Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer (NCT01622543), a randomized phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

The registry describes a randomized phase II comparison of adding reolysin to FOLFOX6 and bevacizumab versus using FOLFOX6 and bevacizumab alone in patients with metastatic colorectal cancer. The clinical question is whether the observed time until progression, relapse, new lesions, or death differed between the groups. Progression-free survival was the primary outcome, and the registry defines its measurement and censoring rules.

The registry also lists changes in CEA levels, objective response rate, and overall survival as secondary outcomes. Together, these address different aspects of the study: change in a laboratory marker, tumor response, and time until death. These outcomes do not replace the primary comparison; they provide additional descriptions of outcomes assessed in the trial.

The question is comparative rather than a test of either regimen against no treatment. The trial therefore informs how the recorded outcomes differed between these two treatment strategies in the randomized participants. The registry does not report the clinical rationale for selecting reolysin beyond the stated study purpose of comparing the combination with standard therapy.

3. Trial Design

This was a randomized, parallel-group phase II study with no masking. The registry lists an enrollment of 109 and status as completed. The start date was 2012-10-26, and the primary completion date was 2017-01-18. The sponsor was Canadian Cancer Trials Group.

The groups were FOLFOX6 plus bevacizumab and reolysin, and FOLFOX6 plus bevacizumab. For the primary outcome, the registry reports 51 participants in the combination group and 52 in the group without reolysin. The primary outcome population is described as all patients randomized. Arm descriptions beyond the intervention names are not reported in the registry record.

Progression-free survival was assessed over a stated timeframe of 19 months. The registry defines it as the time from randomization until objective relapse or progression, appearance of new lesions, or death from any cause. Patients without a recorded event were censored at the date of their last disease assessment, with the assessment date defined using target or non-target lesions as applicable. Progression was defined using RECIST v1.0 criteria.

Secondary outcomes listed in the registry are changes in CEA levels, objective response rate, and overall survival. The CEA outcome was assessed at baseline and at 28 weeks. The objective response outcome has a stated timeframe of 19 months. Overall survival was measured from randomization until death from any cause or censored at the last known alive date, with assessment stated as up to 49 months.

The registry record does not report the original sample-size justification, details of the randomization procedure, or additional eligibility and treatment-administration details. Those design features should not be inferred from the outcome summaries.

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: 6 patients were enrolled in a safety run-in phase of the study before randomized component was started. These 6 patients were not included in the final analysis.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients randomized

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 patients randomized to this study

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival, measured over 19 months.

The primary endpoint was progression-free survival, reported as a median in months with a 95% confidence interval. It measures the time from randomization to the first qualifying event: objective relapse or progression, new lesions, or death from any cause. For participants without a recorded event, the registry specifies censoring at the date of their last disease assessment.

This kind of time-to-event outcome is used when the timing of an event matters and participants may have different lengths of follow-up. It can incorporate information about when events occurred rather than reducing follow-up to a simple event count. Censoring allows the analysis to retain participants whose event was not observed by their last assessment, while recognizing that their later event status is unknown.

The registry defines progression using RECIST v1.0: an increase in the sum of the longest diameters of target lesions, measurable increase in a non-target lesion, or appearance of new lesions. This operational definition makes clear which disease changes qualify as progression for the endpoint.

The median is a summary of the observed time-to-event distribution, not a statement about the experience of every participant. Its confidence interval describes uncertainty around that median estimate. The between-group comparison is reported separately as a hazard ratio from a log-rank analysis. The registry record does not report further details of the time-to-event analysis, such as the model specification or additional assumptions.

7. Results Posted in the Registry

• Folfox Plus Bevacizumab and Reolysin vs Folfox Plus Bevacizumab: hazard ratio 1.59 (95% CI 1.00–2.53), reported p = 0.046 (as reported in the registry).

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.

Changes in CEA Levels

• 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:
  • Folfox Plus Bevacizumab: mean -1,108 versus -14,209 on control; difference 13,101 (95% CI -14,101 to 40,304), standardized effect d = 0.32; z-test p = 0.345.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Folfox Plus Bevacizumab and the control. The interval gives the range of effects that remain compatible with the data.

Objective Response Rate

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Folfox Plus Bevacizumab: 34.6% (18/52) versus 52.9% (27/51) on control; risk difference -18.3 percentage points (95% CI -37.2 to 0.5), risk ratio 0.65 (0.42–1.03); unadjusted two-proportion z-test p = 0.061.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Folfox Plus Bevacizumab and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Folfox Plus Bevacizumab and Reolysin vs Folfox Plus Bevacizumab: hazard ratio 1.24 (95% CI 0.78–1.98), reported p = 0.360 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Folfox Plus Bevacizumab and Reolysin vs Folfox Plus Bevacizumab and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the description of the trial beyond progression-free survival. They cover a laboratory marker, objective response, and overall survival, each with a different scale, analysis population, and statistical method. Their results should be understood as complementary outcome-specific evidence rather than repeated measurements of the primary endpoint.

