Effect of Biphasic Insulin Aspart 30 Combined With Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Biphasic Insulin Aspart 30 Combined With Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin (NCT00669864), a non-randomized phase 4 study. The primary outcome is Change in HbA1c (Glycosylated Haemoglobin A1c).

2. Clinical Question

The clinical question is about change over time within a treated group, not a randomized estimate of the difference between two treatments. That distinction affects what can be concluded from any before-and-after result: a change during follow-up describes the participants' observed course, but by itself does not isolate the effect of treatment from other explanations for change.

The registry also lists secondary outcomes concerning an 8-point plasma glucose profile, achievement of HbA1c thresholds, and hypoglycaemic episodes, including diurnal and nocturnal episodes. Their numerical results are not reported in the registry record. The clinical question can therefore be described from the registered endpoint and outcome list, but the magnitude and precision of the primary change cannot be assessed from the reported outcome information.

3. Trial Design

This was a Phase 4, completed, single-group trial with non-randomized allocation and no masking. The registry describes enrollment of 293 participants and an Asian setting; its brief summary specifies Chinese participants with type 2 diabetes. The trial focused on people inadequately controlled with once- or twice-daily basal insulin.

The treatment arm, named BIAsp 30-30, received individually adjusted biphasic insulin aspart 30 before breakfast and dinner, together with metformin 1000-2000mg up to three times daily. The registry does not describe a parallel control arm. Consequently, the design provides no randomized, concurrent comparison that could distinguish the treatment course from changes that might occur without the regimen or under another regimen.

The primary endpoint was change in HbA1c from week 0 to week 16, with the timeframe recorded as week 0 and week 16. The endpoint is described as a mean continuous measure, with standard error as the dispersion statistic. The primary analysis population is identified as the intention-to-treat analysis set: participants who entered the treatment period and were exposed to at least one dose of trial product. The registry record does not report how many participants contributed data to the primary endpoint.

The recorded study dates are a start in 2007-11 and primary completion in 2009-04; the overall status is completed. The registry record does not report a sample-size justification, a detailed protocol schedule, or the reasons for the chosen treatment duration. It also does not report masking procedures, which is consistent with the recorded masking status of none, or describe a randomized allocation procedure. These features mean that the design should be read as a treatment-period assessment in one group rather than as a controlled comparative trial.

The registry lists secondary outcomes related to glucose profiles, HbA1c target attainment, and hypoglycaemia. Their presence indicates the kinds of additional outcomes considered, but does not supply results or establish how those outcomes were defined or analyzed. The record lists one analysis and six outcome measures, without enough detail to determine the full analysis plan.

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: Eligible subjects, treated with basal insulin, stopped their oral anti-diabetic drug treatment and started a run-in period of forced metformin titration. Subjects on current metformin therapy could go through a modified titration. Doses were up-titrated weekly until either the max tolerated dose of at least 1500mg/day or a max dose of 2000mg/day.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-Treat analysis set (ITT) is all subjects who entered the trial treatment period and exposed to at least one dose of trial product.

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 Change in HbA1c (Glycosylated Haemoglobin A1c), measured over week 0, week 16.

The primary endpoint is the change in glycosylated haemoglobin A1c (HbA1c) from baseline at week 0 to week 16, expressed as a percentage of total haemoglobin. HbA1c is a continuous measure used to characterize blood glucose control over time. A change endpoint compares a participant's measurement at follow-up with the baseline measurement, then summarizes those changes across the analysis population.

Using change from baseline can make the treatment-period course easier to describe than reporting a follow-up value alone, because the comparison is anchored to each participant's starting measurement. The registry specifies the mean as the summary measure and standard error as the dispersion statistic. In general, a mean describes the average change, while a standard error describes the statistical uncertainty around an estimated mean; it is not a description of the spread of individual participant values.

