PRevention Using EPA Against coloREctal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRevention Using EPA Against coloREctal Cancer (NCT04216251), a na phase 1, phase 2 study. The primary outcome is Change in the Marine Omega-3 Polyunsaturated Fatty Acid (MO3PUFA) Composition in Colorectal Tissues as a Result of the AMR101 Treatment..

2. Clinical Question

3. Trial Design

PREPARE, titled “PRevention Using EPA Against coloREctal Cancer,” is registered as a phase 1 and phase 2 study sponsored by Massachusetts General Hospital. The registry lists a single-group model, no masking, and allocation as NA. Enrollment is 81, and the study status is COMPLETED. The recorded start date is 2020-12-09, and the primary completion date is 2022-09-30.

The study evaluates AMR101 in individuals with a history of colorectal adenoma. The registry summary frames the research as an evaluation of AMR101 as a possible chemopreventive agent to reduce colorectal cancer risk. That framing describes the study's purpose; it does not establish a clinical effect. The record lists AMR101 as the intervention and identifies VASCEPA as the study drug name in the brief summary.

The listed study procedures include screening for eligibility, a lifestyle questionnaire, a nutritional survey, flexible sigmoidoscopy, biopsy sampling of normal colorectal mucosa, stool sampling, blood collection, evaluations, and follow-up visits. The procedure description also refers to a predetermined oral protocol, but the complete dosing details are not reported in the registry record.

The primary outcome is change in marine omega-3 polyunsaturated fatty acid composition in colorectal tissue, with a timeframe of 8-12 weeks. Secondary outcomes concern change in gut microbiome composition and change in fecal metabolite levels (butyrate). The registry lists three outcome measures overall, but does not report numerical outcome results or analyses. Because there is no control group, the design describes changes observed during treatment rather than a randomized comparison between treatment and control.

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

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.

Population: We have enrolled 81 healthy participants between the ages of 18 and 80 who have undergone screening or surveillance colonoscopy with removal of at least one adenoma and was not regularly using fish oil supplements or consuming more than 3 servings of fish per week.

6. Primary Endpoint

The registry lists the primary outcome as Change in the Marine Omega-3 Polyunsaturated Fatty Acid (MO3PUFA) Composition in Colorectal Tissues as a Result of the AMR101 Treatment., measured over 8-12 weeks.

The primary endpoint is the change in marine omega-3 polyunsaturated fatty acid composition in colorectal tissue following AMR101 treatment. The measure is expressed as a percentage of total fatty acids, and the registry specifies the mean as the summary parameter with standard deviation as its dispersion measure. Tissue fatty acid is extracted from biopsy material and measured using gas chromatography-mass spectrometry. The timeframe listed for this endpoint is 8-12 weeks.

This tissue measure is relevant to the study's stated biological question: whether treatment is associated with a change in the fatty acid composition of colorectal tissue. A tissue endpoint provides a measurement at the site of interest, while the specified laboratory method quantifies fatty acid composition in the sampled material. The registry record does not explain the choice of this endpoint in more detail, so its validation or relationship to later colorectal cancer outcomes is not reported in the registry record.

The word “change” implies a comparison of measurements over time, but the record does not provide baseline or follow-up means, an estimated change, a standard deviation for the observed change, or an uncertainty interval. It also does not report the analysis population used for the endpoint. As a result, the endpoint's definition and measurement method can be described, but the magnitude and precision of any observed change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean and standard deviation. In general, a mean represents the average value in the analyzed group, while a standard deviation describes how spread out individual measurements are around that average. These summaries answer different questions: the mean locates the group average, and the standard deviation describes variability among measurements. The registry record does not report the observed mean, the observed standard deviation, or an estimated change for this endpoint.

What does a change endpoint mean?

In general, a change endpoint compares measurements made at different times for the same outcome. The PREPARE record names change in tissue marine omega-3 polyunsaturated fatty acid composition and gives a timeframe of 8-12 weeks. It does not specify in the registry record the precise change calculation, the baseline and follow-up values, or how measurements with only one time point were handled. Those details matter because a change score is not interchangeable with a follow-up value: it depends on how the measurements and analysis are defined.

What does the measurement scale describe?

The primary outcome is stated as a percentage of total fatty acids. In general, expressing a component relative to a total describes its composition within that total, rather than its absolute amount alone. A compositional measure can change because the component of interest changes, because other components change, or both. The registry identifies the scale but does not report the underlying component values or further details about how the measured composition was analyzed. The biopsy-based measurement uses fatty acid extraction followed by gas chromatography-mass spectrometry, as recorded.