Across these secondary analyses, the overall pattern does not supply a single, uniformly precise confirmation of the primary comparison. The endpoints measure different events and may point in different directions or carry different amounts of uncertainty. A laboratory change is not equivalent to a time-to-event outcome, and response classification is not equivalent to either progression-free survival or overall survival. The trial’s secondary results are therefore best read as a set of distinct observations rather than combined informally into one overall conclusion.

The secondary analyses also have differing information bases. The CEA analysis includes a subset of participants, whereas the response and time-to-event summaries have their own recorded group sizes and follow-up descriptions. Variation in the amount of observed data affects precision and can make secondary estimates less stable than the primary comparison.

Multiple secondary outcomes create a multiplicity concern: with more statistical tests, the chance of at least one apparently notable result can increase, even if no adjustment is made. The registry record does not report a multiplicity adjustment or a hierarchy of secondary hypotheses. Accordingly, secondary p-values should be treated as exploratory unless a prespecified plan supporting stronger interpretation is documented. They can help identify patterns for further study, but they should not overrule the primary analysis on their own.

The registry’s reported secondary analyses should be interpreted using their specified methods. Summary statistics or unadjusted recalculations can offer context, but they do not change the scope or limitations of the sponsor-reported analyses. The combined evidence across endpoints remains subject to the uncertainty and reporting gaps described for this trial.

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

• Changes in CEA Levels
• Objective Response Rate
• Overall Survival

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports a randomized parallel-group comparison with no masking. Randomization is intended to create groups that are comparable, on average, with respect to measured and unmeasured characteristics at the start of a study. In practice, chance differences can remain, especially in trials of this scale. The posted outcome analysis compares the assigned groups; the record identifies all randomized patients as the primary outcome population.

What does the median summarize?

For a time-to-event endpoint, the median is the time by which half of the estimated event-time distribution has experienced the event, under the analysis used. It is not an arithmetic average and does not say that all participants had an event at that time. Participants who remain event-free at their last disease assessment contribute follow-up information up to that point and are censored, as defined in the registry.

Censoring is not the same as declaring that an event never occurred. It records that the event was not observed before the participant’s last relevant assessment. Valid interpretation depends on the analysis handling censoring appropriately. The registry gives the censoring definition but does not report further diagnostic checks or assumptions for this endpoint.

How should the hazard ratio be read?

The hazard ratio compares the event hazard between the groups over the follow-up period. A value of 1 corresponds to equal estimated hazards under the comparison’s orientation; values above or below 1 indicate the direction of the estimated relative hazard. The registry reports the hazard ratio for the reolysin combination versus FOLFOX6 and bevacizumab and identifies the method as log-rank. The hazard ratio is not a ratio of median survival times and should not be described as a fixed change in an individual’s risk.

The log-rank method compares the timing of events across groups while accounting for follow-up and censoring. Its interpretation depends on the time-to-event data, not just the medians. The registry record does not report whether proportional hazards were assessed or provide details of any supporting model; those methods should not be assumed.

What does the confidence interval add?

A confidence interval gives a range of values compatible with the observed data under the statistical procedure. For the hazard ratio, the interval conveys uncertainty about the relative event hazard; for each median, it conveys uncertainty about that group’s median estimate. Wider intervals indicate less precision. An interval that includes the no-difference value is compatible with no difference as well as effects in either direction, though the degree of compatibility varies across its range.

A p-value measures how unusual the observed data, or data more extreme, would be under a specified null hypothesis and analysis assumptions. It is not the probability that the null hypothesis is true, nor does it quantify the size or clinical importance of an effect. A value near a conventional threshold should not be interpreted as a sharp boundary between meaningful and meaningless evidence. The effect estimate and confidence interval are essential parts of the interpretation.

Why can over-dispersion matter?

Over-dispersion is a general statistical issue in count-data models: the observed variability exceeds what a simple model assumes. When that occurs and the analysis does not account for the extra variability, uncertainty can be understated. The registry’s primary endpoint is time-to-event, and the record does not describe a count-data model or report an over-dispersion assessment. This general concept therefore should not be treated as a finding about this trial.

