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 Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 (RN316) In Hypercholesterolemic Subjects On A Statin (NCT01592240), a randomized phase 2 study. The primary outcome is Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01592240 |
| Phase | Phase 2 |
| Condition | Hypercholesterolemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 354 |
| Arms in the primary outcome | 7 |
| Lead sponsor | Pfizer |
| Results posted | Yes |
2. Clinical Question
Population
Adults with hypercholesterolemia whose LDL-C was at least 80 mg/dL while receiving background statin treatment were the population described in the study summary. The registry record reports that 354 participants enrolled. The primary analysis population was the full analysis set, described as all randomized participants; for the primary outcome, the reported analyzed count refers to participants evaluable for that measure.
Intervention
Participants were assigned to subcutaneous PF-04950615 at different doses and schedules. The every-14-days groups received 50 mg, 100 mg, or 150 mg. The every-28-days groups received 200 mg or 300 mg. The study description also includes placebo groups on both schedules. Background statin treatment was part of the population description.
Comparator
Each dose was compared with placebo on the corresponding schedule: every 14 days for the 50 mg, 100 mg, and 150 mg comparisons, and every 28 days for the 200 mg and 300 mg comparisons. These schedule-matched comparisons help keep the dosing interval aligned between treatment and placebo groups.
Primary question
The primary question was whether LDL-C change from baseline at Week 12 differed between each PF-04950615 dose group and its schedule-matched placebo group. The endpoint is expressed as a mean change in milligrams per deciliter. The sponsor’s reported comparisons use an adjusted mean difference from a mixed models repeated measures analysis, with a 95% confidence interval and p-value for each comparison.
3. Trial Design
The registry describes a Phase 2b, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study. Masking is recorded as triple. The study evaluated subcutaneous PF-04950615 over a six-month treatment period, using an every-14-days schedule and an every-28-days schedule. Placebo groups were included on both schedules.
The primary outcome was change from baseline in LDL-C at Week 12. The registry also lists LDL-C change at Week 24 and additional lipid and apolipoprotein outcomes. Enrollment was 354. The arm descriptions state that seven dose groups across the two schedules were planned, with 50 participants per dose group planned. The analyzed counts for the primary endpoint vary by arm, and the record defines these counts as participants evaluable for that outcome.
The intervention arms reported for the primary endpoint include placebo and PF-04950615 50 mg, 100 mg, and 150 mg every 14 days, plus placebo and PF-04950615 200 mg and 300 mg every 28 days. The sponsor’s efficacy comparisons pair each active dose with the placebo group on its schedule. This design addresses dose and schedule comparisons within the study; the record does not describe a direct randomized comparison between dosing schedules at a common dose.
The study status is completed. The recorded start is 2012-07 and primary completion is 2013-04. The registry record does not report the rationale for the planned group size or further details of the randomization procedure. Details such as allocation concealment and the identities of the masked parties are not reported in the registry 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.
Only the first 6 of 7 groups are shown.
Overall Study
| Stage | Placebo: Every 14 Days | PF-04950615 50 mg: Every 14 Days | PF-04950615 100 mg: Every 14 Days | PF-04950615 150 mg: Every 14 Days | Placebo: Every 28 Days | PF-04950615 200 mg: Every 28 Days |
|---|---|---|---|---|---|---|
| STARTED | 50 | 50 | 52 | 50 | 51 | 50 |
| COMPLETED | 47 | 39 | 45 | 47 | 44 | 47 |
| NOT COMPLETED | 3 | 11 | 7 | 3 | 7 | 3 |
Reasons for not completing this period:
| Reason | Placebo: Every 14 Days | PF-04950615 50 mg: Every 14 Days | PF-04950615 100 mg: Every 14 Days | PF-04950615 150 mg: Every 14 Days | Placebo: Every 28 Days | PF-04950615 200 mg: Every 28 Days |
|---|---|---|---|---|---|---|
| Adverse Event | 1 | 0 | 0 | 1 | 1 | 0 |
| Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Lost to Follow-up | 1 | 3 | 1 | 0 | 3 | 2 |
| Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 4 | 4 | 1 | 3 | 0 |
| Other | 0 | 3 | 1 | 1 | 0 | 0 |
| Did Not Meet Entrance Criteria | 1 | 0 | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set included all participants who were randomized. Here "Overall Number of Participants Analyzed", signifies number of participants those who were evaluable for this outcome measure.
