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 Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1) (NCT01926782), a randomized phase 3 study. The primary outcome is Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01926782 |
| Phase | Phase 3 |
| Condition | Hypercholesterolemia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 803 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Regeneron Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with primary hypercholesterolemia were enrolled. The primary analysis population was narrower: randomized participants who did not receive concomitant statin therapy and had a baseline and at least one post-baseline calculated LDL-C value. The registry record reports total enrollment of 803, but does not report the number in this primary analysis population.
Intervention
The principal regimen of interest was alirocumab 300 mg every four weeks, with an increase to 150 mg every two weeks from Week 12 for participants meeting LDL-C thresholds described in the arm record. Stable statin therapy could be used in the relevant trial arms, although the primary analysis focused on participants without concomitant statin therapy.
Comparator
The placebo group received placebo every two weeks. A separate alirocumab group received 75 mg every two weeks, with an increase to 150 mg every two weeks from Week 12 under the described thresholds. The registry record identifies that 75 mg regimen as a calibrator intended to facilitate comparison with other studies; no statistical comparison was performed for that arm in the primary analysis.
Primary question
Among participants without concomitant statin therapy, what was the percent change from baseline in calculated LDL-C at Week 24, using the intention-to-treat analysis described in the registry record? The registry record specifies adjusted least-squares means and standard errors but does not report the numerical outcome estimates or a statistical comparison for the primary outcome.
This question concerns a laboratory measure and a defined analysis population. It is not a question about every participant enrolled, because the primary population excluded participants receiving concomitant statin therapy and required LDL-C measurements at baseline and after baseline. The trial also included participants receiving stable statin therapy, and several secondary outcomes address statin-use groups and other assessment times. Those additional outcomes do not change the population specified for the primary endpoint.
The central comparison was the every-four-weeks alirocumab regimen against placebo. The 75 mg every-two-weeks group served as a calibrator, rather than as a group for a statistical comparison in the primary analysis. The registry record describes the study purpose as evaluating efficacy, long-term safety, and tolerability, as well as the potential of the every-four-weeks regimen as a starting regimen. Numerical efficacy results, estimates of uncertainty, and statistical test results for the primary question are not reported in the registry record.
3. Trial Design
This was a randomized, quadruple-masked, parallel-group Phase 3 study with placebo control. The registry record gives enrollment as 803 and lists hypercholesterolemia as the condition. The study is marked completed. Its recorded start was 2013-09, and its primary completion was 2014-09. The sponsor was Regeneron Pharmaceuticals.
The trial included a placebo regimen, an alirocumab regimen beginning at 75 mg every two weeks with a possible increase to 150 mg every two weeks, and an alirocumab regimen of 300 mg every four weeks with a possible increase to 150 mg every two weeks. The arm descriptions specify subcutaneous injections and treatment for 48 weeks. They also describe use with or without stable statin therapy. The registry record says the alirocumab 75 mg every-two-weeks regimen was added as a calibrator to support comparison with other studies using that regimen.
The primary outcome analysis was restricted to participants not receiving concomitant statin therapy. Its intention-to-treat population included randomized participants who did not receive concomitant statin therapy and had a baseline and at least one post-baseline calculated LDL-C value, whether measured on or off treatment. The analysis description says available post-baseline data from Week 4 to Week 24 were included regardless of on- or off-treatment status. It reports adjusted least-squares means and standard errors at Week 24 and for an average over Week 21 to 24.
The registry record lists 48 outcome measures and 48 analyses. Secondary outcomes include calculated LDL-C changes at Weeks 12 and 24, separated by concomitant statin use and by analysis approach, along with Apo B outcomes at Week 24. The record does not report details of randomization sequence generation, allocation concealment, the specific masking procedures, or the protocol’s rationale for the planned enrollment. Those details 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.
Before assignment: Randomization was stratified according to statin therapy (with/ without) and cardiovascular risk (moderate vs. high/ very high) within the population receiving concomitant statin. Assignment to treatment arms was done using an Interactive Voice/Web Response System in 2:1:4 (Placebo: 75 mg: 300 mg) ratio after confirmation of selection criteria.
