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 Safety and Effectiveness of Belotero® in Subjects With Fitzpatrick Phototypes IV Through VI (NCT00922623), a non-randomized na study. The primary outcome is Percentage of Subjects With Product-related Adverse Events..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00922623 |
| Phase | NA |
| Condition | Facial Wrinkles |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 93 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merz North America, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with Fitzpatrick phototype scores IV, V, and VI and moderate to severe facial wrinkles, such as nasolabial folds. The registry record describes the study population as subjects enrolled and treated with Belotero®.
Intervention
Belotero®, a dermal filler implanted in the mid-to-deep dermis for correction of facial wrinkles. The listed intervention is a device.
Comparator
No separate control treatment is listed. The study is non-randomized and single-group. The left- and right-fold entries are not a like-for-like comparison with an untreated or alternative-treatment group.
Primary question
What percentage of subjects had adverse events considered possibly, probably, or definitely related to study product over 24 weeks? The registry describes summarizing these events by body system and MedDRA preferred term. It does not report a numerical result for this primary endpoint.
The study title also refers to effectiveness, but the primary outcome listed in the registry record is a safety measure. The record describes the intended wrinkle-correction use and identifies nasolabial folds as an example. It does not provide a separate posted effectiveness result in the registry record for this analysis. Consequently, the central statistical question is about the frequency of product-related adverse events in the treated study population, not a comparative estimate of benefit against another treatment or no treatment.
3. Trial Design
This was a completed, non-randomized, single-group study sponsored by Merz North America, Inc. The registry lists enrollment of 93 and identifies Belotero® as the intervention. Study start was recorded as 2009-05, and primary completion as 2010-07. The stated follow-up timeframe for the primary endpoint was 24 weeks.
The study concerned correction of moderate to severe facial wrinkles, including nasolabial folds, in subjects with Fitzpatrick phototype scores IV, V, and VI. The product was described as being implanted in the mid-to-deep dermis. The registry classifies allocation as non-randomized and masking as none. It gives no separate comparison arm, so the design does not provide a randomized treatment contrast.
The adverse-event record presents separate entries for Belotero in the left and right nasolabial folds. Those entries should be read as fold-specific reporting, not as independent treatment groups or as evidence of a controlled comparison. The registry does not state that one fold received a different treatment or that the two sides were assigned by randomization.
The listed primary outcome is the percentage of subjects with product-related adverse events. The analysis population is described as the Full Analysis Set, consisting of all subjects enrolled and treated with Belotero, under an ITT principle. The registry record does not report the protocol’s sample-size justification, a detailed statistical analysis plan, or any interim-analysis plan. Its status is completed, but completion alone does not establish that all planned analyses or outcomes were posted.
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 | Belotero® |
|---|---|
| STARTED | 93 |
| COMPLETED | 88 |
| NOT COMPLETED | 5 |
Reasons for not completing this period:
| Reason | Belotero® |
|---|---|
| Other | 4 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all subjects enrolled and treated with Belotero (ITT principle).
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 | Belotero® |
|---|---|---|
| Participants analysed | 93 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 81 |
| Age, Categorical: >=65 years | Participants | 12 |
| Age Continuous | years | 51.5 (SD 10.1) |
| Sex: Female, Male: Female | Participants | 80 |
| Sex: Female, Male: Male | Participants | 13 |
| Race/Ethnicity, Customized: Hispanic or Latino | participants | 3 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | participants | 90 |
| Race/Ethnicity, Customized: Unknown or Not Reported | participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Subjects With Product-related Adverse Events., measured over 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of subjects with AEs. |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the percentage of subjects with adverse events considered possibly, probably, or definitely related to study product. The registry sets the timeframe at 24 weeks and says these events are summarized by body system and MedDRA preferred term. This endpoint is intended to describe the frequency of events judged to have a possible relationship to the product during the stated follow-up.
A percentage can communicate how often an event occurs relative to the population assessed, but its interpretation depends on clear definitions of the event, relatedness, follow-up, and analysis population. Here, the record identifies the relatedness categories and the Full Analysis Set definition. It does not post the primary endpoint’s numerical result, its denominator for analysis, or an uncertainty interval. Therefore, the endpoint’s definition is available, but its estimated frequency and precision are not reported in the registry record.
