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 Evaluation of Low Blood Sugar Events in Participants With Diabetes (MK-0431-402) (NCT01278485), a registered phase not stated study. The primary outcome is Number of Participants Experiencing Hypoglycemic Episodes in the 6 Months Prior to Enrollment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01278485 |
| Phase | Phase not stated |
| Condition | Type 2 Diabetes Mellitus |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 726 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
Participants with type 2 diabetes mellitus receiving care in cardiology, nephrology, or family practice settings. The registry summary describes consecutively selected participants treated with sulphonylurea-based therapy for at least 6 months before enrollment.
Intervention
This is not a treatment assignment study. The therapies of interest are sulphonylurea monotherapy and sulphonylurea with metformin, as used in routine care.
Comparator
No randomized comparator is specified. The registry describes a sulphonylurea-based cohort, but does not provide a clear, like-for-like comparison between treatment groups.
Primary question
How many participants reported experiencing hypoglycemic symptoms during the 6 months before enrollment, and what severity did they report?
The study focuses on participants with type 2 diabetes who were receiving care from cardiologists, nephrologists, or family practice doctors. Its stated purpose also includes describing treatment patterns, goal attainment, long-term diabetes complications, and the frequency and severity of hypoglycemic episodes. Quality of life, treatment satisfaction, adherence, fear of hypoglycemia, and body-weight experiences appear among the secondary outcomes.
The primary question is descriptive: it concerns participants’ reported experience during a period before enrollment, rather than a change measured after starting a study treatment. The questionnaire asked whether symptoms occurred and asked participants to classify their severity. The endpoint therefore concerns the number of participants reporting an experience, not a count of every separate episode.
The registry record does not set out a randomized treatment comparison or state that the study was designed to estimate a causal treatment effect. Its results, if reported, would need to be interpreted as observations within the studied care settings and treatment cohort. They would not by themselves establish that one therapy caused more or fewer hypoglycemic experiences than another.
3. Trial Design
This study is described as multicenter, observational, retrospective, and cross-sectional. It concerns a cohort of consecutively selected participants with type 2 diabetes mellitus who received sulphonylurea-based treatment in cardiology, nephrology, or family practice settings. The registry summary describes treatment with sulphonylurea monotherapy or sulphonylurea plus metformin for at least 6 months before enrollment. The record lists enrollment of 726 participants and gives the study status as completed.
The observational design means the registry does not describe investigators assigning participants to a study treatment. Instead, the study evaluates people already receiving treatment in routine practice. The retrospective aspect is reflected in the primary questionnaire’s focus on reported symptoms during the 6 months before enrollment. The cross-sectional description indicates that the study is framed around assessment at enrollment, rather than follow-up of outcomes after a treatment assignment.
The treatment descriptions are not fully aligned. The brief summary refers to both sulphonylurea monotherapy and combination therapy with metformin, while the arm description refers to participants treated with sulphonylurea monotherapy. The registry record does not clarify how those descriptions map to treatment groups or provide a specified allocation process. It explicitly does not describe the arms as a like-for-like control comparison.
The study start is listed as 2011-05, and primary completion as 2012-06. The registry lists quality-of-life, satisfaction, adherence, hypoglycemia-fear, and body-weight outcomes in addition to the primary outcome. The registry record does not report a protocol-level statistical plan, an analysis population beyond the primary outcome’s stated all-enrolled population, or a sample-size justification for the study design.
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: Seven participants who failed to meet all the inclusion criteria were excluded from the study.
Overall Study
| Stage | Adults With Type 2 Diabetes Mellitus ≥30 Years of Age |
|---|---|
| STARTED | 719 |
| COMPLETED | 719 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants.
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 | Adults With Type 2 Diabetes Mellitus ≥30 Years of Age |
|---|---|---|
| Participants analysed | 719 | |
| Age, Continuous | years | 65.91 (SD 9.98) |
| Sex: Female, Male: Female | Participants | 319 |
| Sex: Female, Male: Male | Participants | 400 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Experiencing Hypoglycemic Episodes in the 6 Months Prior to Enrollment, measured over Up to 6 Months Prior to Enrollment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants who experienced hypoglycemic episodes during the 6 months before enrollment. The registry describes a questionnaire asking participants whether they experienced symptoms of low blood sugar, with a yes-or-no response, and asking them to rate severity as mild, moderate, severe, or very severe. The stated population for this outcome is all enrolled participants.