Overall Study
| Stage | Placebo Q2W With Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin | Placebo Q2W Without Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin |
|---|---|---|---|---|---|---|
| STARTED | 157 | 78 | 312 | 73 | 37 | 146 |
| Treated | 157 | 78 | 312 | 72 | 37 | 146 |
| Completed 24 Weeks Treatment Period | 137 | 68 | 285 | 58 | 31 | 120 |
| COMPLETED | 129 | 65 | 272 | 53 | 29 | 105 |
| NOT COMPLETED | 28 | 13 | 40 | 20 | 8 | 41 |
Reasons for not completing this period:
| Reason | Placebo Q2W With Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin | Placebo Q2W Without Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin |
|---|---|---|---|---|---|---|
| Participant moved | 2 | 0 | 1 | 1 | 0 | 3 |
| Physician Decision | 0 | 2 | 1 | 1 | 0 | 0 |
| Other than specified | 2 | 3 | 5 | 12 | 4 | 11 |
| Adverse Event | 13 | 4 | 17 | 4 | 3 | 14 |
| Poor compliance to protocol | 5 | 3 | 8 | 0 | 1 | 6 |
| Randomized and not treated | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrawal by Subject | 6 | 1 | 8 | 1 | 0 | 5 |
| Related to study drug administration | 0 | 0 | 0 | 0 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: ITT population (participants without concomitant statin therapy): all randomized participants who did not receive concomitant statin therapy, with one baseline and at least one post-baseline calculated LDL-C value on- or off-treatment.
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: All randomized population regardless of concomitant statin therapy.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Placebo Q2W With Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W With Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W With Concomitant Statin | Placebo Q2W Without Concomitant Statin | Alirocumab 75 mg Q2W/Up 150 mg Q2W Without Concomitant Statin | Alirocumab 300 mg Q4W/Up 150 mg Q2W Without Concomitant Statin |
|---|---|---|---|---|---|---|---|
| Participants analysed | 157 | 78 | 312 | 73 | 37 | 146 | |
| Age, Continuous | years | 61.6 (SD 9.7) | 60.7 (SD 9.1) | 61.6 (SD 10) | 59.4 (SD 10.2) | 59.3 (SD 11.3) | 59.2 (SD 10.8) |
| Sex: Female, Male: Female | Participants | 56 | 27 | 122 | 33 | 23 | 80 |
| Sex: Female, Male: Male | Participants | 101 | 51 | 190 | 40 | 14 | 66 |
| Calculated LDL-C in mg/dL | mg/dL | 112.1 (SD 37.3) | 114.9 (SD 36) | 112.4 (SD 32.8) | 131 (SD 30.4) | 148.4 (SD 36.8) | 146.1 (SD 33.5) |
| Calculated LDL-C in mmol/L | mmol/L | 2.903 (SD 0.965) | 2.977 (SD 0.933) | 2.912 (SD 0.85) | 3.392 (SD 0.787) | 3.842 (SD 0.953) | 3.785 (SD 0.868) |
6. Primary Endpoint
The registry lists the primary outcome as Percent Change From Baseline in Calculated LDL-C in Participants Not Receiving Concomitant Statin Therapy - ITT Analysis, measured over From Baseline to Week 24.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Standard Error |
| Unit | percent change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is percent change from baseline in calculated LDL-C among participants not receiving concomitant statin therapy. LDL-C is a cholesterol measure, and expressing change as a percentage relates the change to each participant’s baseline value rather than describing only an absolute concentration. The registry record specifies calculated LDL-C and gives the endpoint unit as percent change.
The registry record identifies the endpoint as a continuous measure and reports adjusted least-squares means with standard errors. The primary timeframe is baseline to Week 24. The analysis description also includes an average over Week 21 to 24, using available post-baseline values from Week 4 through Week 24. It states that measurements were included regardless of whether participants were on or off treatment at the time.
As a general statistical point, a continuous outcome retains information about the range of measured values rather than reducing the result to a count of participants above or below a threshold. A percent-change endpoint can make changes interpretable relative to baseline, while adjustment can account for factors included in the fitted model. The registry record does not identify those adjustment factors or provide the numerical least-squares means, standard errors, or between-group contrast. Therefore, the direction, size, and precision of the primary outcome cannot be determined from the registry record.
The record describes the endpoint as an intention-to-treat analysis, but defines the analysis population using absence of concomitant statin therapy and availability of baseline and post-baseline LDL-C measurements. Those criteria are important when interpreting the population to which the endpoint applies.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the trial design and the definition of its primary outcome, but it does not provide the numerical primary outcome results. In particular, no primary least-squares mean, standard error, treatment contrast, confidence interval, or p-value is reported in the record. The primary outcome is also flagged as having several categories or time points and is not reduced to one comparison. As a result, the posted information does not establish the size or precision of a primary treatment contrast.
