Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy (NCT00716976), a randomized phase 3 study. The primary outcome is Incidence of Hearing Loss.

2. Clinical Question

3. Trial Design

The registry record describes a randomized, phase III, parallel-group study with no masking. The trial was listed as completed. Enrollment was 131. The recorded study start was 2008-06-23, and primary completion was 2015-04-09. The sponsor was the Children's Oncology Group.

Participants were assigned to sodium thiosulfate treatment or observation while receiving cisplatin. The sodium thiosulfate arm received intravenous treatment over 15 minutes beginning 6 hours after completion of each cisplatin infusion. The stated dose was 16 g/m2, or 533 mg per kg when the therapeutic protocol administered cisplatin by weight because of young age or small body. The observation arm did not receive sodium thiosulfate. Examination was also listed as an intervention procedure.

The primary outcome was incidence of hearing loss, assessed 4 weeks after the last cisplatin dose. The endpoint definition compared hearing sensitivity at follow-up with baseline measurements using ASHA criteria. The primary endpoint population was narrower than the overall enrollment: 49 eligible participants in the sodium thiosulfate arm and 55 in the observation arm had complete audiometry data for evaluation. The registry record does not report the original trial design assumptions for enrollment or sample size, or give a full account of the allocation procedure beyond describing the study as randomized.

The registry lists additional outcomes covering hearing thresholds at key frequencies, event-free and overall survival, and hearing loss by TPMT and COMT mutation status. Detailed results are present for some frequency-specific outcomes, while quantitative estimates for the other listed outcomes are not reported in the registry record. The available record also does not describe masking, which is consistent with the listed design being unmasked, or give further operational detail about how the outcome assessments were conducted.

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: 55 eligible patients enrolled on the observation Arm had complete audiometry data for evaluation; 49 eligible patients enrolled on the STS arm had complete data audiometry for evaluation.

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 Incidence of Hearing Loss, measured over 4 weeks after last dose of cisplatin.

The primary endpoint is the incidence of hearing loss, expressed as the number of participants meeting the endpoint definition in each arm. Hearing loss was defined by comparing hearing sensitivity at follow-up with baseline measurements using ASHA criteria. The assessment time was 4 weeks after the last dose of cisplatin.

A binary endpoint reduces each participant's follow-up assessment to whether hearing loss was identified or not identified under the stated criteria. Comparing the proportions with the event addresses how often the defined outcome occurred in the evaluated groups. The registry reports 14 participants with hearing loss among 49 with complete audiometry in the sodium thiosulfate arm, and 31 among 55 in the observation arm. This endpoint is clinically relevant to the stated prevention question because it directly records the occurrence of hearing loss rather than a change in a single hearing-frequency measurement.

That simplification also means the endpoint does not show the full pattern of hearing sensitivity. Frequency-specific threshold changes are listed as secondary outcomes, and the registry reports some of those results separately. The primary endpoint is tied to the registry's criteria and follow-up time; it does not, on its own, characterize longer-term hearing status or explain changes across individual frequencies. The registry record does not report additional detail about the operational scoring of the ASHA criteria.

7. Results Posted in the Registry

• STS Arm (Sodium Thiosulfate Treatment): 28.6% (14/49) versus 56.4% (31/55) on control; risk difference -27.8 percentage points (95% CI -46.0 to -9.6), risk ratio 0.51 (0.31–0.84); unadjusted two-proportion z-test p = 0.004.

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.

Change in Hearing Thresholds For Key Frequencies at 500 hz

• 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:
  • STS Arm (Sodium Thiosulfate Treatment): mean -1.45 versus -1.11 on control; difference -0.34 (95% CI -3.45 to 2.77), standardized effect d = -0.05; z-test p = 0.831.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between STS Arm (Sodium Thiosulfate Treatment) and the control. The interval gives the range of effects that remain compatible with the data.

Change in Hearing Thresholds For Key Frequencies at 1000 hz

• 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:
  • STS Arm (Sodium Thiosulfate Treatment): mean -0.68 versus -0.32 on control; difference -0.36 (95% CI -3.32 to 2.61), standardized effect d = -0.05; z-test p = 0.813.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between STS Arm (Sodium Thiosulfate Treatment) and the control. The interval gives the range of effects that remain compatible with the data.

