Randomized Evaluation of Strategic Intervention in Multidrug Resistant Patients With Tipranavir (RESIST): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Randomized Evaluation of Strategic Intervention in Multidrug Resistant Patients With Tipranavir (RESIST) (NCT00054717), a registered phase 3 study. The primary outcome is Treatment Response at Week 48.

2. Clinical Question

3. Trial Design

RESIST is a phase 3, parallel-group study listed as completed. The registry reports an enrollment of 630 and identifies HIV infections as the condition studied. Boehringer Ingelheim is listed as the sponsor. The record gives a start date of 2003-01 and a primary completion date of 2008-09.

The study compared tipranavir with low-dose ritonavir against a comparator protease inhibitor with low-dose ritonavir in people described as highly treatment experienced. The official title characterizes the study as randomized and open-label. However, the allocation field is not stated in the registry record, and the record’s comparison note cautions that the arms are not a like-for-like control comparison. Thus the title alone is not enough to establish the allocation procedure or support treating the contrast as a randomized causal estimate.

The primary outcome was treatment response at week 48, defined using consecutive viral-load measurements and treatment-course conditions. The registry also lists treatment response at week 2, week 4, week 8, week 16, week 24, week 32, and week 40 as secondary outcomes. It records 91 outcome measures and 21 analyses, but the analysis details and the results for the primary endpoint are not reported in the registry record.

The Full Analysis Set is defined as randomized patients treated with at least one dose of study medication. Further details about randomization, allocation concealment, masking beyond the open-label designation, follow-up procedures, and the analysis plan are not reported in the registry record. These omissions limit how fully the conduct and interpretation of the comparison can be evaluated.

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: In the study there were 630 patients entered as stated in the protocol section. There were 10 patients not treated and are not included within the Participant Flow Module or any other analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS, Full Analysis Set includes all randomized patients treated with at least one dose of study medication

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: Safety Set, all patients treated with at least one dose of study drug

6. Primary Endpoint

The registry lists the primary outcome as Treatment Response at Week 48, measured over At week 48.

The primary endpoint is treatment response at week 48, expressed as a percentage of participants. The registry defines response as two consecutive viral-load measurements at least 1 log10 below baseline, provided that the participant did not discontinue study drug, change the antiretroviral background, or experience rebound. This definition combines a virologic threshold with conditions about treatment continuation and changes in background therapy. A participant who did not satisfy all parts of the definition would not meet the recorded response criterion.

A fixed-time response endpoint can describe the proportion of an analysis population meeting a specified outcome by a particular follow-up time. It is easier to interpret as a clinical-trial outcome than a continuous measure when the question is framed as meeting a defined response criterion. Its interpretation still depends on the exact definition, the analysis population, and how missing measurements or treatment changes were handled.

The registry record does not report the number or percentage meeting the primary endpoint in either group, the between-group estimate, or an uncertainty interval. Consequently, the endpoint definition can be described, but the result itself and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary percentage outcome: whether a participant meets the defined treatment-response criterion. It names the primary endpoint and the Full Analysis Set, but does not report an effect estimate or the statistical procedure used to compare groups. The explanations below describe general statistical concepts relevant to this kind of outcome; they are not claims about unreported procedures in this study.

What does a response percentage describe?

For a binary endpoint, each participant is classified as meeting or not meeting the specified criterion. The response percentage describes the share classified as meeting it in an analysis population. A percentage alone is descriptive. For a treatment comparison, interpretation also requires a contrast between groups and an account of uncertainty around that contrast. Neither the group response percentages nor a comparative estimate for the week 48 primary endpoint is reported in the registry record.

The definition matters because it determines who is counted as a responder. In RESIST, response requires two consecutive viral-load measurements meeting the stated threshold, as well as no study-drug discontinuation, no change in the antiretroviral background, and no rebound. A different operational definition could classify some participants differently. The registry gives the endpoint definition, but does not report further details on measurement schedules, adjudication, or how borderline or unavailable measurements were treated.

What would an uncertainty interval add?

In general, a confidence interval describes the range of effect estimates reasonably compatible with the observed data under the method used. It helps readers judge the precision of an estimate, rather than treating a point estimate as exact. A narrow interval generally indicates greater precision than a wide interval, while the interval’s location indicates which effect values remain compatible with the data. The registry record does not report a confidence interval for the primary comparison, so its precision cannot be evaluated.

A significance test and a confidence interval answer related but different questions. A test assesses compatibility with a specified null hypothesis under its assumptions; a confidence interval displays a range of plausible effect values under the selected method. Neither alone establishes clinical importance, and neither resolves bias arising from study conduct or outcome measurement. The registry record does not report the primary test result or statistical method, so no test-based conclusion can be drawn.

Why does the analysis population matter?