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: Full analysis set (FAS) included all participants who were randomized.
Only the first 6 of 8 groups are shown.
| Characteristic | Unit | Placebo: Every 14 Days | PF-04950615 50 mg: Every 14 Days | PF-04950615 100 mg: Every 14 Days | PF-04950615 150 mg: Every 14 Days | Placebo: Every 28 Days | PF-04950615 200 mg: Every 28 Days |
|---|---|---|---|---|---|---|---|
| Participants analysed | 50 | 50 | 52 | 50 | 51 | 50 | |
| Age, Continuous | Years | 60.5 (SD 9.84) | 59.1 (SD 11.26) | 61.9 (SD 9.58) | 61.4 (SD 9.75) | 58.4 (SD 11.62) | 60.3 (SD 9.64) |
| Sex: Female, Male: Female | Participants | 25 | 26 | 26 | 29 | 22 | 31 |
| Sex: Female, Male: Male | Participants | 25 | 24 | 26 | 21 | 29 | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12, measured over Baseline, Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | milligram per deciliter (mg/dL) |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean change from baseline in LDL-C at Week 12, measured in milligrams per deciliter. It describes how the measured LDL-C level at follow-up differs from the participant’s baseline level. In general, a negative change indicates a lower measured LDL-C level at follow-up than at baseline; it is not the same as reporting the absolute LDL-C level at Week 12.
Change from baseline is used to express the direction and size of within-participant change during the study. Comparing average changes between randomized groups then helps assess whether change differed between PF-04950615 and placebo under the study conditions. The registry reports arm-level mean changes with 95% confidence intervals, and the sponsor reports adjusted mean differences between each active dose and its schedule-matched placebo.
The endpoint is measured at Week 12, while the study description covers six months of dosing. The Week 12 result therefore addresses the prespecified early time point, not the full duration of follow-up. Although the registry lists LDL-C outcomes at Week 24 among secondary outcomes, numerical results for those outcomes are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
At Week 12, the reported mean LDL-C change was negative in all three PF-04950615 groups dosed every 14 days. The arm-level means were -36.9 mg/dL for 50 mg, -47.6 mg/dL for 100 mg, and -56.0 mg/dL for 150 mg. The every-14-days placebo group had a mean change of -2.6 mg/dL. In the every-28-days groups, mean changes were -23.0 mg/dL with 200 mg and -40.3 mg/dL with 300 mg; the corresponding placebo group had a mean change of 4.6 mg/dL.
The sponsor’s adjusted comparisons were all negative and each had p < 0.001. For the every-14-days schedule, the adjusted mean differences versus placebo were -34.28 mg/dL for 50 mg, -45.07 mg/dL for 100 mg, and -53.42 mg/dL for 150 mg. For the every-28-days schedule, the adjusted mean differences were -27.58 mg/dL for 200 mg and -44.85 mg/dL for 300 mg. Each reported 95% confidence interval is entirely below zero. These results describe the direction and precision of the Week 12 comparisons as analyzed by the sponsor; they do not establish effects beyond the population, endpoint, and follow-up represented in this study.
The arm-level confidence intervals describe uncertainty around each group’s mean change. The sponsor’s confidence intervals instead describe uncertainty around adjusted between-group differences. They answer related but distinct questions, so an arm’s interval should not be treated as a substitute for the interval on the randomized comparison. The registry does not report standard deviations for the arm-level changes, and they are not needed to quote the sponsor’s adjusted results.
The number analyzed for the primary outcome differs by arm, while the randomized full analysis set is described as including all randomized participants. That distinction matters: the reported outcome counts are evaluable counts, not a restatement of enrollment. The registry record does not explain the reasons for participants being unevaluable or how missing Week 12 measurements were handled.
Overall, the posted primary results show progressively more negative arm-level mean changes across the reported dose groups within each schedule, while the sponsor’s adjusted comparisons favor a more negative change in each active-dose group than its schedule-matched placebo group. This is a description of the reported LDL-C endpoint, not a claim about clinical outcomes or an independent assessment of benefit and risk.
9. Statistical Methods Explained
What does an arm-level mean change represent?
Each arm-level result is a mean change in LDL-C from baseline to Week 12 among participants evaluable for that outcome. A mean condenses the participant-level changes into one group summary. It does not show how individual participants’ changes were distributed, whether responses were similar across participants, or whether a small number of values influenced the average. The registry gives a 95% confidence interval for each arm’s mean but does not give a standard deviation in the primary outcome record.
