PRIMARA: A Prospective Descriptive Observational Study to Review Mimpara (Cinacalcet) Use in Patients With Primary Hyperparathyroidism in Clinical Practice: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRIMARA: A Prospective Descriptive Observational Study to Review Mimpara (Cinacalcet) Use in Patients With Primary Hyperparathyroidism in Clinical Practice (NCT00928408), a registered phase not stated study. The primary outcome is Cinacalcet Dose.

2. Clinical Question

The wider study aim was to review cinacalcet use in routine clinical practice, with prospective data collection for up to one year from treatment initiation. The record also says collection continued for patients who discontinued cinacalcet before that period ended. This makes the study relevant to descriptions of treatment use and follow-up in the enrolled setting. It does not, by itself, answer whether cinacalcet performs better than another treatment or than no treatment. No randomized comparator is described, and the listed primary endpoint concerns dose rather than a clinical outcome. The registry record does not report the primary dose estimate, so conclusions about the observed dose distribution or its precision cannot be drawn from that endpoint entry alone.

3. Trial Design

PRIMARA is a prospective, descriptive, observational study of cinacalcet use in patients with primary hyperparathyroidism. The registry describes a multicentre study of adults receiving cinacalcet in clinical practice in a number of countries in Europe. Enrollment was planned within one month of starting treatment, with data collected prospectively for up to one year from initiation. Collection was to continue for patients who stopped cinacalcet before the end of that period. The listed enrollment is 305.

The intervention is cinacalcet. No comparator is described, and the allocation field is not stated. The registry cautions that the arms are not a like-for-like control comparison. Accordingly, this design is suited to describing treatment use and recorded outcomes among enrolled patients, not to estimating a randomized treatment contrast. The registry does not describe a separate control group or a randomized assignment process.

The listed study status is completed. The recorded start is 2009-10 and the primary completion is 2011-12. Amgen is listed as the sponsor. The record lists 26 outcome measures and no analyses. Those record entries do not supply the primary dose result: its numerical mean and 95% confidence interval are not reported in the registry record.

Prospective collection means information was to be gathered after enrollment as follow-up proceeded, rather than relying solely on a retrospective review. In general, this can establish a planned sequence of observation, but it does not remove selection effects or confounding in an observational study. The record does not report enough detail to assess the specific data collection procedures, the number of participating centres or countries, or how the enrolled population compared with patients not enrolled. No sample-size justification for the observational study is 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Cinacalcet Dose, measured over Initiation of treatment.

The primary endpoint is cinacalcet dose at initiation of treatment, expressed in mg/day. It is a continuous measure, and the registry specifies the mean with a 95% confidence interval for the Full Analysis Set. The timeframe is treatment initiation. This endpoint describes the starting dose used in the enrolled clinical-practice population; it is not itself a measure of subsequent clinical response, safety, or continued use.

In general, a mean provides a single summary of the central level of a continuous measurement. It can be useful for describing typical prescribing levels, though it may be influenced by unusually high or low observations. A confidence interval communicates uncertainty around an estimated mean under the analysis method used: a narrower interval generally indicates greater precision, while a wider interval indicates less precision. It does not describe the range of individual doses, nor does it show how doses vary across patients.

The record names the endpoint and its planned summary, but its numerical mean and 95% confidence interval are not reported in the registry record. The underlying distribution, any other descriptive statistics, and the method used to calculate the interval are also not reported. Consequently, the endpoint definition can be explained, but the observed dose level and its statistical precision cannot be assessed from the registered result information available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary measure is continuous: dose at initiation is recorded in mg/day and summarized as a mean. The registry specifies a 95% confidence interval and names the Full Analysis Set. It does not report the numerical estimate, the limits of the interval, or the calculation method. The explanation below describes statistical concepts generally; it does not establish which procedures were used for PRIMARA.

What does a mean describe?

In general, the mean is calculated by adding measured values and dividing by the number of observations. It summarizes the center of a distribution, but does not show its shape or the spread of individual values. For dose data, different distributions can share the same mean: observations may cluster near the mean, or a smaller number of more extreme values may pull the mean away from most observations. A mean is therefore most informative when read alongside information about variation and distribution. Such additional summaries are not reported for the primary measure in the registry record.

The mean is not necessarily the dose received by a typical individual in the everyday sense, nor does it imply that every patient received the same amount. It describes an average over the observations included in the analysis. The record identifies the Full Analysis Set but does not define membership in that set or explain how missing dose observations were handled. That limits assessment of precisely which observations the mean was intended to summarize.

How should a 95% confidence interval be read?

In general, a confidence interval expresses uncertainty in an estimated population quantity under a statistical model and method. It is a range of values compatible with the observed data at the stated confidence level, according to that method. A confidence interval is not a range containing a specified proportion of individual patient doses. It is also not a guarantee that the true mean lies in the particular interval. Repeated use of a valid procedure under its assumptions would produce intervals that include the target quantity at the stated frequency.