The secondary outcomes use different summaries and methods. The registry lists a Wilcoxon (Mann-Whitney) test for changes in CEA levels and a Cochran-Mantel-Haenszel analysis for objective response. Overall survival is reported with a log-rank hazard ratio. These methods answer different statistical questions, so their estimates and p-values should not be read as interchangeable measures.

For CEA, the posted arm summaries are means and standard deviations, while the sponsor’s reported comparison uses a rank-based test. A rank-based test evaluates the ordering of observations rather than directly testing the difference between means under a normal model. For objective response, a categorical method compares response outcomes between groups. For overall survival, the time-to-event analysis concerns time until death or censoring. The distinct endpoint definitions and methods explain why the results across outcomes may not align exactly.

The registry does not report a complete statistical analysis plan, missing-data methods for the secondary outcomes, or details of multiplicity control. Those details affect how confirmatory the collection of analyses can be considered and are addressed as limitations rather than inferred from the reported tests.

11. Confidence Intervals and Precision

The precision of the primary comparison is conveyed by the confidence intervals around the group medians and the hazard ratio. The median estimates are 7.33 months and 9.13 months, with respective 95% confidence intervals of 5.42 to 9.17 months and 7.39 to 11.83 months. These intervals show that each median is estimated with uncertainty; they should not be mistaken for the range containing every participant’s progression-free survival time.

The hazard ratio is 1.59, with a 95% confidence interval from 1.00 to 2.53. The interval spans values from the boundary of no relative hazard difference to values indicating a higher hazard in the reolysin group under the registry’s comparison orientation. It therefore leaves uncertainty about the magnitude of the group contrast. The reported p-value is 0.046, but the interval and point estimate provide more information about direction and plausible magnitude than a threshold-based label alone.

Confidence intervals are not guarantees that the true value lies within the displayed limits. They are produced by a statistical procedure with repeated-sampling properties under its assumptions. Their width depends on factors including the amount of information in the analysis, the distribution of event times, and the analysis method. The registry does not report enough detail to assess all assumptions or to reconstruct the intervals independently.

Precision differs by endpoint and analysis population. For example, the CEA summaries include fewer participants than the primary outcome groups, so that outcome has a different information base. The confidence intervals on secondary comparisons also express uncertainty and should be considered in light of the endpoint-specific analysis and the number of outcomes examined.

Statistical precision is not the same as clinical importance. A more precise estimate can still describe a small or unimportant effect, while a less precise estimate can include effects of different practical importance. The registry does not supply a threshold for a clinically important difference in progression-free survival.

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.

Sample-size figures are planning illustrations based on the observed effects, not the trial’s original design rationale. For the time-to-event outcomes, the figures are total events needed. For the other outcomes, they are participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario targets the stated fraction of the observed effect.

The 80% power column represents the number of events or participants that a hypothetical study would need, under those assumptions, to have an 80% chance of detecting the specified effect if that effect were the true one. The 90% power column expresses the corresponding target for a 90% chance. These are design probabilities for a hypothetical repeated study, not probabilities that this trial’s finding is correct.

Rows that plan for 100% of the observed effect use the full observed effect as the target. Rows planning for 75% or 50% use smaller target effects. Smaller effects are harder to distinguish from random variation, so they require more events or participants for the same target power. This pattern is a general feature of statistical planning, not a claim about how the trial was designed.

The figures are not observed power. They do not measure the probability that the completed trial detected a true effect, and they do not determine whether the result is valid. The original sample-size assumptions and justification are not reported in the registry record. The illustrations should be read as conditional planning scenarios, not as a reconstruction of the study’s protocol or an explanation for its enrollment.

For survival outcomes, the event totals matter because the comparison’s information depends substantially on the number of observed events, rather than enrollment alone. For other outcomes, the figures are per arm and apply to participants in each group, not the total across groups. Keeping those units distinct is essential when reading the planning values.

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

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.590, so ln(HR) = 0.4637.
2. d = 4 × (1.96 + 0.842)² / [ln(1.590)]² = 146.0, rounded up to 146 events in total 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
hr <- 1.59                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1622543)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 146 (80% power), 196 (90% power)
 75% of observed effect: events = 260 (80% power), 348 (90% power)
 50% of observed effect: events = 584 (80% power), 782 (90% power)
Simulated power with 146 events: 0.811 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is a log-rank hazard ratio of 1.59, with a 95% confidence interval from 1.00 to 2.53 and p = 0.046. The posted primary outcome comparison is already reported using that approach, and the record indicates no discrepancy between the sponsor’s analysis and the displayed primary comparison. There is no separate recalculated primary hazard ratio to substitute for the sponsor’s estimate.

