Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients (NCT02866682), a randomized phase 4 study. The primary outcome is Time to First Occurrence of Acute Rejection, Failure, Death.

2. Clinical Question

3. Trial Design

The registry describes a completed, phase-four, randomized, unmasked, parallel-group study sponsored by the University of California, Los Angeles. The recorded enrollment is 176. The study began on 2018-03-01, and its primary completion date is 2021-06-11. The stated condition is renal transplant rejection.

The planned comparison involved brand tacrolimus and a specific generic product. In the randomized phase, one arm received brand tacrolimus throughout the study and the other received Generic A throughout. The registry’s brief summary also describes a second phase in which participants enrolled only on generic tacrolimus, based on the generic medication available through a participant’s insurance. It says the first phase ended after 40 brand participants were enrolled and describes goals of 160 generic participants and 200 participants overall. These are described as plans; the record’s enrollment field reports 176.

Randomization can reduce systematic differences between treatment groups when it is applied to the comparison being analyzed. It does not, by itself, ensure that all participants included in a later analysis were randomized to both options. The registry does not report which participants were included in the primary outcome analysis, whether the later generic-only phase was combined with randomized participants, or how any such combination was handled.

The study was unmasked, so treatment assignment was not concealed from participants and study personnel after assignment. This may matter for outcomes involving behavior or clinical decisions, although the primary outcome includes clinical events. The registry does not report procedures intended to limit assessment bias. It describes the study as six-center in its summary, but does not report center-specific enrollment or outcomes.

The record lists ten outcome measures and no analyses. It identifies several secondary outcomes, including graft rejection and graft failure at one year, infectious episodes, malignancy, death or loss to follow-up, immune measures, medication adherence and quality of life. The registry does not provide numerical results for those outcomes 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.

Before assignment: 5 participants withdrew prior to randomization.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No participants experienced graft rejection or death in the Brand Tacrolimus group. Only 1 participant on the Brand group experienced graft failure. On the other hand, the generic group had 9 participants that experienced rejection, 1 that experienced graft failure, and 1 that experienced death.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Time to First Occurrence of Acute Rejection, Failure, Death, measured over 1 year post-transplant.

The primary endpoint is labeled time to first occurrence of acute rejection, graft failure or death, with a timeframe of one year after transplant and a unit of days. A time-to-first-event endpoint records how long it takes until the first qualifying event for a participant. It combines the timing of events into a single outcome while avoiding counting later events in the same participant as additional first events.

The registry defines acute rejection as biopsy-proven rejection according to Banff 2007 criteria. Graft failure includes retransplantation or death and, for kidney transplant, return to dialysis. Because death is included in the graft-failure definition and is also named as a component of the composite endpoint, the categories may overlap. The event counts in the record should not be added to create a composite total.

Combining clinically important events can make a single endpoint more informative than considering one event type alone, but the components can differ in frequency and meaning. The interpretation of a composite depends on the definitions, the timing of events and the contribution of each component. The registry gives component counts in narrative form, but does not report participant-level overlap, event times, a composite event count or a between-arm estimate for time to first occurrence.

The outcome metadata describe a mean and standard deviation, but the registry does not report the corresponding group values. Nor does it report a hazard ratio or another numerical comparison of event timing. The endpoint’s stated purpose and definition are therefore available, while its numerical comparative result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group study without masking. It does not report the detailed statistical analysis plan, the method used to analyze the primary endpoint, or a formal comparison of the two treatment groups. The statistical concepts below explain how such data are generally interpreted; they should not be taken as a description of analyses that the investigators performed unless the registry says so.

What does randomization contribute?

In general, random assignment aims to make treatment groups comparable with respect to factors known and unknown at the time of assignment. This supports an interpretation of group differences as potentially related to assigned treatment, provided the randomized comparison is preserved in the analysis and other design and conduct issues are addressed. The registry says that participants were randomized in phase one. It also describes a later generic-only phase, so the presence of randomization in the study does not establish that every participant included in any reported group count was randomized between the two treatments.

The record does not say whether the primary analysis followed an intention-to-treat approach, included only participants who received assigned treatment, or used another analysis population. An intention-to-treat analysis generally retains participants in their assigned groups regardless of later treatment changes. A per-protocol analysis generally applies eligibility or adherence criteria after randomization. These approaches answer different questions and can be affected differently by deviations from assigned treatment. Which approach was used is not reported in the registry record.

How is time to first event usually analyzed?

In general, a time-to-event analysis uses both whether an event occurred and the time until it occurred. It can also account for participants whose event time is not observed during follow-up, using censoring methods. A censoring time indicates that follow-up ended without a recorded event up to that point; it does not establish that an event would never occur. The registry names a one-year timeframe and gives selected component counts, but it does not report event times, censoring information, a survival curve, a hazard ratio or another time-to-event estimate.

