A Study of the Effect of Dalcetrapib on Artherosclerotic Disease in Patients With Coronary Artery Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Effect of Dalcetrapib on Artherosclerotic Disease in Patients With Coronary Artery Disease (NCT01059682), a randomized phase 3 study. The primary outcome is Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS..

2. Clinical Question

The study also intended to examine atherosclerotic disease progression using coronary intravascular ultrasound, quantitative coronary angiography, and carotid B-mode ultrasound. Its stated aims included evaluating lipid and biomarker profiles and long-term safety. The posted primary comparison is specifically about the mean nominal change in coronary percent atheroma volume; it does not by itself summarize every intended measure of disease progression or the broader study aims.

3. Trial Design

This was a randomized, double-blind, placebo-controlled, parallel-group Phase 3 study sponsored by Hoffmann-La Roche. The registry describes it as multicenter. Participants were assigned to dalcetrapib or placebo. The brief summary specifies dalcetrapib 600 mg orally once a day and an anticipated treatment period of 24 months. The registry lists enrollment of 936 and states a target sample size of 800-1000 patients.

The registry records a start date of 2010-01, a primary completion date of 2011-09, and a status of terminated. These entries describe the record’s listed status and dates; the reason for termination is not reported in the registry record. The anticipated treatment period should not be read as confirmation that every participant received treatment for that duration.

The primary outcome was nominal change from baseline to study end in coronary percent atheroma volume of the target coronary artery, assessed by intravascular ultrasound, with a 24-month timeframe. The record also lists five outcome measures and includes posted results for two quantitative coronary angiography secondary outcomes. It does not report the original statistical plan or explain how the listed enrollment target was chosen.

Randomization and masking are features of the assigned study design; they do not, on their own, establish what analysis populations or missing-data procedures were used. Those details are not reported in the registry record. The posted outcome comparisons are therefore best read as summaries of the recorded group results, rather than as a complete account of the prespecified analysis strategy.

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

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 Nominal Change From Baseline to Study End in Coronary Percent Atheroma Volume (PAV) of the Target Coronary Artery Assessed by IVUS., measured over 24 months.

The primary endpoint is the nominal mean change from baseline to study end in coronary percent atheroma volume (PAV) of the target coronary artery, assessed using intravascular ultrasound (IVUS). Its recorded unit is percent change atheroma volume, and its timeframe is 24 months. The study’s stated objective was to evaluate atherosclerotic disease progression; this imaging endpoint was the designated primary measure for that objective.

In general, a continuous imaging measure allows group averages and the spread of participant-level values to be described. Comparing change from baseline focuses the endpoint on how the measured quantity changed during follow-up, rather than on the study-end value alone. The mean difference then expresses the contrast between the average changes in the dalcetrapib and placebo groups. It does not describe every participant’s trajectory, and the group average cannot establish that all participants changed in the same way.

The registry does not provide a fuller operational definition of PAV, details about image reading, or an endpoint-specific analysis population. Those details are not reported in the registry record. Interpretation should therefore stay with the stated measure and the posted group summaries rather than assuming additional measurement or analysis procedures.

7. Results Posted in the Registry

• Dalcetrapib: mean 0.60 versus 0.50 on control; difference 0.10 (95% CI -0.28 to 0.48), standardized effect d = 0.03; z-test p = 0.605.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dalcetrapib: mean -0.10 versus 0.00 on control; difference -0.10 (95% CI -0.12 to -0.08), standardized effect d = -0.68; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically lower for Dalcetrapib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Dalcetrapib: mean 9.20 versus 4.30 on control; difference 4.90 (95% CI 2.63 to 7.17), standardized effect d = 0.27; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Dalcetrapib than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary results do not follow one uniform pattern relative to the primary result. The two quantitative coronary angiography outcomes show unadjusted contrasts with p-values below 0.001, while the primary PAV comparison has a much larger unadjusted p-value and an interval that includes zero. The estimates concern different imaging measures, so their results are not interchangeable and should not be treated as direct replications of the primary endpoint.

These secondary measures provide additional views of atherosclerotic disease progression as defined in the registry, but the record does not report a prespecified hierarchy or an analysis plan explaining how they were to be interpreted alongside the primary outcome. A difference on a secondary imaging measure does not change the estimate for the primary PAV endpoint. Nor can the combination of outcomes, without a stated plan, establish an overall conclusion about the study’s aims.

Unadjusted secondary results carry less weight when several outcomes are examined because the chance of finding one or more apparently notable results can increase as the number of tests grows. This is a general statistical concern, not a claim about the study’s actual analysis process. No multiplicity adjustment is reported in the registry record. The posted secondary p-values should therefore be read as individual unadjusted comparisons, not as a family-wise conclusion across outcomes.

