Mesenchymal Stemcells for Radiation Induced Xerostomia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Mesenchymal Stemcells for Radiation Induced Xerostomia (NCT02513238), a randomized phase 2 study. The primary outcome is Number of Participants With Adverse Events as a Measure of Safety.

2. Clinical Question

The study focuses on safety and feasibility rather than a clinical efficacy endpoint. Its primary outcome is the number of participants with adverse events, with adverse events graded according to the Common Terminology criteria referenced in the registry record. The record describes the study population in relation to previous HPV-positive oropharyngeal head and neck cancer and radiation-induced xerostomia, but further eligibility details are not reported in the registry record.

The central comparison is between a local injection of autologous mesenchymal stem cells and a local injection of the stated placebo suspension. Both procedures are described as injections into the submandibular glands. The posted outcome reports zero participants with adverse events in each arm. That is a description of the observed safety outcome for the stated timeframe; it does not by itself settle whether the treatments have the same underlying safety profile or establish safety beyond the study conditions.

3. Trial Design

The registry record describes a completed, randomized, parallel-group phase 2 study with quadruple masking. It lists enrollment of 30 and reports 15 participants in each arm for the primary outcome. The study start date is 2015-08-08, and the primary completion date is 2017-04-06. Copenhagen University Hospital, Rigshospitalet is listed as the sponsor.

One arm received mesenchymal stem cells injected into the submandibular glands. The description says the cells were autologous and adipose tissue-derived, and that the procedure used local anaesthesia, ultrasonic guidance and sterile technique. The comparator arm received a placebo suspension injected into the submandibular glands. That suspension is described as 2ml of Isotonic NaCl (0,9mg/ml) and HA 1%. The registry record does not explain which specific groups of people were masked, so the masking label should not be expanded into assumptions about who knew treatment assignment.

The record lists one outcome measure and no secondary outcomes. The primary outcome is the number of participants with adverse events, assessed over 4 months. The adverse-event description refers to grading according to Common Terminology criteria, but further details about how events were collected, classified or summarized are not reported in the registry record. The record also does not report a statistical analysis plan, a sample-size justification, or the allocation procedure beyond stating that allocation was randomized.

This design supports a direct comparison of the two randomized arms for the stated safety outcome. Its interpretation is bounded by the population and follow-up described in the registry record. The record does not provide enough detail to characterize the broader clinical history of participants, the exact conduct of follow-up, or whether additional analyses were undertaken outside the posted results.

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 Number of Participants With Adverse Events as a Measure of Safety, measured over 4 months.

The primary endpoint is the number of participants with adverse events during the 4-month timeframe. The registry record identifies this as a measure of safety and says adverse events are graded according to Common Terminology criteria. The outcome is a count of participants with an event, rather than a count of every event episode or a measure of symptom severity.

Safety outcomes are important when a study evaluates a local procedure and an intervention whose potential harms need to be characterized. Recording whether participants experience adverse events provides a way to describe observed harms in each arm. The registry also reports serious adverse events, other adverse events and deaths in its adverse-event information; those figures should be read as separate categories, not assumed to be interchangeable with the primary outcome definition.

The primary outcome reports zero participants with adverse events in both arms. This describes the posted result for the stated follow-up period. The registry does not specify the event threshold used to count a participant for the primary outcome, the handling of repeated events, or a fuller adverse-event collection procedure. Those details are not reported in the registry record, so the endpoint can be interpreted only as it is defined in the posted description.

7. Results Posted in the Registry

• Saltwater Injected Into Submandibularis: 0.0% (0/15) versus 0.0% (0/15) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Statistical Interpretation

9. Statistical Methods Explained

For a binary endpoint, each participant is classified according to whether the specified event occurred during the relevant observation period. The registry describes the primary endpoint as the number of participants with adverse events, so the key outcome is a count of participants meeting that definition in each arm. This differs from counting event episodes: one participant could in principle experience more than one episode, but the primary endpoint is written as a participant count. How repeated events were handled is not reported in the registry record.

A risk is the proportion of participants in an arm who experience the event. A risk difference compares the risks between arms by subtracting one from the other. It is expressed on the same proportion scale, so a value of zero means there is no observed difference between the arm-specific event proportions. In this trial, the posted event counts are zero in both arms, and the registry reports a risk difference of 0.0. The record does not state a direction convention for the comparison, so the result is most clearly described as the reported difference rather than as favoring either arm.

A confidence interval is generally used to convey the range of values compatible with an estimate under a specified statistical procedure. Its interpretation depends on the method and assumptions used to calculate it. The posted interval for the risk difference runs from 0.0 to 0.0. The registry record does not identify the interval method or explain how uncertainty was handled when no events were observed. As a result, the interval should be reported as posted, but should not be taken as a complete account of uncertainty or as proof that the underlying risks are identical.

With sparse binary outcomes, conventional calculations can behave differently depending on whether they use a normal approximation, an exact method, or another approach. A normal approximation can be unreliable when event counts are very small or absent. Other methods may represent uncertainty differently. This is a general statistical consideration, not a statement about which method the trial used; the method is not reported in the registry record. The absence of events in both arms also means that the observed data do not provide a range of event rates that would allow a precise estimate of how often the outcome might occur in similar participants.

