DFA-02 in Patients Undergoing Colorectal Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for DFA-02 in Patients Undergoing Colorectal Surgery (NCT01496352), a randomized phase 1, phase 2 study. The primary outcome is Number of Patients With Adverse Events, Laboratory, Physical Examination Changes.

2. Clinical Question

This is a safety-focused dose-escalation study, not a record of a definitive test of whether DFA-02 prevents surgical site infection. Incidence of surgical site infection appears among the secondary outcomes, alongside maximal plasma concentration, renal function, and antibiotic resistance. The primary endpoint instead captures participants with adverse events or changes in laboratory or physical examination findings. Its scope is therefore broader than any one named clinical event, and the registry record does not show how those different types of findings were categorized or analyzed separately.

The study combines randomization and placebo control with progressive dose cohorts. Those features describe the intended comparison and dose-escalation structure, but they do not by themselves establish that a particular dose is safer or more effective. The posted record gives serious adverse event counts by treatment group, but it does not report a primary-endpoint treatment effect, confidence interval, or statistical test. The clinical question that can be addressed from the registry is consequently limited to describing the recorded study design and safety counts, not estimating a conclusive treatment effect.

3. Trial Design

The registry describes a randomized, double-blind, placebo-controlled, parallel-group study with quadruple masking. It lists both Phase I and Phase II; the brief summary calls it a Phase II study. The stated purpose was to evaluate the safety, tolerability, and pharmacokinetics of DFA-02 in patients undergoing colorectal surgery. The sponsor is Dr. Reddy's Laboratories Limited. The study is marked completed, with 30 participants enrolled.

The arm description specifies progressive cohorts of 10 subjects, with 8 receiving active treatment and 2 receiving placebo, at DFA-02 dose levels of 10, 20, 30 or 40 mL. Placebo is described as matching. The posted safety counts are organized as DFA-02 and DFA-02 Placebo, with 24 and 6 participants at risk, respectively. The registry record does not explain how participants were assigned among dose cohorts, nor does it provide a separate outcome comparison for each dose.

The primary outcome is a participant count for adverse events or changes in laboratory or physical examination findings from baseline through Day 30. The application of DFA-02 is described as occurring during surgery on Day 1. Secondary outcomes include pharmacokinetic and other safety-related measures, as well as incidence of surgical site infection. The registry lists six outcome measures but no analyses. The enrollment total and the as-treated group counts describe different aspects of the record; the latter are the denominators attached to the posted adverse-event data.

The registry lists study start as 2012-02 and primary completion as 2013-04. It does not report the method used to generate the random sequence, the allocation concealment procedure, or which roles were included in quadruple masking. Detailed dose-escalation rules, planned comparisons, and the statistical analysis plan are also 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: As Treated

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 Number of Patients With Adverse Events, Laboratory, Physical Examination Changes, measured over Baseline up to Day 30.

The primary endpoint is the number of patients with adverse events or changes in laboratory or physical examination findings, measured from baseline up to Day 30. DFA-02 application during surgery on Day 1 is identified as the start of treatment. The outcome unit is participants, and the population is listed as As Treated.

A participant count is useful in a safety study because it describes how many people experienced at least one finding within the endpoint's scope. It is not the same as a count of all individual events: a person may have more than one event, while the endpoint title focuses on patients. Nor does a participant count, by itself, describe severity, duration, clinical importance, or whether investigators considered a finding related to treatment.

The endpoint brings together adverse events and laboratory or physical examination changes. These can capture different kinds of safety information, so interpretation depends on how the study defined and grouped them. The registry record does not report category-specific primary-outcome counts, detailed definitions, or a treatment-effect estimate for the endpoint. It also does not report a single comparison reduced to one outcome, noting that the primary outcome has several categories or time points and was not reduced to one comparison.

Safety and tolerability endpoints are used to characterize observed findings during a specified follow-up period. They do not, without additional comparative analysis and appropriate uncertainty estimates, establish whether observed differences are attributable to treatment. The posted information supports a description of the endpoint's purpose and timeframe, but not a conclusion about comparative safety from the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how outcomes are defined, compared, and expressed with uncertainty. For this study, the registry record provides the design description and adverse-event counts, but reports no analyses. It does not report a detailed statistical analysis plan, a primary-endpoint effect estimate, or inferential results. The methods discussion must therefore distinguish general statistical principles from methods documented for this study.

What does randomization contribute?

In general, randomization assigns participants to study groups by chance. When implemented as intended, it can reduce systematic differences between groups at the start of a study. It does not guarantee that groups will be identical, particularly in a small study, and it does not eliminate the need to report group characteristics, outcome definitions, and analysis methods. The registry describes the study as randomized, but the random-sequence method and allocation concealment are not reported in the registry record.

What does masking contribute?

In general, masking can reduce the chance that expectations influence care, outcome assessment, or reporting. The record labels the study quadruple-masked and double-blind in its title and brief description. It does not specify which four roles were masked, how masking was maintained, or whether it was assessed. Those details matter when considering how outcome information might have been collected, especially for outcomes that involve judgment.

How should participant counts be read?