For secondary outcomes, the registry also reports sponsor analyses using methods specific to the outcome. The CEA comparison is reported with a Wilcoxon (Mann-Whitney) test, and objective response is reported with a Cochran-Mantel-Haenszel analysis. Overall survival is reported using a log-rank hazard ratio. These are the sponsor’s analyses and should be distinguished from any simple unadjusted recalculations based on posted summary statistics.

A recalculated summary-statistic comparison can be informative as a check or an approximate alternative, but it may not reproduce the sponsor’s result when the underlying analysis uses ranks, stratification, time-to-event data, or other information not contained in the summaries. In such cases, the sponsor’s own analysis takes precedence. The record’s lack of a discrepancy flag does not establish that every methodological detail is available; it indicates that no reported discrepancy is identified.

Interpretation should therefore begin with the sponsor-reported analysis for each endpoint, while using arm summaries and uncertainty intervals to understand the estimates. A difference between a recalculated p-value and a sponsor-reported p-value would not automatically imply an error, because the methods and data used can differ.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several hypotheses or outcomes are tested. As the number of tests increases, the likelihood of seeing at least one result that appears statistically notable by chance can increase. This matters when interpreting the secondary outcomes, particularly when individual p-values are considered without a stated testing hierarchy or adjustment.

The registry lists CEA changes, objective response, and overall survival as secondary outcomes, in addition to the primary progression-free survival analysis. A multiplicity adjustment, a prespecified ordering of hypotheses, and a distinction between confirmatory and exploratory tests are not reported in the registry record. It is therefore not possible to determine from this record whether the sponsor controlled the overall false-positive rate across outcomes.

The primary outcome is identified as primary, which distinguishes it from the secondary outcomes in the registry description. That designation does not by itself establish all the details of prespecification or analysis conduct. The full statistical analysis plan and protocol details are not reported in the registry record.

Missing-data handling is described for the primary time-to-event outcome in terms of censoring at the last disease assessment when a participant had not progressed or died. The registry gives the definition of the last assessment date used for this purpose. Additional details on the handling of missing or unevaluable measurements for CEA and objective response are not reported in the registry record. Nor does the registry explain how missing data may have affected the secondary analysis populations.

The primary outcome population is stated as all patients randomized. The registry does not report a fuller analysis-population definition, such as whether the primary analysis followed an intention-to-treat principle in all relevant details. Secondary outcome denominators differ, and a full account of exclusions or missing observations is not reported in the registry record.

These omissions limit evaluation of the analysis plan and the potential influence of missing observations or multiple testing. They do not establish that the analyses were inappropriate; they mean that the registry record alone does not contain enough information to assess those issues fully.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lung infection (7.8%), febrile neutropenia (7.7%), sepsis (5.9%), colonic perforation (5.8%), small intestinal obstruction (3.9%).

The registry records serious adverse events in 22 of 51 participants in the FOLFOX6, bevacizumab, and reolysin group and 18 of 52 participants in the group receiving FOLFOX6 and bevacizumab. Other adverse events are recorded for 51 of 51 participants and 52 of 52 participants, respectively. These are participant counts reported for the listed groups, not measures of event severity for every individual event.

The record also reports 39 deaths in each group. The safety summary does not establish that these deaths were caused by treatment, and the counts should not be interpreted as treatment-attributable deaths. The registry lists lung infection, febrile neutropenia, sepsis, colonic perforation, small intestinal obstruction, and acute kidney injury among the most frequent serious adverse-event terms, with percentages displayed for those terms. The record does not assign those listed term percentages to a particular arm in the summary.

Adverse-event counts describe events recorded under the registry’s reporting framework. They do not by themselves establish comparative risk, causation, timing, duration, or severity for each participant. The registry record does not report additional detail needed to assess those dimensions. Safety findings should be read as descriptive data from this trial, not as a complete assessment of risks across other settings or populations.

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

The primary result describes a randomized comparison of progression-free survival between FOLFOX6 and bevacizumab with reolysin and FOLFOX6 and bevacizumab alone. The reported hazard ratio is 1.59, with a 95% confidence interval from 1.00 to 2.53, and the group medians are 7.33 months and 9.13 months, respectively. These estimates indicate the direction and uncertainty of the observed comparison; they do not guarantee what an individual participant would experience.

The registry reports p = 0.046 for the primary log-rank analysis. That value is close to a conventional threshold and should not be treated as a yes-or-no verdict. The confidence interval includes its boundary at 1.00 and allows a range of possible relative hazards. The estimate is imprecise enough that the exact magnitude of the group difference remains uncertain.