The Full Analysis Set is defined as randomized patients who received at least one dose of study medication. This definition excludes patients who were randomized but never treated, while retaining treated randomized patients according to the stated population description. In general, analysis populations influence the estimand: the population and treatment conditions to which the result pertains. The registry does not provide participant flow, explain how missing outcome measurements were handled, or state whether other analysis populations were used.

Because the response definition includes treatment discontinuation and changes in background therapy, handling of these events is particularly important. The record incorporates specified treatment events into the endpoint definition, but does not explain how each event was classified in the outcome data or whether any additional imputation or censoring procedure was used. It is therefore not possible to reconstruct the analysis from the definition alone.

What can be inferred from the analysis listings?

The registry lists 91 outcome measures and 21 analyses. In general, when a study assesses multiple outcomes, timepoints, or analyses, the chance of finding a nominally notable result can increase if many statistical tests are conducted. Multiplicity procedures can address this issue by controlling a chosen error rate or by defining a hierarchy of hypotheses. The record does not report whether a multiplicity adjustment, prespecified hierarchy, or other testing strategy was used. The number of listed measures and analyses alone does not reveal how many tests were performed or how their results were interpreted.

The listed secondary response outcomes cover multiple follow-up timepoints. Repeated measurements can be useful for describing how response changes over follow-up, but results at different timepoints are related rather than independent. In general, their interpretation depends on the analysis strategy and the handling of participants with unavailable measurements. Those details, along with the secondary outcome results, are not reported in the registry record.

How should planning illustrations be read?

In general, a sample-size calculation estimates how many participants would be needed under specified assumptions about the effect, allocation, significance level, and statistical method. It is a planning exercise, not an observed result and not evidence that a completed study had a particular probability of detecting an effect. The planning assumptions recorded for this study describe an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as stated fractions of the observed effect. The record does not report the observed primary effect needed to evaluate such illustrations. No planning count can replace the missing outcome estimate or be interpreted as observed power.

For a binary percentage outcome, the assumptions used in a sample-size calculation should correspond to the chosen contrast and outcome definition. If those assumptions differ from the eventual data or analysis, the planning result may not describe the precision actually achieved. Since the primary response proportions and analysis method are not reported in the registry record, the design illustration cannot be independently connected to the observed week 48 comparison.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Tipranavir(TPV)/Low Dose Ritonavir(r)", "Comparitor Protease Inhibitor(CPR)/Low Dose Ritona")
n      <- c(311, 309)
events <- c(105, 50)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Tipranavir(TPV)/Low Dose Ritonavir(r)  311  105  33.8  28.5  39.3  28.7  39.2  28.7  39.2
ARM  Comparitor Protease Inhibitor(CPR)/Low Dose Ritona  309  50  16.2  12.3  20.8  12.5  20.7  12.5  20.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 91 outcome measures and 21 analyses. It names treatment response at week 48 as the primary outcome and lists treatment response at several earlier timepoints as secondary outcomes. The presence of multiple measures and analyses makes the approach to multiplicity relevant: in general, multiple testing can increase the chance of at least one apparently notable result if each test is treated separately. The registry record does not report a testing hierarchy, multiplicity adjustment, or other strategy for interpreting multiple comparisons. The listed counts alone do not establish how many tests were conducted or which were confirmatory.

The record defines the Full Analysis Set as randomized patients treated with at least one dose of study medication. It does not report participant flow or explain the handling of missing viral-load measurements, withdrawal, or other unavailable endpoint data. Nor does it state whether missing values were imputed, treated as nonresponse, or handled by another method. These choices can affect response percentages and the estimated contrast, so their absence limits reproducibility and interpretation.

The endpoint definition explicitly includes treatment discontinuation, a change in antiretroviral background, and rebound as conditions relevant to response. The registry does not give further analysis rules for these events. It also does not report whether an additional population was used for sensitivity analyses. As a result, the endpoint definition and the named analysis population are available, but the full missing-data and analysis-population strategy is not reported in the registry record.

12. 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: pneumonia (4.2%), pyrexia (3.5%), dehydration (3.2%), diarrhoea (2.9%), renal failure acute (2.9%).

The registry lists serious adverse-event affected counts of 113 for tipranavir with low-dose ritonavir and 61 for comparator protease inhibitor with low-dose ritonavir. The corresponding at-risk counts are 311 and 309. It also records other adverse-event affected counts of 301 and 271, with the same respective at-risk counts. These are descriptive counts as listed; the registry record does not provide comparative estimates or uncertainty intervals for them.

The listed serious-event terms include pneumonia at 4.2%, pyrexia at 3.5%, dehydration at 3.2%, diarrhoea at 2.9%, renal failure acute at 2.9%, and Pneumocystis jiroveci pneumonia at 2.3%. The registry does not give further detail about event definitions, follow-up duration, or how repeated events were counted. Death counts are not reported in the registry record.

