Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer (NCT01414608), a randomized phase 3 study. The primary outcome is Overall Survival Rate at 5 Years.

2. Clinical Question

The clinical question is whether adding adjuvant carboplatin and paclitaxel after cisplatin-based chemoradiation changes the estimated probability of overall survival at 5 years for eligible participants with locally advanced cervical cancer. The registry describes a comparison between standard chemoradiation alone and standard chemoradiation followed by adjuvant chemotherapy.

The intervention contrast matters: both groups received cisplatin with radiation therapy and brachytherapy, while the adjuvant chemotherapy group also received paclitaxel and carboplatin beginning 4 weeks later. The primary endpoint counts survival from randomization, rather than starting the clock at the later chemotherapy phase. Overall survival is defined using death from any cause or last contact, whichever occurs first.

The posted primary estimates are 71.0% for standard chemoradiation and 72.0% for standard chemoradiation with adjuvant chemotherapy. Their 95% confidence intervals are 66.0% to 75.0% and 67.0% to 76.0%, respectively. These estimates describe the observed trial results; they do not by themselves establish that the treatment strategies are equivalent or that either strategy causes a particular result for an individual.

The registry reports a randomized phase III, parallel-group study with no masking. Its recorded enrollment is 926. The trial's stated primary question concerns overall survival at 5 years, with progression-free survival and quality of life among the posted secondary outcomes.

3. Trial Design

The registry identifies NCT01414608 as a randomized phase III trial with a parallel-group model and no masking. The title describes cisplatin and radiation therapy with or without carboplatin and paclitaxel; the official title describes adjuvant chemotherapy following chemoradiation as primary treatment for locally advanced cervical cancer compared with chemoradiation alone. The sponsor is the GOG Foundation.

One group received cisplatin with external-beam radiation and intracavitary brachytherapy. The description specifies cisplatin on days 1, 8, 15, 22, and 29, external-beam radiation once daily, 5 days a week, for approximately 5 weeks, followed by brachytherapy. The other group received those treatments and then began adjuvant chemotherapy 4 weeks later: paclitaxel and carboplatin, repeated every 21 days for 4 courses. The registry description identifies the drugs and routes, but the available text does not give a complete description of every treatment detail.

The conditions listed cover cervical adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma, as well as specified stages from IB through IVA under the stated AJCC versions. The primary outcome population is described as eligible subjects. Further detail about eligibility criteria is not reported in the registry record.

Recorded enrollment is 926. The primary outcome entries list 456 participants for standard chemoradiation and 463 for standard chemoradiation with adjuvant chemotherapy. Those are the denominators attached to the posted primary estimates; the reason they do not match the recorded enrollment is not reported in the registry record.

The primary completion date is 2021-07-09 and the status is completed. The start date is 2012-01-09. These registry dates describe the study record and do not, by themselves, explain the timing or conduct of the statistical analyses. The original sample-size justification, detailed allocation procedures, and full analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible subjects

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: Eligible subjects

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival Rate at 5 Years, measured over 5 years from study randomization.

The primary endpoint is overall survival rate at 5 years from study randomization. The registry defines overall survival as time from randomization to death due to any cause or the date of last contact, whichever occurs first. The reported quantity is a Kaplan-Meier estimate of the probability of being alive at 5 years, expressed as a percentage of participants.

Overall survival is used because it captures death from any cause and does not require deciding whether a death was caused by cervical cancer or treatment. In general, time-to-event methods are useful when participants have different lengths of follow-up or when some are not known to have had the event by the analysis time. Kaplan-Meier estimation accounts for the timing of events and censoring, where censoring means that follow-up ends without the event having been observed.

The primary outcome is therefore not simply a count of participants known to be alive divided by the number randomized. It is an estimated survival probability at a specified time point. Its interpretation depends on the follow-up information and the assumptions of the method, including the handling of censored observations. The registry gives the method and endpoint definition, but detailed information about follow-up completeness and censoring patterns is not reported in the registry record.

The posted estimates are 71.0% for standard chemoradiation and 72.0% for standard chemoradiation with adjuvant chemotherapy. The corresponding 95% confidence intervals are 66.0% to 75.0% and 67.0% to 76.0%. These values summarize the estimated survival probability at the stated time point; they do not describe the timing of every death or the whole survival experience over follow-up.

