Phase 2, Open-Label, Multi-Dose Study of Panhematin in Patients With MDS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2, Open-Label, Multi-Dose Study of Panhematin in Patients With MDS (NCT00467610), a non-randomized phase 2 study. The primary outcome is Safety and Tolerability of Panhematin®..

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, multiple-dose study of Panhematin in patients with MDS. The design is classified as single-group and non-randomized, with no masking. Enrollment was 6. Because there was no concurrent control group, the study can describe observations among participants receiving Panhematin but cannot make a randomized, like-for-like comparison with another group.

The registry lists the study start as 2007-05 and primary completion as 2008-12. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether the planned follow-up was completed.

The brief description lays out a screening period, an 8-week treatment period, and a 6-month post-treatment follow-up. Screening included bone marrow aspiration and biopsy before study medication. Treatment was scheduled for Days 1 through 4 of Week 1 and weekly visits during Weeks 2 through 8. Partial and complete responders in any of the three cell lines could continue treatment for an additional 4 weeks. Monthly clinic visits during Weeks 12 through 40 were planned for follow-up. The record does not report how closely the actual conduct followed this schedule.

The primary outcome is described as a participant count, with follow-up during Panhematin therapy and up to six months after therapy. The timeframe also gives an average of 8 months. The registry record does not report a protocol-level statistical analysis plan, the reason for the chosen enrollment, or details of any interim analyses.

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

Reasons for not completing this period:

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 Safety and Tolerability of Panhematin®., measured over participants were followed during therapy with panhematin, and up to six months post completion of therapy, average of 8 months..

The stated primary endpoint is “Safety and Tolerability of Panhematin®.” Its operational description is the number of patients with no adverse events, with the unit given as participants. The timeframe covers therapy and up to six months after completion of therapy, and is described as an average of 8 months. This is a count endpoint: it is intended to summarize how many participants met the specified no-adverse-events condition during the stated observation period.

In general, a safety endpoint is used to describe unwanted events observed during and after treatment. A count can be useful for reporting how many people meet a defined outcome, but interpretation depends on a clear event definition, consistent collection, and a stated observation period. The registry record does not provide additional criteria defining which events count for the primary endpoint, nor does it report the primary count itself.

The separate safety listing records serious and other adverse events, but those event categories are not interchangeable with the primary endpoint’s “no adverse events” measure. Zero recorded participants affected by serious or other events does not establish how many had no adverse events of any kind. The primary endpoint result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is reported? The primary measure is described as a number of participants, and the registry classifies the outcome as binary: participants either meet a stated condition or do not. Here, the stated condition is having no adverse events. A count reports how many participants meet that condition; a proportion would additionally relate the count to the number assessed. The registry record does not report the primary count or an analysis of it, so no primary proportion can be interpreted from the record.

Why does the design matter? This is a single-group, non-randomized study with no masking. General statistical interpretation of a single-group study is descriptive: outcomes can be observed among the treated participants, but there is no concurrent randomized group to estimate what would have happened under a different treatment or control condition. Random allocation is one way to make groups comparable on average; it was not used. Without a comparator, a before-and-after difference, if one were reported, would not alone identify a causal treatment effect. No such difference is reported in the registry record.

What can the safety counts tell readers? The safety listing separates serious adverse events from other adverse events and gives counts at risk and affected for each category. In general, a count of affected participants is a direct descriptive summary for that category and observation period. It does not characterize event timing, duration, severity beyond the category shown, or repeated events unless those details are separately reported. The record gives 0 affected in each listed category, but does not give a primary count of participants with no adverse events of any kind. These are different summaries and should not be substituted for one another.

How should rates and uncertainty be understood? In general, a rate or proportion places an outcome count in relation to the number observed. A confidence interval can express uncertainty around an estimate; its width depends on the data and method. No primary estimate or confidence interval is reported, and none should be inferred from the safety counts. With few observations, estimates are generally sensitive to individual outcomes. That general caution does not create an unreported estimate or establish the result of an efficacy endpoint.

