Daily Versus Alternate Day Iron Supplementation for the Treatment of Iron Deficiency Anemia in Pregnancy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Daily Versus Alternate Day Iron Supplementation for the Treatment of Iron Deficiency Anemia in Pregnancy (NCT04594070), a randomized phase 4 study. The primary outcome is Difference in Hemoglobin Levels From Enrollment to End of Study.

2. Clinical Question

The planned question was whether hemoglobin levels changed from enrollment to the third trimester in pregnant women with iron deficiency anemia assigned to daily oral ferrous sulfate or an alternate-day schedule. The registry describes the target population as pregnant women in the first or second trimester with a diagnosis of iron deficiency anemia. It does not report how many participants met those criteria or how many were assigned to either arm.

This is a question about a measured blood value over time, not a reported comparison of completed treatment outcomes. The registry identifies randomized allocation and a parallel design, but it does not report the actual allocation sequence, arm sizes, adherence, or the number of participants with endpoint measurements. The trial record states that no data were collected because of early termination. Consequently, the planned comparison cannot be answered from the registry results.

3. Trial Design

The registry identifies NCT04594070 as a Phase 4 randomized trial with a parallel design and no masking. Its title describes a comparison of daily versus alternate-day iron supplementation for iron deficiency anemia in pregnancy. The listed sponsor is The University of Texas Medical Branch, Galveston. The recorded start date is 2020-10-27, primary completion date is 2024-01-12, and status is terminated.

The planned population was pregnant women in the first or second trimester with iron deficiency anemia. The record describes two oral ferrous sulfate regimens: 325 mg once daily, and 650mg once daily every other day. It does not report whether the total planned treatment duration, dose-taking instructions beyond those descriptions, or other aspects of treatment delivery were specified in the protocol. Those details should not be inferred from the brief arm descriptions.

Registry enrollment is 14. That figure is the recorded enrollment field; the record does not say how many participants were randomized, received treatment, or contributed measurements. Nor does it provide the number enrolled in each arm. The stated early termination and absence of collected primary outcome data mean the record contains no completed hemoglobin comparison.

Other listed outcomes include gastrointestinal side effects after 2-4 weeks of treatment, a complete blood count in the third trimester, enrollment measures of serum ferritin, total iron binding capacity and transferrin, use of intravenous iron supplementation, blood transfusion, and postpartum hemoglobin. The registry lists 16 outcome measures overall, but does not report results for them. It lists zero analyses. The reason for termination and details of any protocol changes are not reported in the registry record.

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: The protocol was terminated early due to low accrual.

Overall Study

Analysis population for the primary outcome, as defined in the registry: No data collected due to early termination.

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 Difference in Hemoglobin Levels From Enrollment to End of Study, measured over Baseline and again 8-9 months later (third trimester of pregnancy).

The primary endpoint is titled “Difference in Hemoglobin Levels From Enrollment to End of Study.” Hemoglobin is a blood measurement, and the registry says it was to be assessed by blood draw at enrollment and again in the third trimester, described as 8-9 months later. The endpoint therefore concerns change in a measured value between the initial assessment and a later pregnancy assessment. The record does not specify a unit, summary parameter, or measure of dispersion.

As a general statistical concept, a repeated measurement can describe whether a participant’s measured value changes over time. Comparing changes between randomized groups can address whether the observed trajectories differ under the assigned regimens, provided the endpoint is collected and the analysis is appropriately specified. A difference in change is distinct from a comparison of only the later measurements, because it also uses the initial values.

The registry does not report an observed endpoint value, a group-level change, or a between-group estimate. Instead, the primary outcome population field states, “No data collected due to early termination.” Thus the endpoint was planned and described, but there is no result from which to estimate the size or precision of a treatment-group contrast. The reason hemoglobin was chosen as the endpoint is not reported in the registry record; the general role of a blood measurement as a direct quantitative outcome does not establish the trial’s specific rationale.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a randomized, parallel-group trial with no masking. These design labels describe the intended structure, but they do not establish how randomization was generated or concealed, whether participants followed their assigned schedules, or how the outcome data would have been analyzed. Those details are not reported in the registry record.

What does randomization mean?

As a general statistical concept, randomization assigns participants to study groups using a chance-based procedure. Its purpose is to reduce systematic differences between groups at the time of assignment, including differences in measured and unmeasured characteristics. Randomization does not guarantee that groups will be identical, especially in a small study, and it cannot compensate for outcome data that were never collected. The registry says allocation was randomized, but the sequence-generation and allocation-concealment methods are not reported.

