Once Versus Twice Daily Iron Supplementation in Pregnant Women: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Once Versus Twice Daily Iron Supplementation in Pregnant Women (NCT02839096), a randomized na study. The primary outcome is Hemoglobin.

2. Clinical Question

The registry describes a prospective, randomized, placebo-controlled, double-blinded trial. It records quadruple masking, but does not identify which people or roles were masked. The comparator was not a no-treatment group: participants assigned to once-daily dosing received morning ferrous sulfate and an evening placebo. The research question therefore concerns the dosing schedule of iron supplementation under the regimens recorded, rather than iron supplementation versus no iron.

The registry also lists incidence of blood transfusion at delivery as a secondary outcome. It lists three outcome measures in total, but the record does not report results for the primary hemoglobin comparison or provide a complete account of the other outcome measures. The clinical question can be described from the registered design, but the posted record does not establish the size, direction, or precision of a hemoglobin difference.

3. Trial Design

The registry describes a prospective, randomized, parallel-group trial of once-daily versus twice-daily iron supplementation to treat anemia in pregnancy. Its official title identifies the trial as placebo controlled and double blinded, while the masking field records quadruple masking. The record does not specify the people or roles included in those masking descriptions, the allocation ratio, or the method used to generate the random assignment.

In the once-daily group, participants were assigned 325mg of ferrous sulfate in the morning and placebo in the evening. In the twice-daily group, participants were assigned 325mg of ferrous sulfate in the morning and 325mg in the evening. These descriptions indicate that the morning regimen was the same in both groups and that the evening treatment differed. The registry lists placebo and ferrous sulfate as interventions.

Enrollment is recorded as 20. The phase is listed as NA. The recorded start is 2016-06, and primary completion is recorded as 2019-06. The current status is TERMINATED. The reason for termination and whether the planned recruitment or follow-up was completed are not reported in the registry record. Nor does the record explain why enrollment was 20 or provide a sample-size justification.

Maternal hemoglobin is the primary outcome. The specified timeframe is change from baseline to one day postpartum. Hemoglobin was to be measured at baseline, at admission for labor and delivery, and on postpartum day one. The registry notes that one participant delivered at another hospital, so baseline but not delivery or postpartum hemoglobin measurements were obtained for that participant. Blood transfusion at delivery is listed as a secondary outcome. The registry does not describe the full analysis plan or report a primary outcome analysis.

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

Analysis population for the primary outcome, as defined in the registry: One participant delivered at another hospital and so baseline, but not delivery or postpartum hemoglobin measurements were obtained.

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 Hemoglobin, measured over Change in hemoglobin from baseline to one day postpartum.

The primary endpoint is change in maternal hemoglobin from baseline to one day postpartum, measured in g/dL. Hemoglobin is a continuous measure, and the registry identifies the planned summary as a mean with a 95% confidence interval. It was scheduled for measurement at baseline, at admission for labor and delivery, and on postpartum day one; the primary timeframe compares baseline with the postpartum measurement.

A change endpoint expresses how a measurement differs from its starting value. In a randomized comparison, the difference in average change between groups can describe whether the observed trajectories differ under the assigned dosing regimens. The baseline measurement also gives context for interpreting the postpartum value. The registry record does not report either group's mean change or the estimated comparison between groups, so the direction and magnitude of any observed difference cannot be described from the record.

The record says postpartum day 1 hemoglobin was estimated from hematocrit by dividing by 2.941. This is relevant because the endpoint combines measurements obtained directly as hemoglobin with a postpartum estimate derived from hematocrit, according to the registered description. One participant delivered at another hospital and had baseline but not delivery or postpartum hemoglobin measurements. The record does not specify how that missing postpartum measurement was handled in the primary analysis, or whether additional measurements were unavailable.

Hemoglobin is used as a continuous laboratory endpoint for assessing the trial's registered question about change after the assigned supplementation regimens. The endpoint definition alone does not indicate whether one regimen produced a greater change. That conclusion would require the reported results and their uncertainty, neither of which appears in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies hemoglobin as a continuous outcome summarized by a mean and a 95% confidence interval. The method used to compare the groups, including any adjustment or model, is not reported in the registry record. The methods below explain the statistical ideas relevant to the registered outcome; they do not describe an analysis documented in the record.

What does a mean describe?

A mean is the arithmetic average of a set of measurements. For a continuous endpoint such as hemoglobin, it provides a summary of the group’s measured values or changes. A group mean alone does not reveal how spread out individual measurements are, whether the distribution is symmetric, or whether a few unusual observations influence the average. Those features matter when deciding how well a mean represents the observed data and how appropriate a model based on means may be.

For this trial, the outcome is defined as change from baseline to one day postpartum. A comparison could describe the mean change in each group and the difference between those mean changes. The registry record specifies the endpoint and summary type but does not report these quantities. It also does not say whether the analysis used individual change scores, a model of postpartum measurements adjusted for baseline, or another approach. These approaches can target related questions but need not yield identical estimates, especially when assumptions and available observations differ.

