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 Metformin to Augment Low Milk Supply (MALMS) Study (NCT02179788), a randomized phase 1, phase 2 study. The primary outcome is Peak Change in Milk Output.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02179788 |
| Phase | Phase 1, Phase 2 |
| Condition | Low Milk Supply, Pre-diabetes, Insulin Resistance |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 15 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Children's Hospital Medical Center, Cincinnati |
| Results posted | Yes |
2. Clinical Question
Population
The study focused on mothers with low milk supply who were pre-diabetic or insulin resistant. The registry describes the trial as a preliminary study in insulin-resistant and pre-diabetic mothers, and lists low milk supply, pre-diabetes, insulin resistance, and suppressed lactation as conditions. The primary outcome population is not specified in the registry record.
Intervention
The intervention was metformin together with standard care. The standard-care instructions described for the metformin arm were to thoroughly empty the breasts at least 8 times per day and take the assigned study drug.
Comparator
The comparator was placebo together with standard care. The placebo arm was instructed to thoroughly empty the breasts at least 8 times per day and take the assigned study drug. The registry describes the placebo as methylcellulose USP Powder in opaque capsules.
Primary question
The primary question concerned peak change in milk output from baseline to 4 weeks post-intervention. The registry describes a maximal change in maternal breast milk production, with an analysis adjusted for baseline milk volume, maternal day postpartum at randomization, and baseline fasting plasma glucose. The registry record does not report a direct statistical comparison between the two arms.
3. Trial Design
The MALMS study was registered as a randomized, quadruple-masked, parallel-group Phase I/II trial. It was designed as a preliminary, small-scale randomized study to test for a trend in the hypothesis that metformin might be safe and potentially effective for low milk supply in insulin-resistant and pre-diabetic mothers. The registry reports enrollment of 15 and a completed study. The recorded start was 2014-06, and primary completion was 2016-07.
The two outcome arms were standard care plus metformin and standard care plus placebo. Both groups received instructions to thoroughly empty the breasts at least 8 times per day and take the assigned study drug. The arm descriptions state that 67% of Stage 2 eligible mothers would be allocated to standard care plus metformin and 33% to standard care plus placebo. These are the stated allocation proportions for eligible mothers, not the outcome sample sizes: the posted primary outcome data list 10 participants in the metformin arm and 5 in the placebo arm.
The registry lists standard care as a behavioral intervention and metformin and placebo as drug interventions. Although the title identifies pre-diabetic mothers, further eligibility details are not reported in the registry record. The randomization method, concealment procedure, precise masking roles, and further details of the treatment regimen are not reported in the registry record. The phase designation and preliminary purpose describe the trial's general setting, but do not by themselves establish the precision or reliability of the posted outcome estimates.
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 | Standard Care Plus Metformin | Standard Care Plus Placebo |
|---|---|---|
| STARTED | 10 | 5 |
| COMPLETED | 10 | 5 |
| NOT COMPLETED | 0 | 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 | Standard Care Plus Metformin | Standard Care Plus Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 10 | 5 | 15 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 | 5 | 15 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Age, Continuous | years | 33 (26 to 34) | 35 (32 to 40) | 34 (26 to 36) |
| Sex: Female, Male: Female | Participants | 10 | 5 | 15 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 10 | 5 | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Peak Change in Milk Output, measured over baseline and 4 weeks post-intervention.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | milliliters |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is titled peak change in milk output. It measures the maximal change in maternal breast milk production between baseline and 4 weeks post-intervention. The registry says the outcome was analyzed in a model adjusted for baseline milk volume, maternal day postpartum at randomization, and baseline fasting plasma glucose.
A change from baseline focuses on how the measured output shifted over the study interval, rather than only the output at the final measurement. The maximal-change definition targets the largest recorded change within the stated period; the registry record does not give further detail on how that maximum was identified or measured. The endpoint is reported as a median with an inter-quartile range, a summary suited to describing the center and spread of observed values without requiring the mean to represent the typical participant.
There is an inconsistency in the endpoint's units: the outcome is labeled in milliliters, while its description specifies production in g/24 hours. The registry record does not explain the discrepancy. The arm results report medians of 8.0 for standard care plus metformin and -58.0 for standard care plus placebo; the listed lower and upper limits are -23.0 and 33.0, and -62.0 and -1.0, respectively. The spread field is null for both arms, so an inter-quartile range is not available in the posted arm results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results give a median peak change of 8.0 in the standard care plus metformin group and -58.0 in the standard care plus placebo group. The outcome sample sizes are 10 and 5, respectively. The listed lower and upper limits for the metformin group are -23.0 and 33.0; for the placebo group, they are -62.0 and -1.0. The record does not identify the type or confidence level of these limits, so they should not be interpreted as a particular kind of interval without further documentation.
