This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy (NCT04381988), a randomized phase 2 study. The primary outcome is Cumulative Incidence of SARS-CoV-2 Infection.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04381988 |
| Phase | Phase 2 |
| Condition | COVID-19, Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 4 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with cancer who were receiving radiotherapy. The registry describes eligibility as requiring patients to be scheduled for at least 10 radiation treatments before starting the assigned study tablets. The number enrolled was 4.
Intervention
Hydroxychloroquine, described in the arm information as 400mg daily, after the required radiation-treatment schedule.
Comparator
A placebo tablet described as 400mg daily, after the same radiation-treatment schedule. The registry says the placebo looked like the study drug and did not contain active ingredients.
Primary question
What was the cumulative incidence of SARS-CoV-2 infection within 9 weeks of randomization? The registry states that a positive RT-PCR test during the period counted as an event, but also says primary outcome data were not collected.
The clinical question concerns prevention of infection during radiotherapy, rather than treatment of an established infection. The registry describes a Phase II, randomized, double-blind, placebo-controlled trial. Its stated primary endpoint was cumulative incidence of SARS-CoV-2 infection. A secondary outcome was cumulative incidence of severe COVID-19 or death.
The available record does not provide outcome counts or a comparison of infection rates between the assigned groups. It therefore does not answer the efficacy question. The record also does not report why the trial was terminated or provide an explanation for the absence of primary outcome data. Those omissions limit interpretation of both the trial’s conduct and its clinical findings.
3. Trial Design
This was a Phase II randomized, double-blind, placebo-controlled trial with a parallel-group design. Memorial Sloan Kettering Cancer Center was the sponsor. The registry lists an enrollment of 4 and a status of terminated. It records a start date of 2020-05-07 and a primary completion date of 2021-04-21.
The two groups were hydroxychloroquine and placebo. For both groups, the arm descriptions say patients had to be scheduled for at least 10 radiation treatments before beginning the assigned daily tablets. The descriptions specify 400mg daily for hydroxychloroquine and 400mg daily for placebo. The registry also lists radiation therapy as an intervention, reflecting the clinical context in which the study drug or placebo was to be given.
Randomization is a design method for assigning participants to groups so that, on average, differences in outcomes can be compared without relying on patients or investigators choosing treatment. Blinding is intended to reduce the influence of knowing the assigned group on care or outcome assessment. The registry labels masking as triple, but does not describe which roles were masked or how masking was maintained. Allocation details beyond the randomized designation are not reported in the registry record.
The small enrollment and lack of collected primary outcome data mean that the record cannot support a comparative estimate of infection risk. The reason for termination, the planned enrollment target, and the protocol’s sample-size justification are not reported in the registry record. No conclusion about whether the study ended as planned can be drawn from status alone.
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
| Stage | Hydroxychloroquine | Placebo |
|---|---|---|
| STARTED | 4 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 0 |
Reasons for not completing this period:
| Reason | Hydroxychloroquine | Placebo |
|---|---|---|
| The study was terminated | 4 | 0 |
Analysis population for the primary outcome, as defined in the registry: Data were not collected.
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: The study was terminated before more participants were accrued.
| Characteristic | Unit | Hydroxychloroquine | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 0 | 4 | |
| Age, Continuous | years | 63 (58 to 70) | — | 63 (58 to 70) |
| Sex: Female, Male: Female | Participants | 3 | 0 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 0 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 4 | 0 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 4 | 0 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Incidence of SARS-CoV-2 Infection, measured over within 9 weeks from randomization.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was cumulative incidence of SARS-CoV-2 infection. The registry defines an event as a positive SARS-CoV-2 RT-PCR test at any point during the specified follow-up period. It says outside RT-PCR test results were allowed. The timeframe is stated as within 9 weeks from randomization, while the endpoint description also refers to the 9 weeks following enrollment. The record does not clarify this difference in wording.
Cumulative incidence describes the occurrence of an event over a defined period in a group of participants. It is useful when the research question asks how often an event happens during follow-up, rather than how quickly it happens or how many times it recurs. In this trial, the endpoint was intended to capture detected infection during the stated period after assignment to hydroxychloroquine or placebo.
