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 Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus (NCT00419562), a randomized phase 3 study. The primary outcome is Rate of Type 1 Diabetes Per Year Among Individuals in the Primary Stratum When Treated With Oral Inulin Versus Placebo.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00419562 |
| Phase | Phase 3 |
| Condition | Diabetes Mellitus, Type 1 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 560 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned relatives at risk for type 1 diabetes, with a primary stratum and additional secondary strata described in the registry record. The record gives an enrollment of 560 and reports that the primary outcome was assessed in the primary stratum. It does not give further detail about the characteristics or eligibility criteria of the people included in that primary-stratum analysis.
Intervention
The intervention was oral insulin. The registry describes 7.5 mg oral insulin capsules taken before breakfast on a daily basis. This was compared with a placebo capsule designed to match the appearance of the treatment capsule.
Comparator
The comparator was placebo. The registry reports a randomized, parallel-group trial with triple masking. It does not specify in the record which roles were masked or how masking was maintained.
Primary question
The primary question was whether the rate of type 1 diabetes per year differed between the oral-insulin and placebo groups in the primary stratum. The registry defines the outcome rate using the number of participants who developed diabetes divided by the total years of follow-up. It reports arm-specific rates and confidence intervals, but no direct comparison estimate or test result.
The broader study rationale in the registry describes type 1 diabetes as an autoimmune disease and refers to earlier research in which a possible effect was suggested in a subgroup after the earlier trial had concluded. That background explains why the TrialNet study examined a primary cohort as well as secondary groups at other levels of risk. It does not establish what the present trial found in those secondary groups: numerical results for those outcomes are not reported in the registry record.
3. Trial Design
This was a phase 3, randomized, triple-masked, parallel-group trial sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. The registry lists an enrollment of 560 and a completed status. The recorded start was 2007-02, and primary completion was 2016-12. These registry dates describe the trial record; they do not by themselves give the duration of follow-up for every participant.
Participants were assigned to oral insulin or placebo. The oral-insulin regimen is described as 7.5 mg capsules taken by mouth before breakfast daily. The placebo capsule was designed to match the appearance of the treatment capsule. The registry does not identify which people or groups were masked, nor does it describe the randomization sequence, allocation concealment, or procedures for handling treatment interruptions.
The primary outcome concerned the annual rate of type 1 diabetes among people in the primary stratum. Metabolic and immunological tests were conducted every 6 months, and the registry reports median follow-up of 2.7 years. It states that diabetes diagnosis was based on metabolic testing and assessment of symptoms. The endpoint description says the rate was calculated by dividing the number of participants who developed diabetes by the total years of follow-up.
The record also names secondary outcomes for the rate of type 1 diabetes in Stratum 2 and in Stratum 3+4. Their numerical findings are not reported in the registry record. More detailed protocol information, including eligibility criteria, the randomization procedure, the masking roles, and the planned analysis population, is not reported in the registry record.
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
| Stage | 7.5 mg Oral Insulin Capsules | Placebo Capsule |
|---|---|---|
| STARTED | 283 | 277 |
| COMPLETED | 250 | 246 |
| NOT COMPLETED | 33 | 31 |
Reasons for not completing this period:
| Reason | 7.5 mg Oral Insulin Capsules | Placebo Capsule |
|---|---|---|
| Lost to Follow-up | 12 | 13 |
| Withdrawal by Subject | 20 | 18 |
| Participant Institutionalized | 1 | 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 | Oral Insulin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 283 | 277 | 560 | |
| Age, Continuous | years | 8.2 (5.9 to 12.5) | 8.2 (5.4 to 11.5) | 8.2 (5.7 to 12.1) |
| Sex: Female, Male: Female | Participants | 113 | 107 | 220 |
| Sex: Female, Male: Male | Participants | 170 | 170 | 340 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 27 | 25 | 52 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 256 | 252 | 508 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Self-Reported Race – White | Participants | 252 | 249 | 501 |
| Race/Ethnicity, Customized: Self-Reported Race – African American | Participants | 8 | 9 | 17 |
| Race/Ethnicity, Customized: Self-Reported Race – Asian/Pacific Islander | Participants | 4 | 6 | 10 |
