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 Vyndaqel Drug Use Investigation (Regulatory Post Marketing Commitment Plan) (NCT02146378), a registered phase not stated study. The primary outcome is Percentage of Participants With ADRs in This Study.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02146378 |
| Phase | Phase not stated |
| Condition | Transthyretin Familial Amyloid Polyneuropathy |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 500 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
People with transthyretin familial amyloid polyneuropathy who received Vyndaqel capsules 20mg under actual-use conditions after marketing. The safety analysis set included participants who met the inclusion criteria and received the capsules at least once; participants without administration information were excluded.
Intervention
Vyndaqel capsules 20mg, also identified in the registry as tafamidis meglumine. This was a post-marketing investigation of use in clinical practice, rather than a description of a randomized treatment assignment.
Comparator
No comparator group is described. The registry does not state an allocation method, and its record cautions that the arms are not a like-for-like control comparison. The posted safety counts therefore do not establish a contrast with untreated participants or another treatment.
Primary question
What percentage of participants had adverse drug reactions attributed to Vyndaqel during follow-up? The registry defines an adverse drug reaction as an untoward medical occurrence attributed to Vyndaqel by the physician. The intended observation period was 3 years, except that participants who started the capsules after May 2018 had a 1.5-year period.
The investigation’s stated purpose was to understand long-term safety, including adverse drug reactions, and efficacy data in people receiving Vyndaqel after marketing. Its secondary outcomes covered changes in NIS-LL, Norfolk QOL-DN TQOL, mBMI and total neurological assessment score, as well as ambulatory status and survival time for death from any cause or death associated with ATTR-PN. Those outcomes describe a broad follow-up program, but their inclusion in the registry does not establish that results or analyses were posted for each one.
3. Trial Design
This completed investigation was a post-marketing study of Vyndaqel use under actual-use conditions. The registry lists an enrollment of 500 and one intervention, Vyndaqel. It does not describe a randomized assignment or a control group, and the allocation method is not stated. The record explicitly cautions that the arms are not a like-for-like control comparison. The design is therefore best read as monitoring outcomes among treated participants, not as a controlled estimate of treatment effect.
The study began on 2014-01-10, and its primary completion date was 2023-03-10. The primary safety endpoint was the percentage of participants with adverse drug reactions. Its stated timeframe was 3 years, with a 1.5-year period for participants who started Vyndaqel capsules 20mg after May 2018. These different observation periods matter when considering how much time participants had to experience or report an event.
The safety analysis population was defined as participants who satisfied the inclusion criteria and received Vyndaqel capsules 20mg at least once. Those with no information about administration were excluded. The registry’s posted safety summary lists 400 participants at risk for serious events and 400 at risk for other events. These figures describe the listed safety summary; they should not be treated as a replacement for the enrollment count or as evidence that every enrolled participant was included in each analysis.
Secondary outcomes included changes from baseline in NIS-LL, Norfolk QOL-DN TQOL, mBMI and total neurological assessment score; the time course of ambulatory status; and survival time for death from any cause and death associated with ATTR-PN. The registry record does not report the detailed schedule of assessments, the handling of follow-up after treatment changes, or the methods used to analyze these outcomes.
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: Patient for whom the study completed, data that might be from the same patient were combined and evaluated as the same patient, based on date of birth or age, gender, mutant genotype, name of sites that the patient visited for concomitant diseases or he/she was transferred to.
Overall Study
| Stage | Vyndaqel Capsules 20mg (Tafamidis Meglumine) |
|---|---|
| STARTED | 402 |
| COMPLETED | 400 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Vyndaqel Capsules 20mg (Tafamidis Meglumine) |
|---|---|
| No information of administration | 2 |
Analysis population for the primary outcome, as defined in the registry: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received Vyndaqel capsules 20mg at least once. Participants with no information of administration were excluded.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: A total of 500 participants were enrolled in the study, of which CRFs were collected from 494 participants. Of these 494 participants, 402 participants were determined to be included in the analysis set by data matching and identifying the same participant. Of these 402 participants (after data integration), 2 participants were excluded from the safety analysis set due to no information of administration. A total of 400 participants were included in the safety analysis set.
