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

1. Trial at a Glance

This page covers the registry results for Safety And Efficacy Of Rifabutin In HIV Patients (NCT00810446), a registered phase not stated study. The primary outcome is Number of Patients With Adverse Drug Reactions in This Surveillance.

2. Clinical Question

The surveillance objective was to collect information about adverse drug reactions not expected from the product information, the incidence of adverse drug reactions during surveillance, and factors considered to affect safety or efficacy. That objective is broader than the primary outcome alone. The primary outcome is a participant count for adverse drug reactions, not a measure of comparative efficacy.

The conditions listed include non-tuberculous mycobacterial diseases, tuberculosis, and inhibition of disseminated Mycobacterium avium complex disease associated with HIV infections. These entries describe the record’s clinical context; they do not establish that every participant had each condition or that the study tested rifabutin against another treatment for those conditions. The specific eligibility criteria beyond the safety-set description are not reported in the registry record.

3. Trial Design

This completed record describes a drug-use investigation and post-marketing surveillance of MYCOBUTIN Capsules (rifabutin) in people with HIV. Pfizer is listed as the sponsor. The study started in 2009-06, and primary completion is listed as 2018-03. The record reports enrollment of 72 participants.

The design is not a randomized controlled comparison: the allocation method is not stated, and only a rifabutin group is described. The arm description says patients were administered rifabutin. There is no like-for-like control group against which to compare event counts, safety, or efficacy. The registry record does not report a protocol-level account of how participants were selected or how treatment decisions were made.

The primary outcome is the number of participants with adverse drug reactions. Its timeframe is listed as 6.5 years at maximum for therapeutic use and 8.5 years at maximum for preventive use. These are maximum timeframes in the outcome description; the record does not report how long each participant was followed or how many reached either maximum. They should not be read as a common observed follow-up duration.

The stated surveillance objectives include identifying unexpected adverse drug reactions, describing adverse-reaction incidence, and examining factors thought to affect safety or efficacy. The registry record lists 9 outcome measures, but detailed information about the other measures is not available in the registry record. It lists no analysis entries. The statistical plan, any planned interim analyses, and any sample-size justification are not reported in the registry record.

The enrollment figure is a description of the study record, not evidence that every participant contributed to every outcome. The safety analysis set is defined as participants meeting inclusion criteria who received MYCOBUTIN Capsules at least once. Further participant-flow details, including numbers excluded from particular analyses, 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: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received MYCOBUTIN Capsules 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 72 participants were registered in this study. There was no participant excluded from the baseline analysis.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Adverse Drug Reactions in This Surveillance, measured over 6.5 years at maximum (therapeutic) and 8.5 years at maximum (preventive).

The primary endpoint is the number of participants with adverse drug reactions in the surveillance. The registry defines an adverse drug reaction as an untoward medical occurrence attributed to MYCOBUTIN Capsules in someone who received the capsules. A physician assessed whether an event was related to the drug. The primary measure is therefore a count of participants, rather than a comparison of treatment groups or a time-to-event estimate.

The record also defines a serious adverse drug reaction by its consequences or clinical significance. These include death, a life-threatening experience, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly, or another reason the event was considered significant. This definition concerns severity; it does not by itself establish that the drug caused an event. Attribution was assessed separately by the physician.

In general, a participant count can describe how many people in the observed safety set had a recorded event. It is useful for safety surveillance because it makes the unit of observation explicit and can capture events that merit further review, including unexpected events. A count alone does not describe event timing, duration, recurrence, or the probability of an event in a comparable untreated group. It also does not establish a causal relationship.

The registry lists a maximum timeframe of 6.5 years for therapeutic use and 8.5 years for preventive use. The record does not report a participant-level follow-up distribution, so the endpoint count should not be interpreted as arising from identical observation periods. Details of the endpoint’s collection schedule and handling of incomplete observation are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted primary outcome is a binary participant-level event summarized as a count: a participant either had a recorded adverse drug reaction or did not, for the purpose of this outcome. The record describes counts of participants, rather than a continuous measurement such as a laboratory value. No inferential analysis entries are listed, so interpretation should stay with the reported descriptive results and their definitions.

