PROSPECT II & PROSPECT ABSORB - an Integrated Natural History Study and Randomized Trial.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PROSPECT II & PROSPECT ABSORB - an Integrated Natural History Study and Randomized Trial. (NCT02171065), a randomized na study. The primary outcome is Prospect II: Patient Level Non-culprit Lesion Related Non-Culprit Major Adverse Cardiac Event (NC-MACE) Adjudicated to an Originally Untreated Non-culprit Lesion During the Entire Study Duration.

2. Clinical Question

The registry record covers two related components: a prospective observational study of patients with acute coronary syndrome (ACS), and a randomized substudy comparing ABSORB BVS plus guideline directed medical therapy (GDMT) with GDMT alone. The observational component used multimodality imaging to study non-culprit coronary lesions; the randomized component examined an intervention directed at plaques identified as vulnerable.

The event definition includes cardiac death, myocardial infarction, unstable angina, and progressive angina or anginal equivalent symptoms meeting specified revascularization or angiographic progression criteria. The registry record evaluates events arising from originally untreated non-culprit lesions. This is distinct from a question about all cardiac events, and it is also distinct from the randomized substudy’s stated minimum lumen area question.

3. Trial Design

PROSPECT II & PROSPECT ABSORB is a multicentre study combining a prospective natural history study with a randomized, controlled intervention study. The registry describes the allocation as randomized, the model as parallel, and masking as none. The phase is listed as NA. Uppsala University is the sponsor. The recorded study start is 2014-06, primary completion is 2020-05, and status is completed.

The study summary describes PROSPECT II as an observational investigation of patients with unstable atherosclerotic coronary artery disease. Its stated aim was to examine whether IVUS and NIRS imaging could identify plaques prone to future rupture and clinical events. PROSPECT ABSORB was a randomized substudy of vulnerable-plaque treatment: ABSORB BVS plus GDMT was compared with GDMT alone. The summary describes minimum lumen area at 24 months as the randomized substudy’s intended comparison.

The posted event results distinguish three groups: 89 participants in the GDMT group, 93 in the ABSORB BVS plus GDMT group, and 716 in PROSPECT II Only. The first two groups form the randomized treatment comparison described in the record. The PROSPECT II Only group belongs to the observational component; its results should not be interpreted as if it were another randomized treatment arm. Overall enrollment is 902, which is not the same quantity as the number in any one posted outcome group.

The primary outcome is reported at the longest follow-up available, at the time when the last patient enrolled reached at least 24 months. The stated median follow-up is 3.7 years, with first and third quartiles of 3.0 and 4.4 years. The registry record does not report further details of the randomization procedure, allocation concealment, or the original design assumptions for the randomized substudy.

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: Four patients were disenrolled because non-culprit lesion imaging were not acquired. Among the rest of 898 patients, 182 patients with angiographically nonobstructive lesion but with plaque burden\>=65% were enrolled in PROSPECT-ABSORB, and randomized to Absorb-bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) (n=93) versus GDMT alone (n=89).

Overall Study

Reasons for not completing this period:

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 Prospect II: Patient Level Non-culprit Lesion Related Non-Culprit Major Adverse Cardiac Event (NC-MACE) Adjudicated to an Originally Untreated Non-culprit Lesion During the Entire Study Duration, measured over Median follow-up of 3.7 (first quartile, third quartile; 3.0, 4.4) years.

The posted primary endpoint is the number of participants with a patient-level NC-MACE attributed to an originally untreated non-culprit lesion. The composite includes cardiac death, myocardial infarction, unstable angina, or progressive angina or anginal equivalent symptoms that required CABG or PCI and/or had angiographic core lab-confirmed rapid lesion progression. Events were assessed at the longest follow-up available, when the last enrolled patient reached at least 24 months.

This endpoint is used to capture clinically important events connected to lesions that were not initially treated, rather than focusing only on a single clinical event or on an imaging measurement. Composite outcomes can summarize several event types in one endpoint, but their interpretation depends on the event definition: different components may differ in severity and frequency. The registry record does not report the number of events separately for each component, so the contribution of each type of event to the total cannot be assessed from the posted results.

The stated median follow-up was 3.7 years (first quartile, third quartile; 3.0, 4.4). The registry summary also describes minimum lumen area at 24 months as the randomized substudy’s intended outcome question. A result for that measure is not reported in the registry record; the posted primary outcome is the participant count for NC-MACE.