What does a parallel design mean?

In a parallel design, participants are assigned to one treatment group and followed in that group rather than being assigned to receive both regimens in sequence. This is a general description of the design label in the record. The record names daily and alternate-day oral ferrous sulfate arms, but does not report the numbers assigned to each or the follow-up status of participants.

What is the endpoint contrast?

The primary endpoint describes hemoglobin levels at enrollment and again in the third trimester, 8-9 months later. A general analysis of a repeated-measure endpoint might compare changes between groups, adjust for baseline values, or model measurements over time. These are alternative general approaches, not a description of what this trial planned to do. The analysis method, target estimand, and handling of baseline hemoglobin are not reported in the registry record. The endpoint field also does not provide a unit, parameter, or dispersion measure.

Why does precision matter?

In general, an estimate conveys the size and direction of a contrast, while a confidence interval describes its uncertainty under a specified analysis. A wide interval can reflect limited information or variable measurements; a narrow interval indicates greater precision under the model assumptions. Neither an estimate nor an interval is reported for this trial’s primary endpoint, so its precision cannot be assessed. The recorded enrollment of 14 does not by itself reveal the effective sample size for an endpoint analysis: the number randomized, number measured, and distribution between groups are not reported.

What would a significance test contribute?

As a general concept, a significance test evaluates how compatible the data are with a specified null hypothesis under a statistical model. It does not measure clinical importance, and it does not replace an estimate with uncertainty. No primary outcome test or p-value is reported. The record’s count of analyses is zero, and the statistical analysis plan, significance threshold, sidedness, and any adjustment strategy are not reported. It would therefore be inappropriate to assign a test result or infer a conclusion from the trial’s design description.

What is over-dispersion, and does it apply?

Generally, over-dispersion occurs when observed variability in data is greater than a statistical model assumes. It can matter for outcomes such as counts when a model’s variance assumptions affect standard errors and confidence intervals. The primary outcome is described as hemoglobin levels, but no distributional information, results, or analysis model is reported. There is no basis to say whether over-dispersion was assessed or relevant to the trial’s actual analysis. Any discussion of its potential role is general, not a finding from this record.

Can sample-size planning be interpreted?

In general, sample-size planning depends on a target effect, variability, significance level, allocation, and desired power, among other assumptions. A planning illustration is not an observed result and is not the same as observed power. The record’s stated illustration assumptions include a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of an observed effect. However, no primary endpoint effect is reported, so a trial-specific illustration based on an observed effect cannot be interpreted from this record. The trial’s own sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 16 outcome measures, including the primary hemoglobin endpoint and secondary outcomes covering gastrointestinal side effects, blood measurements, intravenous iron supplementation, transfusion, and postpartum hemoglobin. When a study evaluates multiple outcomes or multiple comparisons, general statistical practice considers the possibility that some findings may appear notable by chance. Prespecified outcome hierarchies or multiplicity adjustments can address particular questions, but neither the intended strategy nor the analysis plan is reported in the registry record. Since zero analyses are listed and no outcome results are reported, there are no reported tests to evaluate for multiplicity.

The primary outcome description refers to measurement at enrollment and again in the third trimester. The record does not report how repeated measurements, incomplete follow-up, or any additional outcome categories would have been handled analytically. The registry indicates that the primary outcome was not reduced to a single comparison in the available analysis information. No reported estimate or test permits assessment of a single prespecified contrast.

Missing-data handling is especially important when participants lack endpoint measurements, because the amount and reasons for missingness can affect the population represented by an analysis. Here, the primary outcome population field states that no data were collected due to early termination. The record does not describe participant-level missingness, follow-up attempts, imputation, or sensitivity analyses. It also does not identify an intention-to-treat, per-protocol, or other analysis population. These methods and populations are not reported in the registry record, so none should be presumed.

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

The record establishes that a randomized comparison was planned, not that a comparison was completed. Its primary endpoint was hemoglobin change from enrollment to the third trimester, but the registry explicitly states that no data were collected because of early termination. There is consequently no posted estimate showing the direction, size, or precision of any difference between the planned regimens.

This distinction matters because a missing result cannot be interpreted as a null result. A finding of little or no difference would require measured outcomes and an analysis capable of estimating the contrast. The registry supplies neither. Similarly, the absence of a reported p-value does not mean that a test was negative, and the zero entries in the adverse-event fields do not establish that no events occurred. They are values in the record, while outcome collection is described as absent.