The registry does not report the mean change, its standard error, a confidence interval, or a statistical test result. Therefore, the endpoint's definition is available, but the observed direction, magnitude, and precision of the change cannot be assessed from the registry record. A within-group change also does not, by itself, estimate how outcomes would have differed under a comparator treatment or no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods that can be described are those explicitly recorded: a Phase 4, single-group, non-randomized, unmasked design; a mean change in HbA1c as the primary outcome; and standard error as its specified dispersion measure. The registry record does not report a fuller statistical analysis plan. The explanations below describe general statistical concepts and distinguish them from details that are unavailable for this trial.

What does a single-group change estimate?

In general, a single-group change estimate summarizes how an outcome differs between baseline and follow-up for participants who were observed. It is a description of change during a study period. A causal treatment effect instead compares outcomes under the treatment with outcomes under a credible alternative for the same target population. Random allocation and a concurrent control can help make that comparison interpretable by reducing systematic differences between groups. This trial has no separate comparator group, so its design does not provide that controlled contrast.

The absence of a comparator does not make a within-group measurement meaningless. It means that the estimate answers a narrower question: what change was recorded in the treated group over the specified period? Other explanations for temporal change cannot be ruled out using a single-group comparison alone. The registry record does not describe an external control or a planned method for constructing one.

What do mean and standard error represent?

For a continuous outcome, the mean summarizes the average value or average change across the observations included in an analysis. The registry identifies the primary parameter as a mean. A standard error describes the statistical uncertainty in an estimated mean, reflecting how estimates would vary across repeated samples under the statistical model. It is different from a standard deviation, which describes variation among individual observations.

Neither the mean change nor its standard error is reported for this endpoint. The specified summary format therefore does not allow the magnitude or precision of the result to be reconstructed. A confidence interval is also not reported. In general, a confidence interval combines an estimate with its uncertainty to show a range of values compatible with the data under stated assumptions. It cannot be inferred from an outcome definition alone.

What does the analysis population mean?

The primary population is described as an intention-to-treat analysis set consisting of participants who entered the treatment period and were exposed to at least one dose of trial product. This definition is stated in the registry record and should not be expanded beyond its wording. The record does not report how many participants met the definition for the primary analysis or how many had measurements at both endpoint timepoints.

In general, analysis populations define which participants contribute to a particular estimate. Different definitions can yield different results, especially when participants discontinue, lack measurements, or are excluded for other reasons. The record does not explain whether all participants in the described population had endpoint observations, how incomplete observations were handled, or whether any additional analysis populations were used.

How should safety counts be interpreted?

Counts of participants affected by adverse events describe observed reports within the study group and the categories used in the registry. They do not, alone, establish whether events were caused by treatment. A comparison of risk generally requires comparable groups, consistent event definitions, and adequate follow-up. This study has no separate comparator group in the registry record. Serious and other adverse events are reported separately; the record does not provide further definitions for the other-event category or list serious event terms.

The safety entries identify 293 at risk in each of the serious-event and other-event categories, with zero affected by serious adverse events and 80 affected by other adverse events. Those counts are descriptive. The record does not report a comparative analysis, event rates over person-time, or a causal assessment. Deaths are not reported in the registry record.

What can be said about planning calculations?

In general, a sample-size planning calculation explores how many participants per arm might be needed to detect a specified effect under assumptions about the statistical test, allocation, and variability. Such a calculation is a design illustration, not an observed result and not observed power. The registry notes planning assumptions of a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects set as stated fractions of an observed effect; it also says the calculations are planning illustrations rather than the trial's own design.

Those assumptions describe a hypothetical two-arm planning exercise, while the registered trial is single-group. The registry record does not report a sample-size justification for the actual trial, nor does it report the numerical observed effect needed to evaluate the planning illustrations. Any planning figures should therefore be interpreted as hypothetical design scenarios, not as results from this study or evidence that the study had a particular probability of detecting an effect.