7. Results Posted in the Registry

• Standard Chemoradiation With Adjuvant Chemotherapy: 71.9% (333/463) versus 71.1% (324/456) on control; risk difference 0.9 percentage points (95% CI -5.0 to 6.7), risk ratio 1.01 (0.93–1.10); unadjusted two-proportion z-test p = 0.770.

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.

Progression-free Survival Rate at 5 Years

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Standard Chemoradiation With Adjuvant Chemotherapy: 63.1% (292/463) versus 62.1% (283/456) on control; risk difference 1.0 percentage points (95% CI -5.3 to 7.3), risk ratio 1.02 (0.92–1.12); unadjusted two-proportion z-test p = 0.753.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Standard Chemoradiation With Adjuvant Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

Quality of Life for Global Health Status

• 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:
  • Standard Chemoradiation With Adjuvant Chemotherapy: mean 2.40 versus 1.70 on control; difference 0.70 (95% CI -4.53 to 5.93), standardized effect d = 0.03; z-test p = 0.793.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Standard Chemoradiation With Adjuvant Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes cover progression-free survival at 5 years, adverse events, patterns of disease recurrence, radiation protocol compliance, and quality of life for global health status. The detailed quantitative secondary results include progression-free survival and global health status quality of life. The overall pattern in those reported results is not sharply separated between the randomized groups, and it does not contradict the close primary survival estimates.

Secondary outcomes offer additional views of the treatment strategies, but they answer different questions. Progression-free survival concerns a different event definition from overall survival, while quality of life describes reported health status rather than time to death. Adverse events, recurrence patterns, and protocol compliance address safety, disease course, and treatment delivery. They should not be treated as interchangeable measures or combined into a single conclusion.

Unadjusted secondary comparisons carry less weight when multiple outcomes are examined because the chance of finding at least one apparently unusual result can increase as more tests are considered. This is a general statistical concern, not a claim that a particular finding is false. The registry does not report a multiplicity strategy or a detailed hierarchy for interpreting the secondary outcomes, so the strength of confirmatory claims based on them is unclear.

The posted results should therefore be read as complementary, descriptive evidence alongside the primary endpoint, rather than as independent confirmation of a single conclusion. The registry record does not report analyses for all listed secondary outcomes, and it does not provide a full account of missing observations or analysis populations for each outcome. Interpretations should remain limited to the outcomes and analyses that are actually posted.

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

• Progression-free Survival Rate at 5 Years
• Number of Participants With Adverse Events (Grade 3 or Higher) in First Year
• Patterns of Disease Recurrence
• Radiation Protocol Compliance
• Quality of Life for Global Health Status

9. Statistical Interpretation

10. Statistical Methods Explained

The registry reports the primary outcome as a Kaplan-Meier estimate of the probability of overall survival at 5 years. The accompanying arm-level confidence intervals quantify uncertainty in those estimates. The group comparison is expressed as an unadjusted risk difference, with an unadjusted p-value. The registry also posts secondary results for progression-free survival and global health status quality of life.

What does Kaplan-Meier estimation do?

In general, Kaplan-Meier estimation is a method for summarizing time until an event when participants may have different follow-up times. It uses the event times and the number still under observation at each event time to estimate the probability of remaining event-free through time. For overall survival, the event is death from any cause. A participant whose last contact occurs before a death is observed contributes follow-up up to that contact and is then censored.

Censoring is not the same as observing that the event did not happen throughout the full study. It means the event status is unknown after follow-up ends. The method relies on assumptions about censoring and the way observation relates to event risk. The registry identifies the Kaplan-Meier method and the endpoint definition, but the amount and pattern of censoring and related diagnostic information are not reported in the registry record.

What does the risk difference represent?

In general, a risk difference compares event probabilities between groups by subtracting one probability from the other. It is expressed on an absolute probability scale, so it describes the size and direction of a difference rather than a relative multiplier. The posted comparison for 5-year overall survival is labeled a risk difference and gives 0.009, with a 95% confidence interval from -0.050 to 0.067. These comparison values are recalculated from posted summary statistics and are unadjusted.

That comparison should not be confused with a Kaplan-Meier model that uses the full event-time information. A time-specific survival probability is estimated from follow-up over time, whereas a simple unadjusted comparison based on arm-level summaries cannot represent every feature of the event-time data. The registry does not report a separate adjusted estimate or model output for this comparison.

How should the p-value be read?

In general, a p-value is calculated relative to a null hypothesis and a specified statistical procedure. It indicates how compatible the observed data are with that null under the procedure's assumptions; it does not give the probability that a treatment works, that the null is true, or that the observed estimate will recur. The unadjusted p-value of 0.77 belongs to the recalculated comparison. It is most informative when read with the effect estimate and confidence interval, rather than in isolation.