| Race/Ethnicity, Customized: Self-Reported Race – Not Reported | Participants | 19 | 13 | 32 |
| Region of Enrollment: Canada | Participants | 17 | 15 | 32 |
| Region of Enrollment: United States | Participants | 226 | 227 | 453 |
| Region of Enrollment: Finland | Participants | 4 | 5 | 9 |
| Region of Enrollment: Italy | Participants | 7 | 7 | 14 |
| Region of Enrollment: United Kingdom | Participants | 6 | 6 | 12 |
| Region of Enrollment: Australia | Participants | 7 | 4 | 11 |
| Region of Enrollment: Sweden | Participants | 5 | 3 | 8 |
| Region of Enrollment: Germany | Participants | 9 | 6 | 15 |
| Region of Enrollment: New Zealand | Participants | 3 | 5 | 8 |
| Stratum: 1 | Participants | 203 | 186 | 389 |
| Stratum: 2 | Participants | 28 | 27 | 55 |
| Stratum: 3 | Participants | 51 | 63 | 114 |
| Stratum: 4 | Participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Rate of Type 1 Diabetes Per Year Among Individuals in the Primary Stratum When Treated With Oral Inulin Versus Placebo, measured over Metabolic and immunological tests were conducted every 6 months; participants were followed for a median of 2.7 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Proportion with diabetes/year |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the rate of type 1 diabetes per year among participants in the primary stratum. The registry describes the unit as proportion with diabetes/year and defines the rate as the number of participants who developed diabetes divided by total years of follow-up. Diagnosis was based on metabolic testing and assessment of symptoms. The registry says metabolic and immunological tests were conducted every 6 months and reports median follow-up of 2.7 years.
A rate uses both the number of observed cases and the amount of time participants were followed. As a general statistical explanation, this can be useful when people contribute different lengths of follow-up: a simple count of cases does not reflect how long each person was observed. A rate nevertheless needs clear definitions of the event, time at risk, and the analysis population to support interpretation. Those details are not fully described in the registry record.
The posted primary-stratum estimates are 0.088 for oral insulin and 0.102 for placebo. Their respective 95% confidence intervals are 0.067 to 0.112 and 0.078 to 0.129. The endpoint is not a direct measure of the timing of diabetes diagnosis for each participant, and the registry does not post a treatment-effect estimate comparing the arms. The estimates therefore describe each reported arm separately; by themselves they do not establish the size or statistical uncertainty of an arm-to-arm effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
In the primary stratum, the posted annual diabetes-rate estimate is 0.088 in the oral-insulin group and 0.102 in the placebo group. The 95% confidence interval is 0.067 to 0.112 for oral insulin and 0.078 to 0.129 for placebo. These are arm-specific estimates. The registry does not report a direct comparison estimate, a p-value, or a test of the difference between the groups.
The confidence intervals overlap. This is a description of the displayed intervals, not a substitute for a formal comparison. General statistical interpretation: a confidence interval conveys uncertainty around an estimate under the assumptions of the method used to construct it. It does not give the probability that the true value lies within that particular interval, and comparing two separate intervals is not the same as calculating a confidence interval for the difference between groups. Because the registry does not post the direct comparison, the magnitude and precision of the treatment contrast cannot be read from these arm estimates alone.
The outcome denominators reported with the estimates are 203.0 for oral insulin and 186.0 for placebo. The safety record lists 283 participants at risk in the oral-insulin group and 277 in the placebo group. The registry does not explain why the reported denominators differ across these outcomes, so they should not be treated as interchangeable or assumed to represent the same analysis population. The record also does not describe exclusions, missing observations, or how follow-up time was handled for participants without complete outcome data.
The record names two secondary outcomes, one for Stratum 2 and one for Stratum 3+4, but numerical findings are not reported in the registry record. Thus, the posted information does not permit interpretation of those secondary outcomes or comparison of patterns across strata. It also does not establish whether any subgroup findings were prespecified or how multiple outcomes were handled analytically.
The registry background notes that an earlier trial did not show an overall delay or prevention of type 1 diabetes, while a post-trial subgroup analysis suggested a potential effect among participants with higher insulin autoantibody levels. That context motivates the current study but is not evidence of the current trial’s result. The current record supports a careful description of the primary-stratum arm estimates, but the absence of an arm-to-arm analysis limits conclusions about the comparative effect.