This measure is useful for describing how commonly participants in the studied care settings report symptoms over the specified retrospective period. It also captures participants’ own assessment of symptom severity. Because the outcome is expressed as a number of participants, it is a participant-level measure: it does not represent the total number of separate hypoglycemic episodes. The registry record does not report an episode rate or a separate primary endpoint estimate for each severity category.
As a general statistical point, binary experience measures distinguish participants who report an event from those who do not. Their interpretation depends on knowing how many participants contributed usable information, how missing responses were handled, and what denominator was used for any proportion. Those details are not reported in the registry record for this endpoint. Without a reported estimate and its denominator, the registry description identifies what was asked but does not establish the observed frequency.
The endpoint is retrospective and self-reported. It can describe reported experience, but it does not itself verify symptoms through an independent measurement, establish when individual episodes occurred, or show that treatment caused them. The registry record does not report additional endpoint validation or ascertainment details.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies hypoglycemic experience in the 6 months before enrollment as the primary outcome, but it does not report a primary outcome count, proportion, confidence interval, or statistical test. As a result, the magnitude and precision of the primary finding cannot be assessed from the registry record. Enrollment is listed as 726, but that number alone does not show how many participants answered the questionnaire or contributed to the endpoint analysis.
The registry also does not report outcome results separately for sulphonylurea monotherapy and sulphonylurea plus metformin. In addition, the brief summary and arm description do not give a consistent account of the treatment groups. Even if group-specific summaries were available elsewhere, the record cautions that the arms are not a like-for-like control comparison and does not state an allocation process. Differences between such groups could reflect participant characteristics, clinical setting, treatment selection, or other factors rather than treatment effects.
General statistical interpretation: an estimate should be considered together with its uncertainty. A confidence interval describes a range of values compatible with the data under the statistical model; a narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. Neither an estimate nor its interval is reported for the primary endpoint in this registry record, so no conclusion about precision or statistical compatibility can be drawn from it.
The registry record lists secondary outcomes involving quality of life, treatment satisfaction, self-reported adherence, fear of hypoglycemia, and weight-related experiences. It does not report results for those outcomes in the information available for this study. The record also does not report analyses connecting these outcomes with hypoglycemic experience or treatment category.
The posted planning illustrations are not observed study findings. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry record does not report a treatment effect estimate that can be interpreted as the study’s primary result, nor does it report the sample sizes resulting from those planning illustrations. Such illustrations describe hypothetical planning scenarios, not the power achieved by this completed observational study.
Overall, the registry supports a description of the study question and design, but not an estimate of how frequently participants reported hypoglycemic symptoms or a comparison of treatment outcomes. The absence of reported results should not be interpreted as evidence that symptoms did or did not occur. The registry record does not report a statistical analysis plan or inferential results for this outcome.
9. Statistical Methods Explained
Statistical methods determine how observations are summarized and how uncertainty is assessed. The registry record describes a binary primary outcome: whether participants reported hypoglycemic symptoms during the 6 months before enrollment. It does not report the analysis method used to summarize that outcome or any inferential model. The discussion below explains relevant general concepts; it does not describe a statistical plan confirmed for this study.
What does a participant-level binary outcome represent?
A binary outcome records whether a participant meets a specified event definition. For this study, the questionnaire’s yes-or-no response distinguishes participants reporting symptoms from those not reporting symptoms. A count of participants with symptoms answers a different question from a count of all symptom episodes. Someone reporting repeated episodes still contributes as a participant who experienced symptoms, unless a separate episode-count analysis is defined.
For a binary outcome, a count is often interpreted alongside a denominator, such as the number of participants with a usable response. A proportion can then express the count relative to that denominator. The registry record does not report the primary outcome count, the analyzed denominator, or a proportion. It also does not describe how incomplete or ambiguous questionnaire responses were handled. Consequently, the outcome definition is available, but its observed frequency cannot be reconstructed from the registry record.
What does a confidence interval add?
As a general explanation, a confidence interval conveys uncertainty around an estimate. It reflects both the observed data and the assumptions of the method used to calculate the interval. A point estimate alone may appear precise while concealing substantial uncertainty; the interval helps readers judge how much the estimate could vary under the method. The record does not report a confidence interval for the primary outcome.
For proportions, methods for intervals may differ, particularly when information is sparse or when the proportion is near an endpoint of its possible range. The choice of method should be specified in the analysis plan or results. The registry record does not state an interval method, and no interval is available to interpret.