In general, a confidence interval expresses uncertainty about an estimated quantity under the analysis and its assumptions. For an arm-level mean, it describes uncertainty around the group mean; for a between-group contrast, it describes uncertainty around that contrast. A narrower interval indicates greater precision than a wider interval, but precision is not the same as clinical importance. Intervals are also not a guarantee that the true quantity lies within the reported limits.
What is the sponsor’s adjusted mean difference?
The sponsor reports adjusted mean differences between each active dose and its schedule-matched placebo. A difference is the estimated contrast between groups, rather than a mean change in one group alone. Here, negative values indicate that the estimated change was more negative in the active-dose group than in its placebo comparator. The confidence interval gives a range of values compatible with the estimated contrast under the model. The sponsor reports a 95% confidence interval for each comparison.
The model is identified as mixed models repeated measures analysis. In general, repeated-measures models can use outcome measurements collected at multiple visits and account for the fact that measurements from the same participant are related. They can estimate group differences over time while accounting for the structure specified in the model. The registry record does not report the model’s covariates, covariance structure, estimation details, or assumptions about missing measurements. Those details should not be inferred from the model name alone.
How should the p-values be read?
A p-value describes how incompatible the observed data are with a specified null hypothesis under the analysis assumptions; it is not the probability that the null hypothesis is true. The sponsor reports p < 0.001 for each of the five primary active-dose comparisons. These reported values are evidence against a zero adjusted mean difference for the individual comparisons under the sponsor’s model. They do not measure the size or practical importance of the difference, and they do not by themselves address the consequences of testing multiple doses.
The registry record does not say whether the primary comparisons were adjusted for multiplicity. A multiplicity procedure can control the chance of false-positive findings across a family of tests, but the appropriate family and method depend on the prespecified analysis plan. No adjustment should be assumed when it is not reported.
Why distinguish adjusted and unadjusted summaries?
The arm-level means are descriptive summaries of observed changes. The sponsor’s model-based contrasts are adjusted estimates for comparisons between randomized groups. Adjustment can account for variables or repeated observations specified by the model, so an adjusted contrast need not equal a subtraction of the displayed arm means. The registry record does not list all elements needed to recreate the model. No independent recalculation of the primary comparison is reported in the registry record, and no discrepancy is flagged between the sponsor analysis and a recalculation.
For the secondary anti-drug antibody comparisons, unadjusted risk differences and p-values are reported alongside confidence intervals. These are distinct from the primary continuous outcome analysis. In general, a risk difference compares the observed proportions in two groups, while its confidence interval conveys uncertainty in that difference. The reported secondary p-values are unadjusted, so they should be interpreted cautiously in the context of multiple secondary outcomes and comparisons.
General statistical caution applies to all these summaries: estimates depend on the chosen outcome definition, analysis population, model, and handling of incomplete measurements. The registry identifies the primary population as all randomized participants, while clarifying that the number analyzed for the outcome is the number evaluable. It does not report enough detail to independently reproduce the adjusted analysis or assess every model assumption.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Mixed models repeated measures analysis | Adjusted mean difference -34.28 | -45.06 to -23.50 | < 0.001 |
| Mixed models repeated measures analysis | Adjusted mean difference -45.07 | -55.93 to -34.21 | < 0.001 |
| Mixed models repeated measures analysis | Adjusted mean difference -53.42 | -64.14 to -42.70 | < 0.001 |
| Mixed models repeated measures analysis | Adjusted mean difference -27.58 | -40.49 to -14.67 | < 0.001 |
| Mixed models repeated measures analysis | Adjusted mean difference -44.85 | -57.65 to -32.05 | < 0.001 |
The sponsor’s own primary analysis is a mixed models repeated measures analysis. It reports adjusted mean differences between each PF-04950615 dose and placebo on the same dosing schedule, with 95% confidence intervals and p-values. All five reported adjusted differences are negative, and each has p < 0.001. The sponsor’s comparisons are the principal inferential results recorded for the primary endpoint.
The arm-level means and their confidence intervals provide descriptive context, but they are not a substitute for the sponsor’s model-based contrasts. Differences between an adjusted contrast and a contrast one might infer from arm summaries can arise because the model estimates an adjusted quantity and may use repeated observations. The model specifications needed to reproduce those estimates are not reported in the registry record.
