Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT) (NCT00000142), a randomized phase 2, phase 3 study. The primary outcome is Survival.

2. Clinical Question

Statistically, the key question is whether the assigned strategies differed on the registered survival outcome. That question cannot be answered from the registry record alone: it gives the outcome name and follow-up description but no survival counts, event times, effect estimate, confidence interval, or test result. The safety figures are a separate part of the record and should not be treated as evidence about the primary outcome.

3. Trial Design

The registry record describes a randomized, parallel-group trial listed as Phase 2 and Phase 3. The trial was unmasked, so masking is recorded as none. The stated enrollment is 64. The record lists Johns Hopkins Bloomberg School of Public Health as sponsor and gives the status as completed. It lists a start date of 1994-04 and a primary completion date of 1996-02.

Three strategies are described: treatment deferral until retinitis progressed, low-dose cidofovir, and high-dose cidofovir. Both cidofovir schedules begin with 5 mg/kg intravenously once weekly for two weeks. The low-dose maintenance schedule is 3mg/kg once every 2 weeks; the high-dose schedule is 5mg/kg once every two weeks. After progression, the deferred-treatment arm description allows either maintenance schedule. The registry record does not explain the reason for that choice or provide further allocation details.

The parallel design means the assigned strategies were compared across groups followed within the same trial, rather than having each participant receive every strategy in sequence. Randomization is intended, in general, to reduce systematic differences between assigned groups. It does not guarantee that groups will be identical, especially when enrollment is limited, and it does not replace reporting of baseline characteristics or outcome analyses. Those details are not reported in the registry record.

The stated follow-up plan was to follow all enrolled patients until a common study closing date. The record does not give the closing date, individual follow-up durations, or details about loss to follow-up. It also does not report the allocation procedure, group sizes for the primary outcome, or the protocol’s statistical plan.

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

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 Survival, measured over All patients enrolled will be followed until a common study closing date.

The registered primary endpoint is survival, with the unit described as participants. In general, survival is an outcome concerned with whether participants remain alive over a defined follow-up period. It can be represented as a status at a specified time or analyzed as time until an event, depending on the protocol and available data. The registry record says all enrolled patients were to be followed until a common study closing date, but it does not give a specific assessment time or a more detailed endpoint definition.

Survival can be clinically important in trials involving serious illness because it directly describes mortality rather than relying only on an intermediate measure. Statistically, a clear definition is needed to interpret such an endpoint: the event, time origin, follow-up window, censoring rules, and analysis population all affect what an estimate means. These details are not reported in the registry record.

The outcome is classified as binary, but the registry record notes that the primary outcome has several categories or time points and does not reduce it to one comparison. No category-specific survival results, event counts, survival estimates, or uncertainty intervals are reported. As a result, the endpoint’s intended meaning can be described, but its observed result and comparative effect cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how a trial turns observations into estimates and how much uncertainty should accompany those estimates. The registry record identifies randomization, an unmasked parallel design, a survival endpoint, and a planning illustration based on general assumptions. It does not report the analysis method used for the primary outcome. The distinctions below are general explanations, not claims about analyses performed in this trial.

What does randomization contribute?

In general, randomization assigns participants to study strategies using a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment. When the process is implemented and analyzed appropriately, it supports interpreting group differences as associated with the assigned strategies rather than with deliberate selection. Randomization does not ensure equal baseline characteristics in every trial, and it does not address problems that arise after assignment, such as missing outcome data or departures from the planned treatment strategy. The allocation procedure and the primary analysis population are not reported in the registry record.

What does an unmasked design mean?

An unmasked design means masking is recorded as none. In general, masking can reduce the influence of knowledge about assigned treatment on care, reporting, outcome assessment, and analysis decisions. Its relevance depends on the outcome and how that outcome is measured. Survival is less dependent on subjective scoring than many outcomes, but the registry record does not describe how survival status was established or whether outcome assessment had safeguards against bias. The unmasked designation alone does not establish that bias occurred.

How should a survival outcome be analyzed?

In general, a survival analysis considers both whether an event occurred and when it occurred. It can use information from participants who have different lengths of follow-up, including participants whose outcome status is not yet known at the end of observation. Such methods require clear rules for the event, time origin, censoring, and follow-up. A common study closing date is described in the registry record, but individual follow-up times, censoring rules, and the analysis method are not reported. Although survival analyses often use time-to-event methods, it would be inappropriate to assume that this trial used a particular model.

