The Safety of Proctofoam-HC in the Third Trimester of Pregnancy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Safety of Proctofoam-HC in the Third Trimester of Pregnancy (NCT00405288), a registered phase not stated study. The primary outcome is Birth-weight.

2. Clinical Question

The central question concerns fetal safety in the context of third-trimester use. Birth weight is the primary outcome, while the listed secondary outcomes include gestational age at delivery, mode of delivery, prematurity, fetal distress, low birth weight at birth, and neonatal health. The registry describes the treatment group as women prescribed Proctofoam-HC® for hemorrhoid symptoms; it describes controls by their lack of exposure to a specified set of substances during pregnancy.

This is not a randomized comparison: the registry states that allocation was not stated. The groups therefore should not be assumed to be comparable in all relevant respects. Differences in participant characteristics, pregnancy circumstances, treatment selection, or other factors could influence birth weight. The record does not report adjustment methods or other information that would establish how such differences were handled.

The clinical question is consequently descriptive as well as comparative: what birth-weight outcomes were observed in each group, and how uncertain was their difference? The registry record does not report those outcome estimates, confidence intervals, or a statistical test result. It therefore does not permit a conclusion about the direction, size, or precision of the birth-weight comparison.

3. Trial Design

The registry record describes a completed study titled “The Safety of Proctofoam-HC in the Third Trimester of Pregnancy,” sponsored by The Hospital for Sick Children. The recorded start was 2006-11, and primary completion was 2009-11. Enrollment is listed as 408. The study’s stated purpose was to evaluate fetal safety following topical application of Proctofoam-HC® in the third trimester of pregnancy.

The design is not described as randomized. The registry explicitly notes that allocation was not stated and that the arms are not a like-for-like control comparison. One group comprised women in the third trimester who were prescribed Proctofoam-HC® aerosol foam for hemorrhoid symptoms. The control group comprised women in the third trimester who were not exposed during pregnancy to teratogens, Proctofoam-HC® or any of its components, or other topical corticosteroids or local anaesthetics. Because treatment was not assigned randomly according to the record, the groups may differ for reasons beyond the exposure of interest.

The primary outcome was birth weight, recorded in grams at delivery. The primary-outcome description says the comparison excluded seven pairs of twin pregnancies. It also gives a planning estimate of 200 patients per arm to detect a 200g difference in birth weight, at 80% power and an alpha of 5%. These are design-planning statements, not observed results or evidence that the planned power was achieved.

The record lists 12 outcome measures and 11 analyses. It names secondary outcomes concerning delivery, prematurity, fetal distress, low birth weight, and neonatal health. It does not report the results for those outcomes, the detailed analysis populations, or the statistical procedures used for the primary comparison. The status is recorded as completed, but completion status alone does not establish that every planned analysis was reported.

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: There were no significant events that occur before assignment of the enrolled patients to groups.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Estimated number of 200 patients per arm, to detect significant difference of 200g in birth weight at a power of 80% and alpha of 5%. Seven pairs of twin pregnancies were excluded from the comparison of birth weight.

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 Birth-weight, measured over until delivery.

The primary endpoint is birth weight: the weight of the baby measured in grams at the time of birth. It is described as a continuous measure, with the mean and standard deviation identified as the intended summary approach. The timeframe is until delivery.

Birth weight is used as an outcome relevant to the study’s stated aim of evaluating fetal safety during third-trimester exposure. Comparing group means can describe whether the average recorded weight differed between the treatment and control groups. The standard deviation describes how much individual birth weights vary around each group’s mean; it is not the uncertainty in the difference between group means.

For interpretation, a mean difference would need to be considered alongside its uncertainty and the way the comparison was conducted. A confidence interval, when reported, describes a range of values compatible with the data and the statistical model; it does not by itself establish a causal effect. In this case, the registry record does not report group means, standard deviations, a mean difference, a confidence interval, or a test result. The outcome’s definition and planning target are therefore available, but the actual birth-weight findings cannot be interpreted from the registry record.

The primary-outcome description notes that seven pairs of twin pregnancies were excluded from the birth-weight comparison. The record does not give further details about the handling of multiple births, missing measurements, or the number of births included in the analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Birth weight is a continuous outcome, and the record identifies the mean and standard deviation as its summary measures. The mean is the arithmetic average of the recorded birth weights in a group. The standard deviation describes the spread of individual measurements around that average. These quantities answer different questions: the mean describes the group’s central value, while the standard deviation describes variability among observations. Neither is reported for the study groups in the registry record.

What would a comparison of means show?

A comparison of means would quantify the average birth-weight difference between the Proctofoam-HC® and control groups. A positive or negative estimate would indicate the direction of the observed difference according to the chosen subtraction order. The size of the estimate would describe the difference in grams. Its interpretation would still depend on the study design, the precision of the estimate, and whether the groups were sufficiently comparable. The registry record does not report a mean difference or identify a subtraction convention.