| Characteristic | Unit | Vyndaqel Capsules 20mg (Tafamidis Meglumine) |
|---|---|---|
| Participants analysed | 400 | |
| Age, Customized: <15 years | Participants | 0 |
| Age, Customized: ≥15 and <65 years | Participants | 178 |
| Age, Customized: ≥65 years | Participants | 222 |
| Sex: Female, Male: Female | Participants | 138 |
| Sex: Female, Male: Male | Participants | 262 |
| Race and Ethnicity Not Collected | Participants | — |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With ADRs in This Study, measured over 3 years (However, the period for participants who started to receive Vyndaqel capsules 20mg after May 2018 was 1.5 years.).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled Percentage of Participants With ADRs in This Study. It is intended to describe how many participants experienced an adverse drug reaction during the defined observation period. The registry defines an adverse drug reaction as an untoward medical occurrence attributed to Vyndaqel capsules 20mg in a participant who received the drug. Relatedness was assessed by the physician, so the endpoint depends not only on whether an event occurred but also on the physician’s attribution.
A count or percentage of participants with attributed reactions is a descriptive safety measure. It can summarize the frequency of reported reactions in the observed treatment group, but by itself it does not show what would have happened to the same participants without treatment or under another treatment. In a study without a stated comparator, that counterfactual is unavailable.
The registry states a 3-year timeframe, with a 1.5-year period for participants who started Vyndaqel capsules 20mg after May 2018. Different follow-up durations can affect opportunities to observe events. The record does not give a primary endpoint estimate, confidence interval or inferential analysis, so the size and precision of the primary endpoint cannot be assessed from the posted information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record describes a long-term, post-marketing safety investigation of Vyndaqel in actual-use conditions. Its primary question concerns adverse drug reactions attributed to the drug by physicians. However, the posted information does not include a reported primary endpoint percentage or a statistical analysis of that endpoint. The safety counts should therefore be read as descriptive entries, not as a complete estimate of the primary endpoint’s frequency or precision.
The listed safety summary reports 124 participants affected among 400 at risk for serious events, and 104 affected among 400 at risk for other events. It also lists 50 deaths. These are distinct entries in the posted safety summary; they should not be added or treated as mutually exclusive categories. The record does not specify whether the serious-event and other-event groups overlap, nor does it provide enough detail to connect the deaths to a particular event category or cause. The listed counts are not, on their own, evidence that an event was attributed to Vyndaqel under the primary endpoint definition.
The record lists the following serious-event terms and percentages: Cardiac failure, 4.8%; Pneumonia, 2.0%; Pneumonia aspiration, 1.8%; Hereditary neuropathic amyloidosis, 1.5%; Vomiting, 1.5%; and Cerebral infarction, 1.5%. The denominator and event-count details for these percentages are not reported in the registry record. These terms also should not automatically be read as drug-attributed reactions: the primary endpoint required physician assessment of relatedness, while the available terms are presented as serious safety events.
Follow-up was not identical for all participants: the stated period was 3 years except for participants who began treatment after May 2018, for whom it was 1.5 years. That difference affects the time available for observing events and limits simple comparisons between participants unless the analysis accounts for exposure and follow-up time. The registry does not describe such an adjustment.
There is no stated control group or randomized comparison. As a result, the observed counts cannot isolate the contribution of Vyndaqel from the underlying condition, other care, or other circumstances. The record also does not report confidence intervals, p-values, or adjusted estimates. Without those results and a comparator, the displayed safety data can describe what was recorded in this treated population, but cannot establish a comparative risk or a causal effect.
9. Statistical Methods Explained
The registry identifies a binary primary endpoint: whether a participant had an adverse drug reaction attributed to Vyndaqel. A binary endpoint records an event status for each participant, rather than the number of repeated episodes or the time until an event. The title describes the target summary as a percentage of participants. The registry record does not list the primary endpoint result or a statistical analysis, so there is no posted estimate to interpret as a calculated percentage.
What does an event count represent?
A count of participants with an event is different from a count of all event episodes. If one participant has more than one event, a participant-level endpoint may count that person once, while an event-level summary may count multiple episodes. The registry’s primary endpoint is framed around participants with reactions, but the safety summary’s detailed counting rules are not reported in the registry record. The listed counts should therefore be described in the terms in which they are presented, without assuming how repeat events were handled.
