Safety And Efficacy Of Rifabutin In Patients For Non-HIV Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety And Efficacy Of Rifabutin In Patients For Non-HIV Patients (NCT00810407), a registered phase not stated study. The primary outcome is Number of Participants With Treatment-Related Adverse Events.

2. Clinical Question

The stated objective was to collect information about adverse drug reactions not expected from the LPD, the incidence of adverse drug reactions in the surveillance, and factors considered to affect the drug’s safety and/or efficacy. This is a safety-surveillance question rather than a direct comparison of rifabutin with a control treatment. The record identifies tuberculosis and non-tuberculous mycobacterial diseases, including MAC disease, as the conditions of interest, and specifies a non-HIV population.

The primary endpoint concerns participants with treatment-related adverse events. The record defines such an event as an untoward medical occurrence attributed to Mycobutin in a participant who received it; the physician or investigator assessed relatedness. The primary endpoint’s observed count is not reported in the registry record. Separate adverse-event summaries report affected-participant counts and serious adverse event terms, but those summaries should not be treated as the unreported primary endpoint result.

3. Trial Design

This is a completed post-marketing surveillance study of rifabutin, described in the official title as a special investigation for non-HIV patients of Mycobutin under a regulatory post-marketing commitment plan. The sponsor is Pfizer. The registry record lists an enrollment of 628 and study dates from 2008-11 to primary completion in 2016-07. It lists one drug intervention, rifabutin, and describes the treatment arm as patients administered rifabutin.

The record does not describe a control arm or a randomized allocation. It explicitly notes that this is not a randomized comparison and that the allocation method is not stated. Accordingly, the treatment arm should not be read as one side of a like-for-like comparison. The design information supports describing surveillance among rifabutin recipients, not estimating a causal treatment contrast against an untreated or alternative-treatment group.

The safety analysis set comprised participants who satisfied the inclusion criteria and had received Mycobutin at least once. Its reported size is 588. This is the population specified for the primary safety endpoint, and it should not be assumed to match the enrollment count or any other outcome-specific analysis population. Details about eligibility criteria beyond this description, recruitment procedures, follow-up completeness, and the handling of participants who stopped treatment are not reported in the registry record.

The record lists nine outcome measures and four analyses. It gives a one-year timeframe for the primary endpoint, but does not provide the full protocol, a detailed visit schedule, or information about whether all participants were followed for the same length of time. The surveillance objective includes safety and efficacy-related factors, but no comparative efficacy design is described. The study status is completed.

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: A total 628 subjects were registered in this study. Of the 628 subjects, 594 subjects CRFs were collected and included in the study. Of the 594 subjects, 6 subjects were excluded from the safety analysis set (SAS). In total, 588 subjects were included in the SAS as the completed the study

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received Mycobutin at least once.

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: A total of 588 participants received Mycobutin at least once in this study. Of the 594 participants, 6 participants were excluded from the baseline analysis due to following reasons: protocol violation and no visit after first day of treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Related Adverse Events, measured over 1 year.

The primary endpoint is the number of participants with treatment-related adverse events, with the unit specified as participants and the measure described as a count. It asks how many people in the defined safety analysis set had an untoward medical occurrence that the physician or investigator attributed to Mycobutin. The timeframe is one year.

A participant count is a direct way to describe how many people had at least one event meeting the endpoint definition. It differs from a count of all event episodes: a participant with multiple events may still contribute as one participant to a participant-based measure, depending on the endpoint’s operational rules. The registry record does not give further rules for handling multiple events, repeated events, or event onset after treatment discontinuation.

Attribution matters to interpretation. The endpoint is not simply every medical event observed during surveillance; it is limited to events considered related to Mycobutin by the physician or investigator. Such assessment is part of the endpoint definition, but the record does not report a formal adjudication process or criteria for making that judgment.

The primary endpoint’s observed count is not reported in the registry record. The record does contain separate adverse-event summaries, but their counts cannot be substituted for the primary endpoint unless they are explicitly identified as the same measure. The endpoint is useful for describing treatment-related safety experience in the specified analysis set; without a comparator, it does not by itself establish how that experience differs from background illness, other treatments, or an alternative care strategy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a count of participants with an event, rather than a continuous measurement or a time-to-event estimate. In general, a participant-based count answers how many people met an event definition over a stated observation period. It is not necessarily the same as the total number of event episodes, because one person may experience more than one event. The record names participants as the unit for the primary endpoint, but does not give additional rules about repeated events or whether each participant was counted once.

The primary endpoint also uses an attribution judgment. An event qualifies when it is an untoward medical occurrence attributed to Mycobutin by the physician or investigator. In general, attribution is distinct from observing that an event happened after treatment: it is an assessment about relatedness. The registry record does not report the criteria used for that assessment, whether assessments were reviewed independently, or how disagreements would have been resolved. Those details matter when interpreting a treatment-related count because judgment can affect which events meet the definition.