However, the registry says that data were not collected for the primary outcome. It reports no group-specific infection counts, cumulative-incidence estimates, confidence intervals, or statistical comparison. Consequently, the endpoint’s definition can be described, but its observed value and the difference between groups cannot be assessed from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry establishes the study question and design, but it does not provide an estimate of the primary outcome. It states that primary outcome data were not collected and lists zero outcome analyses. There are no reported infection counts or group-specific cumulative-incidence values to compare. The record therefore provides no statistical evidence about whether infection incidence differed between the hydroxychloroquine and placebo groups.
The enrollment was 4. The adverse-event listing records 4 participants at risk in the hydroxychloroquine group and 0 in the placebo group. These figures describe the groups represented in that safety listing; they do not supply an efficacy comparison. In particular, the listed safety denominators should not be treated as outcome data for the primary endpoint. The record does not explain why the placebo group has no participants at risk in that listing.
Because no primary outcome data or analyses are reported, there is no effect estimate whose precision can be evaluated. A confidence interval would ordinarily show a range of values compatible with the observed data under the analysis assumptions; neither an interval nor an underlying primary-outcome estimate appears in the record. A p-value is also not reported. Neither statistical significance nor lack of statistical significance can be inferred from the absence of an analysis.
The trial status is terminated, but the reason for termination is not reported in the registry record. Termination does not itself establish that a treatment was beneficial, ineffective, harmful, or impossible to study. Likewise, the very limited enrollment does not establish what the study would have found with a different enrollment or completed follow-up. The record does not report whether participants completed follow-up, whether any were excluded from analysis, or why primary data were not collected.
The secondary outcome was cumulative incidence of severe COVID-19 or death. No results for that outcome are reported either. The serious-adverse-event listing reports no serious events in either listed group, but the unequal at-risk counts mean it cannot be read as a balanced safety comparison. The listing also does not replace a complete assessment of adverse events.
Overall, the record supports a description of the planned comparison, endpoint, and limited safety reporting. It does not support a numerical estimate of treatment effect, a claim of statistical precision, or a conclusion about the clinical effect of hydroxychloroquine in this population.
9. Statistical Methods Explained
The registry describes a randomized, double-blind, placebo-controlled, parallel-group study. These design features matter because a comparison between groups is informative only when the groups, outcomes, follow-up, and analysis are adequately described. In a randomized study, assignment is intended to reduce systematic differences between groups. Blinding is intended to reduce bias that can arise when participants or study personnel know the assignment. The record says masking was triple, but does not identify the masked roles or give operational details.
What would the primary analysis estimate?
The primary endpoint was cumulative incidence of SARS-CoV-2 infection during the specified follow-up period. A trial analysis would ordinarily report the number of events and the number of participants contributing data in each group, then estimate the endpoint for each group and compare them using a prespecified method. The registry does not report those counts, estimates, or a method of comparison. It explicitly states that primary outcome data were not collected, and it lists no outcome analyses.
A confidence interval expresses statistical uncertainty around an estimate. Its width depends on the amount and variability of the information available and on the analysis method. Without outcome counts or an estimate, there is no interval to interpret. A p-value, if reported, would address how compatible the data are with a specified statistical model under a null hypothesis; it would not by itself describe the size or clinical importance of an effect. No p-value is reported in this record.
How should the planning assumptions be understood?
The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The record does not provide a usable observed primary effect because primary outcome data were not collected. No planning counts or protocol sample-size justification are reported in the registry record. A planning illustration is not an observed result, and it is not evidence that a study had a particular probability of detecting an effect. Sample-size calculations are design aids, not a substitute for reported outcomes and uncertainty.
More generally, a planning calculation depends on the effect size the study aims to detect, the chosen significance level, the desired power, allocation, and the assumptions of the statistical method. If an assumed effect is not supported by reliable evidence, the resulting target can be misleading. The registry’s description of an illustration does not establish that those assumptions were the protocol’s design choices.
What does the outcome timeframe imply?
A fixed follow-up window makes the event definition interpretable over a common period, provided participants have comparable follow-up and outcome ascertainment. The registry describes positive RT-PCR tests as events and permits outside test results. It gives the timeframe as within 9 weeks from randomization, but the endpoint description also says the period follows enrollment. The record does not clarify the distinction or report how testing, incomplete follow-up, or outside results were handled in an analysis.