The primary endpoint also depends on attribution. The record defines an adverse drug reaction as an untoward medical occurrence attributed to Vyndaqel and says that relatedness was assessed by the physician. This is a clinical judgment rather than a comparison against an untreated counterfactual. General statistical interpretation: attribution rules can shape which events enter a drug-related endpoint, and judgments may vary across assessors unless assessment procedures are specified. The registry record does not describe those procedures in detail.
Why does a comparator matter?
In a randomized comparison, treatment groups can be compared under an allocation process intended to make their starting characteristics comparable on average. Here, no randomized comparison is described, and the registry warns that the arms are not a like-for-like control comparison. A treated-group count can characterize events observed in the monitored participants, but it cannot show how frequently those events would have occurred without Vyndaqel. Differences in underlying health, follow-up, or care could also affect event counts. These are general limitations of interpreting uncontrolled safety observations, not findings that a particular source of bias occurred in this investigation.
A confidence interval, when reported, expresses uncertainty around an estimate under specified statistical assumptions. It helps distinguish a relatively precise estimate from one that is compatible with a broad range of values. No confidence interval for the primary endpoint is reported in the registry record. Nor are a p-value or adjusted estimate reported, so statistical significance and precision cannot be evaluated from the listed endpoint information.
How should the planning calculations be understood?
The planning illustrations are described as calculations based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms and a normal approximation. They consider effects defined as fractions of the observed effect. For time-to-event outcomes, the stated method uses the total number of events with a Schoenfeld approach; other outcomes are expressed as participants per arm. These are planning assumptions, not proof that the investigation used that design or achieved a particular level of power.
The record does not describe a randomized two-arm design, and it cautions against treating the arms as comparable controls. Any two-arm planning illustration must therefore be distinguished from the actual post-marketing study design. A sample-size calculation based on an observed effect is not observed power, and a planning result does not demonstrate that the study could reliably detect an effect. The registry does not report the origin or precision of the observed effect used for those illustrations, or a protocol-based sample-size justification.
Over-dispersion is a general concern when count data vary more than a model expects; ignoring it can make uncertainty appear too small. That concept is relevant to some event-count analyses, but the primary endpoint is participant-level and binary, and the registry does not report a model for it. No claim can be made about whether over-dispersion was assessed or whether any particular model was used.
Several secondary outcomes involve change from baseline, ambulatory status or survival time. General methods for change scores require a definition of baseline, follow-up timing and handling of incomplete measurements. Time-to-event methods also require rules for follow-up end, censoring and event definitions. The registry lists survival outcomes but does not report the analysis methods or the handling of censoring. It likewise does not describe the statistical approach for the score changes or ambulatory status.
Multiplicity refers to the increased chance of false-positive findings when many outcomes or tests are assessed. General approaches include pre-specifying a primary outcome and adjusting or otherwise organizing secondary analyses. The registry names one primary endpoint and multiple secondary outcomes, but any multiplicity strategy is not reported in the registry record. Since no analyses are listed, there are no reported inferential results to assess for multiplicity.
10. Multiplicity, Missing Data and Analysis Populations
The registry names a primary safety endpoint and several secondary outcomes, including changes in clinical and quality-of-life scores, ambulatory status and survival. Testing many outcomes can raise the chance of at least one apparently unusual result even when no real difference exists; this is the general multiplicity problem. The registry record does not report a strategy for prioritizing, adjusting or interpreting multiple analyses. It also lists no analyses, so there are no posted p-values to evaluate under a multiplicity plan.
Missing-data methods are not reported in the registry record. The safety analysis population excluded participants with no information about drug administration, but this rule does not describe how missing outcome information was handled among included participants. The record does not state whether incomplete follow-up, missing baseline scores, withdrawals, or unavailable event details were imputed, excluded, or handled by another approach. Missingness can affect both the number of participants contributing to an outcome and the meaning of the resulting estimate; the direction or size of any effect cannot be inferred without details.
The safety population is described as participants meeting inclusion criteria who received Vyndaqel capsules 20mg at least once. The registry does not report a broader analysis-population strategy, such as how participants were handled across each secondary outcome. The enrollment of 500 and the safety summary’s 400 participants at risk should not be assumed to represent identical analysis sets. No participant flow or outcome-specific denominators are reported in the registry record.