What analyses are documented? The record lists 0 analyses. It does not report a statistical test, an estimation method, an adjustment for covariates, a confidence interval method, or an analysis population for the outcomes. It also does not report whether outcomes were analyzed as counts, proportions, or in another way beyond the primary outcome’s stated participant count. Thus, there is no basis for describing an unreported inferential analysis or its assumptions.

What does the planning illustration represent? The registry record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumed effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events; for other outcomes, it is participants per arm. These are planning assumptions, not the design of this single-group study. No planning values or observed efficacy effect are reported in the registry record. Such illustrations are not observed power and should not be read as a retrospective measure of whether this trial was adequately powered.

Why can over-dispersion matter in general? For count data, over-dispersion means that variability exceeds what a chosen statistical model expects. A model that ignores it can give uncertainty estimates that are too small. This is a general consideration for count analyses, not a finding about this study: the registry record does not report a count model, a dispersion estimate, or a model-based outcome analysis.

What is absent from the statistical description? The registry record does not report a sample-size justification for the trial, the intended power for its own design, an interim analysis plan, prespecified handling of missing data, or a multiplicity procedure. It does not report confidence intervals or hypothesis tests for the listed efficacy outcomes. These omissions mean the results cannot be assessed against a documented analysis plan from the record alone. They do not establish that a particular method was or was not used outside the registry entry.

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("Group 1")
n      <- c(6)
events <- c(6)
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  Group 1  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 4 outcome measures, including the primary safety and tolerability outcome and secondary hematological improvement outcomes at Week 4 and Week 8. When several outcomes are examined, general statistical practice considers multiplicity: repeated testing can increase the chance of at least one apparently notable finding, depending on the testing strategy. The record does not report a multiplicity adjustment, a hierarchy of outcomes, or which outcomes were designated for confirmatory interpretation. No efficacy analyses are listed, so multiplicity-adjusted or unadjusted findings cannot be evaluated.

Missing-data handling is also not reported in the registry record. The record does not state how withdrawals, incomplete follow-up, unavailable response assessments, or participants who did not complete treatment were handled. The planned schedule includes therapy and post-treatment follow-up, but a planned visit schedule does not establish that each participant attended or had an evaluable outcome at every time point. The reason for termination is not reported, and the record does not describe how termination affected outcome collection.

The analysis population is not reported in the registry record. There is no stated rule identifying which enrolled participants contributed to each outcome, or how denominators were selected. The safety listing gives 6 at risk in Group 1 for each of its two categories, but that does not define the population used for the primary endpoint or the response outcomes. Without an analysis population, missingness approach, and outcome-specific denominators, readers cannot determine whether available outcome counts represent all enrolled participants or a subset. These are reporting gaps, not evidence of a particular method.

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.

The safety listing reports Group 1 with 6 participants at risk for serious adverse events and 0 affected. It also reports 6 at risk for other adverse events and 0 affected. These are counts in the registry’s listed categories, not a complete description of every aspect of safety. No serious adverse-event terms are listed. Deaths are recorded as null, which is not the same as a reported count of zero; the death result is not reported in the registry record.

The primary endpoint is separately described as the number of patients with no adverse events. The safety listing’s zero counts for serious and other adverse events do not establish that endpoint, because it asks about participants with no adverse events rather than only the listed event categories. The primary endpoint result is not reported in the registry record.

In general, zero observed events in a small group does not prove that an event cannot occur or precisely establish its frequency in a broader population. The registry entry does not provide uncertainty intervals, event-level descriptions, or additional follow-up completeness information for interpreting these counts. The safety figures should therefore be read narrowly as the recorded counts for the specified categories.

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

The registry record documents a Phase 2, open-label study of Panhematin in a single group of participants with MDS. Enrollment was 6, and the study status is terminated. The safety listing records 0 participants affected by serious adverse events and 0 affected by other adverse events, among 6 at risk in each category. Those figures describe the entries made for the listed categories.

They do not establish the primary endpoint result. The primary outcome is defined as the number of patients with no adverse events, and that count is not reported in the registry record. The record names hematological improvement outcomes at Week 4 and Week 8 but does not report their results. No efficacy estimate, confidence interval, or statistical test is listed. The available information therefore cannot quantify response or the precision of a response estimate.