Why does the design matter for comparisons?
In a randomized comparison, assignment is intended to create groups that are comparable on average, subject to chance variation and study conduct. This registry describes an observational study, not a randomized treatment assignment. Treatment was received in routine clinical settings, and the record does not state an allocation process. As a general principle, treatment groups in observational data can differ in health status, clinical history, care setting, or reasons for treatment selection. Those differences can influence outcome comparisons.
The registry explicitly cautions that the arms are not a like-for-like control comparison. Therefore, a crude difference between groups, if available, would not automatically represent a treatment effect. Adjustment methods can address measured differences under stated assumptions, but cannot guarantee removal of confounding from unmeasured or poorly measured factors. The registry record does not report an adjusted comparison, covariates, or a model.
What do planning assumptions mean?
The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. These are assumptions for illustrative sample-size calculations, not evidence that the observational study followed that allocation or had a prespecified power target. The record does not report the underlying effect estimate or a sample-size justification for the study itself.
General explanation: a sample-size calculation asks how much information a hypothetical design would need to detect an effect under specified assumptions. Its result depends on the assumed effect, variability or event frequency, allocation, significance level, and statistical method. Changing an assumption changes the planning result. A planning calculation does not establish that an effect was observed, and it is not a measure of achieved or observed power after the study is complete.
The posted planning material uses participants per arm for non-time-to-event outcomes, according to the record’s stated conventions. This endpoint is described as participants with an event, rather than time to an event. The registry record does not report an inferential analysis for the endpoint or a fitted statistical model.
What can be said about the reported analysis?
The registry record does not report analysis results for the primary outcome, a method for handling missing data, or a multiplicity adjustment. It also does not report whether results were adjusted for differences among participants or care settings. Without those details and the underlying estimates, readers cannot evaluate model assumptions, compare unadjusted with adjusted findings, or assess the robustness of the result. These absences limit statistical interpretation; they do not establish that a particular method was or was not used outside the registry record.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Adults With Type 2 Diabetes Mellitus ≥30 Years of | 719 | 305 | 42.4% | 38.8% to 46.1% | 38.9% to 46.1% | 38.9% to 46.1% |
R code and output
arm <- c("Adults With Type 2 Diabetes Mellitus ≥30 Years of ")
n <- c(719)
events <- c(305)
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 Adults With Type 2 Diabetes Mellitus ≥30 Years of 719 305 42.4 38.8 46.1 38.9 46.1 38.9 46.111. Multiplicity, Missing Data and Analysis Populations
The study has a primary outcome and several listed secondary outcomes, covering quality of life, treatment satisfaction, adherence, fear of hypoglycemia, and body-weight experiences. When investigators test or estimate many outcomes, the opportunity to find apparently notable results by chance can increase. As a general statistical principle, multiplicity can be addressed through a prespecified hierarchy, adjustment procedure, or an interpretation that treats secondary analyses as exploratory. The registry record does not report a multiplicity strategy or identify which secondary outcomes, if any, were formally tested.
The primary outcome population is stated as all enrolled participants. That description identifies the intended population for the outcome, but does not report how many participants had a usable questionnaire response. The registry record does not report missing-data counts, reasons for missingness, imputation, or sensitivity analyses. It is therefore not possible to determine whether missing responses affected the endpoint summary or how any such effect was assessed.
The record does not describe an analysis population for secondary outcomes, exclusions from outcome analyses, or methods for accounting for incomplete records. Nor does it report a statistical analysis plan specifying denominators, covariate adjustments, or rules for handling questionnaire responses that do not fit the listed categories. Those details matter because different analysis choices can change which participants contribute to a result and how it should be interpreted.
These limitations concern reporting in the registry record. They do not prove that missing data or multiplicity were mishandled; they mean that the relevant methods are not reported in the registry record and cannot be evaluated from it.
12. What the Result Does, and Does Not, Mean
The study is designed to describe reported hypoglycemic experiences among participants with type 2 diabetes receiving sulphonylurea-based treatment in routine care settings. Its primary questionnaire asks whether symptoms occurred during the 6 months before enrollment and records reported severity. The registry record does not report the outcome count or an estimate of its frequency, so it does not establish how often participants reported symptoms.
The registry also does not support a conclusion that sulphonylurea monotherapy or combination therapy with metformin caused more or fewer symptoms. The study is observational, treatment assignment is not stated, and the registry warns that the arms are not a like-for-like control comparison. A group difference, if reported elsewhere, would need cautious interpretation because the treatment groups could differ for reasons other than the treatment itself.