The outcome is percent change from baseline in calculated LDL-C at Week 24 for the analysis population without concomitant statin therapy. The analysis description also mentions the average from Week 21 to 24. It uses available post-baseline data from Week 4 to Week 24, including data regardless of on- or off-treatment status. These details define what the analysis was intended to summarize; they do not substitute for the numerical estimates needed to interpret the observed outcome.
Adjusted least-squares means are model-based summaries rather than simple arithmetic averages of the observed measurements. Standard errors describe uncertainty in those estimates. In general, a confidence interval would communicate a range of values compatible with the estimate under the statistical model and its assumptions. No confidence interval is reported in the registry record, so the precision of the estimated changes cannot be assessed from the record. No p-value or other inferential result for the primary comparison is reported either.
It is also important not to treat the alirocumab 75 mg every-two-weeks group as a primary comparator. The registry record says this calibrator arm was included to facilitate comparison with other studies and that no statistical comparison was performed for it in the primary analysis. The central stated comparison was the every-four-weeks regimen against placebo, but numerical results for that comparison are not reported in the registry record.
The enrollment figure describes the trial as a whole, not the number of participants contributing to this particular endpoint. The primary population definition requires absence of concomitant statin therapy and at least one post-baseline LDL-C value, and the record does not report the number meeting those conditions. Without that count and without the outcome estimates, the reader cannot assess how much information underlies the primary analysis or how representative the analyzed group was of all enrolled participants.
Accordingly, the available record supports a description of the question, design, endpoint, and analysis approach, but not a conclusion about the observed LDL-C change or its uncertainty. This is a limitation of the information reported in the registry record, not evidence about what the unreported results would show.
9. Statistical Methods Explained
The registry record describes the primary endpoint as a continuous outcome analyzed using adjusted least-squares means, with standard errors. It identifies a repeated-measures model as MMRM and says that available post-baseline data from Week 4 to Week 24 were included. The analysis population was defined as randomized participants without concomitant statin therapy who had a baseline and at least one post-baseline calculated LDL-C value.
What does a repeated-measures model do?
As a general statistical explanation, a repeated-measures model analyzes multiple measurements from the same participant while accounting for the fact that those measurements are related. It can use data from more than one follow-up assessment rather than relying only on a single follow-up value. The registry record says the model included available post-baseline data across the specified period and included observations regardless of on- or off-treatment status.
Using repeated observations can make use of more of the collected outcome data, but it does not remove the need to examine assumptions about the model and the missing-data process. The registry record does not report the covariance structure, the fixed effects or covariates, the estimation details, or the assumptions used to handle missing outcome measurements. Those modeling details are not reported in the registry record.
What are adjusted least-squares means?
As a general explanation, a least-squares mean is a model-based mean estimated after accounting for terms in the statistical model. It is not necessarily identical to the unadjusted mean calculated directly from the observed measurements. Adjustment can support comparisons on a common model basis, but interpretation depends on which variables and modeling choices were included. The registry record states that adjusted least-squares means were used but does not report the adjustment variables or the detailed model specification.
The standard error describes the estimated sampling variability of a model-based estimate. Smaller standard errors generally indicate greater precision under the fitted model, while larger standard errors indicate greater uncertainty. A standard error alone does not convey the full range of uncertainty in the way a confidence interval does, and the registry record does not provide numerical standard errors or confidence intervals for the primary outcome.
What does intention-to-treat mean in this record?
In general, intention-to-treat analysis aims to analyze participants according to their randomized assignment, rather than reassigning them based on later treatment behavior. The registry record uses that label for the primary analysis and defines its population as randomized participants without concomitant statin therapy who had baseline and at least one post-baseline calculated LDL-C value. It also says post-baseline measurements were used whether participants were on or off treatment. The exact handling of participants with missing measurements, treatment discontinuation, or other post-randomization events is not reported in the registry record.
The label should therefore be read alongside the specific population definition. The primary population is not all randomized participants: it excludes those receiving concomitant statin therapy and requires post-baseline LDL-C data. The record does not report the number included in that analysis or the number with missing outcome measurements.
How should the assessment times be understood?
