Islet Transplantation for Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Islet Transplantation for Type 1 Diabetes (NCT00014911), a na phase 2 study. The primary outcome is Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation..

2. Clinical Question

The study addresses whether islet transplantation using the Edmonton Protocol of steroid-free immunosuppression could be repeated in people with type 1 diabetes. Its registry summary describes patients whose blood sugar levels would not stay normal despite intensive insulin therapy. The stated aim also includes learning more about diabetes control after transplantation.

The question is about a defined clinical state at a specified follow-up point, rather than a direct comparison between alternative treatments. The primary outcome requires both no need for exogenous insulin and glycemic control that meets the record’s stated criteria. The study’s stated purpose includes testing whether procedures and results from an earlier study in Edmonton could be repeated. However, the registry record does not report a numerical primary outcome result or a comparison with that earlier study. It therefore allows the question to be described, but not answered from the posted outcome information.

3. Trial Design

The registry classifies the study as Phase 2 and describes a single-group design. The brief summary calls it a Phase I/II study, so the two descriptions differ in how they characterize the phase. Allocation is recorded as NA, and masking is recorded as none. The record lists 36 participants enrolled and marks the study as completed. The recorded start is 2001-04, and primary completion is 2005-06.

All participants are assigned to the islet transplantation group; no parallel control group is listed. This is important to interpretation: results from a single-group study can describe outcomes among participants who received the intervention, but they cannot directly estimate how those outcomes compare with a concurrent alternative. Differences from an external group or earlier study would not be a randomized, like-for-like comparison on the basis of this record.

The intervention list includes the islet transplantation procedure and several drugs: sirolimus, tacrolimus, daclizumab, sulfamethoxazole, ganciclovir, trimethoprim, and pentamidine. The record’s official title identifies steroid-free immunosuppression. Further details about drug schedules, treatment duration, transplantation procedures, eligibility criteria, or participant follow-up are not reported in the registry record.

The primary outcome is defined at one year after each participant’s final islet transplantation. The primary analysis population is identified as intent-to-treat, but the registry does not explain how that population was operationalized or how missing outcome data were handled. The record lists six outcome measures and three analyses. Their full analysis procedures, including any adjustments or prespecified statistical tests, are not reported in the registry record.

The registry summary says the trial was intended to test whether procedures and results from an earlier Edmonton study could be repeated, and to learn more about diabetes control after transplantation. It does not report a sample-size justification, interim analyses, or a detailed statistical analysis plan. The design information therefore supports a broad account of the study structure, but not reconstruction of the planned or performed statistical methods.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat

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 Percent of Participants That Achieved Insulin Independence With Adequate Control of Blood Glucose Levels at One Year Post Final Islet Transplantation., measured over One year status post participant receipt of final islet transplantation.

The primary endpoint is the percentage of participants who achieved insulin independence with adequate blood-glucose control one year after their final islet transplantation. The registry identifies the analysis population as intent-to-treat. Insulin independence is defined as not requiring exogenous insulin while meeting specified glycemic criteria. These criteria make the endpoint more specific than insulin use alone: a participant must also satisfy the stated measures of longer-term and short-term glucose control.

The definition requires a blood glycosylated hemoglobin (HbA1c) level < 6.5%. It also requires a fasting blood glucose level not exceeding 140 mg per deciliter more than three times in any week, and a 2-hour postprandial blood glucose level not exceeding the stated age-specific thresholds more than four times per week: <140 mg/dL for ages up to and including 50 years, <150 mg/dL for ages 50-60 years, and <160 mg/dL for ages 60+.

Using a combined definition can make an endpoint clinically interpretable by requiring both the absence of insulin use and acceptable glucose measures, rather than treating either alone as success. At the same time, the resulting percentage depends on the exact criteria, measurement timing, and data completeness. Those details matter when interpreting the result across studies. Here, the registry provides the endpoint definition but does not report the primary outcome percentage, its numerator and denominator, or an uncertainty interval. Consequently, the endpoint’s operational meaning is clear, but the posted information does not show how many participants met it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a percentage of participants meeting a binary definition: either a participant meets the criteria for insulin independence with adequate blood-glucose control at the specified follow-up, or does not. A percentage is a descriptive summary of the fraction of the analysis population classified as having the outcome. To interpret it, readers need the number meeting the criteria and the denominator used. Neither the primary outcome count nor its percentage is reported in the registry record.