How should a confidence interval be read?

In general, a confidence interval describes the statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values on both sides of a reference value may leave several effect sizes compatible with the data. A confidence interval is not reported for the primary outcome in the registry record, so its precision cannot be evaluated. No p-value or other inferential test result for the primary endpoint is reported either.

What does the study design permit?

The registered model is single group, allocation is NA, and masking is none. In general, a single-group study can describe measurements observed among participants receiving an intervention, but without a concurrent control group it cannot directly estimate a between-group treatment contrast. A before-and-after pattern may be consistent with a treatment-associated change, but it does not by itself establish that treatment caused the change. The registry does not report an adjusted comparison or a causal analysis that would change this design limitation.

The planning assumptions are described as a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are assumptions for a planning illustration, not a description of the trial's single-group design. In general, such calculations estimate how many participants per arm might be needed under specified assumptions; they are not observed power and do not demonstrate that an effect was present. The record does not report the trial's own sample-size justification.

Why can over-dispersion matter?

In general, over-dispersion means the observed variability is greater than a statistical model expects. When a model assumes less variation than the data contain, its uncertainty estimates can be too small and its inferential results too confident. That concern is relevant when outcomes are modeled with a distribution whose variance is tied to its mean, such as count data. The primary endpoint in this study is described as a continuous compositional measure, and the registry does not report an analysis model or a finding of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was present or that a particular correction was used.

The registry lists two secondary outcomes: change in gut microbiome composition and change in fecal metabolite levels (butyrate). The record does not specify their analysis models, estimates, or inferential results. Across the listed outcomes, the registry provides insufficient information to evaluate model fit, covariate adjustment, handling of repeated measurements, or the robustness of any statistical conclusions. These are general considerations for interpreting outcome analyses; they are not claims about procedures used in PREPARE.

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("Pre-treatment", "Post-treatment")
n   <- c(59, 59)
m   <- c(0.54, 2.95)
sp  <- c(0.33, 1.65)
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  Pre-treatment  59  0.540  0.330  0.454  0.626
CARM  Post-treatment  59  2.950  1.650  2.520  3.380

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: the primary tissue fatty acid composition outcome and secondary outcomes concerning gut microbiome composition and fecal metabolite levels (butyrate). When a study evaluates multiple outcomes or performs multiple tests, the chance of at least one apparently notable result can increase. In general, a prespecified testing strategy or multiplicity adjustment can help readers understand how the analysis addressed that issue. The statistical plan for multiplicity, including whether an adjustment or outcome hierarchy was used, is not reported in the registry record. No outcome analyses are listed, so the record does not support assessment of how multiplicity affected results.

Missing-data methods are also not reported in the registry record. The enrollment count alone does not establish how many participants had usable biopsy measurements at each time point, whether any measurements were missing, or how missing observations were handled. The record does not state whether the analysis used complete cases, an imputation method, or another approach. These details affect interpretation because the analyzed participants may differ from everyone enrolled, and different assumptions about missing measurements can produce different estimates.

The analysis population is not described for the primary endpoint. The record does not specify whether participants were analyzed according to a planned population definition, whether adherence or follow-up requirements applied, or how exclusions were handled. With no reported analyses or numerical endpoint results, neither the consequences of missing data nor the population represented by an estimated change can be evaluated.

12. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ischemic right foot with thrombosis of right external iliac artery stent and common femoral artery (1.2%).

The registry reports serious adverse events for the AMR101 group, with 81 at risk and 1 affected; deaths are listed as 0. The serious event term is “Ischemic right foot with thrombosis of right external iliac artery stent and common femoral artery,” and the registry gives its frequency as 1.2%. These are registry counts and a reported percentage, not a comparison with an untreated group.

The record also lists 81 at risk and 20 affected for other adverse events. It does not provide event terms for those other events in the information recorded. The counts do not establish whether the same participants contributed to both the serious and other adverse-event categories, nor do they identify a cause. The registry information does not report a causal assessment or a control-group safety comparison.

Adverse-event counts should be interpreted separately from efficacy outcomes. They do not show whether the primary tissue composition measure changed, and they do not establish an effect on colorectal adenoma or colorectal cancer. The registry reports the counts, but further details about severity grading, event timing, relatedness assessment, or the method used to collect safety events are not reported in the registry record.

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

The registry record establishes that PREPARE was a completed, single-group study of AMR101 with enrollment of 81 and a primary endpoint focused on change in colorectal tissue fatty acid composition over 8-12 weeks. It also identifies how the tissue measure was obtained and lists secondary outcomes addressing gut microbiome composition and fecal butyrate. These details clarify the study question and its measurement approach.