The separate serious and other adverse-event entries do not by themselves supply the missing primary result. The record does not identify those counts as the primary endpoint’s product-related events. A count of events or affected subjects in a safety listing should not be treated as interchangeable with the specified percentage of subjects whose events were judged related to study product.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a safety question for Belotero® in subjects with Fitzpatrick phototypes IV through VI, but it does not post a numerical result for the primary endpoint. The primary measure is the percentage of subjects with adverse events considered possibly, probably, or definitely related to study product over 24 weeks. Without that result and its analysis denominator, the frequency of the defined product-related outcome cannot be interpreted from the primary endpoint entry.
The posted adverse-event information does report serious adverse events affecting 0 of 93 at-risk subjects in the left-fold entry and 0 of 93 in the right-fold entry. It also reports other adverse events affecting 71 of 93 at risk in the left-fold entry and 72 of 93 in the right-fold entry. These are fold-specific registry entries. The record does not establish that the affected-subject counts in the two entries represent separate people, and they must not be added to produce a participant total.
The distinction between serious and other adverse events matters. The zero serious-event counts apply to the serious-event category as listed; they do not mean that no adverse events occurred. The counts for other adverse events are nonzero, but the record does not state that these events were product-related. They cannot be substituted for the primary endpoint’s related-event measure. No serious preferred terms are listed, and the record does not give a numerical death count.
The design also limits what can be inferred. Because the study is non-randomized and single-group, it does not estimate a treatment difference against a concurrent control. The left and right nasolabial-fold entries do not create such a comparison. Without a control group, the observed event listings describe reports in the treated study context but do not isolate how much risk is attributable to the product rather than other causes or background events.
No confidence interval, statistical test, or primary endpoint estimate is reported in the registry record. Thus, the precision of the primary safety estimate cannot be assessed, and no inferential conclusion about a treatment contrast is available. The registry record supports a description of the study design and the posted event counts, but not a comparative efficacy or safety conclusion.
9. Statistical Methods Explained
Statistical interpretation starts with the study question and the structure of the data. This study has a single-group, non-randomized design, with no separate control treatment listed. Its primary endpoint is a percentage: the share of subjects with adverse events judged possibly, probably, or definitely related to study product over 24 weeks. A percentage is a summary of frequency in a defined population and follow-up period. It is not, by itself, a comparison with what would have happened under another treatment.
What does a percentage estimate?
For a percentage to be interpretable, the numerator and denominator need to refer to the same defined outcome and analysis population. The numerator represents subjects meeting the outcome definition; the denominator represents those included in the analysis. In this record, the outcome definition and the Full Analysis Set description are stated, but a numerical result for the primary endpoint is not reported in the registry record. The adverse-event listings provide their own at-risk and affected counts, but those counts are not explicitly identified as the numerator and denominator for the primary product-related endpoint.
Relatedness is also part of the endpoint definition. The primary outcome includes events judged possibly, probably, or definitely related to study product. A general adverse-event count is broader unless the record explicitly applies that relatedness criterion. For that reason, the other-adverse-event counts cannot be read as the product-related endpoint. The record does not report the separate number meeting the primary endpoint definition.
What can a confidence interval add?
In general, a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the statistical method. For a percentage, it can show how compatible the data are with a range of underlying event frequencies. A narrow interval indicates greater precision under those assumptions, while a wide interval indicates less precision. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be evaluated from the posted primary outcome information.
In general, an interval for a single-group percentage would describe the event frequency in that study population; it would not create a controlled treatment comparison. To estimate a difference attributable to treatment, a suitable comparator and a design that supports that comparison are needed. This study is listed as non-randomized and single-group, and its left- and right-fold entries do not provide an untreated or alternative-treatment control.
Why does the design matter?
Randomization can help make treatment groups comparable with respect to both measured and unmeasured characteristics. This study has no randomized allocation and no separate control group listed. Consequently, its event descriptions cannot distinguish product-related risk from other explanations as a controlled comparison might. The registry’s classification of masking as none also means no masking is recorded; the record does not provide further detail about who knew the treatment or how event assessments were conducted.
Fold-specific recording requires care as well. The registry gives an at-risk count and an affected count separately for the left and right nasolabial folds. These entries describe the posted record for each fold. They should not be treated as independent groups of subjects, and the affected counts should not be combined. The record does not report whether the same subjects contributed events to both entries or how repeated events were handled.
What do the event counts mean?