No discrepancy is flagged between the sponsor’s analysis and a recalculation. The registry record does not include a separate recalculated primary comparison. Therefore, there is no competing recalculated estimate to set against the sponsor’s reported results. The sponsor’s model estimates should be read as the reported primary comparisons, with the limitations that the model details and missing-data handling are not fully described.
11. Multiplicity, Missing Data and Analysis Populations
The primary endpoint includes five reported active-dose comparisons: three against the every-14-days placebo group and two against the every-28-days placebo group. The registry reports a p-value and confidence interval for each. It does not report whether these comparisons were treated as a single testing family, whether a multiplicity adjustment was used, or whether a particular comparison had priority. The statistical plan for handling multiple primary comparisons is not reported in the registry record.
The record lists numerous secondary outcomes and reports unadjusted analyses for the anti-drug antibody comparisons. No correction for multiple secondary outcomes or comparisons is described. When many tests are conducted, isolated small p-values can occur by chance more often than in a single prespecified test. This general concern does not change the reported estimates, but it affects how strongly multiple unadjusted findings should be interpreted.
The primary population is described as the full analysis set, including all randomized participants. However, the registry clarifies that the reported number analyzed for the primary outcome is the number evaluable for that measure. The outcome counts are therefore not necessarily the same as the number randomized to each arm. Reasons for missing or unevaluable Week 12 measurements, the analysis’s missing-data assumptions, and any imputation or sensitivity analyses are not reported in the registry record.
The sponsor used a mixed models repeated measures analysis, but the registry record does not specify its covariates, covariance structure, or missing-data assumptions. Interim analyses and any stopping rules are not reported in the registry record.
Any sample-size figures derived from the anti-drug antibody comparisons are planning illustrations based on observed effects, not observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. They do not show the probability that this completed trial detected an effect.
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 |
|---|---|---|---|
| Placebo: Every 14 Days | 7 | 49 | 14.3% |
| PF-04950615 50 mg: Every 14 Days | 4 | 50 | 8.0% |
| PF-04950615 100 mg: Every 14 Days | 2 | 51 | 3.9% |
| PF-04950615 150 mg: Every 14 Days | 4 | 49 | 8.2% |
| Placebo: Every 28 Days | 2 | 51 | 3.9% |
| PF-04950615 200 mg: Every 28 Days | 5 | 50 | 10.0% |
| PF-04950615 300 mg: Every 28 Days | 4 | 51 | 7.8% |
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 |
|---|---|
| Placebo: Every 14 Days | 35 of 49 |
| PF-04950615 50 mg: Every 14 Days | 27 of 50 |
| PF-04950615 100 mg: Every 14 Days | 38 of 51 |
| PF-04950615 150 mg: Every 14 Days | 35 of 49 |
| Placebo: Every 28 Days | 28 of 51 |
| PF-04950615 200 mg: Every 28 Days | 32 of 50 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo: Every 14 Days | PF-04950615 50 mg: Every 14 Days | PF-04950615 100 mg: Every 14 Days | PF-04950615 150 mg: Every 14 Days | Placebo: Every 28 Days | PF-04950615 200 mg: Every 28 Days |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 49 | 0 of 50 | 1 of 51 | 0 of 49 | 0 of 51 | 1 of 50 |
| Transient ischaemic attack | Nervous system disorders | 0 of 49 | 0 of 50 | 0 of 51 | 1 of 49 | 0 of 51 | 1 of 50 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 0 of 49 | 1 of 50 | 0 of 51 | 0 of 49 | 0 of 51 | 1 of 50 |
| Angina unstable | Cardiac disorders | 0 of 49 | 0 of 50 | 0 of 51 | 1 of 49 | 0 of 51 | 0 of 50 |
| Cardiac failure chronic | Cardiac disorders | 0 of 49 | 0 of 50 | 0 of 51 | 1 of 49 | 0 of 51 | 0 of 50 |
| Intestinal obstruction | Gastrointestinal disorders | 1 of 49 | 0 of 50 | 0 of 51 | 0 of 49 | 0 of 51 | 0 of 50 |