The registry record lists one analysis and six outcome measures, but does not give sufficient detail to identify the full model, covariate adjustment, test procedure, confidence level, treatment of repeated measurements, or prespecified testing hierarchy. These omissions prevent a fuller reconstruction of the statistical methods. General descriptions of statistical concepts should not be mistaken for confirmation that a particular procedure was used in this trial.

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("BIAsp 30-30")
n   <- c(293)
m   <- c(-1.303)
sp  <- c(0.056)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
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  BIAsp 30-30  293  -1.303  0.959  -1.413  -1.193

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: change in an 8-point plasma glucose profile, the percentage of participants achieving HbA1c less than 7.0%, the percentage achieving HbA1c below or equal to 6.5%, hypoglycaemic episodes, and diurnal or nocturnal hypoglycaemic episodes. It also records six outcome measures and one analysis. The numerical results for the secondary outcomes are not reported in the registry record.

When a study assesses multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently unusual result can increase. Statistical methods may address this through a prespecified hierarchy or adjustment, but no multiplicity procedure or testing hierarchy is reported in the registry record. It is therefore not possible to determine whether or how multiple testing was addressed, or how any secondary result should be interpreted relative to the primary endpoint.

The primary analysis population is defined as participants who entered the treatment period and received at least one dose of trial product. However, the registry does not report the number included in the primary endpoint analysis, the number with missing week 0 or week 16 measurements, or how missing measurements were handled. It does not report whether imputation, a complete-case approach, or another method was used. No assumptions about missingness can be verified from the record.

The entry of 293 participants and the analysis-set definition do not establish that every participant contributed to every outcome. The available information does not quantify exclusions, withdrawals, or outcome-specific denominators for the primary or secondary endpoints. These gaps limit assessment of both the analysis population and potential bias from incomplete follow-up.

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.

Most frequent non-serious adverse event terms

The registry records zero participants affected by serious adverse events among 293 at risk in the BIAsp 30-30 group. For other adverse events, it records 80 affected among 293 at risk. These are descriptive counts for the recorded categories. The serious adverse event terms list is empty, and deaths are not reported in the registry record.

These entries do not show whether events were judged related to treatment, how event severity was classified beyond the serious category, or how long each participant was observed for safety. The registry does not further define the other adverse event category. It also does not provide a separate comparator group, so the counts cannot be used to estimate a comparative difference in risk attributable to the regimen.

In general, adverse event counts indicate what was recorded in a study, while interpretation depends on event definitions, collection methods, follow-up, and completeness of reporting. A zero count in the serious-event field means no affected participants are recorded in that field; it does not establish that no events occurred outside the recorded data or that risk is absent. The available safety entries should be read narrowly, as reported study-group counts.

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

The trial record establishes that a completed Phase 4, single-group study evaluated biphasic insulin aspart 30 with metformin in Chinese participants with type 2 diabetes inadequately controlled with basal insulin. It defines the primary measure as mean change in HbA1c from week 0 to week 16 and identifies standard error as the dispersion measure. It also reports safety counts for serious and other adverse events.

However, the numerical primary endpoint result is not reported in the registry record. Without the mean change, standard error, confidence interval, or test result, the size and precision of the HbA1c change cannot be described. The record likewise does not report numerical findings for the listed secondary outcomes. Thus, it is not possible to determine from this record whether HbA1c changed, by how much it changed, or how variable or uncertain an estimate might be.

Even if a within-group change were available, the single-group design would remain a limitation for causal interpretation. A before-and-after result describes the observed course in the treated group, but does not show what would have happened to a comparable group under a different treatment or without the regimen. Non-randomized, unmasked conduct also means that the record does not provide a randomized blinded comparison.

The safety entries show zero participants affected by serious adverse events and 80 affected by other adverse events, each recorded among 293 at risk. These counts do not provide a comparative assessment, and deaths are not reported in the registry record. They should not be treated as proof of either the presence or absence of a treatment-caused risk.