The registry record does not report a full statistical analysis plan, including whether a particular primary test was prespecified, what covariates might have been included, or how multiplicity was handled. Such details cannot be inferred from an unadjusted comparison. Nor does the absence of a reported analysis establish that no analysis was conducted; it means the analysis details are not reported in the registry record.

Why can variability matter?

General statistical explanation: observed outcomes vary among participants, and estimates based on a finite group have sampling uncertainty. Confidence intervals reflect uncertainty under the statistical method. For counts or rates, extra variability beyond a model's assumptions can make conventional intervals too narrow; this is commonly called over-dispersion. The primary outcome is a time-to-event estimate, and the registry does not report an over-dispersion analysis. This concept is relevant generally but should not be read as a finding about this trial.

For the quality-of-life outcome, the registry reports means and standard deviations at baseline and 12 months, as well as a recalculated unadjusted mean difference. Standard deviations describe variation among individual scores; they are not confidence intervals for the mean. The mean difference is 0.7, with a 95% confidence interval from -4.532 to 5.932 and an unadjusted p-value of 0.793. The registry does not report the scale's range or a detailed method for handling repeated measurements, missing scores, or baseline adjustment.

For progression-free survival, the registry reports 5-year percentages and confidence intervals, plus an unadjusted recalculated risk difference. The same general distinction applies: an arm-level time-to-event estimate is not the same as a complete adjusted model of time to progression or death. The registry does not report further analysis details for that endpoint.

The planning illustrations use the observed effect as a reference and state assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. The illustrated effect is a specified fraction of the observed effect. These are planning calculations and not the original trial's design assumptions, which are not reported in the registry record. They should not be confused with the uncertainty analysis of the completed trial or with observed power.

11. Confidence Intervals and Precision

A confidence interval gives a range of estimates that are reasonably compatible with the observed data under the statistical method and its assumptions. In repeated use of the same procedure under its assumptions, a 95% confidence interval has a long-run coverage interpretation. It is not a range that guarantees the true value lies inside it, nor is it a probability statement about the true value after these data have been observed.

For 5-year overall survival, the posted estimate is 71.0% in the standard chemoradiation group, with a 95% confidence interval from 66.0% to 75.0%. The estimate in the adjuvant chemotherapy group is 72.0%, with a 95% confidence interval from 67.0% to 76.0%. The intervals indicate uncertainty around both arm-level estimates. Their overlap is substantial, but overlap alone is not a formal comparison test.

The recalculated unadjusted risk difference is 0.009, and its 95% confidence interval runs from -0.050 to 0.067. Because the interval includes zero, it is compatible with no difference as well as with differences in either direction. The width of the interval is important: the point estimate alone does not convey the full range of differences that remain consistent with the data.

Precision is not the same as importance. A narrow interval can still center on an effect with little practical relevance, while a wider interval can leave substantial uncertainty about effects of different sizes. Judgments about clinical importance require a prespecified context or threshold, neither of which is reported in the registry record. The confidence intervals also depend on the methods used and the completeness of the outcome data; detailed information about censoring and missingness is not reported in the registry record.

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 illustrations give the number of participants per arm for 80% power and for 90% power. The outcomes represented in these illustrations are not time-to-event event-count calculations: the stated planning assumptions identify participant counts per arm for these outcomes. In general, 80% power means that a study designed under the stated assumptions would have an 80% chance of detecting the specified effect at the stated significance level if that effect were the true one; 90% power describes a higher chance under the same kind of assumptions.

The calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The illustrated fractions are 100%, 75%, and 50% of the observed effect. For example, the row for planning for 75% of the observed effect means that the target effect is smaller than the full observed effect. Smaller effects are harder to distinguish from random variation, so they require more participants under otherwise similar assumptions.

These are planning illustrations based on the observed effect, not the trial's own design assumptions. The original sample-size justification and other protocol assumptions are not reported in the registry record. The figures are not observed power: they do not describe the probability that the completed trial succeeded, and they cannot determine whether a result is true or important. They instead show how the required group size changes under the listed hypothetical design assumptions.

The calculations also do not substitute for a design tailored to the endpoint's analysis method, follow-up, censoring, expected event frequency, or missing data. The registry's assumptions specify the calculation framework, but do not provide all details needed to treat the illustrations as a full prospective design specification.