| Vomiting | Gastrointestinal disorders | 0 of 49 | 0 of 50 | 0 of 51 | 0 of 49 | 1 of 51 | 0 of 50 |
| Chest pain | General disorders | 0 of 49 | 0 of 50 | 0 of 51 | 0 of 49 | 0 of 51 | 1 of 50 |
| Bronchitis viral | Infections and infestations | 0 of 49 | 0 of 50 | 0 of 51 | 0 of 49 | 0 of 51 | 1 of 50 |
| Cellulitis | Infections and infestations | 0 of 49 | 0 of 50 | 1 of 51 | 0 of 49 | 0 of 51 | 0 of 50 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo: Every 14 Days | PF-04950615 50 mg: Every 14 Days | PF-04950615 100 mg: Every 14 Days | PF-04950615 150 mg: Every 14 Days | Placebo: Every 28 Days | PF-04950615 200 mg: Every 28 Days |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 6 of 49 | 8 of 50 | 7 of 51 | 5 of 49 | 7 of 51 | 6 of 50 |
| Upper respiratory tract infection | Infections and infestations | 7 of 49 | 4 of 50 | 5 of 51 | 3 of 49 | 9 of 51 | 5 of 50 |
| Diarrhoea | Gastrointestinal disorders | 4 of 49 | 3 of 50 | 4 of 51 | 5 of 49 | 2 of 51 | 2 of 50 |
| Bronchitis | Infections and infestations | 4 of 49 | 2 of 50 | 3 of 51 | 5 of 49 | 3 of 51 | 3 of 50 |
| Injection site erythema | General disorders | 2 of 49 | 2 of 50 | 4 of 51 | 5 of 49 | 0 of 51 | 4 of 50 |
| Urinary tract infection | Infections and infestations | 3 of 49 | 1 of 50 | 5 of 51 | 4 of 49 | 1 of 51 | 2 of 50 |
| Sinusitis | Infections and infestations | 2 of 49 | 3 of 50 | 3 of 51 | 3 of 49 | 2 of 51 | 2 of 50 |
| Arthalgia | Musculoskeletal and connective tissue disorders | 2 of 49 | 0 of 50 | 6 of 51 | 4 of 49 | 3 of 51 | 0 of 50 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 49 | 1 of 50 | 4 of 51 | 2 of 49 | 1 of 51 | 4 of 50 |
| Injection site pain | General disorders | 4 of 49 | 4 of 50 | 1 of 51 | 1 of 49 | 2 of 51 | 1 of 50 |
Serious events with the highest arm-level rate: endometrial cancer stage ii (4.0%), prostatic dysplasia (4.0%), angina unstable (2.0%), cardiac failure chronic (2.0%), intestinal obstruction (2.0%).
The registry reports serious adverse events by group as counts of participants affected and participants at risk. The counts affected were 7 of 49 for placebo every 14 days; 4 of 50 for PF-04950615 50 mg every 14 days; 2 of 51 for 100 mg every 14 days; and 4 of 49 for 150 mg every 14 days. For the every-28-days groups, the counts were 2 of 51 for placebo, 5 of 50 for PF-04950615 200 mg, and 4 of 51 for 300 mg. These are descriptive counts; they do not establish that an event was caused by study treatment.
The registry lists serious-event terms including endometrial cancer stage II and prostatic dysplasia, each reported as 4.0%, and angina unstable, cardiac failure chronic, intestinal obstruction, and urinary tract infection, each reported as 2.0%. The record does not map these listed terms to individual treatment groups in the information. Death counts are not reported in the registry record.
Serious-event counts should be interpreted in light of the group sizes and the study’s follow-up, and not as a complete measure of safety. The registry record does not provide event-level timing, duration, relatedness assessments, or a detailed account of how adverse-event collection differed across groups.
13. What the Result Does, and Does Not, Mean
The primary results describe mean LDL-C change from baseline at Week 12 among participants in a randomized, placebo-controlled study of PF-04950615 on background statin treatment. The reported arm means are more negative in the active-dose groups than in the corresponding placebo groups, and the sponsor’s adjusted comparisons are negative with 95% confidence intervals entirely below zero. The estimates and intervals express the size and precision of the measured endpoint under the recorded analysis.
These findings do not, on their own, describe absolute LDL-C levels at Week 12, individual responses, longer-term outcomes, or outcomes beyond those measured in the study. The primary endpoint is a laboratory measure, and the registry results do not establish effects on clinical events or other health outcomes. The registry also does not report enough detail to assess all model assumptions, missing-data handling, or multiplicity procedures.
