Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes (NCT00672204), a na phase 1, phase 2 study. The primary outcome is The Proportion of Insulin-independent Subjects With Full Islet Graft Function.

2. Clinical Question

3. Trial Design

This was a Phase 1 and Phase 2, single-group study sponsored by the University of Minnesota. The registry lists an enrollment of 23, but the primary-outcome population note says Raptiva was removed from the market after 3 subjects were transplanted. These figures describe different record fields and should not be treated as interchangeable counts of participants who received the transplant or completed follow-up.

Allocation is listed as not applicable, and masking is listed as none. There was no concurrent control arm in the record. Consequently, the design is not a randomized comparison and cannot separate changes associated with the treatment regimen from other influences using an internal control group.

The protocol objective was to test the safety and efficacy of maintenance therapy with efalizumab and sirolimus for 1 year, followed by withdrawal of efalizumab and continued sirolimus, for prevention of islet transplant destruction and rejection. The primary outcome was assessed at 1 year following the first islet transplant. The record lists allogeneic islets of Langerhans, Raptiva, sirolimus, and anti-thymocyte globulin as interventions, while the arm description names allogeneic islets of Langerhans.

The study status is terminated. The registry states that efalizumab’s manufacturer voluntarily withdrew the drug from the U.S. market in April of 2009. Previously transplanted subjects were transitioned to alternative immunosuppressives, and no new subjects were to be transplanted under this protocol. The record does not report the number who completed the planned regimen or the primary endpoint follow-up.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Raptiva was removed from market.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Raptiva was removed from market after 3 subjects were transplanted

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 The Proportion of Insulin-independent Subjects With Full Islet Graft Function, measured over 1 year following the first islet transplant.

The primary endpoint is the number of participants classified as insulin-independent with full islet graft function at 1 year following the first islet transplant. The registry’s definition requires being able to titrate off insulin for at least 1 week and meeting all listed laboratory and glucose criteria. These include an HbA1c < 7.0% or a ≥2.5% decrease from baseline; specified limits on fasting and post-prandial capillary glucose readings; fasting serum glucose ≤126 mg/dL (7.0 mmol/L), with confirmation if it is >126 mg/dL (7.0 mmol/L); and evidence of endogenous insulin production, defined by fasting or stimulated C-peptide levels ≥0.5 ng/mL (0.16 nmol/L).

A combined endpoint of this kind makes the intended clinical state explicit: participants must be off insulin and satisfy the stated measures of glucose control and insulin production. Requiring all components means that meeting only one criterion would not meet the registry definition. The measure is reported as a participant count, not as a continuous laboratory value or time-to-event measure. The registry record gives no observed count or analysis result for this endpoint, so it cannot establish how many participants met the definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the record is limited. It identifies a binary primary outcome recorded as a number of participants, but reports no analysis for that endpoint. The record lists 1 outcome measure and 0 analyses. It does not report an effect estimate, confidence interval, hypothesis test, or analysis population for the primary result.

What does a participant count describe?

A count describes how many people met a defined outcome. For a binary endpoint, each participant is classified as meeting or not meeting the criteria. A count can be useful as a direct description, but interpretation also depends on knowing the relevant denominator: for example, whether it includes everyone enrolled, everyone transplanted, or only those with an assessment. The registry record does not provide the primary outcome count or clarify the endpoint denominator. No proportion can therefore be inferred from the record.

What would a confidence interval add?

In general, a confidence interval expresses the precision of an estimate under a statistical model. A narrower interval indicates less sampling uncertainty under that model, while a wider interval indicates more. It does not resolve problems caused by missing outcome data, selection into follow-up, or the absence of a comparison group. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed from the posted information.

What does the single-group design imply?

In general, a single-group study describes outcomes among participants receiving the study regimen but lacks a concurrent control group. Without a like-for-like comparator, an observed outcome cannot be attributed to the regimen by comparison with an internal control. The record lists allocation as not applicable and the model as single group. It also identifies no masking. These design features do not supply evidence about the size of any treatment effect; the primary outcome itself is not reported.

The study’s stated objective included testing safety and efficacy of maintenance therapy with efalizumab and sirolimus, followed by withdrawal of efalizumab and continued sirolimus. The primary endpoint is specified at 1 year after the first transplant. The record does not report a statistical analysis plan describing how that endpoint was to be analyzed, whether adjustments were intended, or how follow-up after the treatment change was to be incorporated. Such details are not reported in the registry record.