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 |
|---|---|---|---|
| Vyndaqel Capsules 20mg (Tafamidis Meglumine) | 124 | 400 | 31.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Vyndaqel Capsules 20mg (Tafamidis Meglumine) | 50 of 400 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0.5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Vyndaqel Capsules 20mg (Tafamidis Meglumine) | 104 of 400 |
Most frequent serious adverse event terms
| Event term | Organ system | Vyndaqel Capsules 20mg (Tafamidis Meglumine) |
|---|---|---|
| Cardiac failure | Cardiac disorders | 19 of 400 |
| Pneumonia | Infections and infestations | 8 of 400 |
| Pneumonia aspiration | Infections and infestations | 7 of 400 |
| Hereditary neuropathic amyloidosis | Congenital, familial and genetic disorders | 6 of 400 |
| Vomiting | Gastrointestinal disorders | 6 of 400 |
| Cerebral infarction | Nervous system disorders | 6 of 400 |
| Atrioventricular block complete | Cardiac disorders | 5 of 400 |
| Femur fracture | Injury, poisoning and procedural complications | 5 of 400 |
| Atrial fibrillation | Cardiac disorders | 4 of 400 |
| Dysphagia | Gastrointestinal disorders | 4 of 400 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Vyndaqel Capsules 20mg (Tafamidis Meglumine) |
|---|---|---|
| Constipation | Gastrointestinal disorders | 11 of 400 |
| Insomnia | Psychiatric disorders | 11 of 400 |
| Diarrhoea | Gastrointestinal disorders | 9 of 400 |
| Hypoaesthesia | Nervous system disorders | 8 of 400 |
| Neuralgia | Nervous system disorders | 8 of 400 |
| Hepatic function abnormal | Hepatobiliary disorders | 7 of 400 |
| Urinary tract infection | Infections and infestations | 6 of 400 |
| Anaemia | Blood and lymphatic system disorders | 5 of 400 |
| Cardiac failure | Cardiac disorders | 5 of 400 |
| Renal impairment | Renal and urinary disorders | 5 of 400 |
Serious events with the highest arm-level rate: cardiac failure (4.8%), pneumonia (2.0%), pneumonia aspiration (1.8%), hereditary neuropathic amyloidosis (1.5%), vomiting (1.5%).
The safety summary lists 124 participants affected among 400 at risk for serious events and 104 affected among 400 at risk for other events. It separately lists 50 deaths. These are counts in the posted summary; they do not by themselves identify how many events were judged related to Vyndaqel, and the record does not specify whether categories overlap. The numbers should not be combined into a total or interpreted as mutually exclusive groups.
The record defines a serious adverse drug reaction as an adverse drug reaction resulting in death, being life-threatening, requiring inpatient hospitalization or prolongation of hospitalization, causing persistent or significant disability or incapacity, resulting in a congenital anomaly or birth defect, or deemed significant for another reason. This definition concerns serious reactions, while the posted serious-event figures do not establish that each listed serious event met the drug-attribution requirement.
The serious-event terms include Cardiac failure, 4.8%; Pneumonia, 2.0%; Pneumonia aspiration, 1.8%; Hereditary neuropathic amyloidosis, 1.5%; Vomiting, 1.5%; and Cerebral infarction, 1.5%. The denominator for these percentages is not reported in the registry record. They are descriptive safety entries, not comparative estimates or proof of causation.
12. What the Result Does, and Does Not, Mean
The registry describes an effort to monitor long-term Vyndaqel use after marketing, including adverse drug reactions and a range of clinical outcomes. The posted safety summary records serious and other events among participants at risk, and it lists deaths and selected serious-event terms. These observations can help characterize what was recorded during follow-up in the monitored population.
They do not, on their own, answer whether Vyndaqel caused a particular event or changed the chance of an event. The primary endpoint requires physician attribution, but the posted safety counts do not provide a reported primary endpoint estimate. Without a comparator, there is no estimate of the corresponding event frequency in a similar group not receiving Vyndaqel. The registry itself cautions that the arms are not a like-for-like control comparison.
The listed counts also do not establish how precise the event estimates are. No confidence intervals, p-values or adjusted analyses are reported in the registry record. The stated follow-up period differs for participants who began treatment after May 2018, and the record does not report an analysis accounting for that difference. The percentages for selected serious-event terms lack a stated denominator in the registry record.
