Pramlintide in Adolescents With Type 1 Diabetes: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pramlintide in Adolescents With Type 1 Diabetes (NCT00842075), a randomized na study. The primary outcome is HbA1c Value After 28 Days.

2. Clinical Question

The clinical question is therefore whether the short-term HbA1c outcome differed between participants assigned to pramlintide plus adjusted mealtime insulin and participants assigned to their usual mealtime insulin regimen. The registry describes a 36 day, randomized, two-arm, open-label study. The primary outcome timeframe is 28 days after randomization, so it is important to distinguish the stated hypothesis about post-prandial glucose concentrations from the outcome actually reported. Those measures address related but not identical aspects of glucose control.

The posted group means are 7.94 for Symlin and 8.72 for Usual Regimen. The registry does not report an estimable two-arm comparison for this continuous outcome, so those descriptive values alone do not establish whether the groups differed beyond what could arise from sampling variability. The record also does not report a separate numerical result for post-prandial glucose concentrations. No treatment conclusion follows from the group means alone.

3. Trial Design

This was a randomized, parallel, two-arm, open-label study sponsored by University of Colorado, Denver. The registry lists the condition as type 1 diabetes and enrollment as 10. The study began in 2006-12, reached primary completion in 2009-12, and is marked completed. The phase is listed as NA. The registry describes the study as lasting 36 day.

In the Symlin arm, participants received a subcutaneous injection of pramlintide prior to each meal, together with a reduction of mealtime bolus insulin. Participants in the Usual Regimen arm received their usual bolus insulin dose at each meal. Because masking is listed as none, the study was open-label: treatment assignment was not masked according to the registry. Allocation is listed as randomized, and the model as parallel, meaning participants were assigned to one of the treatment arms rather than moving between them.

The primary outcome was HbA1c value after 28 days. It is reported as a mean and standard deviation, with 5 participants in each arm. The registry also lists weight change after 28 days as a secondary outcome. It reports two outcome measures in total and zero analyses. The record does not give details about the randomization sequence, allocation concealment, eligibility criteria, treatment adherence, or the specific procedures used to collect outcomes; those details are not reported in the registry record.

The brief summary states that the treatment arm took pramlintide before all meals and that the control arm followed the diabetes regimen as usual. Beyond those descriptions, the record does not specify the dose or the exact insulin adjustment used. The registry does not report a sample-size justification or explain how the planned enrollment was determined. Its sample-size illustration is separate from the study's design information and should not be read as evidence that the trial was planned to detect a particular difference.

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: no comments

Overall Study

Analysis population for the primary outcome, as defined in the registry: pilot 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 HbA1c Value After 28 Days, measured over 28.

The primary endpoint is HbA1c value 28 days after randomization, expressed as HbA1c %. The registry identifies it as a continuous measure and reports the mean and standard deviation for each arm. The reported mean is 7.94 in the Symlin arm and 8.72 in the Usual Regimen arm; the standard deviations are 0.71 and 0.44, respectively. Each arm's reported outcome includes 5 participants.

As a general statistical and clinical concept, HbA1c is a measure of glycated hemoglobin used to assess glucose exposure over time. It can complement measurements that focus on glucose at particular moments, such as the post-prandial concentrations named in the study hypothesis. The measures are not interchangeable. A value collected after 28 days describes the endpoint at that stated follow-up, while the hypothesis concerns glucose concentrations after meals.

Using a mean conveys the group's average endpoint value, while a standard deviation describes the spread of individual values around that average. Neither statistic alone describes the uncertainty in the difference between arms. The registry does not report an estimable comparison, confidence interval, or test result for the primary endpoint. It also does not report individual participant values, so the shape of the outcome distributions cannot be assessed from the posted summaries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a continuous endpoint, a common descriptive summary is the mean together with a measure of spread such as the standard deviation. The mean gives the arithmetic average of observed values in a group. The standard deviation indicates how dispersed those observations are around the mean. In this study, the registry reports HbA1c means and standard deviations separately for the Symlin and Usual Regimen arms. Those are summaries of the observations, not a model-based estimate of the treatment contrast.

To compare two independent groups, an analysis would ordinarily specify a contrast, a measure of uncertainty, and the method used to obtain them. The contrast might be expressed in the endpoint's units, while a confidence interval would communicate its precision. A test could also be used to assess compatibility with a null hypothesis. The registry does not post these comparative results for HbA1c, and the record identifies the two-arm continuous comparison as not estimable. It would therefore be inappropriate to treat a recalculated contrast or an assumed test as the study's result.

As a general statistical concept, the standard error of a mean or contrast represents sampling uncertainty, whereas the standard deviation describes variation among observations. They answer different questions. A standard deviation cannot be read as a confidence interval, and the two arm-specific standard deviations do not reveal the uncertainty of the group contrast without an analysis and assumptions. The individual observations and any adjustment variables are not reported in the registry record.

