Lyophilized Black Raspberries in Adults With Familial Adenomatous Polyposis (FAP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Lyophilized Black Raspberries in Adults With Familial Adenomatous Polyposis (FAP) (NCT00770991), a randomized phase 1 study. The primary outcome is Change From Baseline to End of Study in Number of Rectal Polyps.

2. Clinical Question

3. Trial Design

This was a Phase 1, randomized, unmasked, parallel-group pilot study sponsored by The Cleveland Clinic. The registry lists the condition as familial adenomatous polyposis and describes a 36-week dietary intervention. The recorded study start is 2005-12, primary completion is 2008-09, and status is completed.

The intervention compared a black raspberry slurry plus black raspberry suppositories with placebo slurry plus black raspberry suppositories. The arm descriptions specify 20 grams of the assigned slurry BID and two, 730 mg suppositories HS. The intervention listing also names black raspberry slurry, black raspberry suppositories, and placebo slurry. The registry does not report further details about treatment adherence or how the interventions were administered beyond these descriptions.

Before treatment, participants were to undergo colonoscopy or sigmoidoscopy to determine eligibility. At 36 weeks after treatment initiation, eligible participants were to undergo sigmoidoscopy. The study description says rectal polyp size and number would be documented, and identifies percentage reduction in rectal polyp number between baseline and 36 weeks as an efficacy outcome. The posted primary result is instead expressed as mean change in number of rectal polyps.

The registry records enrollment of 34, while the posted primary outcome gives 7 participants in each treatment arm and an all-participants group of 14. The registry record does not explain the difference between enrollment and the outcome-analysis group sizes, or report participant flow, exclusions, or reasons for missing outcome data. The planned comparison and analysis population are not reported in enough detail to determine how all randomized participants were handled.

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: After potentially eligible subjects signed the informed consent, a physical examination with medical history and colonoscopy or sigmoidoscopy was performed as indicated. Blood and urine samples were collected. Subjects with adequate rectal polyp burden and laboratory results within study guidelines were eligible to be randomized.

Overall Study

Reasons for not completing this period:

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 Change From Baseline to End of Study in Number of Rectal Polyps, measured over Baseline and 36 weeks.

The primary endpoint is change from baseline to the end of the study in the number of rectal polyps, measured in polyps. The stated timeframe is baseline and 36 weeks. The registry describes assessment by sigmoidoscopy at 36 weeks, following baseline colonoscopy or sigmoidoscopy for eligibility, and says polyp size and number were to be recorded.

Polyp count is a continuous outcome in the posted results because each participant’s change can take a range of numeric values. The registry reports group means and standard deviations for this change. A negative mean indicates that the recorded number at follow-up was lower on average than at baseline, under the usual interpretation of change as follow-up minus baseline. The posted summaries do not show the distribution of individual changes or whether a small number of participants had especially large changes.

Using change from baseline can describe how the measured polyp count moved over the study period. It does not, by itself, establish that a difference between groups is attributable to treatment. That interpretation depends on a direct between-group comparison, its uncertainty, and the analysis methods. The registry record does not report a confidence interval or an estimated two-arm contrast for this endpoint.

The protocol description also mentions percentage reduction in polyp number as an efficacy outcome, but the posted primary result is a mean change in the number of polyps. Those are different ways of expressing an outcome. The registry does not report a primary-outcome definition that resolves the distinction or explain how the posted mean-change analysis relates to the percentage-reduction wording.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical trial results can include both descriptive summaries and inferential analyses. Descriptive statistics show what was observed in the groups, while an inferential analysis evaluates a specified comparison and quantifies how compatible the data are with a statistical model or null hypothesis. For this endpoint, the registry posts means and standard deviations for change from baseline, along with a Wilcoxon (Mann-Whitney) test and p = 0.065. It does not post a direct two-arm effect estimate or confidence interval.

What do the means and standard deviations describe?

A mean is the arithmetic average of the observed changes for participants included in a group. The standard deviation describes the spread of individual observations around that group average. A larger standard deviation signals more variation in the observed changes, but does not by itself indicate whether a mean difference between groups is statistically reliable. The posted means are -5.4 for suppositories plus placebo slurry and -1.6 for slurry plus suppositories. Their standard deviations are 5.3 and 9.2, respectively. The registry does not provide individual participant values, so the distribution and influence of individual observations cannot be examined from these summaries.

The all-participants mean and standard deviation describe the posted combined outcome group. They do not express the contrast between randomized arms. A pooled summary may provide a general description of observed change, but it cannot show whether assignment to one regimen rather than the other is associated with a different outcome.

What does the Wilcoxon (Mann-Whitney) test do?

In general, the Wilcoxon rank-sum test, also called the Mann-Whitney test, compares the ordering of observations between groups rather than directly comparing arithmetic means. It is often used when an analysis focuses on ranks or when distributional assumptions for a mean-based test are a concern. Its interpretation depends on the analysis design and the distributions being compared. It is not automatically a test of mean difference.