Change in Hearing Thresholds For Key Frequencies at 2000 hz

• 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:
  • STS Arm (Sodium Thiosulfate Treatment): mean -1.18 versus 0.64 on control; difference -1.82 (95% CI -5.76 to 2.13), standardized effect d = -0.18; z-test p = 0.366.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between STS Arm (Sodium Thiosulfate Treatment) and the control. The interval gives the range of effects that remain compatible with the data.

The detailed secondary hearing-threshold results cover changes at 500 hz, 1000 hz, and 2000 hz. Across these measures, the estimated mean differences are modest in magnitude relative to their uncertainty, and each reported confidence interval includes zero. The unadjusted results therefore do not establish a clear difference at any of these frequencies. They are also not evidence that the groups are identical; the intervals remain compatible with a range of possible differences.

These frequency-specific outcomes complement the primary endpoint but answer a different question. The primary outcome classifies whether hearing loss occurred under ASHA criteria, while the secondary measures describe average threshold change at selected frequencies. A difference in the binary incidence need not translate into the same pattern at each separate frequency. Likewise, the frequency-specific summaries do not replace the primary endpoint or provide a direct explanation for its result.

The registry lists eight secondary outcomes, including additional hearing frequencies, event-free survival, overall survival, and hearing loss by TPMT and COMT mutation status. Quantitative estimates for the remaining listed outcomes are not reported in the registry record. Consequently, the overall secondary-outcome pattern cannot be fully assessed from the available results.

Multiplicity matters because examining many outcomes increases the chance that at least one unadjusted result may appear unusual by chance. In general, unadjusted p-values do not control the overall false-positive rate across a family of comparisons. The registry record does not report a multiplicity plan or adjustment. Secondary results should therefore be interpreted as exploratory or supportive evidence rather than treated as independent confirmatory tests. Their value is in helping characterize the primary finding and identify patterns for further study, while recognizing that the statistical evidence is less secure when many comparisons are considered without reported adjustment.

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

• Change in Hearing Thresholds For Key Frequencies at 500 hz
• Change in Hearing Thresholds For Key Frequencies at 1000 hz
• Change in Hearing Thresholds For Key Frequencies at 2000 hz
• Change in Hearing Thresholds For Key Frequencies at 4000 hz
• Change in Hearing Thresholds For Key Frequencies at 8000 hz
• Event-Free Survival (EFS)
• Overall Survival (OS)
• Hearing Loss Among Patients Carrying/Not-carrying Two Key Gene Mutations (TPMT and COMT)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each evaluated participant either met the hearing-loss definition or did not. The posted counts give the number of events and the number evaluated in each arm. The risk difference compares the event proportions by subtracting the observation-group proportion from the sodium thiosulfate-group proportion. With that orientation, a negative value indicates a lower observed proportion in the sodium thiosulfate arm. The reported risk difference is -0.278.

What do the effect measures describe?

The risk difference expresses the contrast on an absolute scale, using the difference between the two event proportions. Its confidence interval gives a range of values compatible with the observed data under the assumptions of the calculation. The reported interval is -0.460 to -0.096. Because this interval does not include zero, it is compatible with a nonzero difference in the direction of fewer observed events in the sodium thiosulfate arm.

The risk ratio compares the two event proportions as a ratio, while the odds ratio compares the odds of the event. The reported risk ratio is 0.507, with a 95% confidence interval from 0.307 to 0.836. The reported odds ratio is 0.310, with a 95% confidence interval from 0.137 to 0.701. Both are relative measures; their values and interpretation differ from the absolute risk difference. In particular, an odds ratio is not interchangeable with a risk ratio.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.004. In general, a p-value describes how unusual data at least as incompatible with a specified null model would be if that model were true and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or practical importance of an effect. The primary p-value is unadjusted, and the registry record does not report a multiplicity adjustment or a sponsor analysis for this outcome. The p-value is therefore best read alongside the effect estimate, its interval, and the analysis population.

The risk difference, risk ratio, odds ratio, confidence intervals, and p-value are unadjusted recalculations from the posted event counts. The registry record does not report an adjusted primary analysis. The randomized design is relevant to interpretation, but the numerical calculations do not add covariate adjustment or address missing outcome data.

What does randomization contribute?

In general, random assignment is intended to make comparison groups similar, on average, with respect to factors measured and unmeasured at the time of assignment. This supports causal interpretation when the trial is conducted and analyzed appropriately. Randomization does not guarantee that every characteristic is balanced in a finite sample, nor does it resolve differences created by missing outcomes or exclusions after assignment. The registry identifies the study as randomized but does not report enough allocation or analysis detail to evaluate these issues fully.