The registry lists three secondary outcomes as posted, while the record does not provide reported analysis details for those outcomes. The available summary statistics support descriptive comparisons, but do not reveal the original endpoint hierarchy, whether all planned secondary measures were analyzed, or how missing data were handled. The broad pattern is informative as context, while the primary endpoint remains the designated main comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Nominal Changes From Baseline in Minimal Lumen Diameter as Assessed by Quantitative Coronary Angiography
• Blood Lipids, Lipoproteins
• Nominal Changes in Percent Diameter Stenosis as Assessed by Quantitative Coronary Angiography

9. Statistical Interpretation

10. Statistical Methods Explained

What does the mean difference represent?

The primary outcome is continuous, and the registry identifies the reported summary as a mean with standard deviation. A mean is the arithmetic average of the recorded values in a group. The standard deviation describes how dispersed those values are around their group average; it is not the uncertainty interval for the mean and is not a measure of the difference between groups.

The recalculated mean difference compares the two group means, using placebo as the reference and subtracting its mean from the dalcetrapib mean. For the primary outcome, the posted averages are 0.6 and 0.5, respectively, and the recalculated contrast is 0.1. A positive contrast means the recorded mean change was numerically higher in the dalcetrapib group. That arithmetic description does not establish clinical importance or identify the reason for the difference.

What does the confidence interval add?

A confidence interval conveys the uncertainty around an estimated contrast under the assumptions of the method used. In general, it indicates a range of values compatible with the observed data and the interval procedure; it is not a range containing a known proportion of individual participant outcomes. For this primary comparison, the interval crosses zero. Accordingly, the posted summary is compatible with no mean difference and with contrasts on either side of zero. The interval does not prove equality.

How should the p-value be read?

A p-value describes how unusual data at least as inconsistent with a specified null hypothesis would be if that null hypothesis and the test assumptions held. The primary comparison has an unadjusted p-value of 0.605. This does not give the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. It also does not account for other outcomes or analyses unless an adjustment is made. The registry does not report a multiplicity adjustment for this result.

The p-value and confidence interval are complementary summaries. The p-value reflects a test against a null value, while the interval shows the uncertainty and range of contrasts compatible with the data under the interval method. Both are based on an unadjusted recalculation from the posted summary statistics, rather than a registry-listed sponsor analysis.

Why does variability matter?

When participant outcomes vary widely within a group, the mean alone gives an incomplete picture. In general, greater variability can make a group mean less precisely estimated, especially when the number of observations is limited. The primary group standard deviations differ, with a larger value recorded for dalcetrapib than for placebo. The reported comparison uses a pooled standard deviation of 2.982 as part of its recalculation. That pooled summary represents a combined estimate of within-group spread under the calculation used; it is not an observed outcome or an adjusted treatment effect.

Variation can arise for many reasons, but the registry does not identify its sources. No conclusions about participant subgroups or individual responses should be inferred from the group standard deviations alone. The posted mean comparison summarizes average change, not the full shape of the outcome distributions.

What does “unadjusted” mean in this context?

Unadjusted comparisons do not account for a multiplicity correction or for covariates beyond the information used in the calculation. The posted recalculations use group summary statistics and are not described as adjusted for baseline characteristics. Random allocation is part of the design, but the record does not report the analysis method chosen by the sponsor or whether it included additional adjustments. The record lists no reported analysis for the primary outcome.

Because the underlying participant-level data and the original analysis details are not reported in the registry record, these summaries cannot establish whether other approaches would produce the same estimate or uncertainty. A recalculation is useful for describing the posted numbers, but it should be kept distinct from a complete account of the trial’s prespecified statistical analysis.

11. Confidence Intervals and Precision

The primary mean difference is 0.1, with a confidence interval that extends across zero, and the unadjusted p-value is 0.605. Together, these summaries indicate that the estimated contrast is not precise enough to distinguish a zero difference from contrasts on either side of zero using the reported interval. The interval’s breadth is important: a nonsignificant test is not proof that the true group means are identical.

The group means are accompanied by standard deviations of 3.69 for dalcetrapib and 2.01 for placebo. These describe variability among the recorded values, not precision of the treatment contrast itself. Precision of a mean difference depends on variability and the amount of information contributing to each group estimate. The registry lists outcome counts of 474 for dalcetrapib and 462 for placebo, but does not provide details about missing endpoint data or the population used in the analysis.