The serious-event entries report 0 affected among 93 at risk for each fold. The other-event entries report 71 affected among 93 at risk for the left fold and 72 among 93 at risk for the right fold. These are descriptive counts. The record does not provide an inferential comparison between the fold entries, nor does it state that the other events were judged related to the product. A serious-event count of zero does not imply that all categories of adverse events were absent.
In general, adverse-event summaries can be affected by how events are defined, collected, coded, attributed, and counted. Repeated events in one subject may be treated differently from a summary of whether a subject had at least one event. The registry says the primary outcome is a percentage of subjects and that related events are summarized by body system and preferred term, but it does not describe the event-level counting rules or provide the primary result.
How should planning calculations be read?
In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, significance level, allocation, and statistical model. It does not describe an observed trial result or prove that a study had adequate power for the effect actually present. The registry mentions a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect and distinguishes participant-per-arm outputs from total-event outputs for time-to-event methods. The numerical planning outputs are not reported in the registry record details. They should not be mistaken for observed power or for the study’s original design justification.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and reports 0 analyses. A single listed primary outcome can make the main question easier to identify, but it does not establish how multiple statistical tests or multiple outcome summaries were handled. A multiplicity procedure, including whether any adjustment was planned, is not reported in the registry record.
The Full Analysis Set is defined as all subjects enrolled and treated with Belotero, following the ITT principle. The record does not report a separate analyzed denominator for the primary endpoint, the number of subjects with missing primary outcome information, or how missing observations were handled. It also does not describe whether subjects with incomplete follow-up were included in each safety summary or how deviations from the analysis population definition were managed.
In general, missing-data methods matter because conclusions can depend on whether missing observations are excluded, imputed, or addressed through another analysis. The appropriateness of any method depends on why information is missing and on the assumptions made. No such method or missingness assessment is reported in the registry record. The available fold-specific at-risk counts do not resolve missingness for the primary product-related endpoint.
The record also does not describe a hierarchy of outcomes, prespecified secondary analyses, subgroup procedures, or adjustment for repeated testing. These details should not be inferred from the presence of one listed outcome measure or from the number of analyses recorded. The absence of those details limits assessment of how the reported results, if any, relate to a prespecified analysis plan.
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 |
|---|---|---|---|
| Belotero, Left Nasolabial Fold | 0 | 93 | 0.0% |
| Belotero, Right Nasolabial Fold | 0 | 93 | 0.0% |
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 |
|---|---|
| Belotero, Left Nasolabial Fold | 71 of 93 |
| Belotero, Right Nasolabial Fold | 72 of 93 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Belotero, Left Nasolabial Fold | Belotero, Right Nasolabial Fold |
|---|---|---|---|
| Injection site swelling | General disorders | 55 of 93 | 56 of 93 |
| Injection site induration | General disorders | 51 of 93 | 55 of 93 |
| Injection site pain | General disorders | 37 of 93 | 47 of 93 |
| Injection site nodule | General disorders | 31 of 93 | 38 of 93 |
| Injection site erythema | General disorders | 29 of 93 | 29 of 93 |
| Injection site pruritus | General disorders | 19 of 93 | 22 of 93 |
| Injection site bruising | General disorders | 14 of 93 | 22 of 93 |
| Injection site discoloration | General disorders | 15 of 93 | 19 of 93 |
The serious-event entries report 0 affected subjects among 93 at risk for the left nasolabial fold and 0 among 93 at risk for the right nasolabial fold. The record lists no serious preferred terms. These values describe the serious-event fields in the registry; they do not establish that no adverse events of any kind occurred.
For other adverse events, the record reports 71 affected among 93 at risk for the left-fold entry and 72 among 93 at risk for the right-fold entry. These are fold-specific counts. They should not be added, because the record does not say whether the same subjects appear in both entries. Nor should they be interpreted as numbers of product-related events: the registry does not state that the other events meet the primary endpoint’s relatedness definition.
The deaths field is not populated with a numerical value, so a death count is not reported in the registry record. More generally, the event counts do not provide detail on event severity beyond the serious-versus-other distinction, timing, recurrence, or the number of individual events. The primary endpoint’s numerical result for product-related adverse events is also not reported.
12. What the Result Does, and Does Not, Mean
The record describes a completed study of Belotero® in subjects with Fitzpatrick phototypes IV through VI and facial wrinkles, including nasolabial folds. It specifies a primary safety endpoint based on adverse events judged possibly, probably, or definitely related to study product over 24 weeks. The registry also provides serious and other adverse-event counts for left- and right-fold entries.