The study included several doses and two schedules, with each active dose compared to placebo on its own schedule. The reported comparisons do not establish a direct contrast between every-14-days and every-28-days dosing at equivalent doses. The design and results should be interpreted within the population described: participants with hypercholesterolemia and elevated LDL-C despite background statin treatment. Details about participants beyond that description are not reported in the registry record.
Safety counts offer a descriptive account of serious adverse events recorded in the groups, not a definitive causal assessment. Neither the efficacy summaries nor the adverse-event counts alone provide a complete benefit-risk evaluation. The registry record is a record of the study and its posted results, not a substitute for the full analysis plan and detailed clinical report.
14. Why This Trial Matters Statistically
This trial illustrates why randomized comparisons and within-group changes should be distinguished. A mean change describes what happened within an arm, while an adjusted mean difference addresses how the estimated change compares between randomized groups. The sponsor reports both types of information, but the model-based comparison is the relevant inferential contrast for the primary question.
The multiple-dose, two-schedule design also makes the comparison structure important. Each active dose is paired with placebo on the same schedule, and those are the comparisons reported. A dose pattern across arms may be descriptively informative, but it is not a formal test of a dose-response relationship unless the analysis plan and model establish that question. Such a test is not reported in the registry record.
The record also demonstrates how a clear direction of estimates can coexist with limits on interpretation. The adjusted primary comparisons are precise enough to have confidence intervals that exclude zero, while details needed to evaluate multiplicity, model specification, and missing-data assumptions are absent. Statistical evidence for a difference on the registered endpoint should not be confused with proof of a broader clinical effect.
Finally, registry outcome reporting separates the primary endpoint from a broad set of secondary measures. Without numerical results for most listed secondary outcomes, conclusions should remain anchored to the endpoint and comparisons that are reported. This restraint helps keep the interpretation aligned with the evidence available in the registry record.
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 primary outcome is measured at Week 12, whereas the study description covers six months of dosing. The registry lists later LDL-C and other secondary outcomes, but their numerical results are not reported in the registry record. The primary endpoint therefore cannot by itself describe the full time course over the study period.
The study enrolled participants with hypercholesterolemia receiving a statin, but the registry record does not provide detailed characteristics of the enrolled population or specify the background statin regimens in the information. Applicability beyond the population described cannot be assessed from these results alone.
The primary analysis uses a mixed models repeated measures method, but its detailed specification is not reported. The record also does not explain missing or unevaluable outcome data, or report sensitivity analyses that might show how conclusions depend on missing-data assumptions. The difference between the full analysis set definition and the evaluable counts for the outcome is therefore important when interpreting the results.
Multiple doses and secondary outcomes create multiplicity considerations. The registry record does not report how the primary comparisons were prioritized or whether any multiplicity adjustment was applied. It also does not describe a statistical analysis plan sufficient to assess whether all planned outcomes and analyses are represented in the posted results.
Serious adverse-event counts are reported by group, but detailed event-level information and deaths are not reported in the registry record. The counts alone cannot determine causality or provide a comprehensive safety assessment. In addition, the registry record does not give a direct randomized comparison between the two dosing schedules at a common dose.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Monthly And Twice Monthly Subcutaneous Dosing Of PF-04950615 (RN316) In Hypercholesterolemic Subjects On A Statin — NCT01592240.
- Registry record last updated 2017-12-05; status last verified 2017-10.
- Results first posted 2017-12-05.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT01592240 is a completed Phase 2b randomized, double-blind, placebo-controlled, parallel-group dose-ranging study sponsored by Pfizer. It enrolled 354 participants with hypercholesterolemia receiving a statin and evaluated subcutaneous PF-04950615 given every 14 or every 28 days.
The primary endpoint was mean change from baseline in LDL-C at Week 12. The registry reports arm-level means and 95% confidence intervals, plus sponsor-reported adjusted mean differences versus schedule-matched placebo. All five sponsor comparisons have p < 0.001. Serious adverse-event counts are reported by group; deaths are not reported in the registry record. The registry lists secondary lipid, apolipoprotein, and antibody outcomes, but numerical results for most secondary outcomes are not reported in the registry record.
The recorded study start is 2012-07, and primary completion is 2013-04. Details of the full statistical plan, multiplicity handling, and missing-data methods are not reported in the registry record.