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

Worked calculation for this trial

1. Control proportion p₀ = 0.711; treatment proportion p₁ = 0.719; average p̄ = 0.715.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6385 = 1.2514.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6385 = 0.5373.
4. n = (1.2514 + 0.5373)² / (0.0087)² = 42,309.5, rounded up to 42,310 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 <- 0.710526315789474                          # control proportion
p1 <- 0.719222462203024                          # 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(1414608)
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 = 42,310 (80% power), 56,640 (90% power)
 75% of observed effect: n per arm = 75,390 (80% power), 100,925 (90% power)
 50% of observed effect: n per arm = 170,014 (80% power), 227,600 (90% power)
power.prop.test: 42309.5 
Simulated power at n = 42,310 per arm: 0.801 (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.

14. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when researchers examine several outcomes, time points, contrasts, or subgroups. In general, repeated testing can increase the chance that at least one result appears noteworthy by chance, even when no true effects exist. Statistical plans may address this by defining a primary endpoint, ordering secondary tests, adjusting thresholds, or treating additional analyses as exploratory.

The registry identifies overall survival at 5 years as the primary outcome and lists several secondary outcomes. However, multiplicity procedures, a formal outcome hierarchy, and any adjustment of secondary comparisons are not reported in the registry record. The posted unadjusted secondary comparisons therefore should not be read as if they were necessarily protected against multiple testing.

Missing data can also affect interpretation. For time-to-event outcomes, incomplete follow-up may result in censoring; for quality of life, missing questionnaire scores may reduce the number contributing to an analysis. The record gives endpoint-specific participant counts for some results, but a complete account of missingness, reasons for missing data, imputation, censoring patterns, and sensitivity analyses is not reported in the registry record. Differences in analyzed counts should not be assigned a cause without such information.

The primary outcome is described for eligible subjects, while arm-level results list their own denominators. A complete definition of analysis populations—such as intention-to-treat, per-protocol, or safety populations—is not reported in the registry record. The randomized design is clear, but the registry does not explain how participants who did not complete assigned treatment or who had incomplete follow-up were handled in each analysis.

These omissions limit assessment of whether the posted estimates are robust to missingness or analysis choices. They do not demonstrate that the analyses were inappropriate; they indicate that key details needed to assess those issues are not available in the registry record.

15. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: general disorders nos (29.6%).

The posted adverse-event figures list participants at risk and participants affected in each group. For serious events, the registry lists 98 affected among 453 at risk for standard chemoradiation, and 107 affected among 361 at risk for standard chemoradiation with adjuvant chemotherapy. It also lists 438 and 360 participants, respectively, as affected by other events, with the same group-specific at-risk counts.

These are counts, not adjusted comparisons. The at-risk denominators differ from the primary outcome denominators, and the registry record does not explain the reasons for those differences. The figures should not be interpreted as directly comparable rates without considering how the safety population and event collection were defined. The record does not report detailed event timing, exposure duration, statistical comparisons, or methods for handling repeated events.

The registry also lists deaths of 123 and 109 in the two groups. These counts are safety-record entries and should not be substituted for the Kaplan-Meier primary endpoint estimates, which use time-to-event methods and a defined follow-up time. The most frequently listed serious-event term is “General disorders NOS” at 29.6%; the record does not provide further detail about that term in the posted summary.

Serious adverse events and events of grade 3 or higher are distinct classifications in general. The registry lists a secondary outcome concerning grade 3 or higher adverse events in the first year, but the specific results for that outcome are not included in the posted quantitative secondary results.

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

The primary result describes estimated overall survival at 5 years from randomization in the two treatment groups. The posted estimates are 71.0% with standard chemoradiation and 72.0% with standard chemoradiation followed by adjuvant chemotherapy. The confidence intervals show uncertainty around each estimate, and the recalculated unadjusted difference has an interval that includes zero.

This does not prove that the treatment strategies are identical. The comparison interval remains compatible with differences in either direction, and the registry's posted recalculation does not replace a full analysis of the time-to-event data. At the same time, the point estimates alone do not demonstrate a meaningful advantage for either strategy. The result should be described with both its estimated size and its uncertainty.

The endpoint is an estimate for a population of eligible trial participants, not a prediction for a particular person. The registry record lists cervical cancer types and stages and identifies eligible subjects, but it does not provide enough detail in this summary to establish how well the findings apply to every patient group or setting. Individual circumstances and treatment decisions are outside the scope of these statistics.