The primary timeframe is baseline to Week 24. The analysis description reports estimates at Week 24 and for the average over Week 21 to 24, using measurements beginning at Week 4. These are distinct summaries of follow-up information. A Week 24 estimate focuses on that assessment, whereas an average over Week 21 to 24 summarizes measurements within the stated later interval. The registry record does not provide the numerical estimates for either summary.
Multiple assessment times and outcome measures can create a multiplicity issue: when many statistical comparisons are made, the chance of at least one apparently notable result may increase. This is a general statistical concern, not a claim that a particular error occurred in this trial. The registry record lists 48 outcome measures and 48 analyses, but does not report a multiplicity adjustment strategy, a prespecified testing hierarchy, or which results were intended to support formal confirmatory claims.
What can sample-size illustrations establish?
As a general statistical explanation, a sample-size calculation describes the number of participants that a proposed design would require under stated assumptions. The planning assumptions associated with the posted illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event outcomes, the stated convention is a total number of events, while other outcomes use participants per arm.
Such planning illustrations are not observed power and do not show the probability that this completed trial detected an effect. They depend on assumptions about the effect to detect and the design. The registry record does not report the trial’s own sample-size justification or the assumptions used for its original design. No numerical illustration values are reported in the record, so none can be interpreted as a planned or observed participant count.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 48 outcome measures and 48 analyses, including multiple calculated LDL-C outcomes across assessment times, statin-use groups, and analysis approaches, as well as Apo B outcomes. A family of many outcomes can raise multiplicity concerns. In general, testing multiple hypotheses without a suitable strategy can increase the chance of false-positive findings. Whether and how that concern was addressed in this study is not reported in the registry record.
The record does not report a prespecified hierarchy of outcomes, a family-wise error control procedure, a false-discovery approach, or another multiplicity adjustment. It also does not specify which outcomes were confirmatory and which were exploratory. The primary-outcome record notes that there are several categories or time points and does not reduce them to one comparison. The calibrator alirocumab 75 mg every-two-weeks arm was included to facilitate comparison with other studies, and no statistical comparison was performed for that arm in the primary analysis.
The primary analysis population is described as randomized participants who did not receive concomitant statin therapy and had baseline and at least one post-baseline calculated LDL-C value. Available post-baseline measurements from Week 4 to Week 24 were included regardless of on- or off-treatment status. The record does not report the number of participants in that analysis population, the amount or pattern of missing outcome data, reasons for missingness, or sensitivity analyses assessing the impact of missing data.
Although the endpoint is labeled intention-to-treat, the exact operational handling of missing measurements and other post-randomization events is not reported in the registry record. The record also does not describe imputation methods, assumptions about missingness, or whether any alternative analysis populations were used for the primary comparison. These omissions limit assessment of how robust the analysis might be to incomplete follow-up.
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 |
|---|---|---|---|
| Placebo Q2W | 33 | 229 | 14.4% |
| Alirocumab 75 mg Q2W/Up 150 mg Q2W | 13 | 115 | 11.3% |
| Alirocumab 300 mg Q4W/Up 150 mg Q2W | 53 | 458 | 11.6% |
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 Q2W | 118 of 229 |
| Alirocumab 75 mg Q2W/Up 150 mg Q2W | 55 of 115 |
| Alirocumab 300 mg Q4W/Up 150 mg Q2W | 229 of 458 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo Q2W | Alirocumab 75 mg Q2W/Up 150 mg Q2W | Alirocumab 300 mg Q4W/Up 150 mg Q2W |
|---|---|---|---|---|
| Non-Cardiac chest pain | General disorders | 1 of 229 | 1 of 115 | 4 of 458 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 3 of 229 | 0 of 115 | 3 of 458 |
| Angina unstable | Cardiac disorders | 2 of 229 | 0 of 115 | 2 of 458 |
| Myocardial infarction | Cardiac disorders | 3 of 229 | 0 of 115 | 1 of 458 |
| Pneumonia | Infections and infestations | 1 of 229 | 2 of 115 | 1 of 458 |
| Acute myocardial infarction | Cardiac disorders | 1 of 229 | 0 of 115 | 2 of 458 |