9. Statistical Methods Explained
The registry identifies this study as randomized, triple-masked, and parallel-group. These design descriptions indicate that participants were allocated at random to study groups, that masking was used, and that the groups were followed in parallel. General statistical explanation: random allocation is intended to make treatment groups comparable on average with respect to both measured and unmeasured baseline characteristics. Masking can reduce the influence of expectations on care, outcome assessment, or reporting. The registry record does not describe the randomization method, allocation concealment, or which parties were masked, so the practical details cannot be assessed from this information.
What do the arm-specific rates describe?
The primary outcome is expressed as a rate per year. The registry says this is calculated by dividing the number of participants who develop diabetes by total years of follow-up. The posted values are 0.088 for oral insulin and 0.102 for placebo. A rate is not simply a percentage of participants: its denominator incorporates time under observation. General statistical explanation: rates are useful when follow-up time varies, provided the time at risk is defined consistently and the event count and follow-up time are measured appropriately. The registry provides the rate values but does not give the underlying case counts or total person-time in the primary outcome record.
How should the confidence intervals be read?
The registry reports 95% confidence intervals of 0.067 to 0.112 for oral insulin and 0.078 to 0.129 for placebo. In general, a confidence interval is a range generated by a statistical procedure to represent uncertainty about an estimated quantity. Its width reflects both the observed information and the assumptions of the method. It is not a direct measure of clinical importance, and it does not show whether a treatment contrast is statistically distinguishable from no difference. For that question, a direct contrast and its uncertainty are needed. Neither is reported in the registry record.
General statistical explanation: a difference between two groups has its own sampling uncertainty. That uncertainty depends on the variation and information in both groups and on the form of the comparison. Separate confidence intervals do not provide all the information needed to construct the contrast interval or test. The fact that the posted arm intervals overlap can be noted descriptively, but it should not be used as a formal significance test.
What can be inferred from the analysis denominators?
The primary outcome lists 203.0 participants in the oral-insulin group and 186.0 in the placebo group. The serious-adverse-event record lists 283 at risk in the oral-insulin group and 277 in the placebo group. These are different denominators in the registry record, and no explanation for that difference is reported. They may refer to different outcome-specific populations or data availability, but that explanation would be speculation. The analysis population, reasons for missing outcome information, and handling of missing data are not reported in the registry record.
What does the record say about planning?
The registry’s planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. Those assumptions are not a report of the trial’s own design justification. The calculated planning values are not included in the record available for this analysis, so no participant requirement can be stated. General statistical explanation: such planning illustrations explore how an assumed effect and design choices relate to a required sample size. They are not observed power and do not show the probability that the trial found a true effect.
The trial’s original sample-size justification, prespecified effect size, and statistical analysis plan are not reported in the registry record. The record also does not report the statistical model used to estimate the primary rate or construct its confidence intervals. It would therefore be inappropriate to attribute a particular model, adjustment, or variance assumption to the sponsor. General statistical explanation: if event-rate data vary more than a model assumes, a method that does not account for that over-dispersion may understate uncertainty. Whether over-dispersion was assessed or how it was handled in this study is not reported in the registry record.
Why is a direct comparison important?
The posted results give an estimate and interval for each arm, but no numerical arm-to-arm contrast. A comparison might be expressed using a difference, ratio, or another prespecified measure; the choice affects interpretation and requires an analysis appropriate to the design and endpoint. The registry’s endpoint is a rate, but the comparison measure and its uncertainty are not reported. The record also identifies the outcome kind as not reduced to one comparison and says values are missing or not estimable for a two-arm comparison for this count-type endpoint. This limitation means the arm-specific values can be described, but a precise treatment contrast cannot be reconstructed from the posted results alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry names one primary outcome and two secondary outcomes. The secondary outcomes concern diabetes rates in Stratum 2 and Stratum 3+4. Numerical results for those secondary outcomes are not reported in the registry record. Although the primary endpoint is identified, the record does not state whether other planned outcomes or subgroup analyses were considered, or how any multiplicity from evaluating multiple outcomes was addressed. The prespecified hierarchy of outcomes and any multiplicity adjustment are not reported in the registry record.