What does a participant count tell us?

In general, a count communicates the number of people meeting an outcome definition in the observed group. It is distinct from a count of event episodes: one participant can potentially experience more than one event. The registry’s outcome is explicitly described as a number of participants, but the available details do not explain how recurrent events were handled across all safety results. A participant count also differs from a rate, which accounts for how long participants were observed. Although maximum timeframes are listed, person-time or individual follow-up durations are not reported in the registry record.

The adverse-event results list 72 participants at risk for serious events and 15 affected, and 72 at risk for other events and 28 affected. These figures should be read within their listed categories. They should not be added to produce a combined total: the record does not say whether participants could appear in both categories. The listed deaths are also a separate figure, and the record does not establish whether they overlap with the affected counts or were considered drug-related.

What is an adverse drug reaction?

The record defines an adverse drug reaction as an untoward medical occurrence attributed to MYCOBUTIN Capsules in a participant who received them. The physician assessed relatedness. This is not the same as simply observing any medical event after treatment: attribution is part of the definition. However, the registry record does not describe the assessment criteria, the evidence used, or the event-level attribution decisions. The seriousness definition describes consequences or significance, including death, life-threatening experience, hospitalization, disability or incapacity, and congenital anomaly. Seriousness and relatedness are separate concepts: an event may be serious without the record establishing that it was caused by the drug.

Why does a comparator matter?

In general, a randomized comparison can help distinguish treatment-group differences from differences in participant characteristics and other influences. Here, no comparator is described, allocation is not stated, and the record identifies no like-for-like control comparison. The observed counts can therefore characterize events recorded among participants in the rifabutin group, but cannot estimate a treatment contrast. They do not show what the event count would have been in the same population under a different treatment or without exposure.

In general, observational safety surveillance can be useful for collecting information in clinical use, including reports of unexpected events. But a surveillance count can reflect the underlying conditions, other medicines, clinical monitoring, duration of observation, and the way events are recognized and recorded. The posted results do not quantify or adjust for these influences. The objective mentions factors considered to affect safety or efficacy, but the factors and methods for evaluating them are not reported in the registry record.

How should uncertainty be understood?

A confidence interval is a statistical range intended to express uncertainty around an estimate under specified assumptions. The registry record does not list confidence intervals for the participant counts or term-level percentages. It also does not list hypothesis tests or adjusted estimates. Without these, the reader cannot assess inferential precision from the posted results. This is especially important when interpreting event counts in a single group: the observed count is descriptive, and it does not by itself quantify uncertainty or support a comparison.

In general, a p-value summarizes how compatible data are with a specified statistical model under a null hypothesis; it is not a measure of clinical importance or proof of causation. No p-value or statistical analysis result is reported in the registry record. There is therefore no basis for describing any posted outcome as statistically significant or non-significant.

What is not established by the timeframe?

The primary outcome description gives maximum timeframes of 6.5 years for therapeutic use and 8.5 years for preventive use. A maximum is not the same as the observed duration for every participant. In general, unequal follow-up can affect how many opportunities there are to observe an event. Time-to-event methods or person-time rates can address some questions about differing observation time, but the registry record does not report these analyses. No such estimates should be inferred from the maximum timeframe alone.

The record gives a sample-size planning assumption for illustrations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. These are generic assumptions for a planning illustration, not evidence of the study’s own design or an observed-power calculation. Since the study record describes no comparator arm and lists no analysis entries, those assumptions do not establish that this surveillance was designed or analyzed as a two-arm trial. The protocol’s sample-size justification is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 9 outcome measures and no analysis entries. It does not report a statistical plan describing which outcomes were primary or secondary beyond the posted primary outcome, how multiple outcomes were to be interpreted, or whether any adjustment for multiple testing was planned. The surveillance objectives span unexpected adverse drug reactions, adverse-reaction incidence, and factors thought to affect safety or efficacy; the record does not specify how those objectives map to the other outcome measures.