The study was unmasked. In general, lack of masking can affect behavior, co-interventions, and outcome assessment, depending on the trial and how outcomes are measured. Hearing assessment is based on audiometry and specified criteria, but the registry record does not report whether assessors were masked or how measurement procedures were standardized. This is a potential interpretive consideration, not evidence that the recorded outcome was biased.

Why do the threshold outcomes use different methods?

Frequency-specific hearing-threshold changes are continuous outcomes reported as means in decibels with standard deviations. A mean difference compares the average change between arms. In general, a confidence interval for a mean difference indicates a range of values compatible with the data and model used for that comparison. For the detailed frequency outcomes, each reported interval includes zero; the unadjusted p-values are 0.831, 0.813, and 0.366 for 500 hz, 1000 hz, and 2000 hz, respectively. Those comparisons are distinct from the primary binary endpoint and should not be treated as repeated measurements of the same estimand.

Continuous outcomes can be affected by skewness, outliers, and unequal variability. General statistical practice considers whether a mean and its model appropriately represent the data. The registry reports means and standard deviations, but does not report distributional diagnostics or an adjusted analysis for these threshold outcomes. No claim about the shape of the underlying data follows from the summary statistics alone.

For counts and proportions, precision depends on the number of participants and the number of events, not just on the total enrollment. The primary analysis includes complete audiometry from 49 and 55 participants. The registry record does not explain the full flow from enrollment to the analyzed endpoint population. That limits assessment of whether missingness could have influenced the estimates.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.278, and its 95% confidence interval extends from -0.460 to -0.096. This interval conveys uncertainty around the estimated difference: values throughout the interval are compatible with the observed data under the calculation's assumptions. It excludes zero and is entirely in the negative direction for the stated contrast, but it remains a range rather than a precise single value.

Relative effect estimates also have uncertainty. The risk ratio is 0.507 with a 95% confidence interval from 0.307 to 0.836, and the odds ratio is 0.310 with a 95% confidence interval from 0.137 to 0.701. The intervals describe these relative measures, not absolute differences. Because all three measures use the same event counts, they represent different scales for the same comparison rather than separate replications.

In general, confidence intervals reflect sampling uncertainty under the model and calculation used. They do not account automatically for every possible source of bias, including missing outcomes or outcome measurement differences. The primary endpoint analysis comprises eligible participants with complete audiometry, and the registry record does not report enough information to evaluate the missing-data process. Thus, the interval's statistical precision should not be confused with certainty about how the result generalizes beyond the evaluated participants.

The continuous secondary outcomes have wider intervals relative to their point estimates, and each reported mean-difference interval crosses zero. Their available sample sizes vary by frequency. This pattern indicates that those data are compatible with a range of differences in either direction; it does not prove equality between the groups. The primary binary result is more directionally resolved by its interval, although it remains subject to the limitations of its analysis population and unadjusted calculation.

12. Planning a Similar Trial: Sample Size

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

The planning figures are participants per arm for the binary primary outcome, not total events. They illustrate hypothetical planning if the effect to detect were 100%, 75%, or 50% of the observed effect. For example, the values are given separately for 80% power and 90% power at each effect fraction. The 80% column describes the number of participants per arm estimated to give an 80% chance of detecting the specified effect under the planning assumptions, if that effect were the true one; the 90% column uses a higher target chance under the same type of assumptions.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. The original trial's own sample-size assumptions and justification are not reported in the registry record. These planning illustrations are not observed power.

Smaller target effects require more participants because they are harder to distinguish from random variation. Thus, planning for 75% or 50% of the observed effect produces larger participant requirements than planning for the full observed effect. The calculated figures are not a retrospective judgment about the trial's success or a forecast of what would happen under different trial conditions. They depend on the stated assumptions, including equal allocation and the chosen effect size, and are best read as conditional planning examples.