These are separate arm summaries, not a reported estimate of the difference between groups. The registry reports no analyses and indicates that values were missing or not estimable for a two-arm comparison for another endpoint. No direct two-arm estimate, standard error, or p-value for the primary endpoint is posted. The arm summaries therefore do not establish whether the observed pattern is compatible with chance variation or how precisely the groups differ. The small outcome groups, especially the placebo group with 5 participants, also mean that the arm medians describe a limited set of observations.
The primary outcome is described as adjusted for baseline milk volume, maternal day postpartum at randomization, and baseline fasting plasma glucose. However, the posted arm values do not specify how that adjustment relates to the reported medians or limits. The registry record does not report model coefficients, an adjusted treatment contrast, or a detailed analysis output. It is not possible to infer those quantities from the arm summaries.
The outcome measurement also has an unresolved unit mismatch: the endpoint label says milliliters, while the description says g/24 hours. The registry record does not clarify which unit applies to the posted values. The spread field is null, despite the endpoint being specified as a median with inter-quartile range, so the inter-quartile ranges cannot be read from the posted arm results. These reporting gaps constrain interpretation independently of the observed medians.
The trial description characterizes the study as preliminary and intended to test for a trend. Its posted arm-specific results can be read as descriptive observations for the enrolled groups, but not as a definitive estimate of a treatment effect. No conclusion about the treatment's clinical effectiveness or safety follows from these summaries alone.
9. Statistical Methods Explained
The registry describes a randomized, quadruple-masked, parallel-group trial. Randomization is intended to distribute participants between study groups by chance, while masking is intended to limit the influence of knowledge about assignment on participant experience, care, measurement, or interpretation. The record does not specify who was masked or how randomization and concealment were carried out. The parallel-group model means the listed arms represent separate groups rather than a crossover sequence.
What does a median describe?
A median is the central value when observations are ordered. It can be less sensitive than a mean to unusually large or small observations, which can be useful when data are skewed or when the sample is small. The endpoint specifies a median and inter-quartile range, but the posted spread values are null. An inter-quartile range describes the middle portion of a distribution; without the reported values, the spread around each median cannot be assessed from this record.
The arm summaries list lower and upper limits, but do not identify the interval type or its confidence level. A confidence interval, in general, expresses uncertainty about an estimated quantity under a specified statistical procedure. Its interpretation depends on the method and confidence level. Since those details are not identified for these limits, they cannot be assigned a confidence-interval interpretation based on the registry record alone.
What does adjustment mean?
The endpoint description says the analysis adjusted for baseline milk volume, maternal day postpartum at randomization, and baseline fasting plasma glucose. In general, adjustment incorporates specified variables into a model to account for their association with the outcome when estimating a result. It does not, by itself, reveal whether an adjusted contrast was calculated or what its value was. The record does not give the model specification, coefficients, or a direct adjusted comparison between the groups. The relationship between the adjusted analysis described in the endpoint and the posted arm-specific medians is not reported in the registry record.
Why does a direct comparison matter?
Separate summaries describe each arm, while a treatment comparison estimates how the outcome differs between arms under a defined analysis. A comparison can incorporate uncertainty in both groups and, where specified, model adjustment. The registry lists arm medians and limits but reports no analysis results for a two-arm comparison. A reader should not treat the gap between the two medians as a calculated treatment effect or as evidence of statistical significance. No additional numerical comparison can be reconstructed from the posted information without making assumptions about the data and analysis.
The endpoint description refers to maximal change over the period from baseline to 4 weeks post-intervention. In general, an analysis of a maximum depends on how repeated measurements are collected and how the maximum is defined. The registry record does not say how many measurements informed the maximum, how missing measurements were handled, or whether the stated endpoint was calculated from raw measurements or a model. Those operational details matter for understanding what the endpoint represents.
How should planning illustrations be read?
Sample-size illustrations based on an observed effect are planning scenarios, not observed trial outcomes and not evidence that the study had a particular probability of finding an effect. In general, such illustrations depend on assumptions about the effect to detect, significance level, allocation, and statistical model. The registry describes its illustrations as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation, and says the effect to detect is a stated fraction of the observed effect. It also distinguishes participants per arm for most outcomes from total events for time-to-event outcomes. No illustration values are needed to interpret the posted arm summaries, and these planning assumptions are not reported as the trial's own design justification.