In general, testing or highlighting many outcomes can increase the chance that some findings appear noteworthy by chance. Multiplicity procedures can control or describe that issue, but the appropriate approach depends on the prespecified questions and analysis plan. Since those details are not reported, no claim about multiplicity adjustment is warranted. The term-level adverse-event percentages should be treated as descriptive entries, not as evidence that the terms were selected through a prespecified statistical ranking.

Missing-data handling is also not reported in the registry record. The safety analysis set is defined as participants who met inclusion criteria and received MYCOBUTIN Capsules at least once, but this does not explain whether all enrolled participants were included, how missing follow-up was handled, or how incomplete event information was classified. The record does not report numbers with missing outcome data or sensitivity analyses for missingness.

In general, missing safety information can matter when observation duration or completeness differs between participants. Without participant-flow details, follow-up completeness, and missing-data methods, the counts cannot be interpreted as though every participant had identical observation or complete ascertainment. The registry record also does not describe interim analyses, monitoring procedures, or rules for stopping surveillance early.

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 2.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: immune reconstitution inflammatory syndrome (5.6%), cytomegalovirus chorioretinitis (4.2%), pancytopenia (2.8%), nausea (2.8%), mycobacterium avium complex infection (1.4%).

The adverse-event results list 15 participants affected by serious events among 72 at risk, and 28 affected by other events among 72 at risk. These are participant counts within the listed categories. The record does not explain whether people can appear in both groups, so the two affected counts should not be combined. The record also lists 2 deaths but does not provide enough information to determine their relationship to the serious-event count or to rifabutin.

The serious-event terms are reported with percentages: immune reconstitution inflammatory syndrome, 5.6%; cytomegalovirus chorioretinitis, 4.2%; pancytopenia, 2.8%; nausea, 2.8%; Mycobacterium avium complex infection, 1.4%; and arthritis bacterial, 1.4%. These are term-level entries, not a complete account of all events or a comparison with another group. The registry record does not specify whether terms can recur within a participant or how relatedness was assigned for each term.

Seriousness is defined by outcomes or clinical significance, while adverse drug reaction status depends on attribution to the capsules. A serious event is not automatically a serious adverse drug reaction. The primary endpoint definition states that a physician assessed relatedness, but individual attribution results are not reported in the registry record. The counts therefore describe recorded safety events; they do not, on their own, prove that rifabutin caused them.

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

The results describe a completed surveillance record in which 72 participants were listed in the rifabutin group. The posted safety figures include 15 participants affected by serious events, 28 affected by other events, and 2 deaths. The primary outcome concerns the number of participants with adverse drug reactions attributed to MYCOBUTIN Capsules, with relatedness assessed by a physician. These figures offer a descriptive account of events recorded in this group.

They do not establish a causal effect of rifabutin. An observed event during surveillance may relate to the drug, the participant’s underlying illness, another treatment, or other circumstances. The registry record’s definition includes physician assessment of relatedness, but event-level assessments and their criteria are not reported. The listed serious-event terms and percentages likewise do not provide a controlled estimate of treatment-related risk.

The results do not show whether event frequencies differ from those under another treatment or no rifabutin exposure. No comparator is described, allocation is not stated, and the record identifies no like-for-like control comparison. The surveillance objective mentions efficacy and factors considered to affect safety or efficacy, but no specific efficacy results or factor analyses are reported in the registry record.

The results also do not establish the frequency of events over a common duration of exposure. The primary outcome lists maximum timeframes of 6.5 years for therapeutic use and 8.5 years for preventive use, but individual follow-up durations are not reported. Nor does the record report confidence intervals or other inferential analyses that would describe statistical precision.