The appropriate reading is therefore limited: the record describes the question, design, endpoint, analysis population definition, and selected safety counts, but does not provide the primary numerical result or enough comparative information to establish a treatment effect. The trial's design and reporting boundaries are essential to interpreting what these data can mean.

14. Why This Trial Matters Statistically

This trial is statistically notable because its clinical question concerns change in a continuous outcome, while its design has only one treatment group. That combination separates two issues that are sometimes conflated: whether change can be measured within a group, and whether change can be attributed to the treatment. A mean change can answer the first question if the relevant result is reported. A concurrent comparator is needed for a more direct treatment contrast, and none is described in the registry record.

The endpoint definition is clear enough to identify the intended measurement: HbA1c change from week 0 to week 16, summarized as a mean with standard error. But statistical interpretation requires the actual estimate and its uncertainty, not only the name of the outcome and the planned summary. Since the numerical primary result is not reported, readers cannot assess magnitude or precision from this record. This illustrates why transparent outcome reporting matters alongside clear endpoint definitions.

The trial also highlights the importance of keeping planning calculations distinct from observed findings. The registry describes hypothetical sample-size calculations based on assumptions for a two-arm design, while the actual registered study is single-group. Such illustrations can inform planning under their stated assumptions, but they are not evidence about the observed result, a substitute for the trial's own design rationale, or observed power.

Finally, the safety counts and outcome list illustrate the difference between listing what was measured and reporting what was found. Counts without comparative context are descriptive, and secondary outcomes without numerical results cannot support estimates. Reading the design, analysis population, endpoints, uncertainty, and reporting completeness together helps define the limits of valid interpretation without overstating what the record can establish.

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.

The principal trial-specific limitation is the absence of a separate comparator group. This was a single-group, non-randomized study, so a change from baseline cannot be interpreted as a randomized difference between treatment strategies. The recorded masking status is none. The registry record does not describe additional steps that might address these design limitations.

The registry does not report the numerical primary endpoint result. Although it identifies mean change in HbA1c and standard error as the intended summary, the estimate and its uncertainty are absent. Numerical results for the secondary outcomes are also not reported. This prevents assessment of the magnitude, precision, and consistency of the measured outcomes.

The registry describes the intention-to-treat analysis set, but does not state how many participants contributed to the primary endpoint or how missing data were handled. It does not report endpoint-specific denominators, withdrawals, or reasons for missing observations. The extent to which incomplete follow-up could affect the results therefore cannot be assessed.

Additional methodological details are not reported in the registry record, including a full statistical analysis plan, the approach to multiple outcomes, a sample-size justification for the actual single-group design, and the handling of potential confounding in a non-randomized setting. The record also does not provide detailed definitions for all safety categories or event terms. These limitations concern both interpretation of the study design and completeness of the posted results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Biphasic Insulin Aspart 30 Combined With Metformin on Blood Glucose Control in Subjects With Type 2 Diabetes Inadequately Controlled With Basal Insulin — NCT00669864.
• Registry record last updated 2016-04-01; status last verified 2016-03.
• Results first posted 2010-07-05.
• 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 registry describes a completed Phase 4, non-randomized, unmasked, single-group trial with enrollment of 293. It evaluated individually adjusted biphasic insulin aspart 30 before breakfast and dinner, combined with metformin 1000-2000mg up to three times daily, in Chinese participants with type 2 diabetes inadequately controlled with basal insulin.

The primary endpoint was mean change in HbA1c from week 0 to week 16, with standard error specified as the dispersion measure. The registry defines the primary analysis population as participants who entered the treatment period and received at least one dose. The numerical primary outcome and secondary outcome results are not reported in the registry record.

Safety entries record zero participants affected by serious adverse events and 80 affected by other adverse events, among 293 at risk in each category. Serious event terms are not listed, and deaths are not reported in the registry record. No concurrent comparator is described, limiting causal interpretation of within-group change and safety counts.