Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection (NCT02589847), a non-randomized phase 2 study. The primary outcome is Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks.

2. Clinical Question

In statistical terms, the question is whether the observed outcome among evaluable RBX2660 participants can be meaningfully contrasted with the outcome in the retrospective antibiotic-treated control. The design can describe outcomes in the enrolled treatment group and report how they compare with historical experience. It cannot ensure that differences between groups reflect treatment alone: participants in the groups may differ in ways not controlled by random assignment. The record does not report an adjusted estimate, confidence interval, or formal test for the primary outcome. Consequently, the clinical question is clear, but the posted registry information does not quantify the primary outcome or its uncertainty.

3. Trial Design

This was a phase 2 study with a parallel-group structure, non-randomized allocation, and no masking. The study enrolled 272 participants and is recorded as completed. The registry dates the study start to 2015-10 and primary completion to 2017-06. Rebiotix Inc. is listed as the sponsor. The condition was Clostridium difficile infection.

The intervention arm was open-label RBX2660, described as microbiota suspension. The brief summary states that enrolled subjects received one treatment consisting of two doses. The other arm was a retrospective historical control receiving standard-of-care antibiotics. This distinction is important: the control was historical rather than a concurrently randomized comparator. The registry record explicitly warns that this is not a like-for-like control comparison.

In a non-randomized study, treatment assignment does not use random allocation to balance measured and unmeasured characteristics between groups. A historical comparison may therefore be affected by differences in participant characteristics, clinical practice, eligibility, outcome assessment, or the periods from which the groups were drawn. These are general design considerations, not claims that any particular difference occurred in this study. The registry record does not report details sufficient to assess those possibilities or an adjustment strategy that addresses them.

The primary outcome was assessed through 8 weeks after treatment, using the stated definition of being free of CDI diarrhea without retreatment through 56 days after treatment completion. Secondary outcomes include quality of life measured with SF-36 and the number of participants with major complications of recurrent CDI from baseline through 24 months. The registry lists quality of life twice among the secondary outcomes; the reason for the repeated entry is not reported in the registry record. The record lists four outcome measures and zero analyses. Further details about allocation procedures, follow-up completeness, and the statistical analysis plan 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Evaluable Population - All participants evaluable for a treatment outcome through 56 days after completion of treatment.

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: Full Analysis Set included participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Were CDI-diarrhea Free Through 8 Weeks, measured over 8 weeks after treatment.

The primary endpoint counts participants who were CDI-diarrhea free through 8 weeks after treatment. The registry defines success more specifically as no CDI diarrhea and no need for retreatment with C. difficile anti-infective therapy or fecal transplant through 56 days after completion of study treatment. The outcome is therefore a binary participant-level measure: each evaluable participant either meets the stated success definition or does not. The registry describes the analysis population as participants evaluable for a treatment outcome through 56 days after completion of treatment.

Such a composite definition can capture more than a symptom report alone. It includes both the absence of CDI diarrhea and the absence of specified rescue treatment during follow-up. As a general statistical point, a clearly defined binary endpoint can support direct reporting of how many participants meet a clinically specified criterion. Its interpretation depends on consistent outcome ascertainment and complete follow-up, as well as a clear denominator.

The registry record does not report the number of evaluable participants, the number meeting the endpoint, the number not meeting it, or a confidence interval. It also does not report the outcome result for the historical control or a formal comparison. Accordingly, the endpoint definition is available, but its observed frequency and comparative precision are not reported in the registry record. The SF-36 and major-complication outcomes are secondary measures and do not substitute for a reported primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical concepts below are general explanations. The registry record does not identify a complete analysis method for the primary endpoint, so these concepts should not be taken as descriptions of analyses that were necessarily performed.

What does a binary endpoint represent?

A binary endpoint classifies each participant into one of two outcome categories. Here, the stated success category requires being free of CDI diarrhea without the specified forms of retreatment through the follow-up period. An analysis commonly reports the count meeting the definition and the denominator assessed, sometimes alongside the resulting proportion. The registry record gives the endpoint definition and the intended evaluable population, but does not report the outcome count, denominator, or proportion. Without a denominator, a count alone would not show how common the outcome was among participants assessed; without a count, the definition alone does not describe the observed result.

Why does the analysis population matter?

An analysis population specifies which participants contribute to an estimate. The registry describes the primary population as participants evaluable for a treatment outcome through 56 days after completion of treatment. That description makes follow-up and evaluability relevant to the endpoint. In general, excluding participants without complete outcome information can affect an estimate if the excluded participants differ systematically from those retained. Whether any participants were excluded, why they might have been excluded, and how missing outcomes were handled are not reported in the registry record. Enrollment of 272 does not establish the endpoint denominator.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity, such as an outcome proportion or a difference between groups. It is not a guarantee that the underlying value lies within the interval, and it does not resolve design limitations such as confounding. Its width is influenced by the amount of information and the variability of the outcome. The registry record does not report a confidence interval for the primary endpoint or its comparison. Therefore, precision cannot be assessed from the registry record, even though the endpoint and study population are described.