More broadly, statistical precision depends on the amount of information in the data and the analysis method. Small groups can yield unstable estimates, and uncertainty intervals can help convey that imprecision when their method is clearly reported. Here, the outcome group sizes are 10 and 5, the spread fields are unavailable, and the limits lack a stated interpretation. Those features limit what can be inferred about the distributions and the comparative result. The registry record does not report an interim analysis plan, a detailed statistical analysis plan, or a rationale for the enrollment target.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and no posted secondary outcomes. It reports zero analyses. A multiplicity plan describing how the trial handled multiple statistical tests is not reported in the registry record. With no inferential analysis or p-values posted, the record does not permit assessment of how multiplicity may have affected any hypothesis tests.
Missing-data methods are also not reported in the registry record. The record does not state whether every enrolled participant contributed to the primary endpoint, how missing measurements were handled, or whether any participants were excluded from the outcome analysis. The posted primary outcome groups contain 10 participants for standard care plus metformin and 5 for standard care plus placebo, while overall enrollment is 15. The registry does not provide further accounting of participants or explain the analysis population behind those arm counts.
The endpoint description identifies an adjusted model, but the record does not explain whether the analysis followed intention-to-treat principles, used a per-protocol population, or applied another population definition. No protocol deviations, exclusions, or sensitivity analyses are reported in the registry record. These details matter because the interpretation of an estimate can depend on who was included and how incomplete outcome data were treated.
The record also does not report whether there were interim analyses, a prespecified hierarchy of outcomes, or a correction for multiple comparisons. Their status should not be inferred from the trial's phase or size. The available information supports description of the posted endpoint summaries, but does not support an assessment of missing-data assumptions or a full reconstruction of the inferential analysis.
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 |
|---|---|---|---|
| Standard Care Plus Metformin | 0 | 20 | 0.0% |
| Standard Care Plus Placebo | 0 | 10 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Standard Care Plus Metformin | 0 of 10 |
| Standard Care Plus Placebo | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Standard Care Plus Metformin | 13 of 20 |
| Standard Care Plus Placebo | 8 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Standard Care Plus Metformin | Standard Care Plus Placebo |
|---|---|---|---|
| Nausea, vomiting diarrhea-Mom | Gastrointestinal disorders | 6 of 20 | 3 of 10 |
| gas/diarrhea/constipation/reflux-infant | Gastrointestinal disorders | 5 of 20 | 4 of 10 |
| gas/bloating/cramping-mom | Gastrointestinal disorders | 4 of 20 | 0 of 10 |
| Headache-mom | Nervous system disorders | 3 of 20 | 0 of 10 |
| Irritable/other-infant | Nervous system disorders | 2 of 20 | 1 of 10 |
| Runny nose/cold-infant | Respiratory, thoracic and mediastinal disorders | 2 of 20 | 0 of 10 |
| Infant-fever | Infections and infestations | 1 of 20 | 1 of 10 |
| Mom-Breast pain | Reproductive system and breast disorders | 0 of 20 | 1 of 10 |
| insufficient weight gain-infant | Gastrointestinal disorders | 1 of 20 | 0 of 10 |
| Mom-pruritis | Skin and subcutaneous tissue disorders | 0 of 20 | 1 of 10 |
The registry's serious adverse event counts are 0 among 20 at risk in the standard care plus metformin group and 0 among 10 at risk in the standard care plus placebo group. Deaths are recorded as 0 in both groups. These are the posted safety counts; the record does not describe event definitions, assessment procedures, or follow-up duration for safety reporting.
The safety denominators differ from the primary outcome group sizes, which are 10 and 5. The registry record does not explain the difference. It would therefore be inappropriate to assume that safety and primary outcome data came from identical analysis populations or to reconcile the counts without further information.
Other adverse events are recorded for 13 of 20 at risk in the metformin group and 8 of 10 at risk in the placebo group. The registry does not list serious adverse event terms. These counts should be read as the registry's reported event figures, not as a complete assessment of event severity, timing, causality, or comparative risk. A zero count in these small groups does not establish that an event cannot occur or that the groups have equivalent safety. The record does not report a statistical comparison of adverse events.
12. What the Result Does, and Does Not, Mean
The posted data describe a small randomized trial with median peak-change values for each arm and no reported statistical comparison between arms. The median was 8.0 for standard care plus metformin and -58.0 for standard care plus placebo. The primary outcome groups included 10 and 5 participants. Those summaries are observations from the enrolled groups, not a reported estimate of the effect of assigning metformin rather than placebo.