The design also limits causal interpretation. Because the trial was non-randomized and had no comparator group, it cannot show how outcomes would have differed under another treatment or no study treatment. Open-label conduct means the study was not masked. These features matter when interpreting observed outcomes because treatment knowledge and the absence of a control condition can affect how observations are collected and what comparisons can be made.

In general, a clinical trial result is most informative when the outcome definitions, analysis population, missing-data methods, uncertainty estimates, and comparison are clear. Several of these details are not reported in the registry record. The record supports a description of its design and posted safety counts, but it does not support a conclusion about efficacy, a precise estimate of safety, or a causal treatment effect.

14. Why This Trial Matters Statistically

This study is statistically informative in part because its design and outcome reporting show why a count should not be interpreted without its definition and context. The primary measure is the number of participants with no adverse events, while the posted safety listing separately counts participants affected by serious and other adverse events. Those measures address different questions. Keeping them distinct prevents a zero in one category from being mistaken for a result on the primary endpoint.

The single-group, non-randomized design also illustrates the difference between describing outcomes and estimating a comparative treatment effect. A group’s observed experience can be reported, but the absence of a concurrent comparator leaves no randomized contrast. The open-label design and the lack of reported analysis details further limit what can be inferred from the record. These are not merely technical qualifications: they define which questions the available data can address.

Small enrollment makes transparent uncertainty especially important in general. A count can be reported exactly, but it may not by itself show how precisely an underlying event frequency or response rate is known. Here, outcome estimates and confidence intervals are not reported for the primary or efficacy endpoints. The registry record thus highlights the value of publishing complete outcome counts, denominators, follow-up status, analysis populations, and uncertainty measures.

The record also lists a planning illustration based on an observed effect while describing a single-group trial. Planning calculations and observed trial results serve different purposes. A planning illustration is not evidence of observed power, and it does not replace outcome reporting. The design, limited posted results, and absent analysis details make this a useful example of why statistical interpretation must follow the actual comparison and endpoint definitions rather than relying on labels or isolated counts.

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.

Several limitations specific to this trial are apparent from the registry record. Enrollment was 6, and the study had no randomized comparator. The single-group design cannot estimate a comparative treatment effect, and the absence of masking may matter for outcomes involving assessment or reporting. The record does not report participant characteristics, so the enrolled group’s MDS risk profile cannot be described from the posted information.

The study is marked terminated, but the reason is not reported in the registry record. It is also not reported whether participants completed the planned treatment and follow-up, how many had evaluable Week 4 or Week 8 response assessments, or why any data might be missing. The planned schedule is not evidence of completed observation.

The primary endpoint result is not reported. Although the record includes safety counts for serious and other adverse events, those counts do not answer the stated primary question about participants with no adverse events. The response outcomes are named but their results are not reported. No outcome analyses are listed, and no confidence intervals, statistical tests, analysis populations, missing-data procedures, or multiplicity methods are reported.

The record also does not give the trial’s sample-size justification, the reason for termination, or a detailed account of protocol deviations. These gaps prevent a full assessment of precision, completeness, and adherence to the planned methods. The limitations describe what the registry record does not report; they do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2, Open-Label, Multi-Dose Study of Panhematin in Patients With MDS — NCT00467610.
• Registry record last updated 2014-10-24; status last verified 2014-10.
• Results first posted 2014-10-24.
• 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

The registry record describes NCT00467610 as a Phase 2, open-label, non-randomized, single-group study of Panhematin in patients with MDS. Enrollment was 6, and the study status is terminated. The planned treatment period was 8 weeks, with possible additional treatment for responders, followed by a planned 6-month post-treatment follow-up.

The primary outcome was the number of patients with no adverse events during therapy and follow-up. The record does not report that result. It lists 0 participants affected by serious adverse events and 0 affected by other adverse events, with 6 at risk in each category; deaths are not reported as a numeric result. Week 4 and Week 8 hematological improvement outcomes are listed, but their results are not reported. The record lists 4 outcome measures and 0 analyses. It does not report an efficacy estimate, confidence interval, statistical test, analysis population, missing-data method, or multiplicity procedure.