These figures should be read as registry safety listings rather than as adjusted evidence of a difference between groups. The counts alone do not account for uncertainty, differences in follow-up, or other possible influences on event reporting. They also do not replace the absent comparative efficacy result.

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

The registry record establishes what the study set out to compare and how its primary response endpoint was defined. It describes treatment-experienced people with HIV-1 infection, tipranavir with low-dose ritonavir, and a comparator protease inhibitor with low-dose ritonavir. It also identifies the Full Analysis Set and names treatment response at week 48 as the primary outcome. These details help clarify the intended question, but they are not the primary endpoint result.

The record does not report the week 48 response percentages, the contrast between groups, or an uncertainty interval. It therefore does not show the magnitude or precision of the primary comparison. This missing result should not be interpreted as proof of no difference, equivalence, or benefit. Without a reported estimate, none of those conclusions can be assessed from the registry record.

The record’s title describes the study as randomized, while allocation is not stated and a comparison note warns that the arms are not a like-for-like control comparison. This qualification matters when interpreting group contrasts: a treatment comparison is most persuasive when the design and analysis support a fair comparison of groups. The available information is insufficient to resolve how allocation was conducted or how any imbalance or bias was addressed.

Safety counts and event percentages add descriptive information, but do not by themselves establish a comparative safety effect. The record does not provide uncertainty for these counts or the detail needed to assess follow-up and event ascertainment. In general, a trial result is best interpreted by considering its estimate, precision, analysis population, endpoint definition, and design together. Several of those components are not reported in the registry record.

14. Why This Trial Matters Statistically

RESIST illustrates why an outcome definition and an outcome result are different kinds of information. The registry describes a specific week 48 response criterion that combines repeated viral-load measurements with conditions related to treatment discontinuation, background therapy, and rebound. That definition clarifies what the primary endpoint was intended to capture. However, without response proportions and a between-group estimate, the central comparative question remains unanswered in the registry record.

The record also shows why a trial label should not substitute for design detail. Although the official title calls the study randomized, allocation is not stated, and the comparison note cautions against treating the arms as a like-for-like control comparison. Statistical interpretation depends not only on the stated study type but also on whether the actual allocation and analysis support the intended comparison.

Multiple outcomes and analyses make transparent statistical planning important. The registry lists many outcome measures and analyses, but does not describe a multiplicity strategy or give results for the primary and secondary response outcomes. Without those details, readers cannot assess how the analyses were prioritized or how uncertainty from multiple testing was addressed.

Finally, the registry illustrates the distinction between descriptive safety counts and comparative evidence. Counts and listed event percentages communicate what was recorded, but a comparative interpretation requires context, methods, and uncertainty. The record’s limitations are therefore not merely a matter of presentation: they constrain what can be concluded statistically.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting efficacy is that the registry record does not report the primary week 48 response results. No group percentages, comparative estimate, confidence interval, or test result are available in the record. The endpoint can be described, but its observed direction, size, and precision cannot be assessed.

There is also an unresolved design-description issue. The official title describes a randomized study, but allocation is not stated, and the comparison note says the arms are not a like-for-like control comparison. The registry does not explain the basis for that caution or provide sufficient allocation detail to evaluate the comparison independently.

Important analysis details are absent. The record does not describe missing-outcome handling, participant flow, the statistical model or test for the primary endpoint, the treatment of endpoint-related events beyond the definition, or any sensitivity analyses. Although it lists 91 outcome measures and 21 analyses, the analysis plan and any multiplicity approach are not reported.

The registry gives selected safety counts and serious-event percentages but does not report death counts, follow-up duration for safety, event definitions, or comparative uncertainty. The specific comparator drugs are also not identified in the intervention listing. These gaps limit assessment of both safety comparisons and the clinical context of the active comparator. Collectively, they mean the registry record supports a description of the study question and selected recorded outcomes, but not a complete evaluation of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Randomized Evaluation of Strategic Intervention in Multidrug Resistant Patients With Tipranavir (RESIST) — NCT00054717.
• Registry record last updated 2014-07-02; status last verified 2014-04.
• Results first posted 2009-11-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

RESIST is a completed phase 3 parallel-group study sponsored by Boehringer Ingelheim, with enrollment listed as 630. It concerns people with HIV-1 infection who had experience with multiple antiretroviral drugs. The study compared tipranavir with low-dose ritonavir against a comparator protease inhibitor with low-dose ritonavir.

The primary outcome was treatment response at week 48, defined using consecutive viral-load measurements and conditions concerning treatment discontinuation, changes to background therapy, and rebound. The Full Analysis Set is described as randomized patients treated with at least one dose of study medication.

The registry record does not report the primary response results, their comparative estimate, or its precision. Allocation details, missing-data handling, statistical methods, and multiplicity procedures are also not reported. Selected serious and other adverse-event counts are listed, but the record does not provide a comparative safety estimate or death count.