Interval width conveys precision, not clinical importance. A narrow interval may indicate a more precise estimate, while a wide interval may indicate more uncertainty. Interpretation also depends on the study population, how observations were collected, and the assumptions used in calculation. Because neither the primary estimate nor its interval is reported, neither interval width nor the likely dose values can be evaluated for this study.

What do the planning assumptions mean?

The planning illustration is described as being computed from the observed effect, rather than as part of the trial's own design. It assumes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The record also specifies that time-to-event illustrations give the total number of events using the Schoenfeld method, while other illustrations give participants per arm.

These are assumptions for hypothetical planning, not results from an allocated two-arm comparison in PRIMARA. The study is described as observational, with no comparator and allocation not stated. A planning illustration based on two arms does not turn the observed study into a randomized trial. Nor is a planning sample size a measure of observed power. Power is a design concept based on assumed effects and variability; after data collection, a sample-size illustration cannot establish how likely the study was to detect a true effect. The planning values and observed effect magnitude are not reported in the registry record, so no such values or calculations can be interpreted.

What assumptions remain unknown?

The registry does not report how the mean or confidence interval was calculated, whether the distribution was assessed, or whether adjustments were made. It also does not report the amount or pattern of missing dose data, sensitivity analyses, handling of unusual values, or the operational definition of the Full Analysis Set. These details matter because statistical summaries depend on which observations are included and on whether the method is appropriate for the data. In general, missingness can affect an estimate when the observed measurements differ systematically from those not observed. The direction or size of any such effect cannot be inferred without data and methods.

Over-dispersion is generally a concern for count outcomes when their variability exceeds the level assumed by a model. It is not a description of the mean of a continuous dose measure, and no over-dispersion method is reported for this endpoint. For continuous data, relevant considerations instead include the distribution, variation, outliers, and the method used to estimate uncertainty. None of these analytic details should be assumed from the endpoint label alone.

The record lists no analyses. Thus, it does not report a model, adjustment strategy, hypothesis test, or interim analysis for the primary endpoint. The 95% interval in the endpoint description tells readers the intended form of uncertainty summary, but not the computational procedure or result. These distinctions keep the endpoint specification separate from evidence about the actual estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 26 outcome measures and no analyses. It does not report a multiplicity strategy, such as a hierarchy of outcomes, an adjustment to significance thresholds, or a distinction between confirmatory and exploratory analyses. The primary endpoint is identified as cinacalcet dose at treatment initiation, but its estimate and confidence interval are not reported. The presence of multiple registered measures alone does not establish that multiple statistical tests were conducted.

In general, testing many hypotheses can increase the chance of at least one apparently unusual result arising by chance. Methods for addressing multiplicity depend on the questions and analysis plan. Since no analysis plan or analysis results are reported, it is not possible to determine whether multiplicity was considered or how any associated uncertainty should be interpreted.

The registry describes data collection through up to one year after initiation and continued collection after discontinuation. It does not report how much data were missing, the reasons for missingness, or whether follow-up completeness differed across patients or outcomes. It also does not describe imputation, exclusion rules, or sensitivity analyses. Missing-data handling can affect both the number of observations contributing to a measure and the interpretation of its estimate; no direction or degree of impact can be inferred.

The primary endpoint population is named the Full Analysis Set, but its definition is not reported in the registry record. It is therefore unclear from this entry what eligibility or data requirements determined inclusion in that population. The listed enrollment is 305, while the safety entries use 303 at risk; the record does not explain the difference. Those figures should not be reconciled by assumption. Taken together, the lack of analysis-population definitions, missing-data methods, multiplicity procedures, and endpoint results limits assessment of analytic robustness.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypocalcaemia (0.3%), muscle spasms (0.3%), circulatory collapse (0.3%).

The registry lists 2 affected among 303 at risk for serious adverse events in the Cinacalcet group. For other adverse events, it lists 41 affected among 303 at risk. The serious-event terms reported are Hypocalcaemia, Muscle spasms, and Circulatory collapse, each at 0.3%. The registry does not report deaths in the listed entry.

These figures describe recorded events in the study group; they do not establish that cinacalcet caused an event. The study is observational and has no described control group, so there is no like-for-like comparison to show whether event frequency differed from another treatment or from no treatment. The serious-event term percentages should be read as reported, without adding them together or treating them as mutually exclusive. The record does not explain event-level overlap, timing, duration, severity details beyond the serious classification, or attribution to treatment.

In general, adverse-event counts depend on the definitions used, the period of observation, completeness of follow-up, and how events are collected. The registry record does not provide enough detail to assess those factors fully. The number at risk in the safety entry is not the listed enrollment, and the reason for this difference is not reported in the registry record. These summaries are descriptive safety information and should not be interpreted as a comparative risk estimate or a causal finding.

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

PRIMARA addresses a practical descriptive question: what cinacalcet dose was used at treatment initiation among enrolled adults with primary hyperparathyroidism in clinical practice? The registry specifies that the primary measure is the mean dose in mg/day with a 95% confidence interval for the Full Analysis Set. However, the numerical result is not reported in the registry record. The study question and intended summary are identifiable, but the actual starting-dose estimate and its precision cannot be stated.