In general, a descriptive safety record can identify events for further evaluation and provide context about observations in a treated group. It cannot answer every causal or comparative question without suitable design and analysis. The appropriate reading is therefore limited: the registry reports participant counts and selected event terms for a single rifabutin group, while comparative efficacy, causal attribution for individual events, and inferential uncertainty remain unresolved in the registry record.

13. Why This Trial Matters Statistically

This record illustrates an important distinction in clinical statistics: surveillance and comparative trials answer different questions. A surveillance program can collect safety observations during drug use and describe the events reported among exposed participants. This record’s stated objectives include identifying unexpected adverse drug reactions, describing adverse-reaction incidence, and examining factors considered to affect safety or efficacy. Those aims can be relevant even when the design does not include a control group.

At the same time, descriptive counts should not be mistaken for comparative evidence. The record describes one rifabutin group, with no comparator and allocation not stated. As a result, the safety counts characterize observations in that group but cannot show how those counts compare with another treatment or with no exposure. The distinction is central when interpreting post-marketing data: an observed event may prompt attention, while its cause and comparative frequency require additional evidence.

The endpoint definition also demonstrates why operational definitions matter. The primary outcome is not simply any medical event; it is an untoward occurrence attributed to MYCOBUTIN Capsules, with relatedness assessed by a physician. Seriousness is separately defined by consequences or clinical significance. Keeping event occurrence, severity, and attribution distinct prevents a serious event from being automatically read as drug-caused.

Finally, the record highlights the role of completeness and analysis reporting. It lists 9 outcome measures but no analysis entries, and does not report confidence intervals, participant-level follow-up, missing-data procedures, or the statistical plan. Such information is needed to assess precision, ascertainment, and the scope of conclusions. The record is useful as a description of the surveillance question and posted safety observations, while leaving key comparative and inferential questions unanswered.

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 principal limitation is the absence of a comparator. The registry record describes only the rifabutin group, does not state allocation, and explicitly does not provide a like-for-like control comparison. The posted counts therefore cannot establish comparative safety or efficacy and cannot isolate the effect of rifabutin from underlying illness or other influences.

Outcome reporting is limited. The record lists 9 outcome measures but provides no analysis entries. Detailed results for efficacy outcomes, the factors considered to affect safety or efficacy, and the relationship between the primary endpoint and the serious and other event categories are not reported in the registry record. No confidence intervals, p-values, or adjusted estimates are listed.

Follow-up information is incomplete for interpretation. Maximum timeframes are given as 6.5 years for therapeutic use and 8.5 years for preventive use, but individual observation durations and completeness are not reported. The record does not describe missing outcome data, participant flow into the safety analysis set, or methods for handling incomplete follow-up.

The safety definitions provide a framework, but the relatedness assessment criteria and individual event-level attribution results are not reported. The relationship between the 2 deaths and the serious-event counts is also not stated. The serious-event terms and percentages do not clarify possible overlap between events or participants.

Finally, the protocol’s statistical plan, sample-size justification, and any interim analyses are not reported in the registry record. Without those details, it is not possible to evaluate whether the posted outcomes and analyses followed prespecified methods or how the surveillance was intended to quantify uncertainty.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety And Efficacy Of Rifabutin In HIV Patients — NCT00810446.
• Registry record last updated 2019-08-02; status last verified 2019-06.
• Results first posted 2019-08-02.
• 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

NCT00810446 is a completed drug-use investigation of MYCOBUTIN Capsules (rifabutin) in people with HIV, sponsored by Pfizer. The record lists enrollment of 72 participants, a start in 2009-06, and primary completion in 2018-03. Its primary outcome is the number of participants with adverse drug reactions, with relatedness assessed by a physician.

The record reports 15 participants affected by serious events and 28 affected by other events, each among 72 at risk, and lists 2 deaths. Selected serious-event terms are accompanied by percentages. The design has no described comparator, and allocation is not stated. The registry record lists 9 outcome measures and no analysis entries. Comparative efficacy, statistical precision, detailed follow-up, missing-data handling, and the full analysis plan are not reported.