What a confidence interval would add

In general, a confidence interval describes the statistical uncertainty around an estimate. For a percentage, it helps distinguish an estimate that is relatively precise from one that remains compatible with a wide range of underlying outcome frequencies. Its width depends on factors such as the amount of information in the data and the variability of the outcome. A confidence interval does not remove design limitations, and it cannot address the absence of a control group. No confidence interval for the primary endpoint is reported in the registry record.

Why the single-group design matters

A single-group study can estimate the frequency of an outcome among the participants observed, if the outcome data and denominator are reported. It does not create a concurrent counterfactual: the outcome those same participants would have experienced under a different approach. Random allocation in a comparative trial is one way to support causal comparisons, but this study is recorded as single-group, with allocation NA and no comparator arm. Statistical adjustment cannot turn an unobserved control group into a randomized comparison. The record does not report an adjusted comparative analysis.

How the endpoint definition shapes the estimate

The primary endpoint combines no exogenous insulin use with specific blood-glucose criteria. In general, combining conditions into one endpoint means that participants must satisfy all stated conditions to count as having the outcome. A stricter definition can classify fewer participants as meeting the endpoint than a definition based on insulin independence alone, while also making the outcome more specific to the intended clinical state. The registry’s definition includes an HbA1c threshold, a limit on fasting glucose readings, and age-specific postprandial glucose thresholds. How measurements were collected and how borderline or unavailable readings were handled are not reported in the registry record.

What over-dispersion means in general

For count or rate outcomes, a statistical model may assume a particular relationship between the average outcome and its variability. Over-dispersion occurs when the observed variability is greater than that assumed by a model. If it is ignored, standard errors can be too small and confidence intervals or tests can appear more precise than warranted. This is a general statistical issue; the registry record does not report a count-model analysis or say whether over-dispersion was assessed for this trial.

Planning estimates are not trial results

Sample-size calculations are planning tools, not observed outcomes. The planning illustration associated with the posted information is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. It is explicitly a planning illustration rather than the trial’s own design. Such calculations do not show what the trial actually observed, and they are not observed power. In particular, the equal-allocation, two-arm assumptions do not describe the single-group design recorded for this study. The registry record does not report a sample-size justification for the trial itself.

In general, a sample-size calculation estimates how much information a proposed design would need for a specified statistical objective under stated assumptions. Its result depends on the assumed effect, variability or event rate, significance level, power target, and analysis method. If the assumptions differ from the eventual study conditions, the calculation may not describe the precision achieved. A planned sample size also does not guarantee a particular result or establish that a study can answer every clinical question.

What is and is not documented

The registry lists six outcome measures and three analyses, but it does not report the full statistical methods for those analyses. The specific test or model for the primary endpoint, any covariate adjustment, handling of repeated measurements, confidence-interval method, and multiplicity procedure are not reported in the registry record. These omissions prevent independent reconstruction of the analysis from the registry information.

For a binary percentage endpoint, complete outcome data and a defined analysis population are essential to interpretation. If participants do not have measurements at the follow-up point, different missing-data approaches can produce different estimates. For example, an analysis might exclude participants without endpoint data, classify them under a prespecified rule, or use a model-based approach; these are general possibilities, not methods documented for this study. The registry names intent-to-treat as the population but does not state the operational rules for missing outcomes or deviations from the assigned study group.

Interpretation also depends on distinguishing descriptive estimates from inferential claims. A percentage describes observed frequency. A test or interval can quantify some forms of sampling uncertainty, but neither can correct for unmeasured differences, selection, or the lack of a comparator. Because the primary endpoint result and its uncertainty are not reported in the registry record, the posted information does not permit a numerical assessment of endpoint frequency, precision, or statistical evidence.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and three analyses. It identifies the insulin-independence endpoint as primary and lists secondary outcomes concerning partial islet function one year after the final transplantation, insulin independence from the first transplant, and detectable fasting basal C-peptide levels. However, the detailed results and analysis procedures for these outcomes are not reported in the registry record.