For a participant count to be interpretable, its population and observation period must be clear. Here, the safety analysis set is defined as participants who met inclusion criteria and received Mycobutin at least once, and the primary endpoint timeframe is one year. The size of this analysis set is 588. The registry record does not explain whether each participant contributed a full year of observation, how follow-up time was handled, or how missing event information was addressed. A count alone does not account for differing observation time unless the analysis explicitly incorporates it.

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model. For a participant count or a proportion, interval methods can convey how precisely the event frequency is estimated. The registry record does not report a confidence interval for the primary endpoint in the registry record for this analysis, and it does not report the primary endpoint’s observed count. It is therefore not possible to describe its precision from the primary endpoint information. Any interval attached to a different adverse-event summary would pertain to that summary, not automatically to the primary endpoint.

For a binary event outcome, an analysis may report a count, a proportion, or a comparison between groups. Those summaries answer different questions. A count gives the number of affected participants; a proportion relates the count to a defined denominator; and a between-group effect compares outcomes across groups. The record provides affected-participant counts and denominators for the separate serious and other adverse-event summaries. It does not describe a randomized or like-for-like comparison, so those summaries should not be interpreted as comparative treatment effects.

Over-dispersion is a general concern when a statistical model assumes more uniform variation than the data exhibit. For instance, clustering or meaningful differences among participants can make observations more variable than a simple model expects. In a surveillance study, the possibility of variation in participant risk and exposure is a general statistical consideration, not evidence that over-dispersion occurred in this study. The registry record does not report whether over-dispersion was assessed or whether a model requiring such an assessment was used.

The sample-size description is explicitly a planning illustration based on an observed effect, not the study’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm for 80% power or another stated power level; time-to-event illustrations use a total event count. These assumptions do not describe the surveillance design, which has no reported comparator arm and is not described as randomized. The illustration is not observed power and should not be read as evidence that the study was designed to detect a particular effect.

The registry record does not report the statistical analysis plan, model specifications, planned hypothesis tests, or whether any analyses were adjusted for participant characteristics. A recalculated unadjusted result, if presented elsewhere in the posted results, would be a simple re-calculation from summary statistics and would not replace a sponsor’s own analysis where a discrepancy is identified. No discrepancy status or recalculated primary endpoint result is stated in the registry record for this analysis. Interpretation should remain tied to the reported definitions and populations rather than assuming unreported methods.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists nine outcome measures and four analyses, but does not report how the outcomes were ordered for confirmatory testing or whether any adjustment was made for examining multiple outcomes. In general, multiplicity concerns arise when several outcomes or hypotheses are assessed: the chance of a nominally unusual result can depend on how many analyses are considered and how they are related. Without a stated testing strategy, it is not possible to characterize the inferential status of any result as confirmatory or adjusted. The stated surveillance objectives also include several types of information, but the record does not describe a formal hierarchy among them.

Missing-data handling is not reported in the registry record. In general, missing event status can affect a participant-based safety summary if some participants have incomplete observation or unavailable records. The record does not say whether participants with incomplete follow-up were excluded, whether event information was sought after treatment stopped, or how missing observations were handled. The safety analysis set definition establishes that participants received Mycobutin at least once, but does not by itself explain completeness of follow-up.

The primary endpoint’s result is not reported in the registry record, and details about its analysis population beyond the stated safety set are not available. The separate adverse-event summaries have their own reported at-risk counts; those denominators should not be assumed to apply to every outcome. No sensitivity analyses, imputation methods, or missingness assumptions are reported in the registry record. These gaps limit assessment of how robust the reported safety summaries are to incomplete information and how the multiple listed outcomes were interpreted.

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 3.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: liver disorder (3.4%), pyrexia (3.1%), pneumonia (2.0%), decreased appetite (2.0%), uveitis (2.0%).

The serious adverse-event summary for Mycobutin (Rifabutin) reports 184 affected participants among 588 at risk. The other adverse-event summary reports 470 affected participants among 588 at risk. These are counts of affected participants in separate categories; they are not the number of event episodes. The record does not provide enough detail to determine whether the categories overlap, so they should not be combined or treated as mutually exclusive.

The listed serious adverse event terms are Liver disorder (3.4%), Pyrexia (3.1%), Pneumonia (2.0%), Decreased appetite (2.0%), Uveitis (2.0%), and White blood cell count decreased (1.9%). The denominator for these term percentages is not reported in the registry record. The terms and percentages should therefore be read as listed, without deriving counts or comparing their frequency with another population.

These serious-event summaries are not identified as the primary treatment-related endpoint. The primary endpoint requires physician or investigator attribution to Mycobutin, while the serious-event summary is presented separately. The record does not establish that every serious event was treatment-related or that the listed terms were judged related. These observations describe what was recorded in the surveillance group; without a control comparison, they do not isolate an effect caused by rifabutin.

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

The record documents post-marketing surveillance of rifabutin in non-HIV patients with tuberculosis or non-tuberculous mycobacterial diseases, including MAC disease. Its stated purpose was to gather information about unexpected adverse drug reactions, adverse-reaction incidence, and factors considered to affect safety and/or efficacy. The safety summaries provide descriptive information about affected participants and serious adverse-event terms in the Mycobutin group.