The record does not report interim analyses, stopping rules, or whether the analysis plan changed during the study. These features should not be inferred from the trial’s duration or completed status. The statistical analysis plan and the primary-stratum analysis population are also not reported in the registry record.
The primary outcome denominators are 203.0 and 186.0, while the safety groups list 283 and 277 at risk. The record does not explain this difference. Reasons for missing outcome data, loss to follow-up, exclusions from the outcome analysis, and the methods used to address missing data are not reported in the registry record. There is no information about imputation, sensitivity analyses, or whether participants were analyzed according to randomized assignment.
General statistical explanation: missing outcome information can affect both the precision and the interpretation of results, especially if the likelihood of missingness is related to participants’ outcomes or group assignment. An analysis population and transparent handling of missing data help readers understand which participants contribute to each estimate. Without those details, the reported arm estimates remain interpretable as registry-posted summaries, but their relationship to the full randomized population is unclear.
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 |
|---|---|---|---|
| Oral Insulin | 0 | 283 | 0.0% |
| Placebo | 0 | 277 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Oral Insulin | 0 of 283 |
| Placebo | 0 of 277 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Oral Insulin | 150 of 283 |
| Placebo | 133 of 277 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Oral Insulin | Placebo |
|---|---|---|---|
| Infection | Infections and infestations | 67 of 283 | 62 of 277 |
| Pulmonary/Upper Respiratory | Respiratory, thoracic and mediastinal disorders | 30 of 283 | 30 of 277 |
| Musculoskeletal/Soft Tissue | Musculoskeletal and connective tissue disorders | 38 of 283 | 18 of 277 |
| Gastrointestinal | Gastrointestinal disorders | 28 of 283 | 25 of 277 |
| Dermatology/Skin | Skin and subcutaneous tissue disorders | 25 of 283 | 18 of 277 |
| Endocrine | Endocrine disorders | 18 of 283 | 12 of 277 |
| Allergy/Immunology | Immune system disorders | 17 of 283 | 11 of 277 |
The registry lists 283 participants at risk for serious adverse events in the oral-insulin group and 277 in the placebo group. It reports 0 affected by serious adverse events in each group and 0 deaths in each group. No top serious adverse-event terms are listed. These are the serious-event figures recorded for the safety outcome.
The record also lists other adverse events among 150 participants in the oral-insulin group and 133 participants in the placebo group. The corresponding at-risk counts are 283 and 277. These figures describe the registry’s other-adverse-event category; they do not provide event-level detail, severity, timing, or a comparison adjusted for follow-up. The record does not say whether events were judged related to study treatment.
General statistical explanation: an observed count of zero means that no events were recorded in the specified category and group in the posted results. It does not prove that the underlying risk is zero, and it does not by itself establish equivalence between groups. Safety interpretation also depends on the observation period, event definitions, completeness of reporting, and the number of people monitored. Those details are not fully reported in the registry record. The serious-event and death figures should therefore be read as descriptive registry counts, not as a complete assessment of comparative safety.
12. What the Result Does, and Does Not, Mean
The posted primary-stratum results describe annual diabetes-rate estimates of 0.088 for oral insulin and 0.102 for placebo, with 95% confidence intervals of 0.067 to 0.112 and 0.078 to 0.129, respectively. They show the estimates recorded for each arm and the uncertainty intervals attached to them. The intervals overlap, but that observation is not a formal test of the treatment contrast.
The registry does not provide a direct comparison estimate, its confidence interval, or a p-value. It therefore does not establish from the posted primary outcome alone how large or precise the difference between the randomized groups was. The results should not be reduced to a claim that oral insulin did or did not prevent or delay diabetes. The figures are rates in the primary stratum over the recorded follow-up, not a complete statement about every participant or every study stratum.
The record’s background discusses a possible subgroup effect suggested after an earlier trial. That rationale is not a result of this trial. Numerical results for the present study’s secondary outcomes are not reported in the registry record, so the current record cannot confirm or refute a pattern across the additional strata.
General statistical explanation: evidence about a treatment contrast depends not only on the direction of the arm estimates, but also on the estimated contrast, its uncertainty, the analysis population, and the design and analysis assumptions. The registry gives some of this information but not all of it. Missing details include the direct comparison, analysis methods, handling of missing data, and the rationale for the outcome denominators. The registry results can be described accurately without filling those gaps with assumptions.