Randomization is intended to make the treatment groups comparable, on average, with respect to factors that could influence outcomes. It does not guarantee that the arms are identical in every characteristic, especially in a study with limited enrollment. The registry identifies randomized allocation and a parallel design, but details of sequence generation, allocation concealment and baseline characteristics are not reported in the registry record. The posted safety comparison can therefore be understood as an arm-level result in a randomized study, without assuming unreported implementation details.

Masking can reduce the influence of expectations on treatment delivery, outcome assessment or participant reporting. The record labels the study quadruple masked, but it does not identify which roles were masked or describe how masking was maintained. No further claims about the blinding procedure can be made from the registry record. The two procedures are both described as local injections, but the record does not state whether participants or assessors could distinguish the suspensions.

The registry lists planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation. It describes the detectable effect as a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the study had adequate power for a safety conclusion. Their numerical results are not reported in the registry record. More generally, a planning calculation depends on its assumptions and target effect; it does not change what the trial observed.

The registry reports no posted analysis count and does not provide an inferential analysis plan, p-value, or details of covariate adjustment. It also does not report how participants with incomplete follow-up, protocol deviations or missing outcome data were handled. The arm counts and observed outcomes can be described directly, but it is not possible to reconstruct a more elaborate statistical analysis without those details. Any interpretation should distinguish the recorded counts and risk-difference estimate from general explanations of how binary-outcome methods work.

10. Confidence Intervals and Precision

The primary outcome shows zero participants with adverse events in each arm, with 15 participants reported in each arm. A risk difference of 0.0 is posted, with an interval from 0.0 to 0.0. These values communicate the observed result and the interval as recorded, but the interval does not make the underlying safety risks known with certainty.

In general, precision concerns how narrowly an estimate identifies the value that might be expected beyond the observed participants. When few participants are observed and no events occur, the data can remain compatible with a range of underlying event risks even though the observed count is zero. This is a general point about interpreting sparse safety data. The registry does not report an interval for each arm’s event risk or describe the method used for the posted risk-difference interval. It is therefore not possible to infer a more complete uncertainty range from the record.

The zero-to-zero interval should be treated cautiously. It is the interval reported alongside the estimated risk difference, not a guarantee that the true difference is exactly zero. The record does not state its confidence level or calculation method. Those omissions matter because interval width and coverage depend on the method and assumptions. In particular, methods that rely on a normal approximation may not represent uncertainty well when event counts are absent; that is a general statistical consideration, not a claim about the method used.

The 4-month timeframe also limits the scope of the result. The posted outcome does not establish how risks might look over longer follow-up, and longer-term safety results are not reported in the registry record. The study’s observed counts are therefore most informative as a description of the recorded short-term experience, rather than as a precise estimate of uncommon or later events.

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no secondary outcomes. It does not describe a multiplicity adjustment or a hierarchy of outcome tests. Because no inferential test results are posted, the record does not support conclusions about how multiple statistical comparisons were handled. Multiplicity is a general concern when many outcomes or comparisons are tested: repeated testing can increase the chance of a seemingly notable result arising by chance. Whether that issue arose in analyses beyond the listed outcome is not reported in the registry record.

Missing-data handling is not described. The record reports the number of participants in each arm for the primary outcome, but does not explain whether all randomized participants contributed outcome data, how incomplete follow-up was treated, or whether any participants were excluded from an analysis. The reported arm counts should not be used to assume a particular analysis population, such as all randomized participants or only those who completed follow-up.

The registry record also does not report an analysis plan, the timing of any interim analyses, or details of the statistical model or test used for the risk-difference result. These omissions do not change the reported event counts, but they limit assessment of how the result was selected, analyzed and presented. The posted values can be interpreted descriptively; stronger claims about confirmatory testing, prespecification or robustness are not supported by the information reported.

There are no posted secondary outcome results. Although the registry summary discusses salivary gland hypofunction and xerostomia, the record does not report an outcome result for either. It is not possible to determine from the registry record whether other measures were collected but not posted, or whether the listed outcome was the only measure assessed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The serious adverse-event figures are zero in the stem-cell arm and zero in the saltwater arm. The registry reports 15 participants at risk in each arm for this category. It also records zero deaths in each arm. Separately, the other-adverse-event figures are zero in both arms, with 15 participants at risk in each. These are the recorded counts for the adverse-event information in the registry record.

Serious adverse events and other adverse events are distinct categories in the reported data. A zero in the serious category should not be mistaken for a complete description of every possible safety issue, and these counts do not show the severity or timing of individual events. The record lists no serious-event terms and does not provide event narratives or grading distributions. It also does not explain the exact ascertainment procedures beyond referencing Common Terminology criteria for the primary outcome.

These results describe events recorded during the study, not all events that could occur with either procedure. They apply to the reported participants and the stated timeframe; the registry record does not report longer-term safety outcomes. Zero observed events are not proof that the underlying risk is zero, particularly when the event is uncommon or follow-up is limited. The figures are best read as a concise account of what was recorded, with the reporting limitations kept in view.