The record does not report a numerical estimate of change in the primary outcome, its variability, a confidence interval, or a statistical test. Therefore, it does not establish whether the measured tissue composition increased, decreased, or remained similar during the study, nor how precisely any change was estimated. The listing of an endpoint and a completed status cannot substitute for reported outcome results.

The study's stated interest in possible chemoprevention should not be confused with a demonstrated reduction in colorectal cancer risk. The primary endpoint is a tissue fatty acid composition measure, not a reported cancer incidence result. The registry does not report a treatment effect on colorectal cancer, and the single-group design does not provide a randomized control comparison. No conclusion about efficacy or causality can be drawn from the available record.

The safety record lists one serious adverse event, a reported frequency of 1.2%, 20 affected for other adverse events, and zero deaths. These figures describe recorded events in the AMR101 group; without a comparison group and fuller safety details, they do not quantify comparative risk or establish cause. Overall, the registry supports a description of the study design, endpoint, and recorded safety counts, but not a conclusion about treatment benefit or the magnitude of an outcome effect.

14. Why This Trial Matters Statistically

PREPARE illustrates why a registered research question and a reported result are not the same thing. The registry gives a specific tissue endpoint, its measurement scale, laboratory method, and timeframe. Those details are useful for understanding what the study set out to assess. Yet the absence of a numerical endpoint estimate means readers cannot evaluate the direction, magnitude, or precision of the change under study.

The design also makes the choice of interpretation important. A single-group study can document what was observed among participants receiving AMR101, but it does not include a like-for-like control comparison. This distinction matters when readers encounter language about a treatment's possible purpose: an observed before-and-after pattern, even if reported, would not alone separate treatment effects from other changes over time or influences on measurement.

The registry's planning assumptions offer another statistical distinction. A two-arm equal-allocation calculation is a planning illustration, while the actual study is listed as single group. Planning calculations can describe sample-size implications under chosen assumptions, but they are not observed power and do not supply missing outcome evidence. Keeping design, planning, and observed results separate helps prevent a hypothetical calculation from being mistaken for a trial finding.

Finally, the registry's listed adverse-event counts answer a different question from the tissue endpoint. Safety reporting and efficacy estimation require their own interpretation, and the reported event counts do not establish causality or a comparative risk. Taken together, the record is a useful case in reading the boundaries of registry evidence: detailed endpoint and design information can coexist with no reported statistical outcome analysis.

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 central limitation for statistical interpretation is that no numerical results are reported for the primary endpoint, despite the record listing the study as completed. The registry lists zero analyses. Without an estimated change, a measure of variability, or an uncertainty interval, the primary outcome's direction, magnitude, and precision are unavailable. Numerical results for the secondary outcomes are also not reported in the registry record.

The single-group model and absence of masking limit the kinds of comparisons the design can provide. There is no registered control group for a direct treatment contrast, and the record does not report a blinded outcome assessment. A change over time, if one had been reported, could not by itself establish that AMR101 caused that change.

Additional details needed to assess the analysis are not reported in the registry record. These include the analyzed population, the number of participants contributing endpoint measurements, missing-data handling, the precise change calculation, the statistical model, and the approach to multiple outcomes. The treatment dosing details are incomplete in the record. The rationale for the endpoint and its relationship to later colorectal cancer outcomes are also not described there.

The listed safety information is limited to counts, a serious-event term and frequency, and deaths. The registry does not report event timing, relatedness, or further details for the other adverse events in the available record. These limitations prevent a fuller assessment of both outcome analysis and safety interpretation; they do not establish that unreported procedures or analyses were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PRevention Using EPA Against coloREctal Cancer — NCT04216251.
• Registry record last updated 2024-05-03; status last verified 2024-04.
• Results first posted 2024-02-14.
• 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

PREPARE (NCT04216251) is listed as a completed phase 1 and phase 2, single-group study sponsored by Massachusetts General Hospital. The registry records enrollment of 81, no masking, and allocation as NA. The study evaluated AMR101 in individuals with a history of colorectal adenoma.

The primary endpoint is change in marine omega-3 polyunsaturated fatty acid composition in colorectal tissue, measured as a percentage of total fatty acids over 8-12 weeks. Secondary outcomes address gut microbiome composition and fecal metabolite levels (butyrate). The record lists no outcome analyses and does not report numerical results for these measures.

For safety, the AMR101 group lists 1 serious adverse event among 81 at risk, a reported frequency of 1.2%, 20 affected for other adverse events, and 0 deaths. The record does not provide a control-group comparison.