Random allocation can support a causal comparison when the study is conducted and analyzed as planned, because assignment is intended to make groups comparable on average. Randomization does not guarantee that small groups will have similar baseline characteristics, and it does not eliminate uncertainty. The registry identifies the allocation as randomized but does not report the sequence generation or concealment procedures. It also does not report baseline HbA1c values for the two arms, so their starting comparability cannot be assessed from the posted record.

The study is described as open-label, with no masking. In general, lack of masking can affect behavior, treatment delivery, and outcome assessment, depending on the outcome and procedures. HbA1c is a laboratory measure, but the record does not describe laboratory methods, whether assessments were blinded, or how measurements were handled. These are uncertainties in the available documentation, not evidence that bias occurred.

Dispersion matters because a mean can conceal different patterns of individual responses. With small groups, a few observations may exert substantial influence on the mean and standard deviation. A larger standard deviation indicates more observed spread, but it does not by itself show whether an arm's mean is more or less precise; precision also depends on sample size and the analysis. Here, both outcome groups include 5 participants, but no participant-level data or distributional plots are reported in the registry record.

Normal approximations are one way to form planning or inferential calculations under assumptions about sampling behavior. The registry describes its sample-size illustration as using a normal approximation, equal allocation, and a two-sided significance level of 0.05. That statement pertains to the planning illustration, not necessarily to the trial's design or an analysis conducted by its investigators. The registry does not report a protocol-level statistical analysis plan, the test selected for the primary endpoint, or any interim analysis. Those elements are not reported in the registry record.

Over-dispersion is a general concern in data where observed variability exceeds what a chosen model expects. If a model fails to account for excess variability, standard errors can be too small and confidence intervals too narrow. That concept is more directly relevant to certain count or event models than to the posted continuous summary alone. The registry does not report a model for this endpoint, so no claim about over-dispersion or its handling can be made for this study.

Missingness and estimability also affect interpretation. A comparison may be unavailable when necessary data or analysis details are absent, but the registry does not state the reason this comparison was not estimable. It does not report whether participants withdrew, whether any endpoint values were missing, or how missing observations were treated. Thus, the posted group counts should not be taken as a complete account of participant flow or missing-data handling. Such information would be needed to assess whether the reported outcome groups reflect all randomized participants.

The registry's planning illustration is not observed power. Power is a design concept tied to a specified effect, variability, significance threshold, and sample size under assumptions. Retrospective calculations based on an observed effect do not establish the probability that the trial would detect a real effect, and they do not repair the absence of a comparative result. The illustration should be read only as a planning exercise under its stated assumptions; the trial's own sample-size justification is not reported.

Finally, statistical significance and clinical importance are distinct. A test result would speak to compatibility with a statistical model, while clinical interpretation would require considering the magnitude, precision, context, and relevant outcomes. Because the registry provides no inferential comparison for the primary endpoint and no numerical post-prandial glucose result, neither significance nor clinical importance can be determined from the posted primary outcome summaries alone.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("1 Symlin", "2 Usual Regimen")
n   <- c(5, 5)
m   <- c(7.94, 8.72)
sp  <- c(0.71, 0.44)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  1 Symlin  5  7.940  0.710  7.058  8.822
CARM  2 Usual Regimen  5  8.720  0.440  8.174  9.266

11. Multiplicity, Missing Data and Analysis Populations

The registry lists HbA1c value after 28 days as the primary outcome and weight change after 28 days as a secondary outcome. It reports two outcome measures in total, but does not provide a result for the secondary outcome in the registry record for this record. The number of analyses is listed as zero. The registry does not report how many statistical hypotheses were planned, whether one outcome had priority in the analysis plan, or whether any adjustment for multiple comparisons was intended. Multiplicity handling is therefore not reported in the registry record.

As a general concept, testing several outcomes or several contrasts can increase the chance of finding an apparently notable result by chance if no strategy is used to control or interpret that multiplicity. A prespecified analysis plan can clarify which comparisons are primary and how additional findings should be treated. No such plan is described in the registry record, so the scope of any intended statistical testing cannot be assessed.

The registry does not report participant flow, withdrawals, missing endpoint values, or the handling of missing data. It also does not state whether the outcome summaries include all randomized participants or a subset defined by availability or another rule. The observed outcome sample is 5 in each arm, but this does not by itself reveal whether all assigned participants contributed data or why the comparison was not estimable.

The analysis population is not reported in the registry record. In particular, there is no description of an intention-to-treat population, a per-protocol population, or criteria for excluding participants from analysis. No imputation method or sensitivity analysis is reported. These omissions limit assessment of attrition, missingness, and robustness, but they do not establish that any particular problem occurred.

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

The results mean that the registry records different descriptive mean HbA1c values in the two small study arms after 28 days: 7.94 for participants assigned to Symlin and 8.72 for participants assigned to Usual Regimen. The corresponding standard deviations are 0.71 and 0.44. These figures describe the posted outcome summaries and their within-arm variability. The registry does not provide an estimable two-arm comparison, so the summaries do not quantify the uncertainty around a treatment contrast.