When a study examines multiple outcomes or performs multiple statistical tests, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity procedures can control or describe that issue, but they require a prespecified testing strategy and clarity about which outcomes or comparisons form a family. The registry record does not report a multiplicity adjustment, a testing hierarchy, or whether the three listed analyses correspond to particular outcomes or comparisons. No conclusion about multiplicity control can therefore be drawn from the listed counts alone.

The primary outcome population is labeled intent-to-treat. In general, this label refers to analyzing participants according to their original study assignment, but in a single-group study the practical rules still need to specify which enrolled participants contribute to each outcome and how incomplete follow-up is handled. The registry does not report the number with primary outcome data, the missing-data method, reasons for missing measurements, or whether any participants were excluded from the analysis.

Missing outcomes can affect a percentage because the estimated frequency depends on who is included in the denominator and what assumptions are made about unavailable measurements. A complete-case calculation, an explicit classification rule, and an imputation approach can yield different answers. These are general methods, not documented procedures for this trial. The posted record does not provide enough information to determine whether missingness could have changed the primary endpoint estimate or how sensitive results might be to alternative assumptions.

Accordingly, the registry identifies a primary endpoint and analysis population but does not document enough about multiplicity or missing-data handling to evaluate those parts of the statistical plan. The primary result itself is not reported in the registry record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (11.1%), diarrhoea (5.6%), pyrexia (5.6%), pyelonephritis (5.6%), dehydration (5.6%).

The registry lists 36 participants at risk for serious adverse events and 17 participants affected. For other adverse events, it lists 36 at risk and 36 affected. These are counts recorded for the islet transplantation group. The record does not give a death count.

The listed serious adverse-event terms and percentages are neutropenia at 11.1%, diarrhoea at 5.6%, pyrexia at 5.6%, pyelonephritis at 5.6%, dehydration at 5.6%, and anaemia at 2.8%. These are registry-listed term frequencies. They should not be added together: a participant may have more than one event term, and the registry does not state that the categories are mutually exclusive. The term percentages also do not describe a comparison with a control group.

In general, an adverse-event count describes the number of participants recorded as affected, whereas a term-specific rate describes the frequency associated with a named event. Neither alone establishes that an event was caused by a particular intervention. The record does not report event timing, duration, recurrence, detailed severity grades, or attribution. Because there is no comparator group, the listed figures cannot quantify how event frequencies differ from those under another treatment. They describe the safety information recorded for the study group, with these reporting details as limitations.

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

The registry record makes clear what the primary endpoint was intended to measure: insulin independence combined with specified blood-glucose criteria, assessed one year after the final islet transplantation. It also records that all participants were in a single study group and that the primary analysis population was described as intent-to-treat. Those details clarify the research question and broad design.

The primary endpoint result, however, is not reported in the registry record. The record therefore does not establish the percentage of participants who met the endpoint, how many participants met it, or how precisely the result was estimated. It cannot support a numerical conclusion about the endpoint frequency. Describing the endpoint definition is not the same as reporting the outcome.

The design also limits causal interpretation. With no comparator group, a single-group outcome cannot show how the participants would have fared under another treatment or without transplantation. Even if a primary percentage were available, it would describe an outcome frequency in this study group rather than a randomized estimate of the intervention’s effect relative to an alternative. The study’s stated goal of assessing whether an earlier Edmonton result could be repeated does not itself supply comparative evidence; a numerical comparison with that earlier study is not reported in the registry record.

The posted safety figures are informative as counts and listed event-term percentages for the study group. They do not, on their own, establish why events occurred or how the frequencies compare with another approach. The record does not provide the additional detail needed to characterize event timing, recurrence, or attribution.

In general, statistical estimates and their uncertainty should be interpreted alongside study design, outcome definitions, completeness of follow-up, and analysis rules. Here, the endpoint definition and broad design are described, but the primary result, its uncertainty, missing-data handling, and detailed analysis plan are not reported in the registry record. The appropriate interpretation is therefore limited: the registry documents the question and some study characteristics, but not a numerical primary outcome from which to judge the observed endpoint frequency or its precision.