| Angina pectoris | Cardiac disorders | 1 of 229 | 1 of 115 | 1 of 458 |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | 1 of 229 | 0 of 115 | 2 of 458 |
| Transient ischaemic attack | Nervous system disorders | 1 of 229 | 0 of 115 | 2 of 458 |
| Atrial fibrillation | Cardiac disorders | 0 of 229 | 0 of 115 | 2 of 458 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo Q2W | Alirocumab 75 mg Q2W/Up 150 mg Q2W | Alirocumab 300 mg Q4W/Up 150 mg Q2W |
|---|---|---|---|---|
| Injection site reaction | General disorders | 16 of 229 | 10 of 115 | 74 of 458 |
| Nasopharyngitis | Infections and infestations | 18 of 229 | 10 of 115 | 39 of 458 |
| Upper respiratory tract infection | Infections and infestations | 18 of 229 | 8 of 115 | 41 of 458 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 15 of 229 | 7 of 115 | 29 of 458 |
| Headache | Nervous system disorders | 13 of 229 | 6 of 115 | 29 of 458 |
| Diarrhoea | Gastrointestinal disorders | 17 of 229 | 4 of 115 | 25 of 458 |
| Back pain | Musculoskeletal and connective tissue disorders | 14 of 229 | 3 of 115 | 29 of 458 |
| Urinary tract infection | Infections and infestations | 10 of 229 | 7 of 115 | 28 of 458 |
| Sinusitis | Infections and infestations | 11 of 229 | 4 of 115 | 28 of 458 |
| Nausea | Gastrointestinal disorders | 15 of 229 | 7 of 115 | 19 of 458 |
Serious events with the highest arm-level rate: pneumonia (1.7%), myocardial infarction (1.3%), chronic obstructive pulmonary disease (1.3%), angina unstable (0.9%), non-cardiac chest pain (0.9%).
The registry record reports serious adverse event counts and numbers at risk for three groups. For Placebo Q2W, 33 participants were recorded with a serious adverse event among 229 at risk. For Alirocumab 75 mg Q2W/Up 150 mg Q2W, the figures were 13 among 115. For Alirocumab 300 mg Q4W/Up 150 mg Q2W, they were 53 among 458. These are descriptive counts; the registry record does not provide a statistical comparison of these figures.
The record also lists other adverse events: 118 among 229 for Placebo Q2W, 55 among 115 for Alirocumab 75 mg Q2W/Up 150 mg Q2W, and 229 among 458 for Alirocumab 300 mg Q4W/Up 150 mg Q2W. The registry record does not provide definitions or additional analysis details for this other-adverse-event category. Death counts are not reported in the registry record.
The listed top serious adverse event terms and percentages are Pneumonia, 1.7%; Myocardial infarction, 1.3%; Chronic obstructive pulmonary disease, 1.3%; Angina unstable, 0.9%; Non-Cardiac chest pain, 0.9%; and Angina pectoris, 0.9%. The record does not identify these percentages by treatment group in the information. They should not be read as evidence of a treatment effect or as a direct comparison between groups.
As a general statistical point, adverse-event counts and percentages describe observed events in the recorded groups; they do not by themselves establish that a treatment caused or prevented an event. Interpretation also depends on follow-up, event definitions, exposure, and the method used to collect and classify events. Those further details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record supports a clear description of the trial’s intended primary question: a comparison involving percent change from baseline in calculated LDL-C at Week 24 among participants not receiving concomitant statin therapy. It also describes a randomized, quadruple-masked, parallel-group Phase 3 design, a placebo regimen, two alirocumab regimens, and a repeated-measures analysis using adjusted least-squares means and standard errors.
However, the numerical results for the primary outcome are not reported in the registry record. There is no reported primary estimate, treatment contrast, confidence interval, standard error value, or p-value. The record therefore does not establish the direction or magnitude of the observed outcome, or how precisely it was estimated. It also does not provide the number of participants included in the primary analysis, which would help readers understand the information supporting that analysis.
The posted safety figures describe recorded adverse-event counts and selected serious adverse event terms. They are not, on their own, a causal comparison, and the registry record does not provide a statistical comparison for these safety counts. The death count is not reported in the registry record. The listed serious-event terms are not attributed to specific treatment groups in the reported information.
In general, a trial’s design and endpoint definitions explain what investigators set out to estimate; numerical estimates and uncertainty measures are needed to interpret the observed result. Neither a favorable nor an unfavorable efficacy conclusion can be drawn from an endpoint definition alone. Similarly, the presence of adverse-event counts does not establish that an intervention caused an event or that one group had a different underlying risk.