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 = 0.564; treatment proportion p₁ = 0.286; average p̄ = 0.425.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6990 = 1.3701.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6708 = 0.5646.
4. n = (1.3701 + 0.5646)² / (-0.2779)² = 48.5, rounded up to 49 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 <- 0.563636363636364                          # control proportion
p1 <- 0.285714285714286                          # 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(716976)
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 = 49 (80% power), 65 (90% power)
 75% of observed effect: n per arm = 89 (80% power), 119 (90% power)
 50% of observed effect: n per arm = 203 (80% power), 270 (90% power)
power.prop.test: 48.5 
Simulated power at n = 49 per arm: 0.816 (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

The registry record lists one primary endpoint and multiple secondary outcomes. It does not report a statistical plan describing how the primary and secondary tests were ordered, whether any outcomes were designated as confirmatory, or how multiplicity was to be handled. The reported p-values for the primary comparison and detailed secondary comparisons are unadjusted. In general, when many outcomes are tested, interpreting each p-value as if it were the only test can overstate the strength of evidence. Without a reported adjustment or prespecified hierarchy, the secondary findings should be treated cautiously.

The primary endpoint analysis included 49 eligible participants with complete audiometry in the sodium thiosulfate arm and 55 in the observation arm. Overall enrollment was 131. The registry record does not explain why some enrolled participants are not represented in the primary endpoint population, provide a complete participant flow, or report imputation or other missing-data methods. The available data therefore do not establish whether the analyzed participants differ from those without complete audiometry.

In general, missing outcomes can affect a comparison if the probability of having an observed outcome is related to assignment or to the outcome itself. Complete-case results describe participants with complete measurements; their interpretation as a comparison of all randomized participants relies on assumptions that cannot be checked from these summaries alone. The registry record does not report sensitivity analyses for missing audiometry or a detailed analysis population definition beyond eligibility and complete data.

The registry identifies the trial as randomized, but does not report an intention-to-treat analysis or explain whether the primary comparison followed assigned treatment for all randomized participants. It also does not give a detailed statistical analysis plan or report analyses for all listed outcomes. These omissions do not negate the posted results, but they limit assessment of prespecification, missing-data impact, and how the reported comparisons relate to the trial's original analysis strategy.

15. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (20.3%), neutrophil count decreased (16.9%), platelet count decreased (13.6%), white blood cell decreased (13.6%), anemia (11.9%).

The serious adverse-event figures report 59 participants at risk and 21 affected in the sodium thiosulfate arm. For observation, the registry lists 0 at risk and 0 affected for serious adverse events. These are registry-recorded counts; the zero at-risk figure should not be interpreted as proof that serious events were impossible or that all safety information was captured in the same way across arms. Death counts are not reported in the registry record.

The listed serious adverse-event terms include febrile neutropenia at 20.3%, neutrophil count decreased at 16.9%, platelet count decreased and white blood cell decreased at 13.6% each, anemia at 11.9%, and oral mucositis at 8.5%. The registry also reports other adverse events for 51 of 59 at risk in the sodium thiosulfate arm and 57 of 64 at risk in observation.

These summaries describe events recorded in the trial; they do not establish that an intervention caused an event. The registry record does not provide enough detail about event definitions, severity grading, exposure duration, or the basis of the percentages to support more specific comparisons.

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

The primary endpoint data show a lower observed proportion of participants meeting the hearing-loss definition in the sodium thiosulfate arm than in the observation arm among those with complete audiometry. The unadjusted absolute and relative comparisons point in the same direction, and the primary risk-difference interval excludes zero. This is a description of the posted results, not a medical recommendation or a conclusion about every patient or setting.

The result is bounded by the study population and measurement conditions. Participants were young patients receiving cisplatin for the specified newly diagnosed cancers or other malignancy, and the endpoint was assessed 4 weeks after the final cisplatin dose using a comparison with baseline under ASHA criteria. The primary analysis did not include all 131 enrolled participants; it used eligible participants with complete audiometry. The registry record does not report enough information to determine how missing measurements may affect the comparison.

The result does not establish what happens beyond the stated follow-up, whether effects differ by cancer diagnosis or other patient characteristics, or whether the same pattern applies to every listed secondary endpoint. Quantitative results for several listed secondary outcomes are not reported in the registry record. The frequency-specific outcomes that are reported have uncertainty compatible with differences in either direction.

Nor does the primary comparison alone explain the biological process underlying the observed outcomes, address every possible benefit or harm, or establish that the estimates are free of bias. The study was randomized but unmasked, and the registry record does not report a complete analysis plan, allocation details, or missing-data sensitivity analyses. The statistics should therefore be read as estimates from a randomized trial with important details unavailable in the record, not as a complete account of all evidence relevant to clinical decisions.