How should the planning illustrations be understood?

The record describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial had a particular probability of detecting an effect. Sample-size illustrations are not observed power and should not be interpreted as an analysis of trial outcomes.

The illustrations’ equal-allocation, two-arm assumption does not describe the registered single-group design. The record itself notes that the study is not a randomized comparison and that its arms are not a like-for-like control comparison. The registry does not report that these planning assumptions were the protocol’s original design or statistical plan. The sample-size justification and any protocol-specific power calculation are not reported in the registry record.

Why does over-dispersion matter in general?

For count outcomes, a statistical model may assume a particular degree of variability. Over-dispersion occurs when the observed variability exceeds what that model assumes. If it is ignored, uncertainty estimates may be too small and statistical tests may appear more decisive than warranted. This is a general consideration for count-data methods, not a reported feature of this study. The record gives no count-analysis model or dispersion assessment, and the primary endpoint is described as a participant count rather than as a repeated-event rate.

Because no primary analysis or result is reported, there is no basis in the registry record to judge model fit, precision, or statistical significance. The defensible interpretation is descriptive: the record documents the intended endpoint and design, while leaving the endpoint result and its analysis unreported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Allogeneic Islets of Langerhans")
n      <- c(3)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Allogeneic Islets of Langerhans  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 1 outcome measure and 0 analyses. It does not report a set of hypothesis tests, a testing hierarchy, or a multiplicity adjustment. The primary endpoint is identified, but the record does not state whether other outcomes were part of a broader confirmatory testing plan or how multiple comparisons would have been handled. Those features are not reported in the registry record.

The record also does not describe the analysis population for the primary endpoint. It does not say whether the analysis was intended to include all enrolled participants, transplant recipients, or only participants with a 1-year assessment. Nor does it give a participant flow accounting for enrollment, transplantation, follow-up, and outcome availability. Although enrollment is listed as 23 and the outcome population note refers to 3 subjects transplanted before Raptiva was removed from the market, those details do not establish the endpoint denominator.

Missing-data methods are not reported in the registry record. There is no statement about how missing 1-year measurements, incomplete criteria, or withdrawal from the planned regimen would be handled. General statistical practice distinguishes observed outcomes from missing outcomes rather than assuming that an unrecorded result is either a success or a failure. Without a reported handling rule and outcome data, neither missingness nor its effect on the primary estimate can be assessed.

The record does not report interim analyses or stopping rules. The termination is linked in the registry summary to efalizumab’s voluntary withdrawal from the U.S. market, but no analysis plan is given for data collected before termination. No conclusion about multiplicity control, missing-data bias, or the intended analysis population can be drawn beyond these reporting gaps.

12. 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.

For the allogeneic-islet group, the registry reports 3 participants at risk, 0 affected by serious adverse events, and 0 affected by other adverse events. These are the counts in the posted safety fields. They should be read as registry-reported counts for that group, not as a complete description of every possible safety outcome or of events outside the record’s reporting scope.

The deaths field is null. That is not the same as a reported count of zero; deaths are not reported in the registry record. The list of top serious adverse event terms is empty, which indicates that no terms are listed there, not additional evidence about unreported events. The record does not provide event-level descriptions or further detail about safety follow-up in the listed fields.

The small reported at-risk group and the absence of a control arm limit what these figures can establish. Counts alone do not provide a comparative safety estimate, and they do not quantify uncertainty. The registry also does not report a safety analysis plan or a full account of the safety population. These entries therefore describe only what is recorded, not a general assurance about safety.

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

The record establishes what the investigators intended to study: a regimen involving efalizumab and sirolimus in people receiving allogeneic islet transplants, with a primary endpoint based on insulin independence and full islet graft function at 1 year following the first transplant. It also documents a single-group design, no masking, and termination after the manufacturer voluntarily withdrew efalizumab from the U.S. market. These are features of the study and its conduct, not evidence of the primary outcome.

The registry does not report how many participants met the primary endpoint. It therefore does not show the observed frequency of insulin independence with full graft function, the precision of an estimate, or a statistical comparison. The record’s enrollment figure and the note about 3 subjects transplanted do not supply the missing endpoint count or clarify the denominator.