A confidence interval is a general statistical way to express uncertainty around an estimate. It reflects the range of values compatible with the observed data under the analysis assumptions. A narrow interval indicates greater precision than a wide interval, but neither width nor location can be assessed without a reported interval. The registry record does not report a confidence interval for birth weight. A p-value, if available, would address compatibility with a specified null model; it would not establish clinical importance or prove a causal effect. No birth-weight p-value is reported.

Why does the design matter?

Random allocation can, in general, help balance measured and unmeasured characteristics between groups. The registry does not describe random allocation and states that allocation was not stated. It also warns that the arms are not a like-for-like control comparison. Therefore, an unadjusted difference, if one were reported, could reflect exposure, group differences, or both. Statistical adjustment can sometimes account for measured characteristics, but it cannot automatically remove bias from unmeasured factors. The registry record does not report whether adjusted analyses were conducted or which characteristics were considered.

The control group is defined by lack of exposure to teratogens, Proctofoam-HC® or its components, and other topical corticosteroids or local anaesthetics during pregnancy. This differs from simply assigning otherwise comparable participants to no treatment. The record does not report the reasons for control-group eligibility, group characteristics, or the methods used to make the groups comparable. This limits interpretation of any between-group contrast.

What does the planning statement mean?

The primary-outcome description estimates 200 patients per arm to detect a 200g birth-weight difference with 80% power and an alpha of 5%. In general, a power calculation is a design exercise: it estimates how likely a planned analysis would be to detect a specified effect under particular assumptions. It does not show that the effect occurred, and it does not describe the observed result. The listed 80% is a planning target, not observed power.

The record also describes sample-size illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. These are assumptions for planning illustrations, not a report of the trial’s original design. No numerical illustration results are reported in the registry record. The observed effect needed to interpret such illustrations is also not reported in the registry record, so their numerical implications cannot be assessed from the recorded information.

How should the safety counts be understood?

The registry lists serious adverse events and other adverse events by group, with 204 at risk in each group for each category and zero affected in each. These are counts as recorded, not estimates of comparative risk with uncertainty. A zero count does not show that the underlying risk is exactly zero; rare outcomes may not occur in a group even when their true probability is not zero. No confidence intervals or formal safety comparisons are reported. The death entries are not reported in the registry record.

General statistical interpretation also depends on the analysis population and data completeness. The registry record does not report how missing birth weights were handled, whether all eligible births were included, or whether the outcome analysis followed a prespecified population definition. It does not describe interim analyses, a detailed statistical analysis plan, or methods for multiple outcomes. These omissions matter because analytic choices can affect both estimates and uncertainty, especially when several outcomes are examined.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Proctofoam-HC®", "Control")
n   <- c(201, 201)
m   <- c(3406.9, 3487.7)
sp  <- c(452.7, 491.4)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Proctofoam-HC®  201  3406.900  452.700  3343.935  3469.865
CARM  Control  201  3487.700  491.400  3419.353  3556.047

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 12 outcome measures and 11 analyses, with birth weight identified as the primary outcome and several additional delivery and neonatal outcomes listed as secondary. It does not report a multiplicity strategy, such as whether testing was limited to a prespecified primary comparison or whether significance thresholds were adjusted across outcomes. In general, examining multiple outcomes can increase the chance of at least one apparently unusual result. Without a reported strategy, the interpretation of any secondary statistical tests would require caution. The registry record does not report the results of those secondary outcomes.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how many birth-weight measurements were available, how incomplete records were handled, or whether exclusions beyond the stated exclusion of seven pairs of twin pregnancies applied to the primary comparison. It also does not report whether the analysis included all enrolled participants or a defined subset. Enrollment of 408 should not be read as the number included in the birth-weight analysis.

The record does not report an interim-analysis plan, stopping rules, or a detailed statistical analysis plan. It also does not report whether any analyses were adjusted for participant characteristics. These are unknowns rather than evidence that a particular method was or was not used. Without information on outcome completeness, analytic populations, multiplicity, and adjustment, it is not possible to evaluate the full analysis process or determine how robust a reported result would be. Since comparative birth-weight results themselves are not reported, no estimate can be checked against alternative assumptions about missing data or multiple testing.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

For the Proctofoam-HC® group, the registry lists zero serious adverse events among 204 at risk and zero other adverse events among 204 at risk. For the control group, it likewise lists zero serious adverse events among 204 at risk and zero other adverse events among 204 at risk. These are the recorded counts in the registry; they are not estimates of the probability of an event in all similar pregnancies.

A count of zero means no events are listed for that category in the recorded group. It does not establish that the underlying event risk is zero. Rare events may be absent from a particular group even when risk remains, and event counts alone do not provide an uncertainty interval or a formal comparison between groups. The registry record does not report confidence intervals or a statistical safety analysis for these counts.

The death entries are not reported in the registry record. The listed adverse-event counts also do not replace the missing birth-weight results, and they do not resolve whether the treatment and control groups were comparable. The record’s nonrandomized comparison and the way the control group was defined remain relevant when interpreting any safety contrast.