What does a confidence interval add?

A confidence interval expresses the uncertainty around an estimated quantity under a specified statistical procedure. A narrower interval indicates greater precision under that procedure; a wider interval indicates less precision. The interval should be interpreted together with the estimate and the clinical and measurement context. It is not a substitute for the estimate and does not show the range of individual participant outcomes.

The registry lists a 95% confidence interval as the dispersion measure for the primary outcome. It does not provide the interval itself or identify the method used to calculate it. Without an estimate and interval, readers cannot assess whether the posted comparison is precise, whether it is compatible with a range of effects, or whether the data support a clear distinction between the groups. The stated confidence level does not by itself indicate that an effect is important or that a particular treatment schedule should be chosen.

Why does the endpoint's measurement schedule matter?

The registered schedule includes baseline, admission for labor and delivery, and postpartum day one measurements, while the primary timeframe specifies change from baseline to one day postpartum. The intervening measurement may be informative descriptively, but the registry does not identify it as part of the primary comparison. Multiple time points can create multiple possible summaries and comparisons. A clear prespecified primary time point helps distinguish the principal question from additional analyses.

The record notes that postpartum day 1 hemoglobin was estimated from hematocrit by dividing by 2.941. This means the endpoint description includes a derived postpartum value. Statistical interpretation should account for how the conversion was applied and whether the measurement process was consistent across groups; the registry does not provide further detail. It also records a participant with baseline data but no delivery or postpartum hemoglobin measurement because delivery occurred at another hospital. Missing outcome values can reduce information and may affect the comparison, depending on their cause and the analysis method.

What can be said about planning illustrations?

The sample-size assumptions describe illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. These are planning calculations, not observed power and not evidence about the trial’s original design. The record does not provide its own sample-size justification, and the primary effect is not reported in the registry record. The numerical planning values therefore cannot be independently interpreted from the registered information.

In general, planning calculations ask how many participants per arm would be needed to detect an effect under stated assumptions. Their conclusions depend on the target effect, variability, significance level, allocation, and analysis method. Using a fraction of an observed effect illustrates how a smaller target effect changes planning needs, but it does not establish that such an effect is clinically important. These calculations should not be confused with power calculated after a study has been completed.

Why is the analysis plan important?

Randomization supports a comparison based on assigned groups, but it does not specify how outcome data are analyzed. A statistical analysis plan would clarify the estimand, treatment of missing measurements, any covariate adjustment, assumptions about the outcome distribution, and handling of additional outcomes or time points. Those details are not reported in the registry record. The record lists zero analyses, so there is no posted model specification or inferential result to evaluate.

General statistical methods can explain what the registered endpoint and summary would mean, but they cannot recover unreported data or determine which method the investigators used. The appropriate interpretation remains that the registry describes a randomized design and a continuous primary outcome, while leaving the primary analysis and its results unavailable.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies hemoglobin as primary, with incidence of blood transfusion at delivery as a secondary outcome. It does not provide a complete description of all outcome measures in the record. The primary outcome is also flagged as having several categories or time points and is not reduced to one comparison. This leaves the specific primary comparison and any hierarchy among time points or categories unclear.

When a study examines multiple outcomes, time points, or comparisons, the chance of at least one apparently notable result can increase. General approaches to multiplicity include identifying a primary comparison in advance, using a testing hierarchy, or adjusting inferential procedures. The registry does not report whether any such approach was planned or used. No multiplicity adjustment should be assumed from the registered design alone.

The record identifies one participant who delivered at another hospital and therefore had baseline but not delivery or postpartum hemoglobin measurements. The missing-data method, the analysis population, and whether other measurements were missing are not reported in the registry record. It also does not state whether the primary analysis followed assigned treatment regardless of adherence, or used another population definition. These details affect what population a reported estimate would represent and how robust it might be to incomplete follow-up.

Because no primary results or analyses are listed, the impact of multiplicity or missing measurements on the reported comparison cannot be assessed. The registry does not report interim analyses, and no interim analysis plan should be inferred from the record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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 lists serious adverse events for the once-daily group as 0 affected among 11 at risk, and for the twice-daily group as 0 affected among 9 at risk. Deaths are recorded as 0 in both groups. The record lists no serious adverse event terms.

For other adverse events, the registry records 6 affected among 11 at risk in the once-daily group and 5 affected among 9 at risk in the twice-daily group. These are descriptive counts in the registry record. They do not, on their own, establish whether the regimens differ in safety or whether an event was caused by the assigned treatment. The record does not provide event-level detail, severity classifications for these other events, or a comparative statistical analysis.