7. Results Posted in the Registry

• ABSORB + GDMT in PROSPECT-ABSORB and PROSPECT II: 10.8% (10/93) versus 16.9% (15/89) on control; risk difference -6.1 percentage points (95% CI -16.1 to 3.9), risk ratio 0.64 (0.30–1.34); unadjusted two-proportion z-test p = 0.232.
• PROSPECT II Only: 5.7% (41/716) versus 16.9% (15/89) on control; risk difference -11.1 percentage points (95% CI -19.1 to -3.2), risk ratio 0.34 (0.20–0.59); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a binary outcome: each participant either had at least one qualifying NC-MACE during the assessed follow-up or did not. The registry reports participant counts in each group. Such counts are easy to interpret, but they do not show the timing of events, how many events occurred in participants with repeated events, or which component of the composite occurred. Those details are not reported in the registry record.

What does a risk difference express?

A risk difference compares the event proportions in two groups by subtracting one proportion from the other. The reported estimate for ABSORB BVS plus GDMT compared with GDMT alone is -0.061. The sign indicates that the estimated proportion in the ABSORB BVS plus GDMT group was lower in this comparison. The confidence interval is needed alongside the estimate because it represents uncertainty about the size and direction of the difference. The registry record labels the p-value as unadjusted.

General statistical explanation: a risk difference is an absolute measure, expressed on the event-proportion scale. It answers a different question from the relative risk or odds ratio, which express comparisons on relative scales. These measures can have different numerical values and interpretations; none should be read without considering the group definitions, event counts, and uncertainty. The registry reports relative risk and odds ratio estimates for the comparisons, but the interpretation focuses on the posted risk differences and their intervals.

What does the p-value contribute?

General statistical explanation: a p-value assesses how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the magnitude or clinical importance of an effect. The reported p-value of 0.232 for the randomized comparison is unadjusted. The reported p-value for the GDMT versus PROSPECT II Only comparison is <0.001, also unadjusted. The registry record does not report the test procedure or whether other analyses were considered when these p-values were selected.

Because the outcome is binary and the posted comparisons use participant counts, the analysis is a comparison of event proportions. The record does not report a time-to-event analysis, adjustment for covariates, or a model accounting for differences in follow-up. The stated follow-up is a median of 3.7 years, but that summary does not by itself tell how event timing was handled in the group comparisons. Without a reported analysis method, it is not appropriate to infer one.

Why distinguish randomized and observational comparisons?

General statistical explanation: random assignment is intended to make treatment groups comparable, on average, with respect to factors measured and unmeasured at baseline. An observational group comparison does not have that same basis for causal interpretation. Here, the ABSORB BVS plus GDMT and GDMT groups are the randomized treatment comparison described by the record. PROSPECT II Only is an observational group, so its contrast with GDMT should be treated as descriptive rather than as an estimate of a randomized treatment effect.

The registry calls the study randomized and reports no masking. It does not report how the random sequence was generated, how allocation was concealed, or the analysis population used for the randomized contrast. It also does not report whether analyses followed an intention-to-treat approach or how crossovers and protocol deviations were handled. These omissions limit assessment of the analysis beyond the posted group counts and summary estimates.

The primary endpoint is a composite. General statistical explanation: composites can increase the number of observed events and combine outcomes that are related to the research question, but interpretation can be driven by more frequent components. As the component counts are not reported, readers cannot determine whether one event type accounts for most of the composite or whether component patterns differ between groups.

The study summary’s stated randomized question concerns minimum lumen area at 24 months, whereas the posted primary result concerns participant-level NC-MACE over follow-up. The registry record does not report the minimum lumen area result or any posted secondary outcome analyses. That gap means the posted event analysis cannot be used as a substitute for an unreported imaging outcome.

10. Confidence Intervals and Precision

The randomized comparison has a risk difference of -0.061 and a 95% confidence interval from -0.161 to 0.039. General statistical explanation: a confidence interval gives a range of values compatible with the observed data under the assumptions of the method. It conveys the uncertainty around an estimate; it is not a guarantee that the true value lies in the interval. Because this interval includes zero, the posted estimate does not pin down the direction of the group difference with high precision.

The interval for GDMT compared with PROSPECT II Only is -0.191 to -0.032 around a risk difference of -0.111. This interval does not include zero, but the comparison is between the randomized GDMT group and an observational cohort. Its statistical precision does not remove the design limitation or make the contrast causal.

Precision depends in part on the number of participants and events, and the posted counts are limited in the randomized groups: 15 events in GDMT and 10 in ABSORB BVS plus GDMT. Confidence intervals make the uncertainty visible in a way that a point estimate or p-value alone cannot. The registry also reports relative risk and odds ratio intervals, but they describe different scales and should not be substituted for the risk-difference interval.