A confidence interval, in general, gives a range of values compatible with the observed data under the analysis assumptions. Its width indicates statistical precision: a wider interval reflects more uncertainty about the estimated effect, while a narrower interval reflects greater precision. An interval is not reported for the primary outcome, so the precision of any survival comparison cannot be assessed. A p-value, if reported, would address compatibility with a specified null hypothesis under a statistical model; it would not by itself describe the size or clinical importance of an effect. No primary-outcome p-value is reported.

What does the planning illustration describe?

The registry record states that its sample-size assumptions are for a planning illustration computed from the observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events; for other tables, it is participants per arm. These are planning assumptions, not evidence about the trial’s original sample-size justification or actual statistical power. The registry record does not report the original protocol’s sample-size calculation or justification. A planning illustration based on an observed effect should not be described as observed power.

General sample-size planning asks how much information would be needed to detect an effect of a specified size under stated assumptions. Results depend on the chosen effect, variability or event frequency, significance threshold, allocation, and analysis method. Changing an assumed effect changes the planning requirement. Such calculations do not recover missing outcome data and cannot show that the completed trial did or did not detect an effect. No planning result values are reported in the registry record.

Why are outcome details and uncertainty important?

A treatment comparison needs a defined contrast, an outcome at a defined time or over a defined follow-up period, and an estimate of effect. The estimate describes the observed difference or association; its uncertainty describes how much the data leave unresolved. In general, counts alone can be difficult to interpret when groups differ in follow-up or when event definitions and denominators are unclear. A full analysis would make those elements explicit. The registry record does not report a primary survival comparison, so neither its magnitude nor its precision can be described.

10. Multiplicity, Missing Data and Analysis Populations

The registry record notes that the primary outcome has several categories or time points and is not reduced to one comparison. When several outcomes, time points, or treatment comparisons are examined, the chance of a nominally unusual result can increase if each is tested separately. In general, multiplicity methods can define a primary contrast in advance, adjust statistical thresholds, or otherwise account for the set of analyses. The record does not report a multiplicity strategy, a hierarchy of comparisons, or which time point or category was intended to carry the main inference.

Missing data can also affect interpretation. In general, incomplete outcome follow-up may bias a comparison if the likelihood of missingness is related to treatment assignment or outcome status. Analysis methods rely on assumptions about why observations are missing; sensitivity analyses can examine how conclusions change under different assumptions. The record says all enrolled patients were to be followed until a common study closing date, but does not report completeness of follow-up, missing outcome counts, reasons for missingness, or methods for handling missing data.

The analysis population is not reported in the registry record. It is therefore unclear whether the primary analysis included participants as randomized, only those who received treatment, or another defined group. The registry record also gives no primary analysis results or protocol-level statistical plan. These omissions prevent assessment of how multiplicity, missing outcomes, and analysis-population choices were handled.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: proteinuria 2+ (66.7%).

The registry record lists serious adverse-event counts of 3 for treatment deferral, 13 for cidofovir (low dose), and 8 for cidofovir (high dose). It lists other adverse-event counts of 0, 2, and 2 for those groups, respectively. The listed serious-event counts at risk are 26, 26, and 12; the listed other-event counts at risk are also 26, 26, and 12. The record identifies Proteinuria 2+ as a top serious term and gives 66.7%.

These are safety figures, not the primary survival outcome. The record does not explain the event definitions, event collection period, severity grading details, or whether the counts refer to participants with at least one event or to event occurrences beyond the general classification as participants with an event. The listed figures should therefore be interpreted in the context of those reporting limits. The Proteinuria 2+ percentage is reported without a group assignment in the record, so it cannot be attributed to a particular treatment group from this information alone.

Differences in recorded counts do not, by themselves, establish that a treatment caused an event or that one strategy is safer. Follow-up time, definitions, and statistical comparisons matter, and those details are not reported in the registry record.

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

The registry record supports a description of the trial’s purpose, treatment strategies, design, and registered primary outcome. It does not provide the survival results needed to judge the size or direction of a difference between treatment deferral and the cidofovir schedules. It also does not report uncertainty intervals or a statistical test for survival. Consequently, the record cannot support a conclusion that any strategy changed survival, or that the strategies had equivalent outcomes.