The posted serious-event entries each show 0 affected among 93 at risk. The other-event entries show 71 affected among 93 at risk for the left fold and 72 among 93 at risk for the right fold. These summaries are descriptive, and the record does not establish that the affected counts in the fold entries are distinct people or that other adverse events were product-related. They do not replace the missing numerical result for the defined primary endpoint.
The study’s single-group, non-randomized design does not provide a randomized comparison with another treatment or a control. The recorded counts therefore cannot estimate a causal difference between Belotero® and an alternative. The fold-specific entries should not be construed as a controlled comparison.
The record does not report an effectiveness result, an uncertainty interval for the primary endpoint, or an inferential test. Accordingly, the posted information does not support a conclusion about comparative effectiveness, the precision of the product-related event frequency, or a causal safety effect. It does support a limited description of the study population, design, endpoint definition, and adverse-event counts recorded in the registry.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why design and endpoint definition matter when reading safety results. Its primary outcome is not simply any adverse event: it is the percentage of subjects with events judged possibly, probably, or definitely related to study product. That distinction determines which events belong in the endpoint and prevents a general adverse-event listing from being treated as the primary result.
The record also illustrates the limits of descriptive safety counts. The serious-event entries report zero affected subjects for each fold, while the other-event entries report affected subjects for each fold. Without the relatedness status and a numerical primary endpoint estimate, those summaries answer different questions. Fold-specific entries also require care because the record does not say whether the same subjects contributed to both.
Design constrains interpretation. A non-randomized, single-group study can describe events observed during treatment, but it does not provide a randomized comparator for estimating a treatment difference. Separating these descriptive findings from causal claims is essential, particularly when the primary endpoint result and its uncertainty are not posted.
Finally, the registry record makes clear that a study’s completion status is not the same as a complete statistical report. The endpoint definition and some safety counts are available, but the primary estimate, confidence interval, missing-data approach, and multiplicity procedures are not reported. Recognizing those gaps is part of sound statistical interpretation, not a judgment about the product.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The most direct limitation is that the registry record does not report a numerical result for the primary endpoint, despite defining the measure and its 24-week timeframe. Without the estimate, analysis denominator, and a measure of uncertainty, the primary product-related adverse-event frequency cannot be evaluated for magnitude or precision.
The design is listed as non-randomized and single-group, with no separate control treatment. This limits causal interpretation and prevents a controlled estimate of relative safety or effectiveness. Masking is listed as none; further information about outcome assessment and event attribution is not reported in the registry record.
The adverse-event information is presented separately for left and right nasolabial folds. The record does not explain whether the same subjects contributed to both entries, how events affecting both folds were handled, or whether repeated events were counted. The fold-specific counts therefore should not be combined or treated as independent groups. The relation of the other adverse events to study product is not reported in those entries.
The record does not provide a numerical death count, detailed event timing, or further event-level descriptions in the registry record for this analysis. It also does not report the primary endpoint’s confidence interval, statistical test, missing-data handling, multiplicity procedure, or detailed analysis plan. A sample-size justification and interim-analysis plan are not reported in the registry record. These omissions limit assessment of precision, analysis choices, and the completeness of the posted results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Effectiveness of Belotero® in Subjects With Fitzpatrick Phototypes IV Through VI — NCT00922623.
- Registry record last updated 2013-04-26; status last verified 2013-04.
- Results first posted 2012-01-30.
- 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
NCT00922623 is a completed, non-randomized, single-group study titled “Safety and Effectiveness of Belotero® in Subjects With Fitzpatrick Phototypes IV Through VI.” The study lists enrollment of 93, with start in 2009-05 and primary completion in 2010-07. It evaluated Belotero® for facial wrinkles, including nasolabial folds, over a stated primary endpoint timeframe of 24 weeks.
The primary endpoint is the percentage of subjects with product-related adverse events, but its numerical result is not reported in the registry record. The serious-event entries report 0 affected among 93 at risk for each fold; other-event entries report 71 of 93 for the left fold and 72 of 93 for the right fold. These counts are descriptive and are not identified as the primary product-related outcome.
The single-group design does not provide a randomized control comparison. The registry record does not report a primary endpoint uncertainty interval, detailed missing-data methods, or a multiplicity procedure.