They do not establish that pramlintide caused a change in HbA1c, nor do they establish that the regimens had equivalent outcomes. A lack of a posted comparison is not evidence of no difference. Conversely, the numerical separation between the means is not enough to demonstrate a reliable effect. The record contains no confidence interval or p-value for the primary endpoint and no numerical primary result for post-prandial glucose concentrations.

The primary endpoint is HbA1c at the specified follow-up, while the investigators' stated hypothesis concerns post-prandial glucose concentrations. A descriptive result for one should not be treated as a direct measurement of the other. The registry also lists weight change after 28 days as a secondary outcome, but no result for that outcome is included in the record summarized in the registry record.

As a general principle, a small pilot study can describe feasibility or generate questions for further research, but its estimates may be imprecise and its findings may not generalize broadly. The registry calls this a pilot study and reports 10 participants enrolled. It does not provide evidence to determine how representative participants were or whether the observed data reflect outcomes in a wider population.

No medical advice or treatment conclusion follows from these summaries. They describe what was posted for this study and the limits of the available statistical comparison, not whether a regimen should be selected for an individual.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between having arm-level summaries and having an interpretable comparative result. The registry reports means, standard deviations, and outcome group sizes for HbA1c, yet marks a two-arm comparison of the continuous endpoint as not estimable. Statistical interpretation depends on both the observed summaries and a valid estimate of uncertainty around the contrast; descriptive values alone do not answer the comparative question.

The small pilot design also makes precision central. With 5 participants in each outcome group, the summaries can be sensitive to individual observations. That does not invalidate the data, but it means that readers should avoid treating a numerical difference between means as decisive without a reported uncertainty estimate. The registry does not provide participant-level values that would allow an independent examination of distributions or influential observations.

The distinction between the hypothesis and the reported primary measure is another important statistical point. The investigators' hypothesis concerns post-prandial glucose concentrations, whereas the posted primary outcome is HbA1c after 28 days. Related outcomes can answer different questions, and one should not be used as a substitute for the other. A clear account of how endpoints relate to the stated objective helps readers interpret what a result can address.

Finally, the record illustrates why trial registration details and posted analyses serve different purposes. Registration identifies the planned study framework and outcomes, while an analysis report conveys estimates, uncertainty, and methods. The registry lists zero analyses and does not include a sample-size justification or analysis plan. Those gaps leave important questions about precision and analysis choices unresolved, without implying why the information is absent.

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 main limitation for interpreting the primary result is that the registry does not provide an estimable two-arm comparison. It gives arm-specific means and standard deviations, but no comparative estimate, confidence interval, or p-value. This prevents assessment of the precision of the contrast and limits conclusions to description of the posted group summaries.

The study is a pilot with enrollment of 10 and 5 participants in each reported outcome group. Such a small study can provide limited information about variability and may be sensitive to individual observations. The registry does not report individual data, baseline HbA1c summaries, or enough methodological detail to assess the balance of prognostic characteristics between arms.

The design is open-label, and the record does not describe outcome collection procedures, laboratory methods, or whether outcome assessors were masked. It also does not report the randomization sequence or allocation concealment. These missing details limit assessment of potential sources of bias; they do not establish that bias occurred.

The registry does not report participant disposition, reasons for missing outcomes, analysis-population definitions, or methods for handling missing data. It lists a secondary outcome of weight change after 28 days, but no result for that endpoint appears in the registry entries. Details of eligibility, dose, adherence, and the exact insulin adjustment are likewise not reported in the registry record.

The primary endpoint differs from the post-prandial glucose outcome named in the investigators' hypothesis. The available record therefore does not provide a numerical result for the hypothesis as stated. The study's own sample-size rationale, statistical analysis plan, and any interim analyses are not reported. These documentation limits make the scope and robustness of the intended analysis difficult to assess.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pramlintide in Adolescents With Type 1 Diabetes — NCT00842075.
• Registry record last updated 2015-06-23; status last verified 2012-09.
• Results first posted 2012-10-19.
• 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

NCT00842075 is a completed, randomized, open-label, parallel, two-arm pilot study sponsored by University of Colorado, Denver. It concerns type 1 diabetes and has enrollment of 10. The record gives the study start as 2006-12 and primary completion as 2009-12. The brief summary describes a 36 day study.

The intervention arm received subcutaneous pramlintide before meals with a reduction of mealtime bolus insulin; the comparator arm followed its usual bolus insulin regimen. The primary outcome was HbA1c value after 28 days, reported as a mean and standard deviation. The Symlin arm had a mean of 7.94 and standard deviation of 0.71, with 5 participants; the Usual Regimen arm had a mean of 8.72 and standard deviation of 0.44, also with 5 participants.

The registry does not report an estimable two-arm comparison for the primary continuous outcome. Weight change after 28 days is listed as a secondary outcome, but its result is not reported in the registry record. No analysis results are listed.