Confidence intervals are generally more informative than a p-value alone because they show the range of effects compatible with the data under the method’s assumptions. Here, the interval includes the null value and also allows for contrasts in either direction. The registry does not state what range of PAV differences would be clinically important, so statistical precision cannot be translated into a judgment about clinical importance from this record alone.

These precision statements apply to the recalculated, unadjusted comparison from posted summary statistics. The analysis method, covariate adjustments, and missing-data handling are not reported in the registry record. The available interval therefore should not be read as a full reconstruction of the trial’s original analysis.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total event counts. They are illustrations computed from the observed effect, not a report of the trial’s original design calculation. The registry record does not report the original sample-size assumptions or justification.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is a stated fraction of the observed effect. The rows correspond to planning for the full observed effect, 75% of the observed effect, and 50% of the observed effect. The figures are shown separately for 80% and 90% power.

In plain terms, the 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the assumed effect under those planning assumptions. The 90% column gives the corresponding illustration for a 90% chance. These are prospective planning probabilities conditional on the assumed effect and model, not guarantees about a future study’s result. These figures are not observed power.

For the same endpoint and planning assumptions, a smaller effect is harder to distinguish from random variation, so the illustration requires more participants per arm when the target effect is reduced. These calculations are anchored to observed estimates and should not be treated as evidence that the original trial was planned with those assumptions. The registry does not report whether its target enrollment of 800-1000 patients was based on a different effect, a different endpoint, or other considerations.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 0.100; pooled standard deviation σ = 2.982.
2. n = 2 × (1.96 + 0.842)² × 2.982² / 0.100² = 13,954.7, rounded up to 13,955 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 0.1                      # observed difference in means
sigma <- 2.98154591780123                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1059682)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 13,955 (80% power), 18,682 (90% power)
 75% of observed effect: n per arm = 24,809 (80% power), 33,212 (90% power)
 50% of observed effect: n per arm = 55,819 (80% power), 74,726 (90% power)
power.t.test: 13955.7 
Simulated power at n = 13,955 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and multiple additional outcomes, including secondary measures, but does not report a multiplicity strategy. When multiple outcomes or statistical tests are evaluated, the probability of at least one apparently unusual result may rise. Statistical methods can address this in different ways, but the record does not state whether any adjustment, gatekeeping procedure, or outcome hierarchy was used. The posted p-values are unadjusted and should be interpreted as individual comparisons rather than as a multiplicity-controlled set of findings.

The record reports no analyses for the primary outcome and lists no reported analyses for the posted secondary outcomes. The numerical group summaries and recalculated comparisons describe what is posted, but they do not show whether the calculations match the sponsor’s original analysis plan. The original model, covariate adjustment, and analysis population are not reported in the registry record.

Details about missing outcome data are also not reported in the registry record. The outcome counts are listed by group, but the record does not explain whether all randomized participants contributed to each outcome, how unavailable measurements were handled, or whether any imputation was performed. The listed enrollment should not be assumed to be the analysis population for every endpoint.

The record does not identify an intention-to-treat, per-protocol, or other analysis population for these results. It also does not provide reasons for missing measurements or a sensitivity analysis addressing their possible impact. These gaps matter because incomplete outcomes can affect the group comparison, depending on who is missing and why. Without these details, the posted estimates remain interpretable as summaries of the registry results, but their relationship to a prespecified confirmatory analysis is uncertain.

15. 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: chest pain (1.5%), angina pectoris (1.1%), angina unstable (0.6%), prostate cancer (0.6%), pancreatitis (0.6%).

The registry records 61 serious adverse events in the dalcetrapib group and 63 in the placebo group. The corresponding groups at risk are listed as 474 and 462. For other adverse events, the recorded counts are 255 and 199, respectively. These are group-level counts as recorded; they should not be interpreted as rates or as a comparison adjusted for follow-up time.

The registry lists chest pain at 1.5%, angina pectoris at 1.1%, and angina unstable, prostate cancer, pancreatitis, and atrial fibrillation at 0.6% each among the top serious terms. The record does not provide enough context to infer the denominator or comparative risk for each term. Death counts are not reported in the registry record.

These safety summaries do not establish whether an event was caused by treatment, and a direct safety comparison would require fuller information on definitions, exposure, follow-up, and analysis. The posted figures are descriptive registry results, not medical advice or a complete assessment of safety.

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

The primary posted result describes a small positive difference between the group means for change in coronary PAV: 0.6 for dalcetrapib and 0.5 for placebo, with an unadjusted mean difference of 0.1. Its confidence interval crosses zero and its unadjusted p-value is 0.605. The data therefore do not provide clear evidence of a mean difference on this primary measure, but they also do not demonstrate that the groups were identical or rule out all potentially relevant differences.