The comparison evaluates a treatment strategy in which adjuvant chemotherapy followed chemoradiation. It does not isolate the independent effect of each drug, and it does not show what would happen under a different schedule or treatment sequence. Nor does overall survival alone summarize progression, quality of life, treatment burden, or adverse events. Those outcomes require their own results and interpretation.

Finally, the registry record does not report the original sample-size justification, detailed analysis plan, multiplicity procedures, or full missing-data account. Those absences limit how completely the analysis can be evaluated. They do not change the numerical estimates, but they constrain the strength and scope of conclusions drawn from the record.

17. Why This Trial Matters Statistically

This trial addresses a central design question in comparative clinical research: whether adding a further treatment phase after a shared initial regimen changes a patient-important time-to-event outcome. The randomized parallel-group structure provides a framework for comparing the assigned strategies, while the primary endpoint uses survival from randomization and includes death from any cause.

Statistically, the record is useful for distinguishing an estimate from its precision. The arm-level 5-year survival estimates are close, but the confidence intervals and the interval for the recalculated comparison show that the evidence is not a precise declaration of equality. A point estimate without its interval can overstate certainty; a p-value without the effect estimate can obscure the size and range of plausible differences.

The record also illustrates why different analyses should not be conflated. Kaplan-Meier estimates summarize time-to-event outcomes, while the simple unadjusted risk-difference calculation is based on posted summary information. Planning illustrations answer a separate hypothetical question about sample sizes under stated assumptions. None of these quantities is interchangeable with the others, and the planning figures do not reveal the probability that the completed study detected an effect.

Finally, the presence of secondary outcomes makes multiplicity and reporting completeness important. Secondary measures can broaden understanding, but their interpretation depends on prespecification, analysis methods, missingness, and how many comparisons were considered. The registry supplies some of these outcome definitions and numerical results, but not all details needed to evaluate the full analysis strategy. Reading the findings with these distinctions in mind keeps conclusions proportional to the posted evidence.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific limitations follow from the level of detail in the registry record. Although the study is identified as randomized and parallel, the randomization procedure, allocation concealment, stratification factors, and intended analysis population are not reported in the registry record. Masking is listed as none, but the record does not describe how lack of masking may have affected outcome assessment or treatment delivery.

The primary endpoint is a Kaplan-Meier estimate, yet detailed follow-up information, censoring patterns, and numbers at risk over time are not reported in the registry record. The summary therefore does not allow a full assessment of follow-up completeness or whether censoring assumptions are plausible. The posted arm denominators also differ from recorded enrollment, and the reasons are not reported in the registry record.

The registry lists several secondary outcomes, but only some have detailed numerical results in the posted outcomes. It does not report multiplicity procedures, a full statistical analysis plan, or detailed methods for missing data and repeated quality-of-life observations. Without those details, secondary findings are harder to classify as confirmatory or exploratory and their robustness is difficult to judge.

The sample-size illustrations use the observed effect and stated hypothetical assumptions; the original design justification is not reported in the registry record. These illustrations therefore do not establish the intended power of the trial or explain the enrollment target. Likewise, the primary comparison statistics are unadjusted recalculations from summary information, not a substitute for a full sponsor analysis of time-to-event data.

These limitations concern transparency and interpretation of the registry record. They do not imply that the study did not conduct additional analyses; those analyses and details are simply not reported in the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer — NCT01414608.
• Registry record last updated 2022-11-07; status last verified 2022-10.
• Results first posted 2022-11-07.
• 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

NCT01414608, the OUTBACK trial, is a completed randomized phase III parallel-group trial sponsored by the GOG Foundation. It compared standard chemoradiation with the same regimen followed by adjuvant carboplatin and paclitaxel in eligible subjects with locally advanced cervical cancer. The registry lists enrollment of 926 and no masking.

The primary outcome is overall survival at 5 years from randomization, estimated by Kaplan-Meier. The posted estimates are 71.0% for standard chemoradiation and 72.0% for standard chemoradiation with adjuvant chemotherapy. Their 95% confidence intervals are 66.0% to 75.0% and 67.0% to 76.0%. The recalculated unadjusted risk difference is 0.009, with a 95% confidence interval from -0.050 to 0.067 and an unadjusted p-value of 0.77.

Progression-free survival and global health status quality of life are among the posted secondary results. Important details about the original sample-size justification, full analysis plan, multiplicity, and missing-data handling are not reported in the registry record.