The results do not establish why the groups differed as observed, do not describe every possible outcome, and do not imply a fixed change in an individual’s progression time. They also do not provide evidence about treatment comparisons outside the two strategies studied. The trial is a phase II randomized study, and the registry record does not report all details needed to assess generalizability, the original design rationale, or the full statistical plan.

Secondary outcomes offer additional context but do not remove uncertainty in the primary result. They address distinct clinical and statistical questions and may be affected by smaller analysis populations and multiple testing. Their findings should not be combined selectively or interpreted as independent confirmation without considering those limitations.

These statistical results are not medical advice and do not determine a treatment choice. Their meaning is limited to the recorded outcomes, analysis methods, and participants in this trial. Further interpretation would require clinical context and complete study documentation beyond what is reported in the registry record.

18. Why This Trial Matters Statistically

This trial is statistically informative because it makes a randomized comparison of adding reolysin to an existing regimen, with progression-free survival designated as the primary endpoint. The comparison is directly between two treatment strategies rather than between treatment and no treatment. Randomization provides a framework for comparing the groups, while the reported estimates and intervals show how much uncertainty remains in the observed contrast.

The primary outcome combines progression, relapse, new lesions, and death within a time-to-event definition. That structure makes it possible to account for event timing and censoring, but also means the result depends on endpoint definitions, follow-up, and assumptions about the analysis. The registry’s explicit progression and censoring definitions help readers understand what event was analyzed.

The result also illustrates why estimates, confidence intervals, and p-values should be read together. The primary p-value is near a conventional cutoff, while the confidence interval communicates a range of compatible hazard ratios and the group medians describe the event-time distributions. No single statistic gives the full picture of direction, magnitude, and precision.

The secondary outcomes add breadth but bring their own statistical concerns. Different endpoints use different methods and information bases, and multiple testing can make isolated findings less persuasive without a reported plan for multiplicity. Distinguishing the primary endpoint from secondary analyses is therefore important to a disciplined reading of the evidence.

Finally, the record demonstrates the limits of registry summaries. Important details about the original sample-size rationale, missing-data handling across outcomes, and analysis plan are not reported. Recognizing these gaps is part of interpreting the estimates accurately, rather than filling them with assumptions.

19. 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 gives the main outcome definitions and reported analyses but does not report the original sample-size justification or the assumptions used to plan enrollment. The planning illustrations based on observed effects cannot reconstruct the trial’s design rationale. The record also does not report the full protocol or statistical analysis plan.

Further methodological details are not reported, including the randomization procedure, any stratification factors, whether proportional hazards were assessed, and the full handling of missing or unevaluable secondary outcome data. Although the primary endpoint’s censoring rule is described, the record does not provide enough detail to evaluate all assumptions behind the time-to-event analysis.

The CEA analysis includes a subset of participants, and the registry does not explain fully how that analysis population was formed or how missing values were handled. The secondary analyses cover several outcomes, but multiplicity control and a hierarchy of hypotheses are not reported. These gaps make it difficult to determine how strongly the secondary findings should be treated as confirmatory.

The registry lists serious adverse-event counts and selected serious event terms, but the summary does not give sufficient detail to assess timing, duration, attribution, or the distribution of those terms by treatment group. The recorded death counts likewise do not establish cause.

Finally, this is a phase II trial with the recorded group sizes and follow-up described for each outcome. The registry record alone cannot establish how representative the participants were of broader patient populations or whether findings would be consistent in other settings. These are limits on interpretation, not evidence that the reported analysis is invalid.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Reolysin in Combination With FOLFOX6 and Bevacizumab or FOLFOX6 and Bevacizumab Alone in Metastatic Colorectal Cancer — NCT01622543.
• Registry record last updated 2023-08-23; status last verified 2020-03.
• Results first posted 2019-12-13.
• 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.

23. Record Summary

NCT01622543 is a completed randomized phase II study in metastatic colorectal cancer, sponsored by Canadian Cancer Trials Group. It compared FOLFOX6 and bevacizumab with reolysin against FOLFOX6 and bevacizumab alone, without masking, in a parallel-group design.

Progression-free survival was the primary outcome, defined from randomization to progression, relapse, new lesions, or death, with censoring at the last disease assessment for participants without a recorded event. The sponsor-reported log-rank comparison was a hazard ratio of 1.59, with a 95% confidence interval from 1.00 to 2.53 and p = 0.046.

Secondary outcomes were changes in CEA levels, objective response rate, and overall survival. The registry also reports adverse-event counts and selected serious adverse-event terms. The original sample-size rationale, multiplicity approach, and several analysis details are not reported in the registry record.