The primary outcome is defined as the number of participants with adverse events or changes in laboratory or physical examination findings. For a participant-level endpoint, a count generally reflects people meeting a specified event definition, rather than the total number of event occurrences. Clear rules are needed for deciding what qualifies, how multiple findings for one person are handled, and whether events are grouped by severity or type. Those rules and category-level primary results are not reported in the registry record.

In general, a comparative analysis might express a difference or ratio between groups and accompany it with a confidence interval. A confidence interval describes the range of values compatible with the data under the analysis assumptions and conveys precision; it is not a guarantee that the true effect lies within the interval. No primary-endpoint estimate or confidence interval is reported for this study. No p-value for a primary comparison is reported either. Without these results, the posted counts should not be turned into a claim of statistical significance or lack of significance.

Why do group size and dose matter?

The safety counts are presented for a DFA-02 group and a placebo group, while the design also describes progressive dose cohorts. When dose levels are part of a study, pooling participants across doses can conceal differences among dose groups. Conversely, separating the data by dose can leave few observations in each group and make estimates imprecise. The registry does not provide dose-specific outcome results or explain how dose was incorporated in an analysis. The posted aggregate counts therefore cannot characterize dose-response patterns.

In general, unequal group sizes affect precision: the smaller group often contributes less information to a comparison. A raw count should be read with its denominator, but a count and denominator still do not communicate the full uncertainty around a treatment comparison. Statistical methods may account for study design and prespecified factors, but the methods used for such adjustments are not reported in the registry record.

What do planning calculations mean?

General sample-size planning asks how many participants would be needed to detect an effect under specified assumptions, such as a target effect, significance level, allocation, and statistical model. The registry's planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the target effect is stated as a fraction of the observed effect. These calculations are planning illustrations, not observed power and not the study's own sample-size justification. They do not change the fact that 30 participants were enrolled, and they do not demonstrate that the trial was adequately powered for a particular endpoint.

In general, analyses of binary outcomes depend on event definitions and how the comparison is specified. When event rates vary substantially across groups or are very low, the suitability of a normal approximation may require consideration. This is a general methodological point, not a finding about the analysis performed in this study. No model, adjustment, or inferential method for the posted binary adverse-event counts is reported.

Finally, a registry entry is a structured record of study information and posted results, not necessarily a complete statistical report. A reader can identify the endpoint, follow-up window, arms, and reported counts, while still lacking the information needed to reproduce an analysis or evaluate all modeling assumptions. In this case, the absence of reported analyses and primary-endpoint comparisons limits interpretation to the design and descriptive safety information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including a safety endpoint, pharmacokinetic measures, renal function, antibiotic resistance, and incidence of surgical site infection. When a study assesses multiple outcomes, time points, dose levels, or statistical comparisons, the chance of a seemingly notable result arising by chance can increase. General approaches to multiplicity include prespecifying a primary comparison, adjusting inference across selected tests, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or a detailed analysis plan.

The primary outcome is described as having several categories or time points and is not reduced to one comparison. This makes it especially important to know how categories and time points were intended to be handled. Those details are not reported, and no primary-outcome analysis is listed. It is not possible to determine from the registry whether any adjustment was planned or used.

The record identifies the primary-outcome population as As Treated, but does not report how participants with missing outcome data were handled, whether any participants were excluded from a particular analysis, or whether imputation was used. Missing-data methods can affect estimates when the chance of missingness is related to participant characteristics or outcomes. Without information about completeness and handling, the potential effect of missing data cannot be assessed.

Randomization is reported, but the registry does not give an intention-to-treat analysis population or explain how participants were assigned to analyses. The posted adverse-event denominators are 24 for DFA-02 and 6 for placebo; the record does not provide a participant flow account explaining exclusions or deviations. These omissions limit assessment of how closely the analyzed groups reflect the randomized groups.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: surgical site infection (16.7%), death (16.7%), bowel obstruction (4.2%), anastomotic leak (4.2%), post-operative bleeding (4.2%).

The registry reports serious adverse events for 5 of 24 participants in the DFA-02 group and 2 of 6 in the DFA-02 Placebo group. It also reports other adverse events for 23 of 24 and 6 of 6 participants, respectively. These are participant counts with the corresponding group denominators. They describe what was recorded; they do not establish that treatment caused an event or that one group had greater underlying risk.

The serious-event terms listed are Surgical Site Infection and Death at 16.7%, with Bowel Obstruction, Anastomotic Leak, Post-operative Bleeding, and Anastomotic Dehiscence at 4.2% each. The registry does not identify the group denominator for these term percentages or explain whether one participant could appear under more than one term. Group-level death counts are not reported. The listed Death term should not be interpreted as a count of deaths in either treatment arm.

Serious adverse events are not interchangeable with all adverse events, and the top-term list does not provide severity, timing, relatedness, or case-level detail. The registry's counts are descriptive and lack a reported comparative statistical analysis or uncertainty estimates. They are not sufficient on their own to establish a difference between groups.

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

The registry record establishes that DFA-02 was studied in patients undergoing colorectal surgery in a randomized, placebo-controlled, masked dose-escalation design. It identifies safety, tolerability, and pharmacokinetics as the study's aims, gives a Day 30 safety endpoint, and posts adverse-event counts for the DFA-02 and placebo groups. It also lists serious adverse event terms and secondary outcome topics.