The outcome metadata identify a mean and standard deviation in days. A mean describes an average, while a standard deviation describes the spread of observed values around that average. However, neither group’s mean nor standard deviation is reported. These summaries alone would not show the full timing pattern, and the registry does not explain how those summaries relate to the composite time-to-first-event definition. No missing time values or methods for handling them are reported.

Why does a confidence interval matter?

In general, a confidence interval expresses the uncertainty associated with an estimate under a specified statistical procedure. It shows a range of values compatible with the observed data and the method’s assumptions; it is not a guarantee that the true value lies in that particular interval. A point estimate without an interval gives limited information about precision, while a p-value alone does not describe the size of an effect. The registry does not report a confidence interval or p-value for the primary outcome, so neither the magnitude nor its statistical precision can be assessed from a formal comparison.

What can the planning assumptions tell readers?

The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation and a normal approximation. The illustration is described as targeting a stated fraction of the observed effect. For time-to-event outcomes, the stated method gives a total number of events using Schoenfeld; for other outcomes, it gives participants per arm. These are planning assumptions, not a report of the trial’s original design justification or a measure of observed power. The registry does not report the original sample-size justification or any interim analyses. The numerical outputs of the planning illustration are not reported in the registry record.

In general, a planning calculation estimates the information or enrollment that might be needed to detect a chosen effect under stated assumptions. It does not show the probability that the completed study detected an effect, and it does not replace the observed estimate and its uncertainty. If the effect used in a planning illustration is estimated from the same data being evaluated, it also does not provide independent confirmation of that effect.

What is not available for evaluating the analysis?

The record lists no analyses and does not report the model, covariate adjustment, treatment of repeated or competing events, or a multiplicity strategy. It also does not report detailed follow-up completeness or the handling of missing outcome data. These omissions prevent readers from reproducing or fully evaluating a comparative analysis. They do not prove that no analyses were conducted; they mean the relevant methods and results are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists ten outcome measures, including the primary time-to-first-event outcome and secondary measures of rejection, graft failure, infection, malignancy, death or loss to follow-up, immune response, adherence and quality of life. When several outcomes are examined, the chance of at least one apparently notable finding can increase if each is tested separately without accounting for the number of tests. A multiplicity plan may specify which outcomes are confirmatory, how tests are ordered, or whether significance thresholds are adjusted. The registry does not report a multiplicity strategy, an outcome hierarchy beyond identifying a primary outcome, or the results of formal tests.

Missing data can also affect interpretation. For a time-to-event outcome, incomplete follow-up may mean the event time is censored; for other outcomes, a measure may be absent or unavailable. Different methods make different assumptions about why data are missing and how the missing observations relate to outcomes. The registry lists death or loss to follow-up at one year as a secondary outcome, but does not give numerical results for it or describe how loss to follow-up was handled in the primary analysis. The reasons for missing data and any imputation or sensitivity analyses are not reported in the registry record.

The record does not identify the primary analysis population, state whether all randomized participants were analyzed in their assigned groups, or describe exclusions from analyses. It also does not provide outcome-specific denominators for the primary endpoint. The safety summaries report their own at-risk counts, but those figures cannot be substituted for an analysis population for efficacy outcomes. These reporting gaps limit assessment of whether missingness, exclusions or multiple testing affected the conclusions that might be drawn from the data.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: re-hospitalization (33.3%), prolonged hospitalization (25.6%), important medical event requiring medical intervention (2.6%), life threatening event associated with an immediate risk of death (0.8%).

The safety summary reports serious adverse events for 19 of 39 participants at risk in the brand tacrolimus group and 43 of 132 in the Generic A group. For other adverse events, it reports 32 of 39 and 105 of 132, respectively. These are safety summaries for the groups named in the registry; they are not the primary endpoint counts and should not be used as denominators for the primary outcome. The record also reports zero deaths in the brand group and one in the generic group in its adverse-event summary. This safety reporting is separate from the primary outcome narrative, which describes deaths as a component of the primary endpoint.

The listed serious adverse-event terms include re-hospitalization, prolonged hospitalization, an important medical event requiring intervention, and a life-threatening event associated with immediate risk of death. The registry gives percentages for those terms but does not specify in the record whether participants could contribute to more than one term or provide the denominator used for each percentage. The percentages therefore should not be summed or treated as mutually exclusive categories.

In general, adverse-event summaries describe events reported during a study; they do not by themselves establish that an event was caused by a treatment. The registry does not report a comparative statistical analysis of these safety outcomes or enough detail to evaluate differences in exposure time, event recurrence or attribution.

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

The posted results show that the registry recorded different component-event counts across the brand and generic groups: no rejection or death and one graft-failure report in the brand group, compared with nine rejection reports, one graft-failure report and one death in the generic group. Those counts are descriptive. The record does not give the participant-level overlap among the components or the time to first event, so they cannot be converted into a composite endpoint estimate.

The study’s primary question concerns time to first occurrence, not simply a comparison of isolated counts. A statistical comparison would ordinarily need an estimate that reflects the endpoint definition and follow-up, along with information about its precision. The registry does not report such an estimate, a confidence interval or a formal test. The counts therefore do not establish the size, direction or precision of a comparative effect on the primary endpoint.