The registry labels the reported method as Wilcoxon (Mann-Whitney), but associates the analysis with the all-participants group. It does not identify the two groups entered into the test or state the parameter being tested. Therefore, the registry record does not support a confident interpretation of p = 0.065 as a test of the randomized-arm contrast. The record also does not provide enough detail to determine whether the test was selected in advance or how it relates to the posted mean-change summaries.

How should a p-value be read?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the chosen statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. Its meaning requires knowing the hypothesis, analysis groups, test specification, and assumptions. For this study, p = 0.065 is reported, but the registry record does not fully identify the comparison attached to it. It should therefore be reported as the registry’s analysis result without assigning it a more specific interpretation than the record supports.

Why does a confidence interval matter?

In general, a confidence interval gives a range of values compatible with an estimate under a stated statistical procedure. It communicates precision as well as the direction and magnitude of an estimated effect. A narrow interval indicates greater precision than a wide interval, while an interval spanning values on both sides of no difference can reflect uncertainty about direction. No confidence interval for the randomized-arm contrast is reported in this registry record. The group standard deviations are not substitutes for such an interval because they describe within-group spread, not uncertainty around the between-group effect.

What are the planning illustrations?

In general, a sample-size planning illustration estimates how many participants per arm might be needed to detect a specified effect under stated assumptions. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of the observed effect. These are planning illustrations based on the observed effect, not a record of the trial’s original design justification and not observed power. The registry record does not report the trial’s own sample-size justification or enough information to treat the planning assumptions as its protocol analysis plan.

Such illustrations are sensitive to the observed effect: a smaller target effect generally requires more information to detect than a larger one, all else equal. When the observed effect is estimated from a small pilot, it can be unstable. Accordingly, planning based on it should be treated as exploratory rather than as a definitive estimate of the sample size needed for a future study. No sample-size illustration values are interpreted as observed trial results.

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("Lyophilized Black Raspberry (BRB) Suppositories Pl", "Lypholized BRB Suppositiry Plus BRB Slurry")
n   <- c(7, 7)
m   <- c(-5.4, -1.6)
sp  <- c(5.3, 9.2)
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  Lyophilized Black Raspberry (BRB) Suppositories Pl  7  -5.400  5.300  -10.302  -0.498
CARM  Lypholized BRB Suppositiry Plus BRB Slurry  7  -1.600  9.200  -10.109  6.909

11. Analyses Reported by the Sponsor

The registry reports the sponsor-associated analysis as a Wilcoxon (Mann-Whitney) test with p = 0.065 and a 95% confidence level listed, but no confidence-interval limits or test parameter are posted. The analysis is associated with the all-participants group. The record does not identify a direct two-arm estimate from this test, so it cannot be directly matched to a recalculated treatment contrast.

The registry also indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. Consequently, there is no posted two-arm recalculation to compare with the sponsor’s analysis. The record does not flag a discrepancy. The sponsor’s reported analysis remains the available inferential result, but the missing comparison details limit what can be concluded from it.

The means and standard deviations by arm are descriptive results and should not be mistaken for the sponsor’s direct test of an arm difference. A valid comparison requires a defined contrast and an analysis appropriate to the study’s outcome and data. The registry does not report enough detail to establish that the p-value evaluates the difference between the two assigned regimens.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of change from baseline to end of study in number of rectal polyps and a secondary outcome concerning apoptosis and cell proliferation measured by percent difference in staining. It also records three outcome measures and three analyses. The record does not explain how these measures and analyses map to the stated primary and secondary outcomes, or identify a hierarchy of hypotheses.

When a study tests multiple outcomes, time points, groups, or statistical models, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity procedures may control that risk, but the registry record does not report whether any adjustment was planned or used. The record also does not report interim analyses or a statistical analysis plan. Those details should not be inferred from the number of listed outcomes or analyses.

The record does not report how missing outcome data were handled, whether any participants lacked follow-up measurements, or whether the analysis used an intention-to-treat, per-protocol, or other analysis population. The posted group sizes are 7, 7, and 14, while registry enrollment is 34; no participant-flow explanation connects these figures. It is therefore not possible to assess whether the outcome summaries represent all randomized participants, a subset with observed measurements, or another defined group.

In general, missing data can affect both the estimated outcome and its uncertainty, especially when the reasons for missingness are related to treatment or outcome. Without participant-level flow, missingness information, and an analysis-population definition, the robustness of the posted results cannot be assessed. The registry record does not report imputation methods, sensitivity analyses, or other approaches to missing data.

13. 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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: small bowel obstruction (8.3%).

The registry reports serious adverse events for two safety groups. In the group titled Black Raspberry Placebo Slurry Plus 2 Berry Suppositories, 0 serious adverse events are reported among 12 at risk. In the group titled Black Raspberry Slurry Plus 2 Berry Suppositories, 1 serious adverse event is reported among 12 at risk. The top serious-event term is Small Bowel Obstruction, listed at 8.3%.

These figures describe the safety entries recorded in the registry; they do not establish whether an event was caused by treatment. The registry does not give enough detail in these entries to determine the relationship of the listed serious-event term to the treatment groups or the event’s clinical course. Deaths are not reported in the registry record.

