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 Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency (NCT00655707), a na phase 1, phase 2 study. The primary outcome is Number of Patients Who Tolerated the Maximum Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00655707 |
| Phase | Phase 1, Phase 2 |
| Condition | Liver Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 5 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Imperial College London |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with liver insufficiency; the record also lists Liver Disease as the condition. It was described as a study in people with end stage liver failure. Enrollment was 5 participants. The registry does not report further eligibility details or a description of the analyzed population.
Intervention
Participants received autologous expanded CD34+ haemopoietic cells. The study summary describes dose escalation and infusion into either the hepatic artery or portal vein. The cells were expanded in an approved Good Manufacturing Practice facility. The registry does not report participant-level doses, routes, or treatment exposure.
Comparator
There was no comparator group. The design is recorded as single-group, with allocation listed as NA and masking as none. Thus, the study was not a randomized comparison, and its safety counts cannot be interpreted as a direct contrast with an untreated group or another intervention.
Primary question
The primary endpoint was the number of participants who tolerated the maximum dose, assessed over 12 months. The stated aim was to determine the maximum tolerated dose when cells were infused into either the hepatic artery or portal vein. The registry does not report the observed number who tolerated the maximum dose, a dose-specific result, or an estimate of the maximum tolerated dose.
The broader study aim also included assessing liver function through serological and biochemical analysis and determining whether participants reported symptomatic improvement. Those are aims described in the study summary, but the registry record does not report results for those outcomes. Accordingly, the clinical question can be described from the planned aims, while the posted results do not establish what was observed for the primary endpoint or for the broader liver-function and symptom aims.
3. Trial Design
This was a prospective Phase I/II study, recorded as completed, with an enrollment of 5 participants. Its design was single-group, with no allocation to a parallel control arm and no masking. Imperial College London is listed as the sponsor. The recorded start was 2006-01 and primary completion was 2009-04. The registry does not report additional design details such as eligibility criteria, planned follow-up beyond the primary endpoint timeframe, or a statistical analysis plan.
The intervention was autologous expanded CD34+ haemopoietic cells. The study summary describes successive groups of two patients receiving ascending doses, with infusion into either the hepatic artery or portal vein. It also describes the cells as being expanded in an approved Good Manufacturing Practice facility. These details describe the intended dose-escalation approach; the registry does not report the actual dose sequence, the number treated at each dose, or which infusion route each participant received.
The primary endpoint was a count of participants who tolerated the maximum dose, with a timeframe of 12 months. The record lists two outcome measures, but no analyses. The main reported safety counts are for the Autologous CD34+ Cells group. Because there was no control group, the observed counts are descriptive rather than comparative. A single-group design can describe what was recorded among treated participants, but cannot by itself separate intervention-related events from events that might have occurred for other reasons.
The study's dose-escalation purpose makes participant-level dose and tolerability information important for understanding its findings. Those details, including the number of participants reaching each dose and the criteria used to define dose-limiting toxicity, are not reported in the registry record. Therefore, the design can be characterized, but its dose decisions and escalation outcomes cannot be reconstructed from the 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: The planned dose escalation design did not work due to low participants number. All participants received similar dose of Autologous expanded CD34+ cells .
Overall Study
| Stage | Treatment |
|---|---|
| STARTED | 5 |
| COMPLETED | 5 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Autologous CD34+ Cells |
|---|---|---|
| Participants analysed | 5 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 5 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 49.4 (42 to 61) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 4 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Number of Patients Who Tolerated the Maximum Dose, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants who tolerated the maximum dose, measured over 12 months. It is a count endpoint: the intended result is how many participants met the study's tolerability definition, rather than a change in a continuous measurement. The registry describes its purpose as determining the maximum tolerated dose of autologous adult stem cells infused into either the hepatic artery or portal vein.
In a dose-escalation study, tolerability at higher exposure is central to deciding whether that dose can be advanced or accepted under the study's safety criteria. This is a general explanation of why a tolerability endpoint may be used; the exact decision rules for this trial are not reported in the registry record. The registry also does not describe how tolerability was defined, whether events were attributed to treatment, or how participants who did not complete the full 12 months were handled.
The record does not report the observed count for this primary endpoint, a denominator for participants who reached the maximum dose, or the maximum tolerated dose itself. Without those results and the underlying dose-specific information, the endpoint's outcome cannot be evaluated from the registry record. Liver-function and symptom changes were additional aims in the study summary, but their results are not reported either.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a prospective, single-group Phase I/II dose-escalation study with 5 participants. It identifies the intervention, the primary tolerability question, and safety-event counts. It does not report the primary endpoint result: the number who tolerated the maximum dose over 12 months is not reported in the registry record. The maximum tolerated dose is also not reported. Consequently, the central dose-escalation question cannot be answered from the posted results.