In general, missing outcome information can affect estimates if the likelihood of missingness is related to a participant’s outcome or assigned group. Statistical approaches may require assumptions about why data are missing. The registry does not report a missing-data method, the extent of missingness, or an analysis population for the primary endpoint. Since it says primary data were not collected, there is no basis in the record for judging how missingness was handled.
Why do group counts matter?
For a two-group comparison, the number of participants contributing outcome information in each group is important for both the estimate and its precision. Randomization alone does not guarantee that the analyzed groups remain balanced, especially when enrollment is limited or outcomes are unavailable. The registry reports enrollment of 4, while the safety listing identifies 4 at risk in the hydroxychloroquine group and 0 in the placebo group. Those safety figures do not supply the missing primary outcome data and should not be used to infer the number analyzed for efficacy.
Over-dispersion is a general statistical concern when observed variability exceeds what a chosen model assumes; it can make standard errors too small if ignored. Whether over-dispersion is relevant depends on the outcome and model. The registry does not report a primary analysis model or enough outcome data to assess this issue. No particular adjustment or model can be attributed to this study from the record.
Likewise, the registry does not report interim analyses, stopping rules, covariate adjustment, an intention-to-treat analysis, a per-protocol analysis, or a prespecified method for handling multiple outcomes. These methods may be important in clinical trials, but their use in this study cannot be inferred from general design labels. The statistical interpretation must therefore remain limited to the design and reporting details that appear in the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome of cumulative incidence of SARS-CoV-2 infection and a secondary outcome of cumulative incidence of severe COVID-19 or death. It does not report a statistical plan for testing these outcomes, an order of testing, or an adjustment for multiple comparisons. Multiplicity refers generally to the increased chance of false-positive findings when several hypotheses are tested. Whether and how that issue was addressed is not reported in the registry record.
The record states that primary outcome data were not collected and lists no outcome analyses. It does not report results for the secondary outcome. There is therefore no set of reported outcome tests from which to assess multiplicity in practice.
Missing-data methods, the extent and reasons for missing outcome information, and the analysis population are not reported in the registry record. The record does not say whether all randomized participants were intended to be included in an intention-to-treat analysis, whether a per-protocol population was planned, or how participants with incomplete follow-up would be handled. These details should not be inferred from the randomized design.
The status is terminated, but the reason for termination and any decision process related to the missing data are not reported. The registry also does not report interim analyses or stopping rules. Without those details, it is not possible to assess how the final analysis plan, outcome availability, or trial stopping affected the reported evidence.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Hydroxychloroquine | 0 | 4 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Hydroxychloroquine | 0 of 4 |
| Placebo | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Hydroxychloroquine | 0 of 4 |
| Placebo | 0 of 0 |
The serious-adverse-event listing reports 0 serious events in the hydroxychloroquine group and 0 in the placebo group. It lists 4 participants at risk in the hydroxychloroquine group and 0 in the placebo group. No serious-event terms are listed.
These figures need to be read with the group denominators in view. The placebo listing has no participants at risk, so it does not provide a meaningful safety comparison between groups. The record does not explain why the placebo at-risk count is 0 or describe the completeness of adverse-event reporting. The total enrollment was 4, but the safety listing should not be assumed to represent a complete, balanced safety population.
A report of 0 serious events in a listed group does not establish that no adverse events occurred, nor does it demonstrate the absence of risk. It describes only the serious-event counts recorded in this listing. The registry does not provide a full account of non-serious adverse events or additional details needed to interpret safety. These figures also do not answer the primary efficacy question, for which the registry says data were not collected.
12. What the Result Does, and Does Not, Mean
The record describes a planned comparison of hydroxychloroquine and placebo among people receiving radiotherapy, with SARS-CoV-2 infection as the primary endpoint. It also records randomization, double-blind, placebo-controlled, parallel-group design features and an enrollment of 4. These details explain the study’s aim and broad structure.