The enrollment figure of 14 does not resolve these limitations. It does not identify the number randomized, the number assigned to each arm, or the number with follow-up measurements. No inference about adherence, tolerability, or comparative effects can be drawn from the enrollment field alone.

As a general statistical distinction, evidence about an effect requires both an estimate and a description of uncertainty, interpreted in light of study conduct and analysis choices. None of these outcome-based elements is reported for the primary comparison. The results therefore do not establish that either regimen is superior, equivalent, or inferior. They also do not establish that the planned secondary outcomes were measured or that safety outcomes were absent. The valid conclusion is limited to the registry’s account of a terminated trial with no collected primary endpoint data.

12. Why This Trial Matters Statistically

The statistical importance of this record lies in the difference between a registered research question and an answer supported by outcome data. The trial was designed to compare two dosing schedules using a repeated hemoglobin measurement, but early termination meant that the registry reports no primary data. A clearly specified question does not itself provide an effect estimate or establish how precisely the question could be answered.

The record also illustrates why enrollment, randomization, and analysis counts are not interchangeable. Enrollment is recorded as 14, while the number randomized, the arm-specific totals, and the number with complete outcome data are not reported. The registry lists zero analyses. Without these details, a reader cannot reconstruct participant flow or determine what information would have contributed to a group comparison.

More broadly, a trial’s status and outcome reporting shape what can be learned from its record. Termination and missing endpoint data limit the evidence available for both effectiveness comparisons and secondary questions. The absence of results should not be converted into a claim of no effect or no adverse events. It is a limitation of available information, not a statistical finding about the two regimens.

For biostatistical interpretation, the case emphasizes the need to distinguish protocol-level plans from observed results and to keep estimates, uncertainty, missingness, and analysis populations conceptually separate. Here, the planned endpoint and the parallel randomized design are identifiable, but the analysis choices and outcome evidence are not. That distinction supports a cautious account that is informative about the record while avoiding conclusions the data cannot support.

13. 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 is explicit: the primary outcome population field says no data were collected because of early termination. Without endpoint observations, there is no estimate or uncertainty interval for the planned comparison. The record does not state why the trial was terminated, so the reason and its implications cannot be assessed.

The enrollment figure is 14, but the record does not report how many participants were randomized, assigned to each arm, treated, followed, or assessed. It does not provide participant flow, baseline characteristics, adherence, treatment discontinuation, or reasons for missing measurements. These omissions prevent assessment of whether the planned groups were comparable in the enrolled sample or whether any data could support secondary analyses.

The primary endpoint has no reported unit, parameter, or dispersion measure. The registry describes the assessment times but does not report the statistical model, analysis population, missing-data procedure, covariate adjustment, or multiplicity strategy. A sample-size justification for the trial itself is not reported in the registry record. The available assumptions for an effect-based planning illustration do not supply an observed endpoint effect.

The secondary outcomes are listed without results. The recorded adverse-event fields contain zero counts for the listed categories in both arms, but the record’s statement about absent primary outcome collection means those entries cannot be treated as a complete account of observed safety. In combination, these limitations mean the registry supports description of the planned design and the lack of reported endpoint data, but not comparative estimates or broader conclusions about the regimens.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Daily Versus Alternate Day Iron Supplementation for the Treatment of Iron Deficiency Anemia in Pregnancy — NCT04594070.
• Registry record last updated 2024-06-24; status last verified 2024-06.
• Results first posted 2024-06-24.
• 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.

17. Record Summary

NCT04594070 is a Phase 4 randomized, parallel trial with no masking, sponsored by The University of Texas Medical Branch, Galveston. It planned to compare oral ferrous sulfate, 325 mg once daily, with 650mg taken once daily every other day in pregnant women with iron deficiency anemia. The primary endpoint was hemoglobin change from enrollment to the third trimester, described as 8-9 months later.

The registry records enrollment of 14, a start date of 2020-10-27, a primary completion date of 2024-01-12, and terminated status. It states that no primary outcome data were collected because of early termination. The registry lists 16 outcome measures and zero analyses, but does not report results for the primary or secondary outcomes. Arm-specific enrollment, participant flow, the reason for termination, and the trial’s statistical analysis plan are not reported in the registry record. No comparative effect or precision estimate can therefore be drawn from the posted results.