13. Why This Trial Matters Statistically

This study illustrates why reading the outcome definition and study design together matters. The primary endpoint is not simply the absence of insulin use: it combines insulin independence with specified HbA1c, fasting glucose, and postprandial glucose criteria at one year after the final islet transplantation. That definition gives the research question a clear operational form, while also making clear that participants must satisfy several conditions to count as meeting the endpoint.

The single-group design is equally important. A percentage in a single group, when reported, describes the observed frequency in that group. It does not by itself estimate the difference between transplantation and a concurrent alternative. The registry lists no comparator group, so the trial’s structure cannot support a direct randomized comparison. This distinction is central when interpreting intervention studies, especially when the stated aim is to assess whether earlier findings can be repeated.

The record also demonstrates that a precise endpoint definition does not guarantee a complete statistical account. It names an intent-to-treat analysis population and lists outcome measures, but the primary outcome result and its uncertainty are not reported in the registry record. Information about missing data, multiplicity, and the detailed analysis method is also not reported. Without those elements, readers cannot assess the observed primary outcome frequency or how robustly it was estimated.

Safety counts add a separate kind of information. The record lists affected-participant counts and serious adverse-event terms, but without a comparator those figures describe the study group rather than differences between approaches. The distinction between a descriptive safety summary and a comparative estimate is another important statistical reading skill.

Statistically, the study matters as an example of the difference between a well-defined question and an answerable inference. The endpoint and design can be described from the registry, but the missing primary result and limited comparative structure leave important questions unresolved. Clear reporting of estimates, denominators, uncertainty, and analysis procedures is necessary for readers to evaluate both the observed data and the strength of conclusions drawn from them.

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 most immediate limitation for interpreting the primary endpoint is that its result is not reported in the registry record. Although the endpoint definition and timeframe are given, the number meeting the criteria, the percentage, denominator, and uncertainty interval are not reported. The posted information therefore does not permit assessment of the primary outcome frequency or precision.

The study is recorded as single-group, with allocation NA and no masking. No concurrent comparator is listed, so the design does not provide a direct like-for-like control comparison. This limits causal interpretation and prevents a randomized estimate of a difference between transplantation and an alternative.

The registry identifies an intent-to-treat population but does not explain its implementation for the primary endpoint. The numbers with available follow-up, reasons for missing outcomes, treatment of missing measurements, and handling of deviations are not reported in the registry record. These details matter because they determine who contributes to the outcome estimate and how the denominator is defined.

The study enrolled 36 participants. The registry record does not report a trial-specific sample-size justification, so the basis for the planned enrollment is not documented. It also does not report a detailed statistical analysis plan, the method used for the primary endpoint, the confidence-interval approach, or a multiplicity strategy. The listed counts of outcome measures and analyses do not resolve these omissions.

Safety information is limited to participant counts and listed serious adverse-event terms and percentages. Details about event timing, duration, recurrence, attribution, and the handling of overlapping event terms are not reported. The registry does not list a death count. These limitations are specific to the information recorded for this study and should be kept distinct from the broader limitations of interpreting any single-group clinical study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Islet Transplantation for Type 1 Diabetes — NCT00014911.
• Registry record last updated 2017-03-15; status last verified 2017-02.
• Results first posted 2012-10-17.
• 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 describes a completed Phase 2 study of islet transplantation for insulin-dependent diabetes, with 36 participants enrolled. Its brief summary describes a Phase I/II study, while the registry classification lists Phase 2. The study is recorded as single-group, with allocation NA and no masking. All participants were assigned to the islet transplantation group.

The primary outcome is the percentage achieving insulin independence with adequate blood-glucose control one year after the final transplantation. The endpoint criteria and an intent-to-treat analysis population are stated, but the primary result is not reported in the registry record. The listed secondary outcomes concern partial islet function, insulin independence from the first transplant, and detectable fasting basal C-peptide levels.

The safety record lists 17 of 36 participants affected by serious adverse events and 36 of 36 affected by other adverse events. Several serious-event terms and percentages are listed; a death count is not reported in the registry record. The primary outcome result, detailed analysis plan, missing-data procedures, and multiplicity approach are also not reported in the registry record.