record highlights the importance of reporting analysis populations, missing-data methods, multiplicity handling, and the relation between outcome summaries. Those details help readers distinguish descriptive safety reporting from formal between-group inference. Their absence limits the conclusions that can be drawn, while making the posted outcomes valuable as a starting point for more complete future reporting.

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.

Several limitations specific to this trial affect interpretation. The randomized arm sizes reported for the primary endpoint are 12 and 11, and the registry does not reconcile them with the enrollment of 24. The adverse-event groups list 12 participants per arm. Participant flow, withdrawals, and outcome-specific availability are not reported, so the population contributing to each outcome cannot be fully established from the registry record.

The primary outcome is a count, but the registry provides neither a comparative estimate nor an uncertainty interval. The reason is recorded as values missing or not estimable for a two-arm comparison. The zero event totals therefore cannot support a precise comparison. The record also does not report a statistical model for count outcomes or how repeated events, if any, would have been handled.

Only a subset of the many listed outcomes has recalculated comparative results available. The statistical analysis plan, multiplicity strategy, covariate adjustment, interim analyses, and missing-data methods are not reported. As a result, readers cannot determine whether the available secondary comparisons correspond to prespecified confirmatory analyses or represent exploratory summaries.

The adverse-event presentation adds another limitation: the registry provides group-level counts of participants affected and percentages for serious adverse-event terms, but does not explain the denominator or the relationship between those summaries and the primary endpoint. The relationship between the primary severe hypoglycemia count and the serious adverse-event term listing is not reported in the registry record.

Finally, the registry describes the trial as an exploratory pilot feasibility study. Its small sample and broad outcome set limit precision and make chance variation a substantial concern. The posted planning illustrations rely on observed effects and assumptions rather than a reported trial design justification.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pregnancy Intervention With a Closed-Loop System (PICLS) Study — NCT03774186.
• Registry record last updated 2023-11-28; status last verified 2023-11.
• Results first posted 2023-11-28.
• 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

NCT03774186, the Pregnancy Intervention With a Closed-Loop System (PICLS) Study, is recorded as a completed, randomized, single-masked, parallel-group trial sponsored by University of Colorado, Denver. The registry lists enrollment of 24 and phase NA. The recorded study dates are 2019-03-21 to primary completion on 2022-03-08.

The study compared hybrid closed-loop therapy with sensor-augmented pump therapy in pregnant women with type 1 diabetes. The primary outcome was the number of severe hypoglycemia episodes requiring third-party assistance through study completion, an average of 9 months. The posted primary values are zero episodes in each arm, with no comparative estimate reported.

Selected secondary comparisons are available as unadjusted recalculations from posted summary statistics. Their confidence intervals include no difference, and the registry does not report sponsor analyses for these outcomes. The record does not report the statistical analysis plan, multiplicity handling, missing-data methods, or analysis populations. The results are therefore best read as descriptive findings from an exploratory pilot trial.