The serious-adverse-event and death counts are also descriptive. Zero recorded serious events and zero recorded deaths in both groups do not demonstrate that risks are identical or absent. The record does not provide event timing, exposure-adjusted safety comparisons, or treatment-relatedness assessments. These limitations apply to interpretation of the posted safety counts, not just to the primary efficacy outcome.
13. Why This Trial Matters Statistically
This trial is statistically notable for examining a question motivated by earlier work that had an overall result described as not delaying or preventing type 1 diabetes, alongside a potential subgroup signal identified after that earlier trial concluded. The current study extended the investigation to a primary stratum and additional risk strata. That context makes clear why subgroup definitions and the distinction between prespecified questions and later exploratory findings matter when interpreting trial evidence.
The registry reports an annual-rate endpoint, arm-specific estimates, and confidence intervals. This gives readers more information than a simple case count alone because the endpoint definition incorporates follow-up time. At the same time, the record does not supply the direct comparison result needed to quantify the randomized treatment contrast. The difference between describing each arm and estimating the contrast is a central statistical distinction in a randomized trial.
The outcome denominators also differ from the safety at-risk counts, without an explanation in the registry record. That makes transparent reporting of analysis populations and missing-data procedures important. A reader needs to know which participants contributed to each estimate and why the denominators differ before relating outcome summaries to the full enrolled population.
Finally, the record lists secondary outcomes but does not report their numerical results, and it does not describe multiplicity procedures or the analysis plan. These gaps limit how fully the evidence can be evaluated. The trial illustrates why registry entries are most informative when they report not only estimates but also a prespecified comparison, uncertainty for that comparison, analysis methods, and the disposition of participants across outcomes.
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-stratum outcome is posted as separate arm estimates, without a direct comparison statistic. There is no reported contrast, confidence interval for the contrast, or p-value. This prevents a complete assessment of the size and precision of the randomized comparison from the registry results alone. The reported arm-level confidence intervals do not replace a direct comparison analysis.
The record gives outcome denominators of 203.0 for oral insulin and 186.0 for placebo, while safety at-risk counts are 283 and 277. It does not explain why these populations differ. Eligibility and analysis-population details, participant flow, reasons for missing outcome information, and methods for handling missingness are not reported in the registry record. The relationship between the outcome estimates and the full enrolled population is therefore not clear.
The registry does not report the statistical model used for the annual-rate estimates or confidence intervals, the planned treatment-effect measure, the analysis plan, or the trial’s sample-size justification. It also does not report whether there were interim analyses, protocol changes, or multiplicity adjustments. The planning assumptions describe an illustration based on an observed effect, but this is not the original design justification or observed power.
Numerical results for the two named secondary outcomes are not reported in the registry record. The record’s rationale discusses a subgroup signal from earlier research, but does not provide enough detail to assess whether subgroup hypotheses in this trial were prespecified or how they were evaluated. Safety reporting is also limited: serious-event and death counts are given, but event timing, severity details, treatment relatedness, and a comparative safety analysis are not reported. These limitations constrain interpretation of the registry record; they do not establish what the unreported analyses would have shown.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus — NCT00419562.
- Registry record last updated 2020-05-07; status last verified 2020-04.
- Results first posted 2020-02-18.
- 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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18. Record Summary
NCT00419562 is a completed phase 3, randomized, triple-masked, parallel-group trial sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. The registry lists an enrollment of 560, a start of 2007-02, and primary completion in 2016-12. Participants were assigned to daily 7.5 mg oral insulin capsules or a matching placebo capsule.
The primary outcome was the annual rate of type 1 diabetes in the primary stratum, with diagnosis based on metabolic testing and assessment of symptoms. The registry reports median follow-up of 2.7 years and testing every 6 months. The posted arm estimates are 0.088 for oral insulin and 0.102 for placebo, with respective 95% confidence intervals of 0.067 to 0.112 and 0.078 to 0.129. No direct comparison result is reported. Numerical findings for the two secondary outcomes are not reported in the registry record. Serious adverse events and deaths are recorded as 0 in both groups; other adverse events are listed for 150 oral-insulin participants and 133 placebo participants.