The record does not provide a two-arm estimate, p-value, or an interpretable confidence interval for the primary outcome. It also does not provide inter-quartile ranges, although the endpoint is specified as a median with that measure of spread. The posted limits have no stated interval type or confidence level. As a result, the precision and statistical compatibility of the arm summaries cannot be fully evaluated from the registry record.
The endpoint's units are inconsistent: the label states milliliters, while the description specifies g/24 hours. This unresolved issue affects how the magnitude of the posted values should be understood. The registry record also does not explain how the adjustment described for the endpoint connects to the arm medians.
The study was described as preliminary and intended to test for a trend. It can therefore be understood as an early, small randomized investigation, not as a conclusive test. The registry does not establish that a difference between the arm medians is statistically reliable, clinically important, or attributable to the intervention. Nor do the posted zero serious adverse event counts establish absence of risk. The figures describe what was recorded in the trial groups; broader conclusions are not supported by these results alone.
13. Why This Trial Matters Statistically
This trial illustrates how randomized design and limited sample size can coexist with substantial uncertainty in the interpretation of results. Random allocation and masking are features intended to reduce some sources of bias, but they do not guarantee precise estimates. The primary outcome groups contain 10 and 5 participants, and the registry reports only separate arm summaries rather than a treatment contrast.
For readers, the distinction between an arm-specific median and a between-arm estimate is central. The medians describe the centers of the posted group results. A direct comparison would address the difference between groups under a specified analysis and would ordinarily include an account of uncertainty. That comparison is not reported in the registry record, so the observed medians should not be substituted for it.
The record also demonstrates the importance of reporting outcome definitions and units consistently. The endpoint label uses milliliters, while its description refers to g/24 hours. The median and inter-quartile range are identified as the summary approach, but the spread values are unavailable. These reporting details affect whether readers can interpret the scale and variability of the outcome.
Finally, preliminary trials and planning calculations serve different purposes. The registry describes the study as a small trial intended to test for a trend, and its sample-size assumptions are described as planning illustrations based on an observed effect. Such illustrations do not replace a trial's observed results, and they are not observed power. Keeping these distinctions clear helps prevent descriptive findings and planning scenarios from being read as stronger evidence than the posted analysis supports.
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 outcome sample sizes are limited to 10 participants in the metformin arm and 5 in the placebo arm. The record does not report a direct comparison or detailed uncertainty estimate, limiting assessment of the size and precision of any between-group difference. The listed limits have no stated interval type or confidence level, and the spread fields are null despite the endpoint's specification as a median with inter-quartile range.
The endpoint's units are inconsistent: the title labels the measure in milliliters, while the description specifies g/24 hours. The record does not resolve this discrepancy or clarify how the adjusted model relates to the arm summaries. Further measurement and analysis details, including how maximal change was defined, are not reported in the registry record.
Overall enrollment is 15, but the safety counts use denominators of 20 and 10, while the primary outcome counts are 10 and 5. The registry does not explain these differences. Eligibility criteria beyond the broad description of pre-diabetic or insulin-resistant mothers with low milk supply, missing-data procedures, analysis-population definitions, and handling of protocol deviations are also not reported in the registry record.
The record does not provide a detailed statistical analysis plan, sample-size justification for the trial, or information on interim analyses. The stated sample-size illustrations are planning scenarios based on the observed effect and should not be mistaken for the trial's own design justification. These reporting limits make the posted summaries useful as a description of the recorded groups, but constrain inference about comparative effects, precision, and generalizability.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Metformin to Augment Low Milk Supply (MALMS) Study — NCT02179788.
- Registry record last updated 2020-10-19; status last verified 2016-09.
- Results first posted 2020-10-19.
- 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.
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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The MALMS study is a completed randomized, quadruple-masked, parallel-group Phase I/II trial of standard care plus metformin versus standard care plus placebo. It enrolled 15 participants and focused on low milk supply in pre-diabetic or insulin-resistant mothers. The primary endpoint was peak change in milk output between baseline and 4 weeks post-intervention, described as adjusted for baseline milk volume, maternal day postpartum at randomization, and baseline fasting plasma glucose.
The posted arm medians are 8.0 for metformin and -58.0 for placebo, with outcome group sizes of 10 and 5. No direct two-arm analysis is reported. The inter-quartile ranges are unavailable, the interpretation of the listed limits is not specified, and the endpoint label and description give different units. The registry record does not report enough detail to resolve these issues or to determine the precision of a comparative effect.