Zero recorded serious events does not establish that serious events cannot occur, particularly when the registry lists a limited enrollment. Nor do the other-event counts provide a complete assessment of safety without information about event definitions, observation periods, ascertainment, and missing safety data. These details are not reported in the registry record. The figures should therefore be read as the recorded counts, not as proof of absence of risk or as evidence of a safety difference.

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

The registry record establishes that investigators planned a randomized comparison of once-daily and twice-daily ferrous sulfate supplementation in women diagnosed with anemia in the mid-trimester of pregnancy. It specifies the dosing schedules, the primary hemoglobin timeframe, and a secondary outcome of blood transfusion at delivery. This information helps define the study question and the kinds of outcomes the investigators intended to assess.

The record does not report the primary hemoglobin results, an estimated difference between groups, a confidence interval, or an analysis. It therefore does not show whether average hemoglobin change was greater in either group, how large any difference may have been, or how precise an estimate would be. It also does not establish that the groups were equivalent. An absent result cannot be interpreted as a finding of no effect.

The trial status is TERMINATED and recorded enrollment is 20, but the reason for termination is not reported in the registry record. Neither fact explains the missing results or indicates whether the termination was related to the treatment comparison. The record also does not provide the trial’s sample-size justification or analysis plan, including how missing hemoglobin data were handled.

Thus, the material supports a description of the registered design and its outcome definitions, not a conclusion about the comparative effect of the regimens. The safety counts likewise remain descriptive and do not establish causation or comparative safety. Conclusions about efficacy, safety, precision, or clinical importance would require results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its registered question is specific: it compares two dosing schedules that share a morning ferrous sulfate dose and differ in the evening assignment. A placebo in the evening for the once-daily group helps define that regimen contrast. Understanding the contrast is essential when interpreting any eventual estimate: it would concern these assigned schedules, not iron versus no iron.

The primary outcome is a change in a continuous measure, with a specified postpartum time point and a reported approach to estimating postpartum hemoglobin from hematocrit. These details make the measurement definition central to interpretation. The note about a participant who lacked delivery and postpartum measurements also illustrates why missing-data handling should be explicit for a change endpoint.

The record is also a useful example of the distinction between a registered design and a reported analysis. Randomization and masking describe planned design features, but do not supply an outcome estimate, confidence interval, or account of the analysis population. The record lists no analyses, so statistical interpretation must stop short of estimating the comparative result.

Finally, the sample-size assumptions describe planning illustrations based on an observed effect, not the original design rationale or observed power. Separating those concepts helps prevent a planning calculation from being mistaken for evidence about the strength of the trial's findings. In this record, the absence of reported primary results makes that distinction especially important.

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 most consequential limitation of the registry record for statistical interpretation is that it does not report the primary hemoglobin results or any analyses. There is no group-level estimate, between-group comparison, confidence interval, or inferential result to assess. The record therefore cannot support a conclusion about the direction, magnitude, or precision of the primary outcome.

The registry records enrollment of 20 and status TERMINATED, but does not give the reason for termination, the intended enrollment, or a sample-size justification. It is not possible to determine from the record whether enrollment ended as planned or why the trial stopped. The planning assumptions described for sample-size illustrations are not a substitute for the trial's own design rationale.

Outcome reporting is incomplete for interpretation. The registry lists three outcome measures, but the primary outcome has several categories or time points and is not reduced to one comparison. The complete endpoint hierarchy and multiplicity strategy are not reported. The analysis method, analysis population, and treatment of missing data are also not reported in the registry record. This matters because one participant had baseline but not delivery or postpartum hemoglobin measurements after delivering at another hospital.

The record states that postpartum day 1 hemoglobin was estimated from hematocrit by dividing by 2.941, but gives no further detail about the measurement or conversion process. It does not provide event-level safety descriptions or a comparative safety analysis. These limitations restrict assessment of both the primary endpoint and the adverse-event counts, regardless of the randomized design.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Once Versus Twice Daily Iron Supplementation in Pregnant Women — NCT02839096.
• Registry record last updated 2024-09-19; status last verified 2024-08.
• Results first posted 2024-09-19.
• 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

The registry describes a prospective, randomized, parallel, placebo-controlled trial comparing once-daily with twice-daily ferrous sulfate supplementation for anemia in pregnancy. The once-daily regimen was 325mg in the morning and placebo in the evening; the twice-daily regimen was 325mg in both the morning and evening. The record lists quadruple masking, enrollment of 20, status TERMINATED, and phase NA.

The primary outcome was change in maternal hemoglobin from baseline to one day postpartum, summarized as a mean with a 95% confidence interval. Postpartum day 1 hemoglobin was estimated from hematocrit by dividing by 2.941. One participant had baseline but not delivery or postpartum measurements after delivering at another hospital. The registry lists blood transfusion at delivery as a secondary outcome and records zero analyses. Primary hemoglobin results, the reason for termination, the analysis plan, and the handling of missing data are not reported in the registry record.