The registry record also does not report the full statistical analysis plan, multiplicity handling, missing-data methods, or the original sample-size justification. These are material details for evaluating how the analyses were planned and how robust the findings might be. The available information is therefore useful for understanding the clinical question and analytic framework, but it does not permit a quantitative interpretation of the primary efficacy result.
13. Why This Trial Matters Statistically
This study raises several important statistical questions that apply to trials with repeated laboratory measurements and multiple outcomes. First, the primary outcome is continuous and measured more than once after baseline. A repeated-measures analysis can use follow-up information across the specified period, but readers need the estimated effects and their uncertainty to understand what the analysis found. Those numerical primary results are not reported in the registry record.
Second, the primary analysis population is specific: randomized participants without concomitant statin therapy who had baseline and at least one post-baseline LDL-C value. This definition matters because the enrolled population also included statin-use groups and because the number included in the primary analysis is not reported. A clearly described target population helps readers distinguish the question asked from broader questions about all participants.
Third, the trial included multiple outcomes, assessment times, and analysis approaches. This makes multiplicity planning relevant. The registry record lists 48 outcome measures and 48 analyses, but does not describe a testing hierarchy or multiplicity adjustment. Without that information, readers cannot determine how the analyses were intended to support confirmatory conclusions.
Finally, the study’s alirocumab 75 mg every-two-weeks group was identified as a calibrator and was not statistically compared in the primary analysis. Recognizing the role of each group prevents interpreting every arm as part of the same confirmatory comparison. The registry record is therefore informative about design distinctions and analysis populations, while its missing numerical results and unreported methods limit statistical interpretation of the trial’s findings.
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.
Several trial-specific details needed for a fuller evaluation are not reported in the registry record. Although the study is identified as randomized and quadruple-masked, the record does not describe the randomization procedure, allocation concealment, or how masking was maintained. It also does not report the full protocol or the detailed statistical analysis plan. The rationale for the planned enrollment and the original sample-size assumptions are not reported in the registry record.
The primary outcome is described using an MMRM, adjusted least-squares means, and standard errors, but the model specification is not given. Covariance structure, adjustment variables, estimation approach, and diagnostic procedures are not reported. No numerical primary results or treatment contrast are reported, and the primary-outcome record notes multiple categories or time points rather than reducing the outcome to a single comparison.
The population definition requires participants to have a baseline and at least one post-baseline LDL-C measurement, but the number meeting that definition is not reported. The amount, timing, and reasons for missing data are also not reported. The registry record does not describe imputation, sensitivity analyses, or the assumptions used to handle missing measurements. The stated inclusion of measurements regardless of on- or off-treatment status clarifies one analysis feature but does not resolve these unreported missing-data details.
The record lists many outcomes and analyses but does not report how multiplicity was handled or which analyses were intended to be confirmatory. Safety information is also limited: death counts are not reported, the listed serious adverse-event terms are not attributed to treatment groups in the reported information, and no statistical comparison of the adverse-event counts is described. These reporting gaps constrain interpretation; they do not establish what unreported analyses or results would show.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of an Every Four Weeks Treatment Regimen of Alirocumab (REGN727/ SAR236553) in Patients With Primary Hypercholesterolemia (ODYSSEY CHOICE 1) — NCT01926782.
- Registry record last updated 2017-03-21; status last verified 2017-01.
- Results first posted 2017-03-21.
- 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.
18. Record Summary
This completed Phase 3 study was randomized, quadruple-masked, and parallel-group, with placebo control. The registry record gives enrollment as 803 and lists hypercholesterolemia as the condition. It records a study start of 2013-09 and primary completion of 2014-09, with Regeneron Pharmaceuticals as sponsor.
The trial evaluated alirocumab regimens of 300 mg every four weeks and 75 mg every two weeks, alongside placebo; the latter alirocumab regimen was described as a calibrator. The primary outcome was percent change from baseline in calculated LDL-C at Week 24 in participants not receiving concomitant statin therapy. The analysis description specifies adjusted least-squares means and standard errors using an MMRM and available measurements from Week 4 to Week 24.
The registry record does not report numerical primary outcome results, confidence intervals, p-values, or the number included in the primary analysis. It also does not report the trial’s detailed statistical plan, multiplicity strategy, or missing-data methods. Serious adverse-event counts are listed by group, while death counts are not reported in the registry record.