What does a p-value address?

In general, a p-value evaluates how compatible observed data are with a specified null model, under the assumptions used for the test. It does not measure the probability that a treatment works, the size or importance of an effect, or the probability that the null hypothesis is true. A p-value also does not correct a non-randomized comparison for systematic differences between groups. No primary-outcome p-value or test method is reported in the registry record, so no significance claim can be evaluated from the posted information.

Why is randomization relevant to the comparison?

Random allocation is a design method intended to make treatment groups comparable, on average, with respect to both measured and unmeasured factors. This study was non-randomized and used a retrospective historical control. As a general matter, historical groups may differ in eligibility, patient characteristics, care practices, follow-up, or how outcomes were recorded. Statistical adjustment can sometimes address measured differences, but it cannot automatically remove differences that were not measured or correctly modeled. The registry record does not report an adjusted primary estimate or the covariates, if any, used for adjustment.

What can planning calculations tell a reader?

Sample-size planning is generally used to estimate the amount of information needed to detect a prespecified effect under stated assumptions. The registry's planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; it also varies the fraction of the observed effect to detect. These are planning assumptions, not evidence that the trial was designed around those assumptions. The registry does not report its own sample-size justification. Planning illustrations do not constitute observed power, and they do not replace a confidence interval or an observed outcome estimate. The numerical planning results and the observed effect used for them are not reported in the registry record.

How should multiple outcomes be considered?

When a study assesses several outcomes, the chance of at least one apparently unusual result can rise if many separate tests are performed. General approaches include identifying a primary outcome in advance, controlling error across tests, or treating secondary analyses as exploratory. The registry lists four outcome measures, including the primary endpoint, SF-36 quality-of-life measures, and major complications of recurrent CDI through 24 months. It lists zero analyses. A multiplicity procedure, prespecified testing hierarchy, and analysis plan are not reported in the registry record, so the status of any testing across outcomes cannot be assessed from it.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome: participants free of CDI diarrhea through 8 weeks under the stated no-retreatment definition. It also lists secondary outcomes involving SF-36 quality of life and major complications of recurrent CDI from baseline through 24 months. The quality-of-life outcome appears twice in the list. The reason for the duplicate listing and the intended relationship among these measures are not reported in the registry record. Four outcome measures are listed, while the number of analyses is recorded as zero.

Multiplicity concerns arise generally when several outcomes or statistical tests are examined. If each is treated as a separate opportunity to declare a finding, the chance of at least one apparently unusual result can increase. Studies may address this through prespecified hierarchies, adjusted significance thresholds, or by interpreting secondary outcomes as exploratory. The registry record does not report whether any such approach was planned or used. No analysis plan or inferential results are listed, so the treatment of multiple outcomes cannot be evaluated.

Missing-data handling is also not reported in the registry record. The primary population is described as participants evaluable through 56 days after treatment completion, but the number evaluable and the number with missing endpoint information are not given. The record does not describe imputation, sensitivity analyses, or the classification of participants with incomplete follow-up. These details matter because an evaluable-only result can depend on who remains evaluable and why.

The registry also does not report the statistical analysis population for secondary outcomes or the extent of follow-up for those measures. The absence of these details is not evidence that no procedures were used; it means their impact cannot be assessed from the registry record.

11. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (5.4%), sepsis (5.4%), clostridium difficile infection (4.0%), cardiac failure congestive (3.4%), urinary tract infection (3.4%).

The registry lists safety figures separately for the RBX2660 open-label group and the historical control antibiotics group. For serious events, it records 52 affected among 149 at risk in the RBX2660 group and 30 among 104 at risk in the historical control group. For other recorded events, the corresponding counts are 118 among 149 at risk and 62 among 104 at risk. Deaths are listed as 15 and 5, respectively. These are descriptive counts, not adjusted comparisons.

The record also lists the most frequent serious-event terms with percentages: Pneumonia, 5.4%; Sepsis, 5.4%; Clostridium difficile infection, 4.0%; Cardiac failure congestive, 3.4%; Urinary tract infection, 3.4%; and Acute myocardial infarction, 2.9%. The registry entry does not provide additional context for the percentages in this listing, such as a separate analysis definition. They should be read as posted values, not used to infer an unreported comparative effect.

Because the groups were not randomized and one was historical, differences in safety counts do not by themselves establish that treatment caused a difference. The registry record does not report adjustment, event timing, exposure-adjusted rates, or inferential comparisons for these figures. Counts also do not convey severity beyond the serious-event classification or resolve whether events were related to treatment. These safety data describe recorded events in the listed groups; they do not support a causal conclusion on their own.

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

The study record describes an evaluation of RBX2660 for recurrent CDI, with a retrospective historical group treated with standard-of-care antibiotics. It specifies a primary endpoint based on being free of CDI diarrhea without retreatment through 56 days after treatment completion. It also records adverse-event counts and secondary outcome topics. Those elements establish what the study intended to assess and what types of information were registered.