Other adverse events are reported for 7 participants among 12 at risk in the placebo-slurry group and 10 among 12 at risk in the black-raspberry-slurry group. The registry’s summary does not provide further event-level detail. Safety counts from a pilot study should be read as descriptive observations, not as precise estimates of event risk or as a basis for comparing safety between regimens.

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

The results describe rectal-polyp count changes recorded during a 36-week pilot study. The posted arm means are negative, indicating lower average counts at follow-up than at baseline under the usual change-score convention. The mean change was -5.4 in the suppository-plus-placebo-slurry group and -1.6 in the slurry-plus-suppository group. These summaries show observed changes in the outcome groups, but do not by themselves establish that the regimens differed.

The registry does not report a direct estimate of the difference between randomized arms or a confidence interval for that effect. It reports p = 0.065 for a Wilcoxon (Mann-Whitney) analysis associated with all participants, without specifying the comparison in sufficient detail. That result cannot be treated as a definitive test of the randomized-arm contrast based on the registry record alone.

The posted data also do not establish whether any observed change was clinically meaningful, how consistently participants changed, or whether the results would apply beyond the participants represented in the outcome summaries. The group sizes are small, and no individual-level outcome data, participant flow, or missing-data methods are reported. The secondary outcome is named, but its results are not reported in the registry record.

These findings are not evidence that a regimen does or does not work. They are limited registry results from a pilot study, with descriptive group summaries and incomplete information about the inferential comparison. The record does not report longer-term outcomes, and the primary endpoint concerns polyp number rather than broader clinical outcomes. Interpretation should remain tied to what was measured and posted.

15. Why This Trial Matters Statistically

This trial illustrates why the distinction between within-group change and between-group effect matters. A group can show a negative mean change from baseline, but a treatment comparison asks whether the change differs between assigned regimens. The registry posts arm-specific means and standard deviations, yet does not post a direct treatment-effect estimate or its confidence interval. The descriptive summaries therefore cannot answer the comparative question on their own.

It also shows the importance of knowing which observations a test compares. A p-value has meaning only in relation to a specified hypothesis and analysis. Here, the reported Wilcoxon (Mann-Whitney) result is associated with the all-participants group, while the tested groups and parameter are not clear in the registry record. Without that information, the result should not be assigned a more specific interpretation than the registry supports.

The record separates enrollment from the group sizes reported for the primary outcome but does not explain the relationship. This makes participant flow and analysis populations central to interpretation, rather than administrative details. Knowing who was included, who was missing, and why would help assess how representative the outcome summaries are of the randomized study population.

As a pilot, the study also highlights the difference between exploratory planning and definitive evidence. Planning illustrations based on an observed effect can inform future study design, but are not observed power and can be unstable when based on limited data. Clear reporting of the estimand, analysis population, uncertainty interval, and missing-data approach would make the evidence easier to interpret and use in subsequent research.

16. 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 registry record leaves key details about the primary-outcome analysis unresolved. It does not report a direct two-arm estimate, confidence interval, or a clear description of the comparison underlying the Wilcoxon (Mann-Whitney) p-value. Although group means and standard deviations are posted, these descriptive values do not provide the uncertainty around the treatment contrast.

The outcome group sizes do not match the recorded enrollment, and the registry does not report participant flow or explain how participants entered the analysis groups. It is not possible to determine from the registry record whether the primary results include all randomized participants, only those with follow-up measurements, or another population. Reasons for missing outcomes and methods for handling missing data are not reported.

The intervention descriptions and safety group titles use related but not identical wording. The registry describes both efficacy arms as including black raspberry suppositories, with active or placebo slurry, while the safety entries refer to berry suppositories. The record does not provide further detail to reconcile these labels. The study is also unmasked, so the record does not establish whether outcome assessment or other procedures were protected from knowledge of treatment assignment.

The protocol summary mentions percentage reduction in polyp number, whereas the posted primary result is mean change in number of polyps. The registry does not explain this difference. It also does not report results for the listed apoptosis and cell-proliferation outcome, or a statistical analysis plan, multiplicity procedure, or the trial’s sample-size justification. These omissions limit assessment of prespecification, precision, and the completeness of outcome reporting.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Lyophilized Black Raspberries in Adults With Familial Adenomatous Polyposis (FAP) — NCT00770991.
• Registry record last updated 2016-02-15; status last verified 2016-02.
• Results first posted 2016-02-15.
• 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.

20. Record Summary

NCT00770991 is a completed, randomized, unmasked, parallel-group Phase 1 pilot study sponsored by The Cleveland Clinic. It investigated lyophilized black raspberries in adults with familial adenomatous polyposis over 36 weeks. The primary outcome was change from baseline to end of study in number of rectal polyps.

The registry posts mean changes of -5.4 and -1.6 in the two treatment arms, with 7 participants in each arm, and an all-participants mean of -3.5 for 14 participants. It reports a Wilcoxon (Mann-Whitney) p-value of 0.065, but does not establish that this is a direct test of the randomized-arm contrast. No two-arm effect estimate or confidence interval is reported. Participant flow, analysis-population definitions, and missing-data methods are not reported in the registry record.