The safety record lists 1 participant affected by a serious adverse event among 5 at risk, 5 participants affected by other adverse events among 5 at risk, and 0 deaths. Urinary Tract Infection is the listed top serious adverse-event term, at 20.0%. These counts describe events recorded for the study group. They do not show whether the events were judged related to the intervention, how severe individual events were beyond their classification, or when they occurred. The record does not give a comparator group, so the counts cannot be interpreted as a difference in risk attributable to treatment.
Small participant counts limit the precision of descriptive safety summaries. A count from a small group can change substantially in its apparent meaning if even one participant's status differs, and uncertainty around an event rate would ordinarily be important. The registry record does not report confidence intervals for the safety counts. No uncertainty interval should be inferred from the listed percentages or counts.
The trial summary states that the investigators also sought to assess liver function through serological and biochemical analysis and to identify symptomatic improvements reported by participants. The registry record does not report those outcome results, the measures used, or their timing. It also does not report analyses of the two listed outcome measures.
Interpretation should therefore remain limited to what is registered: the study's design and stated purpose, plus the descriptive safety figures. The record does not establish the maximum tolerated dose, demonstrate a change in liver function, or show a treatment effect. It also does not provide enough information to judge how complete the follow-up was or how the tolerability endpoint was applied.
9. Statistical Methods Explained
The registry identifies the design as single-group and the trial as a Phase I/II dose-escalation study. These features determine what statistical conclusions are possible. In a single-group study, outcomes are observed among participants who receive the intervention, without a parallel group for direct comparison. The results can describe the recorded experience of this group, but they cannot estimate a treatment-versus-control difference. This is a general design principle, not a claim that an unreported comparison was performed.
What does a dose-escalation design ask?
A dose-escalation study explores tolerability as exposure increases. Investigators ordinarily need a prespecified definition of unacceptable toxicity and a rule for moving between dose levels. The registry summary describes successive groups of two patients receiving ascending doses, but the specific escalation rules, dose levels used, and toxicity criteria are not reported in the registry record. The actual number of participants treated at each dose is also not reported. These omissions prevent a reader from retracing dose decisions or identifying the evidence used to select a maximum tolerated dose.
How should a count endpoint be understood?
The primary outcome is a count of participants who tolerated the maximum dose over 12 months. Counts are interpreted in relation to the eligible or treated participants who could have met the endpoint. The record does not report the observed count or the number who reached the maximum dose, so an endpoint proportion cannot be assessed. General statistical practice would also consider how the endpoint is defined for participants who stop treatment, miss visits, or have incomplete follow-up. Those rules are not reported, and no missingness pattern should be assumed.
For a binary participant-level outcome, a confidence interval can express uncertainty around the proportion meeting the endpoint. In general, a wider interval indicates less precision, and a small study often yields substantial uncertainty. No confidence interval for the primary endpoint is reported in the registry record. Since neither its count nor the relevant denominator is reported, there is no basis in the record for recalculating an interval or a proportion.
What can the adverse-event counts show?
The safety results give numbers at risk and numbers affected for serious and other adverse events. Such counts are useful descriptions of recorded events, but they do not by themselves determine whether an event was caused by an intervention. A comparison group, event timing, clinical assessment, and clear definitions can inform causal interpretation; those elements are not fully reported in this record. The listed 20.0% for Urinary Tract Infection is a reported term frequency, not an estimate of comparative risk.
In general, event data may be more variable than a simple statistical model assumes when participants differ in exposure, follow-up time, or susceptibility. Over-dispersion means that observed variation exceeds what a chosen model expects; allowing for it can make uncertainty estimates more realistic. This is a general concept only. The registry does not report a model, an over-dispersion assessment, person-time analyses, or adjusted safety estimates. The available safety results are counts, and no model-based result should be inferred from them.
What analysis was reported?
The record lists no analyses. It does not report an inferential test, an effect estimate, a confidence interval, or a statistical model for the primary endpoint or the broader liver-function aims. The statistical analysis plan, including any covariate adjustment or methods for repeated measurements, is not reported in the registry record. Therefore, the reported counts should be read descriptively, and the absence of a posted analysis should not be replaced by an assumed one.