The record also describes a later generic-only phase, in addition to the randomized phase. Since it does not clarify which participants contributed to the reported primary outcome narrative or how the two phases were treated in analysis, the counts cannot be assumed to represent a direct randomized comparison of all enrolled participants. The safety group denominators are not a substitute for missing primary-outcome denominators.

These limitations do not mean the study had no useful data or that no analysis was conducted. They mean the registry record does not report the information needed for readers to assess a formal comparative result. The completed status and recorded enrollment describe the study’s status and size, not the statistical certainty of any treatment difference.

In general, interpreting a clinical trial requires attention to the design, the outcome definition, the analysis population, the amount and pattern of missing data, and the estimated effect with its uncertainty. For this record, the design and selected event counts are described, but key comparative analysis details are not reported. Conclusions should therefore remain limited to what the registry explicitly records rather than extending to a claim that one treatment is superior, equivalent or ineffective.

13. Why This Trial Matters Statistically

This study addresses a statistical question that is common in clinical research: how to compare a brand-name treatment with a generic product when the outcome of interest is a clinical event rather than a pharmacokinetic measure. The registry identifies acute rejection, graft failure and death as the components of its primary endpoint and specifies a time-to-first-event framing. Those choices make the endpoint definition, follow-up and analytic approach central to interpretation.

The record also illustrates why randomization and the analysis population need to be considered together. A randomized phase is described, but the study summary also describes a later generic-only phase. Without a clear account of which participants enter each analysis, readers cannot assume that all group counts retain the balance created by random assignment. The registry’s open-label design and its limited reporting of outcome assessment methods are further considerations when interpreting clinical event data.

Finally, the difference between a descriptive count and an estimated treatment effect matters. Event counts can show what the registry recorded, but a comparative estimate and its uncertainty are needed to understand how compatible the data are with a range of possible effects. Here, the record reports selected counts but no numerical primary endpoint comparison or confidence interval. That makes transparent reporting of endpoint definitions, analysis populations, missing-data handling and statistical methods especially important.

The record is therefore statistically informative about the planned question and the categories of events reported, while leaving substantial uncertainty about the comparative analysis. It provides a useful example of why registry status, enrollment, event counts and inferential results are distinct kinds of information.

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 for interpreting this trial record is that the primary outcome’s numerical comparative result is not reported. The registry supplies a time-to-first-event definition and selected event counts but no group-specific event-time summaries, formal estimate, confidence interval or p-value. The participant-level overlap among rejection, graft failure and death is also not stated, so a composite count cannot be reconstructed.

The record’s design description includes a randomized phase and a later generic-only phase. It does not report whether the primary outcome narrative concerns only the randomized participants, includes later-phase participants, or uses another analysis population. The recorded enrollment is 176, while the brief summary describes a planned total of 200 and phase goals of 40 brand and 160 generic participants. The registry does not explain the difference between the stated plan and recorded enrollment.

The study was unmasked. The record does not describe whether outcome assessment was blinded, how event adjudication was conducted, or whether assignment could affect reporting or clinical decisions. The registry identifies biopsy-proven acute rejection according to Banff 2007 criteria, but does not provide further detail about ascertainment or adjudication in the reported results.

The primary outcome is specified for one year after transplant, but the record does not report completeness of follow-up, primary-outcome denominators, or handling of loss to follow-up and missing data. It lists death or loss to follow-up as a secondary outcome without numerical results in the record. The safety summaries give at-risk denominators, but it is not reported whether these correspond to the efficacy analysis population or how recurrent events were handled.

Finally, the statistical analysis plan, multiplicity approach, interim analyses and original sample-size justification are not reported in the registry record. These omissions restrict assessment of the analysis and the strength of any comparative inference.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prospective Study Comparing Brand and Generic Immunosuppression on Transplant Outcomes, Adherence, & Immune Response in Kidney Transplant Recipients — NCT02866682.
• Registry record last updated 2023-04-28; status last verified 2023-04.
• Results first posted 2023-04-28.
• 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

The registry describes a completed phase-four, randomized, unmasked, parallel-group study sponsored by the University of California, Los Angeles. Its recorded enrollment is 176, with a start date of 2018-03-01 and a primary completion date of 2021-06-11. The randomized phase compared brand tacrolimus (Prograf) with Generic A; the study summary also describes a later generic-only phase.

The primary endpoint was time to first occurrence of acute rejection, graft failure or death within one year after transplant. The registry reports selected component counts in narrative form, plus serious and other adverse-event summaries. It does not report a numerical primary endpoint comparison, confidence interval or formal test. The record lists ten outcome measures and no analyses, and does not report the primary analysis population, multiplicity strategy or missing-data methods.

The results should therefore be read as limited descriptive registry reporting, not as a quantified comparison of the primary endpoint. The status is marked completed, but the registry record does not report the statistical information needed to assess the magnitude and precision of a treatment difference.