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

The posted result establishes a narrow descriptive fact: for the primary safety outcome, the registry reports zero participants with adverse events in each arm during the 4-month timeframe. It also reports zero serious adverse events, zero other adverse events and zero deaths in each arm. The risk-difference estimate is 0.0, with an interval from 0.0 to 0.0. These results describe the recorded data; they do not demonstrate that the two interventions have identical underlying safety profiles.

The result does not show that the stem-cell procedure is safe in every setting or that adverse events cannot occur. A study with no recorded events can still leave uncertainty about uncommon harms, events not captured by the reporting process and outcomes arising after the reported follow-up. The registry does not provide detailed event descriptions, an account of missing outcome data, or a method for the posted interval. These limits make it important not to interpret a zero count as a guarantee.

Nor does this primary endpoint establish clinical benefit. The registry describes the study as assessing safety and feasibility in the context of radiation-induced salivary gland hypofunction and xerostomia, but the posted outcome is adverse events. No secondary outcome results are listed for xerostomia, salivary gland function or quality of life. The safety result cannot establish that either injection improves those outcomes, or that one is preferable for them.

The record also does not provide a formal equivalence or non-inferiority analysis. A risk difference of 0.0 in the observed data is not the same as demonstrating that any true difference is small enough to be clinically unimportant. Such a conclusion would require a defined margin and a suitable analysis, neither of which is reported in the registry record. The most defensible reading is therefore limited: no participants with the listed adverse-event outcomes were recorded in either arm in this study’s reported follow-up, while broader conclusions about safety, comparative risk and clinical effects remain unresolved.

14. Why This Trial Matters Statistically

Safety studies are statistically important because treatment decisions and later research depend on understanding what harms were observed and how much uncertainty remains. This trial addresses a local injection procedure in participants with radiation-induced xerostomia, and its primary outcome directly counts participants with adverse events. Reporting the observed event counts alongside the arm sizes gives readers a basic account of the safety data in each randomized group.

The result also illustrates why zero observed events require careful interpretation. When no events are recorded, the observed comparison is simple, but the underlying risk is not thereby known to be zero. The posted risk difference and its zero-to-zero interval may look exact, yet the registry does not report the interval method or confidence level. Statistical reporting needs to make methods and uncertainty clear so readers can distinguish a descriptive result from a precise estimate of risk.

The study is described as safety and feasibility research, which is a relevant role for an early clinical evaluation. The registry record lists randomized allocation, masking and a parallel design, but does not supply details needed to judge the analysis plan, missing data or outcome ascertainment in depth. These gaps matter statistically because design labels alone do not show how the analysis was implemented.

Finally, the record underscores the importance of separating safety endpoints from efficacy questions. The primary result concerns adverse events, while outcomes such as xerostomia severity and salivary gland function are not reported as secondary results. Keeping that distinction clear prevents a safety count from being mistaken for evidence about symptom improvement or clinical benefit.

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.

The posted results are limited to one primary outcome measure and a 4-month timeframe. The registry record does not report results for secondary outcomes, including measures of xerostomia or salivary gland function. As a result, the record supports a safety description but not an assessment of symptom change or treatment benefit.

Safety reporting is brief. The record gives counts for serious adverse events, other adverse events and deaths, but does not provide event narratives, grading distributions, timing or detailed definitions. Although the primary outcome description refers to Common Terminology criteria, the specific grading information and event-collection procedures are not reported in the registry record. It is therefore difficult to assess the breadth and completeness of safety ascertainment.

The record does not report how missing data were handled, whether all randomized participants were included in the outcome analysis, or whether follow-up was complete. It also does not describe the statistical analysis plan, the method for the risk-difference interval, or any inferential test. These omissions limit evaluation of precision and of the robustness of the posted comparison. The interval from 0.0 to 0.0 should not be treated as eliminating uncertainty about the underlying event risks.

Further details about eligibility, baseline characteristics, allocation procedures and the roles included in quadruple masking are not reported in the registry record. The results should therefore be interpreted in the context of the population description that is available, without assuming unreported participant characteristics or implementation details. Longer-term outcomes are also not reported, so the short-term event counts cannot characterize later safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Mesenchymal Stemcells for Radiation Induced Xerostomia — NCT02513238.
• Registry record last updated 2022-12-28; status last verified 2022-11.
• Results first posted 2022-12-28.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed randomized, parallel-group phase 2 study of mesenchymal stem-cell injection versus a saltwater placebo injection into the submandibular glands. It lists quadruple masking, enrollment of 30 and 15 participants in each arm for the primary outcome. The study concerns radiation-induced xerostomia in participants described as having previous HPV-positive oropharyngeal head and neck cancer.

The primary outcome is the number of participants with adverse events over 4 months, with grading referenced to Common Terminology criteria. The posted count is zero in each arm. The registry also reports zero serious adverse events, zero other adverse events and zero deaths in both arms, and a risk difference of 0.0 with an interval from 0.0 to 0.0.

The record lists no secondary outcomes and does not report an inferential test, analysis plan, missing-data procedure or interval method. The results are therefore best read as descriptive safety findings for the stated follow-up, not as proof of identical risks or evidence about clinical benefit.