Even if a single-group outcome count were available, it would describe participants in that group rather than establish a comparative treatment effect. The absence of a concurrent control group means that the record cannot provide a randomized, like-for-like comparison with another regimen. No conclusion about what would have happened under a different treatment follows from this design alone.

The safety fields report no affected participants for the listed serious and other adverse event counts, while deaths are not reported. These fields should not be expanded into a claim that no safety events occurred beyond what was recorded. The available information is limited to the registry entries, and the record does not provide broader follow-up or analysis detail.

Overall, the registry supports a description of the intended question, design, endpoint definition, and reason for termination. It does not support a conclusion about the primary endpoint result or a comparative assessment of efficacy. The missing result should be treated as unreported, rather than interpreted as a positive, negative, or null finding.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and outcome reporting must be considered together. The primary measure is defined through several clinical and laboratory criteria, including being off insulin for at least 1 week and satisfying specified glucose and C-peptide conditions. Such detail clarifies what would count as success under the registry’s definition, but it does not reveal how many participants met it. Without the observed count and denominator, the endpoint cannot be summarized quantitatively.

The record also makes clear that enrollment, transplantation, and outcome follow-up are not interchangeable concepts. Enrollment is listed as 23, while the population note refers to 3 subjects transplanted before Raptiva was removed from the market. Keeping these fields distinct avoids treating the enrollment figure as the number who received the transplant, contributed outcome data, or completed the assessment.

Design matters for interpretation. A single-group study can document outcomes among treated participants, but it does not provide an internal control comparison. Here, the absence of a comparator is particularly important because no primary result is reported at all. Statistical methods cannot recover an unreported endpoint or compensate for the absence of a comparison group.

Finally, the record connects study termination to the voluntary market withdrawal of efalizumab and notes that previously transplanted subjects transitioned to alternative immunosuppressives. This context helps readers understand why the protocol did not proceed as planned, while also underscoring the need for transparent reporting of follow-up and analysis after a study ends. The record is informative about design and context, but incomplete for evaluating the stated primary outcome.

15. 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 are specific to this record. The study was single group, with allocation listed as not applicable and no masking. There was no concurrent control group for a direct comparison. The registry notes that arms are not a like-for-like control comparison; the available design information does not support a randomized treatment contrast.

The primary outcome result is not reported. The registry defines insulin independence with full islet graft function at 1 year following the first transplant, but provides no count meeting the criteria. It also does not report the endpoint denominator, the number assessed at that time, or how participants with incomplete follow-up were handled. Enrollment of 23 and the note that 3 subjects were transplanted are not enough to resolve those questions.

The protocol was terminated after efalizumab’s manufacturer voluntarily withdrew the drug from the U.S. market in April of 2009. The registry says previously transplanted subjects transitioned to alternative immunosuppressives and no new subjects would be transplanted under the protocol. It does not report how many participants continued follow-up, when outcome collection ended, or whether the primary endpoint was assessed as planned.

Statistical analysis details are sparse. Although the record lists 0 analyses, it does not describe an analysis population, missing-data approach, multiplicity plan, interim analyses, or protocol-specific sample-size justification. The sample-size assumptions described in the record are planning illustrations based on a two-arm framework, which is not the registered single-group design. The registry does not establish that those assumptions were the trial’s original statistical plan.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Raptiva and Sirolimus in Islet Transplantation for Type 1 Diabetes — NCT00672204.
• Registry record last updated 2017-10-25; status last verified 2017-09.
• Results first posted 2013-03-27.
• 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.

19. Record Summary

The University of Minnesota sponsored this Phase 1 and Phase 2 study of efalizumab (Raptiva) and sirolimus in type 1 diabetic islet allograft recipients. The record lists an enrollment of 23, a single-group model, allocation not applicable, and no masking. Its primary endpoint was the number of participants with insulin independence and full islet graft function at 1 year following the first islet transplant.

The record states that efalizumab was voluntarily withdrawn from the U.S. market in April of 2009. Previously transplanted subjects were transitioned to alternative immunosuppressives, and no new subjects would be transplanted under the protocol. The study status is terminated. No primary endpoint result or statistical analysis is reported in the registry record.