This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
CORAL was a randomized phase 3 parallel-group treatment trial evaluating two salvage chemotherapy approaches in adults aged 18–65 with relapsed diffuse large B-cell lymphoma.
| Feature | CORAL |
|---|---|
| Condition | Lymphoma, Large-Cell, Diffuse |
| Phase | Phase 3 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Lead sponsor | Lymphoma Study Association |
2. Clinical Question
The clinical question was whether two different salvage treatment approaches, R-ICE and R-DHAP, produced different outcomes in patients aged 18–65 with relapsed diffuse large B-cell lymphoma.
Population
Patients aged 18–65 with relapsed diffuse large B-cell lymphoma.
Interventions
R-ICE and R-DHAP treatment strategies incorporating chemotherapy agents and subsequent autologous stem cell transplantation.
Comparator
The randomized comparison was between the two parallel treatment groups.
Primary questions
How do the treatment groups compare for mobilization adjusted response rate and event free survival?
3. Trial Design
R-ICE
- Rituximab
- Ifosfamide + Mesna
- Carboplatine
- Etoposide
R-DHAP
- Rituximab
- Cisplatine
- Cytosine Arabinoside
- Dexamethasone
4. Endpoints
| Endpoint | Time frame | Description |
|---|---|---|
| MARR (mobilization adjusted response rate) | 3 months | Primary endpoint. |
| EFS (event free survival) | 2 years post transplantation | Primary endpoint. |
5. Planned Analysis
The ClinicalTrials.gov record lists primary endpoints but does not report posted statistical analyses or endpoint results.
For mobilization adjusted response rate, the typical statistical approach would compare response proportions between randomized groups using methods appropriate for binary outcomes, with confidence intervals used to describe uncertainty around the treatment difference.
For event free survival, the typical analysis would use time-to-event methods such as Kaplan-Meier estimation to describe event-free probability over time, together with comparison methods such as log-rank testing and regression models such as the Cox proportional-hazards model when appropriate.
6. Statistical Methodology
Response rate analysis
MARR is a binary endpoint because patients are categorized according to whether they meet the response definition. Binary endpoints are commonly summarized using response proportions, absolute differences between groups, relative measures, and confidence intervals.
The confidence interval describes uncertainty around the estimated difference and helps distinguish precise from imprecise estimates.
Event-free survival analysis
EFS measures the time until a defined event occurs. Because not every participant necessarily experiences an event during follow-up, survival methods account for censored observations.
Kaplan-Meier methods estimate the event-free survival curve while retaining information from participants whose follow-up ends before an event.
7. Statistical Methods Explained
Why use Kaplan-Meier methods for EFS?
Patients have different follow-up times. Kaplan-Meier estimation allows analysis of event timing while handling censoring.
Why is randomization important?
Randomization creates treatment groups that can be compared without intentionally assigning prognostic factors.
Why are confidence intervals reported?
Confidence intervals describe uncertainty around an estimate and provide information about statistical precision.
What does an event-free survival curve show?
It describes the estimated probability of remaining free of the defined event over time.
Why analyze response and survival separately?
Response rate measures early treatment activity, while EFS captures the timing of clinically relevant events.
Why does censoring matter?
Censoring allows participants without observed events at last follow-up to contribute partial information.
8. Limitations
- No posted statistical analyses: The registry does not report endpoint estimates, confidence intervals, or p-values for the primary endpoints.
- Endpoint interpretation: MARR and EFS measure different aspects of treatment effect and should not be interpreted as interchangeable outcomes.
- Time-to-event uncertainty: EFS estimates depend on follow-up duration and censoring patterns.
- Trial population: Eligibility criteria limit interpretation to the population represented by the study.
- Multiple treatment components: The intervention strategies include combinations of agents and procedures, making the treatment pathways multidimensional.
9. Why This Trial Matters Statistically
CORAL is a useful statistical teaching example because it combines randomized treatment comparison, binary response assessment, and time-to-event methodology in a phase 3 clinical trial setting.
| Concept | How it appears in CORAL |
|---|---|
| Randomization | Randomized allocation between two parallel treatment strategies. |
| Binary outcomes | MARR as a response-based primary endpoint. |
| Survival analysis | EFS evaluated over a defined post-transplantation time frame. |
| Censoring | Relevant to event-free survival follow-up. |
| Clinical endpoints | Different endpoints capture different dimensions of treatment effect. |
10. Related Tutorials
Learn more about the methods used in this trial:
11. Related Calculators
12. Sources
- ClinicalTrials.gov: NCT00137995
- PubMed: Publication record
- PubMed: Publication record
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