The primary endpoint was designed to count participants with treatment-related adverse events over a one-year timeframe. The registry record does not report the observed primary endpoint count. As a result, the primary endpoint cannot be used to quantify the frequency of treatment-related events. The separate counts for serious and other adverse events should not be substituted for that missing result because the record does not identify them as equivalent measures.

The findings do not provide a randomized comparison or a like-for-like control group. They therefore cannot show whether event counts would have been different under another treatment or without rifabutin. A safety event observed during surveillance is not, by itself, proof that the drug caused it; the primary endpoint includes an investigator’s relatedness assessment, but the event summaries do not establish that all reported events met that attribution standard.

The results also do not establish the absence of events that were not observed, reported, or included in the registry summaries. The record does not report the statistical plan, handling of missing information, or follow-up completeness. Its surveillance design and posted summaries support a descriptive reading, with uncertainty about the completeness and comparability of the observations. No numerical efficacy result is included in the registry record described for this analysis, so the record cannot support a conclusion about efficacy.

13. Why This Trial Matters Statistically

Post-marketing surveillance addresses a different statistical question from a randomized efficacy trial. It can describe events observed among people receiving a drug in clinical practice and can be structured to gather information about unexpected reactions and potential safety factors. The record’s stated objectives reflect those descriptive goals, including attention to adverse-reaction incidence and factors considered relevant to safety or efficacy.

The design also illustrates why outcome definitions and denominators matter. The primary endpoint is a count of participants with events attributed to Mycobutin, whereas the separate safety summaries report affected-participant counts for serious and other adverse events. Those measures are not interchangeable merely because they concern adverse events. Keeping the event definition, attribution rule, population, and timeframe distinct prevents a descriptive count from being misread as a treatment-related endpoint result.

The absence of a randomized comparison is especially important for interpretation. Surveillance can identify and describe events, but a group without a comparable control does not separate treatment-associated risk from underlying illness, concurrent care, or other sources of variation. The record explicitly cautions that the arm is not a like-for-like control comparison. This makes careful descriptive language more appropriate than a causal claim.

The record also highlights a reporting issue: the primary endpoint is defined, but its observed value is not reported in the information available for this analysis. A clear endpoint definition cannot replace an outcome estimate. Likewise, a planning illustration based on an observed effect should not be mistaken for the study’s own design or for observed power. Statistical interpretation depends on transparent outcome reporting, analysis populations, and methods as well as on the study’s stated purpose.

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 most direct limitation is that the observed result for the primary endpoint is not reported in the registry record. Although its definition, unit, population, and timeframe are specified, the count of participants meeting that definition is unavailable. This prevents a direct descriptive estimate for the primary safety question.

The study is not described as randomized, the allocation method is not stated, and no like-for-like control comparison is reported. The posted adverse-event counts therefore cannot be interpreted as comparative effects. The record does not describe an external comparison group, adjustment strategy, or methods for separating treatment-related events from events associated with disease or other care.

The safety analysis set is defined, but follow-up completeness and missing-data handling are not reported. The record also does not specify whether participants contributed equivalent observation time, how repeated events were handled, or how treatment discontinuation affected observation. These details could affect interpretation of counts and event frequencies.

For the serious adverse-event terms, the record gives listed percentages but does not report their denominator in the registry record for this analysis. The record does not state whether the listed terms were judged treatment-related. The serious and other adverse-event summaries are separate from the defined primary endpoint, and the information does not establish whether their categories overlap.

Finally, the registry record does not report a detailed statistical analysis plan, multiplicity strategy, or efficacy result in the registry record. These omissions limit assessment of the inferential methods and the extent to which the surveillance objectives were addressed. They do not negate the descriptive observations, but they narrow the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety And Efficacy Of Rifabutin In Patients For Non-HIV Patients — NCT00810407.
• Registry record last updated 2019-03-07; status last verified 2018-11.
• Results first posted 2019-03-07.
• 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

NCT00810407 is a completed post-marketing surveillance study sponsored by Pfizer. It concerns rifabutin (Mycobutin) in non-HIV patients with tuberculosis or non-tuberculous mycobacterial diseases, including MAC disease. The record lists enrollment of 628, study start in 2008-11, and primary completion in 2016-07.

The primary endpoint is the number of participants with treatment-related adverse events during a one-year timeframe, among a safety analysis set of 588 participants who met inclusion criteria and received Mycobutin at least once. The observed primary endpoint count is not reported in the registry record. Separate safety summaries report 184 affected participants among 588 at risk for serious adverse events and 470 among 588 at risk for other adverse events.

No randomized comparison or like-for-like control arm is described. The record lists nine outcome measures and four analyses, but the statistical plan, missing-data handling, and multiplicity approach are not reported in the registry record. The results are therefore best read as descriptive safety information, not as a comparative estimate of rifabutin’s effects.