What the record does not establish is whether hydroxychloroquine changed the incidence of infection. Primary outcome data were not collected, no outcome analyses are listed, and no comparative estimates or confidence intervals are reported. There are also no reported results for the secondary outcome of severe COVID-19 or death. The absence of results is not evidence that the groups had the same outcomes, nor is it evidence that one group did better.
The serious-adverse-event listing records 0 events in each group, but the placebo group has 0 participants at risk in that listing. These counts do not provide a balanced comparison or a complete assessment of safety. They should be understood as limited registry reporting, not as proof that serious events could not occur.
The registry status is terminated. The reason for termination, the planned enrollment, the sample-size justification, and the handling of missing outcome information are not reported in the registry record. These gaps prevent conclusions about why the study ended, what level of precision was intended, or how the absence of primary data arose.
The appropriate statistical reading is therefore descriptive: the record documents a research question and design, but supplies no analyzable primary outcome result. It cannot support a claim that the intervention worked, did not work, or had a particular safety profile.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its design and its results record tell different parts of the story. Randomization and blinding describe ways a trial can seek a fair comparison, while outcome data and analysis are needed to estimate that comparison. In this record, the design is described, but the primary outcome data were not collected and no outcome analyses are listed.
The enrollment of 4 also emphasizes why the number of participants contributing outcome information matters. Small or incomplete datasets can leave estimates imprecise, but no estimate or interval is available to quantify precision. It would be inappropriate to turn the enrollment figure into an observed treatment effect or into a statement about statistical power.
The safety listing illustrates another important point: event counts need their denominators and context. Although the listing records 0 serious events in each group, it records 0 participants at risk in the placebo group. That makes the figures unsuitable as a balanced between-group safety comparison.
Finally, a terminated status is not an outcome. Without a reported reason for termination or an analysis plan, readers cannot determine whether termination reflected recruitment, feasibility, data availability, safety, or another cause. The record’s limits are not a statistical finding about treatment; they are limits on what can be learned from the reported 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 is that the registry says primary outcome data were not collected. No infection counts, group-specific estimates, confidence intervals, or statistical tests are reported. The secondary outcome is named, but no results are reported for it. This prevents assessment of either efficacy endpoint.
Enrollment was 4, and the safety listing reports 4 participants at risk in the hydroxychloroquine group and 0 in the placebo group. The record does not explain this discrepancy in group representation. Consequently, the safety counts cannot be interpreted as a balanced comparison, and the registry does not establish how many participants contributed to any efficacy analysis.
The reason for termination is not reported in the registry record. The planned enrollment, protocol sample-size justification, analysis populations, missing-data methods, and statistical analysis plan are also not reported. Interim analyses, stopping rules, and any multiplicity strategy are not described.
The endpoint timeframe is worded as within 9 weeks from randomization in the outcome field and as the 9 weeks following enrollment in its description. The record does not clarify whether those reference points were intended to be equivalent. It also does not detail how outside RT-PCR results, incomplete follow-up, or outcome ascertainment were handled.
These limitations mean the registry supports a description of the trial, not a treatment-effect estimate. They do not establish why information is missing or what the unreported results would have been.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Hydroxychloroquine vs Placebo to Prevent COVID-19 Infection in Patients Receiving Radiotherapy — NCT04381988.
- Registry record last updated 2021-10-27; status last verified 2021-04.
- Results first posted 2021-10-27.
- 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.
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18. Record Summary
The registry describes a Phase II randomized, double-blind, placebo-controlled, parallel-group trial sponsored by Memorial Sloan Kettering Cancer Center. The study compared hydroxychloroquine with placebo for prevention of SARS-CoV-2 infection among people receiving radiotherapy. The arm descriptions specify 400mg daily after patients were scheduled to receive at least 10 radiation treatments.
The registry reports enrollment of 4 and status of terminated. The primary endpoint was cumulative incidence of infection during a stated 9-week period, defined by a positive RT-PCR test. The record says primary outcome data were not collected and lists no outcome analyses. It also lists severe COVID-19 or death as a secondary outcome but provides no results for it.
The serious-adverse-event listing records 0 events in each group, with 4 participants at risk in the hydroxychloroquine group and 0 in the placebo group. The reason for termination and the protocol’s statistical plan are not reported in the registry record.