The posted registry information does not report the primary endpoint result, its denominator, or a comparison estimate. No confidence interval or statistical test result for that endpoint is reported. The record therefore does not allow readers to determine the observed frequency of success, how precise an estimate might be, or how the outcome compared with the historical control. This absence should not be interpreted as a finding of no effect or as evidence of benefit.

Even if a numerical difference between groups were available, the design would require caution. Non-randomized treatment allocation and a retrospective comparator can leave differences between groups that affect outcomes. The registry record itself notes that the arms are not a like-for-like control comparison. The counts and endpoint definition cannot remove that design limitation.

The safety figures describe events among participants listed as at risk, but they are not a causal comparison and do not supply a complete account of event timing or adjustment. Similarly, secondary outcome names indicate areas assessed but do not provide their results. General statistical interpretation distinguishes descriptive data from estimates supported by an analysis and distinguishes association from causal attribution. On the available registry information, the evidence can be described in terms of the registered design and recorded counts, but efficacy and comparative safety conclusions are not established by a reported primary analysis.

13. Why This Trial Matters Statistically

This trial is statistically instructive because its clinical question is paired with a comparison that is not randomized. The registry identifies an open-label RBX2660 group and a retrospective historical antibiotic control, and explicitly cautions that the groups are not a like-for-like comparison. This makes the distinction between describing outcomes and attributing differences to treatment central to interpretation. A numerical contrast, even if reported, would not by itself remove the possibility of systematic group differences.

The primary outcome also illustrates why endpoint definitions and analysis populations must be read together. The endpoint requires absence of CDI diarrhea without specified retreatment through 56 days, while the stated population includes participants evaluable through that follow-up. Both the numerator and denominator are needed to understand an outcome frequency. The registry record provides the definition but not the result or denominator, so the clinical meaning cannot be quantified from the posted information.

The safety listing is another reminder that raw event counts are descriptive. The groups have different at-risk denominators, and the design is non-randomized; interpreting counts as treatment effects would require additional analysis and careful assumptions. The record does not report an adjusted comparison for these events.

Finally, the registry lists several outcome measures but no analyses. Without an analysis plan, missing-data methods, multiplicity approach, or inferential results, readers cannot assess how outcome selection and analysis choices shaped conclusions. These are general statistical considerations, not proof that a particular procedure was omitted from study conduct. The record's value is that it makes the design and outcome definitions visible while also showing how much is required beyond an endpoint label to support a precise comparative conclusion.

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.

A key limitation for interpreting the registry record is that it describes the primary endpoint but does not report its result. Neither the number meeting the endpoint nor the number evaluable is available, and no effect estimate, confidence interval, or test result is reported. Enrollment of 272 does not resolve this gap because the endpoint population is defined by evaluability through follow-up.

The study's non-randomized, open-label design and retrospective historical control limit causal interpretation. The record explicitly says the arms are not a like-for-like control comparison. It does not report enough detail to assess how participants were selected into each group, whether outcome ascertainment was comparable, or whether statistical adjustment addressed group differences. These concerns are specific to the comparator structure registered for this trial.

Other limitations in the posted information include the absence of a reported statistical analysis plan, missing-data approach, multiplicity strategy, and analyses. The record lists four outcome measures but zero analyses. It also lists SF-36 twice among secondary outcomes; the reason is not reported. For the secondary major-complication outcome, the specified observation period extends through 24 months, but the registry record does not report outcome results or completeness of follow-up.

The adverse-event counts are descriptive and do not include a reported adjusted or inferential comparison. The record does not provide enough detail to interpret event timing, exposure, or the basis of the listed serious-event percentages beyond their displayed terms and values. These limitations restrict what can be concluded from the registry record; they do not establish that additional analyses or procedures were absent from the broader study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Microbiota Restoration Therapy for Recurrent Clostridium Difficile Infection — NCT02589847.
• Registry record last updated 2021-03-26; status last verified 2021-02.
• Results first posted 2020-05-11.
• 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

NCT02589847 is a completed phase 2 study of RBX2660 for recurrent Clostridium difficile infection, sponsored by Rebiotix Inc. It enrolled 272 participants, with a start date of 2015-10 and primary completion in 2017-06. The design was open-label, non-randomized, and parallel, comparing RBX2660 with a retrospective historical control receiving standard-of-care antibiotics.

The primary outcome counted participants free of CDI diarrhea through 8 weeks after treatment, without specified retreatment through 56 days after treatment completion. The primary population was defined as participants evaluable through that follow-up. The registry record does not report the primary outcome result, its denominator, or an inferential comparison. It lists four outcome measures and zero analyses. Safety counts are recorded for both groups, but the registry does not report an adjusted safety comparison. The historical-control design and absent outcome estimates limit interpretation of comparative efficacy and safety.