The registry also includes planning illustrations based on an observed effect and hypothetical assumptions: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning assumptions, not the design of this single-group trial. The record does not describe a randomized two-arm comparison in this study, and the planning illustrations do not represent observed power. No sample-size justification for the actual trial is reported in the registry record.
General statistical interpretation separates the size of an estimate from its precision. A small p-value, when calculated under a defined model, addresses compatibility with a null hypothesis; it does not itself measure clinical importance or prove causation. A confidence interval communicates a range of values compatible with the data and model, subject to assumptions. Neither an inferential p-value nor an interval for the primary endpoint is reported. Given the missing outcome result and analysis details, these concepts explain what a full analysis might communicate, but they cannot be applied to produce a trial-specific conclusion.
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.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Autologous CD34+ Cells | 5 | 5 | 100.0% | 47.8% to 100.0% | 56.6% to 100.0% | 54.1% to 99.6% |
R code and output
arm <- c("Autologous CD34+ Cells")
n <- c(5)
events <- c(5)
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 Autologous CD34+ Cells 5 5 100.0 47.8 100.0 56.6 100.0 54.1 99.611. Multiplicity, Missing Data and Analysis Populations
The registry record lists two outcome measures and describes several aims: determining the maximum tolerated dose, assessing liver function through serological and biochemical analysis, and considering symptomatic improvement reported by participants. It does not report a hierarchy among these aims beyond identifying the tolerability count as the primary endpoint. The statistical plan for handling multiple outcomes or multiple comparisons is not reported in the registry record.
Multiplicity is a general concern when many outcomes, time points, subgroups, or statistical tests are examined. If conclusions are selected from numerous analyses without an appropriate plan, the chance of highlighting a result that appears unusual can increase. Common approaches include prespecifying a primary outcome, controlling error rates, or treating secondary analyses as exploratory. These are general methods, not methods documented for this study. No multiplicity adjustment or rationale for omitting one is reported.
Missing-data methods are also not reported. The registry does not describe whether all 5 enrolled participants completed the 12-month timeframe, how withdrawals or incomplete assessments were handled, or whether any imputation was used. The absence of a reported method does not show that data were missing; it means the record does not permit assessment of completeness or handling.
The analysis populations are not reported. It is not stated whether results were intended for all enrolled participants, only those receiving cells, or another defined group. The registry lists no analyses, so no analysis population can be identified from posted results. The protocol or statistical analysis plan, including rules for outcome windows and incomplete follow-up, is not reported in the registry record.
12. 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 |
|---|---|---|---|
| Autologous CD34+ Cells | 1 | 5 | 20.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Autologous CD34+ Cells | 0 of 5 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Autologous CD34+ Cells | 5 of 5 |
Most frequent serious adverse event terms
| Event term | Organ system | Autologous CD34+ Cells |
|---|---|---|
| Urinary Tract Infection | Renal and urinary disorders | 1 of 5 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Autologous CD34+ Cells |
|---|---|---|
| Nausea | Gastrointestinal disorders | 5 of 5 |
| Fever | Immune system disorders | 4 of 5 |
| Pain | Surgical and medical procedures | 4 of 5 |
| Ascites | Hepatobiliary disorders | 3 of 5 |
| Jaundice | Hepatobiliary disorders | 1 of 5 |
Serious events with the highest arm-level rate: urinary tract infection (20.0%).
The safety record reports 1 participant with a serious adverse event among 5 at risk, 5 participants with other adverse events among 5 at risk, and 0 deaths in the Autologous CD34+ Cells group. Urinary Tract Infection is the top serious adverse-event term listed, with a reported frequency of 20.0%. These are descriptive counts for the study group, not comparisons with another treatment or with no treatment.
A serious adverse event is a classification of an event's seriousness, not a statement that the intervention caused it. The registry does not report whether the listed events were considered related to the cells, the timing of the events, their duration, or participant-level event histories. It also does not clarify whether the top serious term represents all serious events or the most frequent named term. The figures therefore describe what was recorded, but do not establish causality or provide a complete clinical account of each event.
The numbers at risk are small, so the counts should not be treated as precise estimates of event frequency in a broader population. The registry record does not report confidence intervals or exposure-adjusted safety analyses. The 20.0% figure should be read as the registry's reported percentage for the named term, not as evidence of comparative risk.
13. What the Result Does, and Does Not, Mean
The record establishes that a prospective Phase I/II dose-escalation study of autologous expanded CD34+ cells was conducted in a single group, with 5 participants enrolled. It states that the primary question concerned tolerating the maximum dose over 12 months. It also records adverse-event counts and a count of deaths. These details support a limited description of the study's design and the safety information posted to the registry.