The observational design also has a clear interpretive boundary. It records treatment use rather than assigning treatment randomly against a comparator. The results can describe enrolled patients and their recorded experience, but they cannot, on their own, establish what would have happened under another treatment or without cinacalcet. Differences in patient characteristics and clinical decisions could influence observed outcomes. The registry itself cautions against treating the arms as like-for-like controls.

The safety entries report events among patients at risk and list serious-event terms with percentages. They can be read as descriptive reports from the study, not as evidence of causation or comparative safety. The record does not provide deaths, event timing, treatment attribution, or a controlled comparison in the listed information.

The study's prospective follow-up plan, including continued collection after discontinuation, helps define the intended observation period. It does not show how complete follow-up was or provide results for each point in time. The missing endpoint result and unreported analysis details constrain how much can be concluded statistically. In particular, no result should be inferred from the endpoint description, enrollment figure, safety summaries, or planning assumptions alone. The study provides a registry description of a clinical-practice investigation, while its primary numerical result and several details needed to judge precision and bias are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates a distinction that matters in biostatistics: a well-defined endpoint is not the same as a reported result. PRIMARA identifies mean cinacalcet dose at initiation, its unit, the intended confidence interval, and the analysis population label. Yet the registry record does not report the mean or interval. A reader can understand what the investigators intended to summarize without knowing the observed value or its precision. Statistical interpretation must keep those two things separate.

It also demonstrates why study design sets limits on causal claims. Prospective observation can describe treatment use in clinical practice and document a follow-up plan. Without a stated randomized comparator, however, observed outcomes cannot be interpreted as a treatment effect isolated from patient differences and clinical decisions. The registry's warning against treating arms as like-for-like controls makes that distinction especially important.

The safety entries offer another statistical lesson: counts, numbers at risk, and reported percentages are not interchangeable with comparative risks or causal effects. The serious-event summary is informative as a description of what was recorded, but does not answer whether the events were attributable to cinacalcet or more common than under an alternative. Nor can unreported event detail be recovered from a summary percentage.

Finally, the record includes planning assumptions for hypothetical sample-size illustrations, including two-arm allocation, while describing an observational study without a comparator. Such planning illustrations are not a substitute for the trial's own design rationale, an analysis plan, or observed power. Reading the record carefully means distinguishing registry specifications, descriptive observations, planning scenarios, and missing statistical results. Those distinctions support appropriately bounded conclusions rather than false precision.

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 limitations arise from what the registry record does not report. The primary dose endpoint is defined, but its numerical mean and 95% confidence interval are absent. Consequently, neither the observed starting dose nor uncertainty around that estimate can be assessed. The record also does not give the distribution of doses or other summaries that might help characterize variation across the enrolled population.

The study is observational and no comparator is described. The record states that allocation was not stated and warns that arms are not a like-for-like control comparison. Therefore, any grouped differences cannot be treated as a randomized treatment contrast. The record does not report adjustment for potential confounding or a model for any comparison.

The listed enrollment is 305, whereas the safety entries report 303 at risk. No explanation for this difference is reported in the registry record. The definition of the Full Analysis Set is also not reported. Although prospective collection was intended for up to one year and was to continue after discontinuation, follow-up completeness, missingness, and the handling of missing values are not described.

The registry lists 26 outcome measures but no analyses. It does not specify how multiplicity was handled, whether interim analyses occurred, how the confidence interval was calculated, or whether sensitivity analyses were performed. The planning illustration assumptions are not a reported justification for the observational study's enrollment, and no such study-specific sample-size justification is reported. Finally, the safety information does not give timing, attribution, event overlap, or a comparator. These gaps restrict precision, reproducibility, and causal interpretation without establishing that any particular bias or analytic problem occurred.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: PRIMARA: A Prospective Descriptive Observational Study to Review Mimpara (Cinacalcet) Use in Patients With Primary Hyperparathyroidism in Clinical Practice — NCT00928408.
• Registry record last updated 2018-08-01; status last verified 2015-09.
• Results first posted 2013-11-14.
• 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.

18. Record Summary

PRIMARA is a completed, prospective descriptive observational study of cinacalcet use among adults with primary hyperparathyroidism in clinical practice in a number of countries in Europe. Amgen is listed as sponsor; the registry records a start of 2009-10 and primary completion of 2011-12. Listed enrollment is 305.

Patients were to be enrolled within one month of initiating cinacalcet, with prospective data collection for up to one year from initiation and continued collection after discontinuation. The primary measure is mean dose at initiation in mg/day, with a 95% confidence interval for the Full Analysis Set. Its numerical result is not reported in the registry record. The record lists 26 outcome measures and no analyses.

Safety entries report 2 affected among 303 at risk for serious adverse events and 41 affected among 303 at risk for other adverse events. The listed serious-event terms each carry a reported percentage of 0.3%. The study has no described comparator, and the registry cautions against treating arms as like-for-like controls.