The record does not report confidence intervals for the individual participant counts, component-specific results, or a separate interval for minimum lumen area. The absence of those results means precision cannot be assessed for those outcomes from the registry entry.

11. 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 illustrations based on the observed effect, not the trial’s original design assumptions. For these binary outcome comparisons, the figures are participants per arm, not total events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Each scenario uses the stated fraction of the observed effect as the effect to detect. The registry record does not report the trial’s original sample-size justification or original design assumptions.

The 80% power column gives the illustrative number of participants per arm for a design that would have an 80% chance of detecting the specified effect under those assumptions. The 90% power column describes the corresponding planning target for a 90% chance. These are design calculations for hypothetical future studies, not evidence about the probability that the completed trial detected an effect. They are not observed power.

For the ABSORB BVS plus GDMT versus GDMT comparison, the illustration for 100% of the observed effect is 501 participants per arm for 80% power and 670 for 90% power. For planning at 75% of the observed effect, the figures are 932 and 1,247 participants per arm; at 50%, they are 2,189 and 2,929. Smaller effects require more participants to detect under the stated assumptions.

The separate GDMT versus PROSPECT II Only illustration gives 126 and 168 participants per arm at 100% of the observed effect, 249 and 333 at 75%, and 612 and 819 at 50%, for 80% and 90% power respectively. Since PROSPECT II Only is observational, these planning figures should not be read as evidence that the observational comparison is a randomized treatment question. A planning curve, if consulted, reflects the same assumptions and should be read as an illustration rather than a description of the trial’s achieved power.

12. 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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.169; treatment proportion p₁ = 0.108; average p̄ = 0.138.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.4878 = 0.9561.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.4859 = 0.4089.
4. n = (0.9561 + 0.4089)² / (-0.0610)² = 500.6, rounded up to 501 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
p0 <- 0.168539325842697                          # control proportion
p1 <- 0.10752688172043                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2171065)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 501 (80% power), 670 (90% power)
 75% of observed effect: n per arm = 932 (80% power), 1,247 (90% power)
 50% of observed effect: n per arm = 2,189 (80% power), 2,929 (90% power)
power.prop.test: 500.6 
Simulated power at n = 501 per arm: 0.804 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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.

13. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan addressing the number of endpoints, comparisons, or analyses. It posts one primary outcome and no secondary outcome results or outcome analyses. The study summary nevertheless describes two components and a randomized minimum lumen area question, while the posted primary result is NC-MACE. The record does not report how the analyses were ordered or whether one was designated as confirmatory for the randomized substudy.

Multiplicity matters in general because testing several outcomes or contrasts can increase the chance of obtaining a small p-value by chance. The posted p-values are identified as unadjusted, and no adjustment procedure is reported in the registry record. It is therefore not possible to determine from the record whether the reported p-values account for other planned or conducted analyses.

Missing outcome data and participant flow are also not described in enough detail to assess their potential impact. Overall enrollment is 902, while the posted outcome groups list 89, 93, and 716 participants. The registry record does not report how many participants were eligible for each analysis, whether any participants were excluded from the outcome denominators, how missing outcomes were handled, or whether follow-up completeness differed across groups.

The record does not report the analysis population for the randomized comparison, such as whether all randomized participants were analyzed according to assigned group. It also does not describe handling of withdrawal, loss to follow-up, treatment crossover, or protocol deviations. Those details are important for assessing the robustness of a randomized comparison. Their absence does not establish that data were missing or that analyses were inappropriate; it means their treatment is not reported in the registry record.

14. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: intravascular imaging related major complications requiring treatment (0.3%).

The serious adverse event figures list 0 affected participants among 89 at risk in the GDMT group, 0 among 93 at risk in the ABSORB BVS plus GDMT group, and 2 among 716 at risk in PROSPECT II Only. The record separately lists deaths as 0, 2, and 16 for those groups. The death counts are presented separately from the serious adverse event counts and should not be assumed to be included in them based on the information reported.

The most common serious adverse event term listed is “Intravascular imaging related major complications requiring treatment,” at 0.3%. The registry record does not report the event definition details, timing, or group-specific breakdown for that term. The counts are descriptive; they do not by themselves establish comparative safety, particularly because the groups differ in study role and the reported numbers of participants at risk.

Zero serious adverse events in a group does not establish that no adverse events of any kind occurred. These figures concern the reported serious adverse event category, and the record does not provide a complete account of non-serious events or the duration of adverse-event surveillance.

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

The registry results show that participants in each posted group experienced the defined NC-MACE endpoint during follow-up. In the randomized comparison, the estimated risk difference favors the ABSORB BVS plus GDMT group in direction, but its confidence interval includes zero and the unadjusted p-value is 0.232. These data therefore leave considerable uncertainty about the magnitude and direction of the group difference; they do not establish equivalence.