The record does not report the primary endpoint result or the maximum tolerated dose. It therefore does not show how many participants tolerated the maximum dose, whether dose escalation reached the planned maximum, or which dose was judged tolerable. The registry also does not report results for liver-function measures or symptomatic improvement, although those aims appear in the study summary.
The safety counts alone do not establish whether the intervention caused an event. Without a comparator, the study cannot provide a randomized estimate of the difference in safety or efficacy between treatments. And because the registry does not report an analysis, uncertainty intervals, or participant-level dose and follow-up information, the precision of any broader inference cannot be evaluated.
This is not evidence that the intervention did or did not improve liver function, symptoms, or outcomes. It is also not evidence that the reported adverse events were unrelated or related to the intervention. The appropriate reading is narrower: the registry describes a small, uncontrolled dose-escalation study and posts selected safety counts, while omitting the central tolerability result and other outcome analyses needed to answer the stated clinical questions.
14. Why This Trial Matters Statistically
This study illustrates a core statistical challenge in early-phase clinical research: the main purpose may be dose and tolerability assessment rather than a controlled estimate of treatment effect. In a dose-escalation design, interpretation depends on more than the overall number enrolled. Readers need to know which doses participants received, how tolerability was defined, what escalation rules were used, and how events influenced dose decisions. The registry summary gives a broad description of ascending doses and successive groups, but does not report those operational details or the resulting maximum tolerated dose.
The single-group structure also matters. Without a comparator, adverse-event counts describe the participants in the study but cannot separate intervention effects from other influences. This is a general limitation of uncontrolled comparisons and is especially important when the group is small. The record's safety counts remain useful as a registry description, but they cannot be read as a comparative treatment estimate.
Completeness of outcome reporting is another statistical issue. The stated primary question is identifiable, but its observed result is absent. Liver-function and symptom aims are described without posted results. When outcome values, denominators, and analysis methods are unavailable, readers cannot assess effect size, precision, or the consistency of findings across outcomes.
The record also illustrates why planning calculations must be distinguished from trial evidence. The planning illustrations use hypothetical two-arm assumptions, whereas this registered study is single-group. Such illustrations are not observed power and do not substitute for a documented sample-size justification or an analysis of the trial's outcomes. Clear reporting of design-specific methods and endpoint results is necessary for readers to judge what a small early-phase study can and cannot establish.
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 affect interpretation. Enrollment was 5 participants, and there was no comparator group. The registry does not report the distribution of participants across dose levels, which infusion route each participant received, or whether all participants reached the maximum dose. These details are particularly relevant to a dose-escalation question, because an overall study count does not show the experience at each exposure.
The primary endpoint result and the maximum tolerated dose are not reported in the registry record. The endpoint's operational definition and the rules used to judge tolerability are also not reported. Without this information, the principal study question cannot be evaluated from the posted results. The registry additionally does not report results for the stated serological, biochemical, or symptom aims.
There is no reported analysis, statistical plan, confidence interval, or description of missing-data handling. The record does not state whether participants completed the 12-month timeframe or identify the population used for analyses. No assumption about completeness, attrition, or analytic exclusions can be made from the available record.
The posted safety figures are descriptive and do not include a comparator. Event attribution, timing, duration, and participant-level details are not reported. These limitations make the safety counts unsuitable for estimating a comparative effect or establishing causation. The planning assumptions described in the registry are based on a hypothetical two-arm framework and do not provide a design justification for this single-group study.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Phase I/II Safety and Tolerability Dose Escalation Study of Autologous Stem Cells to Patients With Liver Insufficiency — NCT00655707.
- Registry record last updated 2019-10-31; status last verified 2019-10.
- Results first posted 2019-10-31.
- 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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19. Record Summary
NCT00655707 is a completed Phase I/II prospective dose-escalation study sponsored by Imperial College London. The registry records a start of 2006-01, primary completion of 2009-04, and enrollment of 5 participants. The study used a single-group design with no masking or randomized allocation.
The intervention was autologous expanded CD34+ haemopoietic cells. The stated primary endpoint was the number of participants who tolerated the maximum dose over 12 months. The study summary also describes aims concerning liver function and participant-reported symptoms.
The registry posts safety counts, including 1 participant with a serious adverse event among 5 at risk, 5 participants with other adverse events among 5 at risk, and 0 deaths. Urinary Tract Infection is listed at 20.0% as the top serious adverse-event term. The primary endpoint result, maximum tolerated dose, liver-function results, symptom results, and statistical analyses are not reported in the registry record.