What the record does not establish is a comparative effect on the primary safety endpoint. It does not provide a single primary-outcome comparison, an effect estimate, a confidence interval, or a statistical test. The absence of an inferential analysis is not evidence that the groups were the same, nor does it show that a difference exists. The record does not report the results for the secondary incidence-of-surgical-site-infection outcome or the other named secondary outcomes.

The posted group counts are descriptive, and the groups differ in size. The serious-event term percentages are not accompanied by a clear group-specific denominator in the record. Without analysis details, outcome definitions, and uncertainty estimates, the counts cannot be used to make a reliable comparative claim. They also do not establish that a particular event was caused by DFA-02 or placebo.

In general, a randomized study can support causal inference when its conduct, outcome measurement, and analysis are appropriate and adequately reported. Randomization and masking are important design features, but interpretation also depends on participant flow, missing data, outcome definitions, and the statistical plan. Several of those details are not reported in the registry record. The available information therefore supports a limited description of the study and its posted safety data, not a conclusion about treatment benefit, lack of benefit, or comparative safety.

Planning calculations based on an observed effect are not observed power and do not replace trial results. They illustrate sample sizes under specified assumptions; they do not retrospectively prove that the study could detect an effect. The record does not report the trial's own sample-size justification.

13. Why This Trial Matters Statistically

This study raises several important statistical issues that commonly arise in early dose-escalation research. Its purpose includes safety, tolerability, and pharmacokinetics, while its design includes multiple DFA-02 dose levels and a placebo group. A single pooled treatment count may not describe how findings vary across doses, but dose-specific comparisons can be difficult to estimate when each cohort is small. The registry does not provide dose-specific outcomes or explain how the planned analyses addressed this structure.

The primary endpoint combines adverse events with laboratory and physical examination changes. This breadth can be useful for capturing a range of safety signals, but it also makes transparent definitions and reporting important. A participant-level count can conceal differences in event type, severity, and timing. The registry identifies a follow-up period but does not report category-specific primary results or a single comparison.

Another statistical lesson is the distinction between descriptive evidence and inferential evidence. Counts tell readers what was recorded in each group; they do not by themselves show the precision of a comparison or whether observed differences could plausibly reflect chance variation. The absence of reported confidence intervals and analyses leaves that uncertainty unquantified. This is particularly relevant when the group sizes are unequal and the study is intended for dose escalation.

Finally, the study illustrates why registry results should be read alongside design details and reporting gaps. Randomization, masking, and a placebo comparator provide useful context, but a reader also needs participant flow, missing-data handling, endpoint definitions, and a prespecified analysis strategy to assess the strength of conclusions. Those details are not reported in the registry record. The available information is most informative as a description of study structure and posted safety counts.

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 limitation for interpretation is that the registry does not report a primary-outcome comparison or any analyses. The primary endpoint includes multiple types of findings and time points, and the record notes that it was not reduced to one comparison. No effect estimate, confidence interval, or test result is available to quantify the comparative safety findings.

The design describes progressive dose cohorts, but the record does not provide dose-specific participant counts or outcome results. Aggregate DFA-02 counts cannot show whether findings varied across the listed dose levels. The record also does not explain the dose-escalation decision rules or how dose was included in any analysis.

Several details needed to assess data quality and potential bias are not reported in the registry record: the random-sequence and allocation concealment methods, the roles included in quadruple masking, participant flow, missing-data handling, and any analysis population beyond the primary outcome's As Treated label. The definitions and category-level results for the broad primary safety endpoint are also not given.

The serious-event terms include percentages without a stated group-specific denominator, while group-level death counts are not reported. The posted counts do not include uncertainty estimates or a comparative analysis. The record does not provide enough information to determine how repeated events, severity, timing, or treatment relatedness were handled.

Finally, the registry lists secondary outcomes but does not report their results in the information available for interpretation. It also does not report the trial's own sample-size justification. These limitations prevent a full assessment of efficacy, comparative safety, precision, or the robustness of the study's conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: DFA-02 in Patients Undergoing Colorectal Surgery — NCT01496352.
• Registry record last updated 2014-09-01; status last verified 2014-08.
• Results first posted 2014-09-01.
• 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

NCT01496352 is a completed randomized, double-blind, placebo-controlled, quadruple-masked, parallel-group study of DFA-02 in patients undergoing colorectal surgery. The registry lists Phase I and Phase II and reports enrollment of 30 participants. Its stated focus is safety, tolerability, and pharmacokinetics, with progressive cohorts described at 10, 20, 30 or 40 mL and matching placebo.

The primary endpoint counts participants with adverse events or laboratory or physical examination changes from baseline through Day 30. The posted serious adverse event counts are 5 of 24 in the DFA-02 group and 2 of 6 in the placebo group. No primary-outcome comparison or statistical analyses are reported. Secondary outcomes include pharmacokinetic measures, renal function, antibiotic resistance, and surgical site infection incidence, but their results are not reported in the registry record.