The investigation’s secondary outcomes cover neurological scores, quality of life, body mass index, ambulatory status and survival. Their presence in the registry indicates planned outcome domains, not that a change was observed or that an analysis was completed. The registry does not report results or methods for these outcomes.
Accordingly, the record supports a descriptive reading of the posted safety entries and the study’s intended questions. It does not support a comparative treatment-effect conclusion, a causal interpretation, or a claim about the precision of the primary endpoint. Those limits reflect the absence of reported analyses and a stated control comparison, not a conclusion that an event did or did not occur because of treatment.
13. Why This Trial Matters Statistically
Post-marketing investigations address use in actual clinical conditions and can collect safety information beyond the controlled circumstances of a trial. This record is statistically informative because it makes clear that its primary aim was to describe adverse drug reactions during long-term use, while also listing broader clinical and survival outcomes. The distinction between monitoring and comparison is essential: observed event counts can describe what was recorded, but they cannot alone isolate a treatment effect.
The record also illustrates why analysis populations and denominators matter. Enrollment is listed as 500, while the safety summary lists 400 participants at risk for serious events and 400 for other events. These are not interchangeable quantities. Without participant flow and outcome-specific denominators, readers cannot determine from the registry how the full enrolled group relates to each safety entry.
Follow-up duration is another key part of interpretation. The stated primary timeframe is 3 years, with 1.5 years for participants who started Vyndaqel capsules 20mg after May 2018. Event counts accumulated over unequal observation periods do not necessarily represent comparable exposure time. The record does not report an adjustment for that difference, so the appropriate interpretation remains descriptive.
Finally, the registry names outcomes but does not list analyses. That gap separates an outcome plan from an evidence estimate. Without an endpoint result, uncertainty interval, analysis methods or a suitable comparator, readers cannot assess precision or comparative effects. This is a useful reminder that a completed study status and a substantial enrollment do not by themselves provide the statistical information needed to answer every clinical question.
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 registry does not report a primary endpoint estimate, confidence interval, p-value or adjusted analysis. Although the primary endpoint is defined as the percentage of participants with adverse drug reactions, the posted summary counts do not provide that result directly. This prevents assessment of the endpoint’s magnitude and statistical precision.
No comparator group or randomized allocation is described, and the record warns that the arms are not a like-for-like control comparison. Consequently, the safety counts cannot support a controlled estimate of relative risk or a causal conclusion. The registry does not state how any potential differences between groups were handled.
The listed serious-event and other-event summaries each use 400 participants at risk, while total enrollment is 500. The record does not provide a participant flow diagram, outcome-specific denominators or enough detail to reconcile those populations. It also does not state whether serious and other event categories overlap. The 50 deaths are not accompanied by details sufficient to connect them to specific causes or event categories.
Follow-up was 3 years for the stated period, except for participants who started Vyndaqel capsules 20mg after May 2018, for whom it was 1.5 years. The registry does not report methods to account for differing observation time. It also does not give the denominator for the percentages listed beside serious-event terms.
Details of missing-data handling, multiplicity, outcome-specific analysis populations, protocol-based sample-size justification, interim analyses and statistical methods are not reported in the registry record. The record lists secondary outcome domains but does not report their results or analyses. These omissions limit assessment of bias, precision and the extent to which the stated questions were answered.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vyndaqel Drug Use Investigation (Regulatory Post Marketing Commitment Plan) — NCT02146378.
- Registry record last updated 2025-02-03; status last verified 2025-01.
- Results first posted 2025-02-03.
- 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
NCT02146378 is a completed post-marketing investigation of Vyndaqel capsules 20mg for transthyretin familial amyloid polyneuropathy. Its stated purpose was to describe safety and efficacy data during long-term use under actual-use conditions. Enrollment was 500; the study began on 2014-01-10, and primary completion was 2023-03-10.
The primary endpoint was the percentage of participants with adverse drug reactions, with physician-assessed relatedness. The stated follow-up was 3 years, except for participants who started after May 2018, who had a 1.5-year period. The safety population required qualifying participants to have received the capsules at least once; those without administration information were excluded.
The posted safety summary lists 124 affected among 400 at risk for serious events, 104 affected among 400 at risk for other events, and 50 deaths. No primary endpoint estimate, inferential analysis or comparator-based result is reported in the registry record. Secondary outcomes include score changes, ambulatory status and survival, but their analyses and results are not reported.