17. Why This Trial Matters Statistically

This trial illustrates how the choice of endpoint shapes a clinical comparison. Its primary outcome reduces hearing assessment to an event classification based on follow-up relative to baseline, while secondary outcomes describe average changes at specific frequencies. Those measures answer related but nonidentical questions. Keeping the distinction clear prevents a binary incidence result from being treated as a complete summary of hearing changes.

It also shows why counts, effect estimates, and intervals belong together. The event counts are readily interpretable, the risk difference describes an absolute contrast, and the relative measures express the comparison on ratio scales. Confidence intervals reveal that an estimate is uncertain even when its direction is consistent across measures. A p-value alone would not convey the size or precision of the result.

The analyzed population is another key statistical detail. Enrollment was 131, but the primary outcome uses complete audiometry from 49 participants in the sodium thiosulfate arm and 55 in observation. Transparent reporting of the path from assignment to endpoint analysis is essential for evaluating whether the comparison represents the randomized groups. The registry record does not provide that full account.

Finally, the registry lists numerous secondary outcomes but does not report a multiplicity strategy, and quantitative results are not available for every listed outcome. This highlights the need to distinguish a primary analysis from supporting or exploratory comparisons. The trial is statistically informative because it presents a randomized comparison with a defined hearing outcome, while its interpretation also demonstrates the importance of complete analysis plans, missing-data reporting, and appropriately cautious treatment of multiple outcomes.

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.

Several limitations arise from the information recorded for this trial. The primary endpoint was available for eligible participants with complete audiometry, rather than all enrolled participants. The record does not describe why other enrolled participants were not included, whether missingness differed by group, or how missing outcomes were handled. This leaves uncertainty about the effect of complete-case analysis on the comparison.

The study was not masked. Hearing loss was assessed using audiometry and ASHA criteria, but the registry record does not say whether outcome assessors were masked to assignment or give further details on assessment procedures. Lack of masking does not by itself establish biased measurement, but it is relevant when interpreting an outcome that depends on follow-up assessment.

The posted primary comparison is unadjusted, and the registry record lists no reported analyses. It does not provide a full statistical analysis plan, the original sample-size justification, or a multiplicity strategy. Thus, it is not possible to determine from the record whether the displayed comparisons correspond to all prespecified analyses or how secondary tests were intended to be interpreted.

Follow-up for the primary endpoint was 4 weeks after the last cisplatin dose. The record does not report a longer-term hearing outcome for this endpoint. Although several secondary outcomes are listed, quantitative results for all of them are not reported in the registry record. The available results therefore do not establish whether the observed primary pattern extends to other hearing measures, survival outcomes, or mutation-status groups.

Finally, the primary endpoint population and the overall enrollment are not interchangeable. The posted counts and recalculated estimates apply to the evaluated participants, and any broader interpretation depends on assumptions that the registry record does not allow readers to check.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Sodium Thiosulfate in Preventing Hearing Loss in Young Patients Receiving Cisplatin for Newly Diagnosed Germ Cell Tumor, Hepatoblastoma, Medulloblastoma, Neuroblastoma, Osteosarcoma, or Other Malignancy — NCT00716976.
• Registry record last updated 2023-11-09; status last verified 2021-07.
• Results first posted 2014-02-26.
• 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

NCT00716976 is a completed randomized phase III parallel-group study with no masking, sponsored by the Children's Oncology Group. Enrollment was 131. It compared sodium thiosulfate treatment with observation in young patients receiving cisplatin for newly diagnosed cancers including germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or another malignancy.

The primary outcome was incidence of hearing loss 4 weeks after the last cisplatin dose, defined by change in hearing sensitivity from baseline using ASHA criteria. Complete audiometry was available for 49 eligible participants in the sodium thiosulfate arm and 55 in observation. The posted counts were 14 and 31 participants with hearing loss, respectively. The unadjusted recalculated risk difference was -0.278, with a 95% confidence interval from -0.460 to -0.096 and an unadjusted p-value of 0.004.

The registry also lists frequency-specific hearing thresholds, event-free and overall survival, and mutation-status outcomes. Detailed quantitative results are available for some frequency outcomes, while results for other listed secondary outcomes are not reported in the registry record. Important details about missing data, multiplicity, and the original statistical plan are also not reported in the registry record.