The comparison of GDMT with PROSPECT II Only shows a risk difference whose confidence interval excludes zero and an unadjusted p-value of <0.001. However, PROSPECT II Only is an observational cohort rather than a randomized arm. That contrast is descriptive and cannot be interpreted as a causal treatment effect solely on the basis of its p-value or interval.

The endpoint is specific to events attributed to originally untreated non-culprit lesions and combines several clinical and angiographic criteria. The posted counts do not show which components occurred, when events occurred, or whether participants experienced repeated events. The study summary’s separate randomized question about minimum lumen area at 24 months does not have a posted result in the registry record.

These results describe the outcome data and statistical uncertainty recorded for this study. They do not answer every question raised by the study design, establish a mechanism, or determine what treatment is appropriate for any individual. The registry record does not report enough detail about analysis populations, missing data, or endpoint components to resolve those issues from the posted results alone.

16. Why This Trial Matters Statistically

This study is statistically notable because it combines an observational natural history study with a randomized intervention substudy. Keeping those components distinct is essential: a randomized arm comparison and a contrast involving an observational cohort answer different questions and support different levels of causal interpretation.

It also illustrates why the endpoint and the posted analysis must be read together. The study summary describes imaging aims and a randomized minimum lumen area question, while the posted primary outcome is a composite of participant-level NC-MACE events over follow-up. Readers should not treat these measures as interchangeable. The record’s event endpoint concerns clinical and angiographic events attributed to originally untreated lesions; the minimum lumen area outcome is not reported.

The randomized comparison has a broad confidence interval around the risk difference. That precision information is central: the point estimate and p-value alone would give an incomplete account of what the data can support. The observational contrast has a smaller p-value, but its design does not make it a randomized treatment result. This distinction is a useful example of why statistical significance and study design must be considered together.

Finally, the registry record leaves important analysis details unreported, including multiplicity handling, missing-data procedures, and the analysis population. Identifying these unknowns is part of sound statistical interpretation, not a reason to infer details that are absent. The case demonstrates how a careful reading can separate observed counts, estimated comparisons, uncertainty, and unanswered methodological questions.

17. 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 posted outcome groups combine a randomized comparison with a separate PROSPECT II Only observational cohort. The latter is not a randomized control group, so its numerical contrast with GDMT should not be interpreted as a causal treatment comparison. The record does not report adjusted results for this contrast.

The primary outcome is a composite, but counts for cardiac death, myocardial infarction, unstable angina, and the qualifying forms of progressive angina are not posted separately. Event timing and recurrent event information are also not reported. The stated follow-up is a median of 3.7 years, but the registry record does not explain whether or how differences in individual follow-up duration were incorporated in the comparisons.

The study summary describes minimum lumen area at 24 months as the randomized substudy’s question, but no result for that measure is reported in the registry record. The record also posts no secondary outcome analyses. Therefore, the posted NC-MACE findings do not provide a substitute for the unreported imaging result.

Further limitations arise from unreported methodological details: the original sample-size rationale, randomization procedures, allocation concealment, analysis population, missing-data handling, and multiplicity plan are not reported in the registry record. These gaps restrict assessment of possible selection, attrition, and analysis effects. The registry also lists no masking. The posted serious adverse event counts are descriptive and do not provide enough detail to assess timing or the full adverse-event profile.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: PROSPECT II & PROSPECT ABSORB - an Integrated Natural History Study and Randomized Trial. — NCT02171065.
• Registry record last updated 2021-08-10; status last verified 2021-07.
• Results first posted 2021-08-10.
• 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.

21. Record Summary

NCT02171065 is a completed multicentre study sponsored by Uppsala University, combining the PROSPECT II prospective natural history study and the randomized PROSPECT ABSORB substudy. The recorded study start is 2014-06, primary completion is 2020-05, and overall enrollment is 902. The registry describes randomized allocation, a parallel model, and no masking.

The posted primary outcome is the participant count for NC-MACE attributed to originally untreated non-culprit lesions, assessed at the longest available follow-up. Median follow-up is 3.7 years, with first and third quartiles of 3.0 and 4.4 years. The randomized comparison reports 15 events among 89 GDMT participants and 10 among 93 ABSORB BVS plus GDMT participants. A separate outcome group contains 41 events among 716 PROSPECT II Only participants.

The randomized risk-difference interval includes zero; the observational comparison has a distinct design and should be interpreted descriptively. A result for the stated minimum lumen area question, along with secondary outcome analyses and several analysis-plan details, is not reported in the registry record.