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

The registry record shows that a study was conducted to evaluate fetal safety in relation to topical Proctofoam-HC® use during the third trimester, with birth weight designated as the primary outcome. It describes a treatment group, a defined control group, a planning target for the birth-weight comparison, and recorded adverse-event counts. It also identifies secondary outcomes covering gestational age at delivery, mode of delivery, prematurity, fetal distress, low birth weight, and neonatal health.

It does not report the group birth-weight summaries or an estimated difference. There is therefore no basis in the registry record for describing whether birth weight was higher or lower in either group, how large a difference might have been, or how precisely it was estimated. The planned detectable difference of 200g is not an observed difference. Likewise, the planning target of 80% power is not evidence that the study achieved that power or that the planned effect was present.

The zero adverse-event counts are limited to the categories and groups recorded. They do not establish the absence of all possible adverse outcomes or show that risks are identical between groups. Deaths are not reported in the registry record, and results for the listed secondary outcomes are not reported.

The design further limits causal interpretation. The registry does not describe random allocation and explicitly notes that allocation was not stated and that the groups are not a like-for-like control comparison. Even if outcome estimates were available, differences between groups could be related to factors other than the treatment. The record does not report adjustment methods that would address this concern.

Accordingly, the available information describes the study’s question and some design and safety details, but it does not establish a birth-weight result or a causal treatment effect. Missing results should not be interpreted as evidence of no difference, nor should the planning assumptions be mistaken for observed outcomes.

14. Why This Trial Matters Statistically

This study raises a practical statistical issue: a clinically relevant question and a stated primary outcome do not by themselves allow readers to evaluate the evidence. For birth weight, interpretation requires the group summaries or a direct estimate of the difference, together with information about uncertainty. The registry record gives the outcome definition and planning target but does not report those results. Readers therefore cannot assess the size or precision of the comparison.

The study also illustrates why the comparison structure matters. The registry says allocation was not stated and that the arms are not a like-for-like control comparison. In general, nonrandomized groups may differ in ways related to the outcome. An estimate can then combine the association with treatment and the effects of group differences. Statistical methods may address some measured differences, but the registry does not report whether adjustment was used, and adjustment cannot guarantee removal of unmeasured confounding.

Planning information is useful when kept in its proper role. The estimate of 200 patients per arm for detecting a 200g difference, at 80% power and an alpha of 5%, describes a design target. It is not a substitute for the eventual results and should not be interpreted as evidence that a difference was found. Distinguishing planning assumptions from observed outcomes is essential to avoid treating a study’s intended sensitivity as a finding.

Finally, zero recorded adverse-event counts need careful framing. They are descriptive counts, not proof of zero underlying risk, and they do not supply precision estimates. The record’s missing primary and secondary results, analysis details, and completeness information show why transparent reporting of estimates, uncertainty, populations, and methods is central to statistical interpretation.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most direct limitation is that comparative birth-weight results are not reported in the registry record. Group means, standard deviations, a difference estimate, confidence interval, and test result are absent. Without them, the primary outcome cannot be assessed for direction, magnitude, or precision. Results for the listed secondary outcomes are also not reported.

The registry identifies the comparison as nonrandomized and says allocation was not stated. It further cautions that the arms are not a like-for-like control comparison. The control group is defined by lack of exposure to specified substances, while the treatment group comprises women prescribed Proctofoam-HC® for hemorrhoid symptoms. The record does not provide baseline characteristics or explain whether statistical adjustment was used, limiting assessment of comparability and potential confounding.

The primary-outcome description states that seven pairs of twin pregnancies were excluded from the birth-weight comparison. The registry does not explain the handling of other multiple births or provide the number of birth-weight observations analyzed. It does not report the extent or handling of missing outcome data, analysis populations, or exclusions beyond the twin-pregnancy statement. Enrollment of 408 cannot therefore be treated as the analysis sample size.

The record also does not report a multiplicity approach for the 12 outcome measures and 11 analyses, a detailed statistical analysis plan, interim analyses, or outcome-specific uncertainty estimates. The serious and other adverse-event entries list zero affected in each group, but no uncertainty intervals or comparative safety analysis are reported; deaths are not reported in the registry record. These limitations concern what can be learned from the registry record and should not be taken as evidence that any unreported method or result had a particular value.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Safety of Proctofoam-HC in the Third Trimester of Pregnancy — NCT00405288.
• Registry record last updated 2014-02-05; status last verified 2014-01.
• Results first posted 2014-02-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed, nonrandomized study of Proctofoam-HC® use in the third trimester of pregnancy, sponsored by The Hospital for Sick Children. It lists enrollment of 408 and identifies birth weight in grams at delivery as the primary outcome. The control group was defined by non-exposure to specified substances during pregnancy; the registry notes that allocation was not stated and that the arms are not a like-for-like control comparison.

The primary-outcome description gives a planning estimate of 200 patients per arm to detect a 200g difference at 80% power and an alpha of 5%, and notes exclusion of seven pairs of twin pregnancies from the birth-weight comparison. Group birth-weight results, analysis populations, missing-data methods, and comparative estimates are not reported in the registry record. Serious and other adverse-event counts are recorded as zero affected among 204 at risk in each group for each category. Deaths and results for the listed secondary outcomes are not reported in the registry record.