The result applies to the endpoint as recorded: nominal change in PAV of the target coronary artery assessed by IVUS at the 24-month timeframe. It does not establish what happened on every other imaging measure, nor does it describe outcomes beyond those reported in the registry. The secondary results concern different measures and are unadjusted; they should be interpreted in that context rather than used to replace the primary comparison.

A statistical result is not, by itself, a judgment about clinical importance. The registry does not report a clinically important difference threshold for PAV, and the posted analysis does not provide enough detail to assess the original analysis plan. The estimate should not be read as a treatment recommendation or as proof for or against a broad effect on cardiovascular disease.

The record also includes adverse-event counts, but those summaries do not establish causality or provide a full comparative safety analysis. Overall, the posted numbers support a cautious description of the observed group summaries and their uncertainty. Stronger claims about treatment effects, the reason for the study’s terminated status, or the completeness of its outcome analyses are not supported by the registry information.

17. Why This Trial Matters Statistically

This trial illustrates why the primary endpoint, the estimated effect, and its uncertainty need to be read together. The point estimate alone shows the direction and size of the posted mean contrast, but the confidence interval and p-value indicate how uncertain that contrast is. Here, the primary interval includes zero and the unadjusted p-value is 0.605, so the point estimate should not be presented as conclusive evidence of a group difference.

It also demonstrates that different outcomes within one study can tell different statistical stories. The secondary angiography comparisons have smaller unadjusted p-values than the primary PAV comparison, but they measure other features and were not accompanied by a reported multiplicity plan. Treating the most striking result as the study’s overall answer would ignore the primary endpoint designation and the uncertainty introduced by examining multiple outcomes.

The planning illustrations are another useful distinction. Sample sizes based on observed effects can help readers understand how assumed effect size relates to design requirements, but they do not reveal the original rationale for the trial’s enrollment target. Nor do they measure the probability that the observed result is true. Keeping planning calculations separate from observed trial results avoids confusing design scenarios with evidence.

Finally, a registry record can offer useful group summaries while leaving important analysis details unresolved. Missing information about populations, missing data, adjustment, and multiplicity limits reconstruction of the intended inferential procedure. Statistical interpretation therefore depends not only on the reported estimate, but also on how completely the record documents the path from randomized assignment to analyzed outcome.

18. 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 record does not explain why the study was terminated, so the status should not be taken as evidence of a particular reason or outcome. It lists an anticipated treatment period of 24 months, but does not establish that every participant completed that period or had a measurement at the intended time.

The record does not report the original statistical analysis plan, the analysis population, or how missing endpoint measurements were handled. It also does not provide a multiplicity strategy for the primary and secondary outcomes. These omissions prevent a full assessment of whether the posted comparisons align with the original planned analyses and how incomplete data might affect the estimates.

The primary comparison is a simple unadjusted recalculation from posted group summaries. Participant-level data are not reported in the registry record, so distributional details, subgroup patterns, and alternative model results cannot be assessed. The primary interval crosses zero, and the record gives no clinical threshold for interpreting the size of a PAV difference.

Secondary outcomes are also reported without analysis details, and their unadjusted results require caution in the context of multiple outcomes. Safety information is limited to recorded event counts and selected serious-event terms; deaths are not reported in the registry record, and the summaries do not establish event causality. These limitations constrain what can be inferred from the posted results, without implying that unreported procedures were or were not conducted.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of the Effect of Dalcetrapib on Artherosclerotic Disease in Patients With Coronary Artery Disease — NCT01059682.
• Registry record last updated 2020-03-24; status last verified 2020-03.
• Results first posted 2020-03-24.
• 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.

22. Record Summary

The registry record describes NCT01059682, a randomized, double-blind, parallel-group Phase 3 study sponsored by Hoffmann-La Roche. It compared dalcetrapib 600 mg taken orally once a day with placebo in patients with coronary artery disease. Listed enrollment was 936; the status is terminated.

The primary outcome was nominal change from baseline to study end in coronary percent atheroma volume of the target coronary artery, assessed by IVUS, with a 24-month timeframe. The posted group means were 0.6 for dalcetrapib and 0.5 for placebo. The recalculated unadjusted mean difference was 0.1, with an unadjusted p-value of 0.605 and a confidence interval crossing zero.

The record also posts quantitative coronary angiography results and adverse-event summaries. The original statistical plan, analysis populations, missing-data procedures, and multiplicity strategy are not reported in the registry record.