General statistical explanation: descriptive findings can characterize the participants and experiences measured, while causal conclusions require stronger design features or defensible assumptions about confounding. Precision also matters. Without a reported estimate and uncertainty interval, readers cannot judge whether a result is tightly or weakly estimated. No such primary outcome estimate or interval is reported in the registry record.
The endpoint is self-reported and retrospective. It records participants’ reported experience, rather than independently verified episodes. The registry description does not provide enough detail to assess recall, symptom classification, or questionnaire response completeness. The number of participants enrolled is not equivalent to the number with complete outcome data.
The results that would be needed to assess the stated question are not reported in the registry record. That absence does not show that no symptoms occurred, that treatment had no effect, or that the study failed to collect information. It means that the registry record describes the question and study design without reporting the primary result needed to answer it.
13. Why This Trial Matters Statistically
This study addresses an outcome that is relevant to understanding participants’ experiences during routine diabetes care: self-reported hypoglycemic symptoms and their severity. Its observational approach places those experiences in cardiology, nephrology, and family practice settings, rather than describing a randomized treatment assignment. The registry also identifies related outcomes involving quality of life, medication satisfaction, adherence, fear of hypoglycemia, and body-weight concerns.
Statistically, the study illustrates the difference between defining an outcome and reporting an estimate for it. The registry specifies a participant-level yes-or-no measure and a retrospective timeframe, but does not report the primary count, denominator, or uncertainty. Without those elements, readers cannot judge the frequency or precision of the observed experience. A clearly stated endpoint is valuable, but it cannot substitute for outcome results.
The record also makes the design distinction important. Routine-care treatment groups may not be comparable, and the registry explicitly cautions against treating the arms as like-for-like controls. That warning is central to interpreting any proposed treatment comparison: a descriptive contrast is not automatically evidence of a causal difference.
Finally, the planning illustrations should be kept separate from observed findings. They use stated assumptions for hypothetical sample-size planning, while the record does not report a primary effect estimate or an analysis result. Distinguishing planning from evidence prevents a calculation from being mistaken for a finding about participants in this completed study.
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 interpretation is that the registry record does not report the primary outcome result. It gives the questionnaire definition and retrospective timeframe, but no count of participants reporting symptoms, no denominator for that count, and no uncertainty estimate. This prevents assessment of the endpoint’s observed frequency and precision.
The study is observational, retrospective, and cross-sectional. It does not describe randomized treatment assignment, and the registry cautions that treatment arms are not a like-for-like control comparison. The brief summary discusses sulphonylurea monotherapy and combination therapy with metformin, while the arm description refers to sulphonylurea monotherapy. The record does not clarify the group structure or how the treatment descriptions correspond to analyzed participants.
The primary endpoint relies on self-report about the period before enrollment. The registry does not report further details on recall procedures, verification, questionnaire completeness, or missing-response handling. It also does not report a statistical analysis plan, a model, adjustment for participant or care-setting differences, or methods for secondary-outcome multiplicity.
The record lists enrollment of 726, but does not report the number contributing data to each outcome. Thus enrollment should not be treated as the endpoint denominator. The record also does not report results for the listed secondary outcomes. These limitations describe what cannot be assessed from the registry record; they do not establish that the study lacked other analyses or procedures outside the record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Low Blood Sugar Events in Participants With Diabetes (MK-0431-402) — NCT01278485.
- Registry record last updated 2015-07-28; status last verified 2015-07.
- Results first posted 2013-08-26.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT01278485 is a completed, multicenter, observational, retrospective, cross-sectional study of participants with type 2 diabetes mellitus receiving sulphonylurea-based treatment in cardiology, nephrology, or family practice settings. The registry lists enrollment of 726, a study start of 2011-05, and primary completion of 2012-06. The sponsor is Merck Sharp & Dohme LLC.
The primary outcome is the number of participants reporting hypoglycemic episodes during the 6 months before enrollment, assessed by questionnaire. The study summary also describes treatment patterns, goal attainment, long-term complications, and hypoglycemia, with listed secondary measures covering quality of life, treatment satisfaction, adherence, fear of hypoglycemia, and weight-related experiences.
The registry record does not report a primary outcome estimate, analysis results, or a statistical analysis plan. It cautions that the treatment arms are not a like-for-like control comparison.