The treatment descriptions show that the active schedules used intravenous cidofovir, with different stated maintenance doses. The deferred strategy delayed treatment until retinitis progressed and then described either maintenance schedule. These details identify the strategies under study; they do not show how participants responded, whether they adhered to treatment, or whether retinitis progressed. Such results are not reported in the registry record.

The safety figures provide recorded serious and other event counts, along with the listed counts at risk and a reported serious term. They should not be treated as a complete account of safety or as a direct comparison of risks without further information about definitions, timing, and analysis. In particular, the record does not connect the Proteinuria 2+ percentage to a particular group.

In general, a trial result needs to be interpreted through its estimate, uncertainty, endpoint definition, analysis population, and limitations. A completed status does not replace those results. The appropriate reading is therefore descriptive: the registry records a randomized, unmasked trial of cidofovir strategies for retinitis, with survival as the primary outcome, but does not report the primary comparative findings. No treatment recommendation follows from the information in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized, parallel-group comparison of treatment strategies with a survival endpoint, while its registry record leaves the primary comparative results unreported. That contrast illustrates an important distinction: a trial’s design can establish what researchers intended to compare, but the design description alone cannot show what the observed data imply.

The record also highlights why endpoint specification matters. Survival is a meaningful outcome, but interpretation depends on the time frame, event definition, handling of incomplete follow-up, and chosen comparison. The registry record gives a common study closing-date description but does not give the analysis details or result estimates needed to assess those issues. A result without an effect estimate and uncertainty would be difficult to interpret; in this record, those primary results are absent.

The trial’s three strategies and the outcome’s several categories or time points also make the choice of comparison important. In general, an explicit analysis plan helps readers understand which contrast is primary and how multiple comparisons are handled. That plan is not reported in the registry record, so readers cannot determine how the outcome categories or possible comparisons were addressed.

Finally, the record separates planning assumptions from evidence about the completed trial. A planning illustration based on an observed effect is not the same as the original design justification and does not establish observed power. This distinction matters when reading sample-size material: planning calculations can help frame future research, but they do not substitute for reporting the trial’s outcome estimates and their precision.

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 important limitation for statistical interpretation is that primary survival results are not reported in the registry record. There is no primary effect estimate, uncertainty interval, survival count, or test result. The record also says the outcome has several categories or time points and does not reduce it to one comparison, leaving the intended comparison and relevant time point unclear.

Important details for judging the analysis are also absent. The registry record does not report the statistical plan, analysis population, handling of missing data, completeness of follow-up, or the method used to analyze survival. It gives a common study closing-date description but not the closing date or individual follow-up information. Baseline characteristics and the allocation procedure are not reported either.

The design is listed as unmasked, but the record does not describe outcome-assessment procedures. The safety information has limited context: event definitions and observation periods are not reported, and the Proteinuria 2+ percentage is not linked to a particular treatment group. The registry record also does not explain why either maintenance schedule could be used after progression in the treatment-deferral arm.

These reporting gaps limit what can be inferred from the registry entry. They do not establish that the trial lacked an analysis or that any particular bias occurred; they mean that those details are not reported in the registry record. The adverse-event counts and design description cannot fill the gap left by absent primary outcome results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT) — NCT00000142.
• Registry record last updated 2015-11-17; status last verified 2015-07.
• Results first posted 2015-11-17.
• 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 record describes the completed Studies of the Ocular Complications of AIDS (SOCA)--HPMPC Peripheral CMV Retinitis Trial (HPCRT), a randomized, unmasked, parallel-group study listed as Phase 2 and Phase 3. It lists enrollment of 64 and intravenous cidofovir strategies for retinitis: treatment deferral until progression, low-dose cidofovir, and high-dose cidofovir. The registered primary outcome is survival, with follow-up planned until a common study closing date.

Primary survival results and a comparative analysis are not reported in the registry record. The record notes that the primary outcome has several categories or time points and is not reduced to one comparison. Serious and other adverse-event counts are reported by group, as is Proteinuria 2+ at 66.7%, but the record does not provide enough context to interpret these as a complete comparative safety analysis.