Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through Vitamin D Pathway: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through Vitamin D Pathway (NCT01499940), a na phase 2 study. The primary outcome is Number of Participants With Peripheral Neurotoxic Reactions.

2. Clinical Question

The clinical rationale in the registry record is that oxaliplatin can cause peripheral neuropathy, with symptoms affecting the hands and feet. The study description proposes that Vitamin D might have a protective role in the nervous system and tests that idea by giving Vitamin D3 while participants receive oxaliplatin.

The question is about prevention during treatment, not about comparing two assigned treatment strategies. Because there is no control group, the design cannot directly estimate how often peripheral neurotoxic reactions would have occurred over the same period without Vitamin D3. The record also says that study participation would not affect how the participant’s cancer was treated.

The registry lists a primary endpoint concerning the number of participants with peripheral neurotoxic reactions, but does not report a result for that endpoint. The posted safety figures are a separate record of adverse events and should not be substituted for the primary endpoint result.

3. Trial Design

This was a phase II, single-group study of Vitamin D3 during oxaliplatin treatment. The registry lists enrollment of 9, allocation as NA, and masking as none. The study status is terminated. Its recorded start was 2012-01, and primary completion was 2012-12.

The intervention was Vitamin D3 2000 IU/day. The arm description says dosing began on the day of the first oxaliplatin cycle and continued as long as the participant was treated with oxaliplatin and remained on study. The registry describes the study as intended to examine whether Vitamin D could help prevent peripheral neuropathy during oxaliplatin treatment. It also says participation would not affect cancer treatment.

There was no randomized or concurrent control arm. Accordingly, this design can describe observations among participants receiving the intervention, but it cannot provide a like-for-like comparison with participants not receiving Vitamin D3. Changes over time, background risk, and other factors cannot be separated from any intervention effect by a single-group comparison alone.

The primary endpoint is listed as the number of participants with peripheral neurotoxic reactions, measured using NCI CTCAE Version 4.0, over up to 12 months. The registry record does not report the primary endpoint result, the number of participants assessed for it, or details of the assessment schedule.

The record does not report a statistical analysis plan, sample-size justification, interim-analysis plan, or analysis population. It lists no analyses. The study status and enrollment information describe the registry record, but do not by themselves establish why the study ended or whether the planned enrollment was achieved.

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:

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 Number of Participants With Peripheral Neurotoxic Reactions, measured over Up to 12 months.

The primary endpoint is the number of participants with peripheral neurotoxic reactions. It is a participant-level count outcome: the focus is whether a participant met the endpoint, rather than the number of separate symptom episodes. The registry specifies NCI CTCAE Version 4.0 and a timeframe of up to 12 months.

Peripheral neurotoxicity is relevant to this study because the registry describes it as a possible consequence of oxaliplatin treatment, with symptoms affecting the hands and feet. Counting participants with a reaction offers a direct way to describe how many participants experienced the outcome under the study’s intervention and follow-up conditions. It does not, by itself, measure symptom duration, severity over time, impact on daily functioning, or changes in oxaliplatin dosing.

General statistical context: a count of participants with an event is often reported alongside the number assessed, so readers can understand the observed frequency in the study population. For a single-group study, such a result would describe participants receiving the intervention; it would not establish what would have occurred to comparable participants without it.

The registry record names the endpoint and its assessment framework, but does not report the primary endpoint result or its analysis. The adverse-event figures recorded elsewhere are not identified as the primary endpoint result and cannot fill that gap.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a participant-count endpoint, but does not report an analysis for it. Statistical methods can therefore be discussed only in general terms; there is no reported model, estimate, confidence interval, hypothesis test, or adjustment to interpret for the primary endpoint.

What does a participant-count endpoint represent?

The endpoint concerns whether participants experienced a peripheral neurotoxic reaction during follow-up. A count of participants with an event is distinct from a count of all event episodes: one participant may have more than one symptom or episode, but the endpoint title refers to participants. The registry does not give a separate count of episodes, nor does it report severity-specific primary outcome results.

General statistical context: an event count is most interpretable when accompanied by the number of participants assessed and a clear definition of how an event was determined. The registry names NCI CTCAE Version 4.0 and gives a timeframe of up to 12 months, but the primary result and its analysis population are not reported. Readers therefore cannot determine from this record how many participants had adequate endpoint follow-up or how missing assessments were handled.

What can a single-group design estimate?

In a single-group study, the observed event count describes what happened among participants who received the intervention and were observed. It does not directly estimate a contrast against a group receiving no Vitamin D3 or another intervention. The registry lists no control group and flags that the arms are not a like-for-like comparison. The design consequently does not support a randomized comparative treatment-effect estimate.

General statistical context: a comparison group helps account for the fact that outcomes may occur without the study intervention. Without one, the observed outcome can reflect the intervention, the underlying course of illness, concomitant treatment, participant characteristics, or other influences. Statistical adjustment cannot reliably replace a missing concurrent comparator when the relevant factors and their relationships are not documented.

How should uncertainty be understood?

No primary endpoint estimate or confidence interval is reported. Thus, readers cannot assess the precision of the endpoint result from the registry record. General statistical context: a confidence interval conveys uncertainty around an estimate under assumptions of a statistical method. It is not a guarantee that the true value lies in the interval, and it cannot resolve design limitations such as the lack of a control group.

The enrollment figure alone does not provide an estimate of precision. That assessment also requires the observed endpoint data, the number evaluated, and a suitable analysis. The registry does not report those primary endpoint details. The sample-size assumptions recorded for planning illustrations are not a trial-specific design justification, and no calculated planning results are described in this discussion. Such illustrations, when available, concern hypothetical planning rather than observed power or evidence about the trial outcome.

What is known about the analysis plan?

The record lists no analyses and does not report a statistical analysis plan. It does not specify whether the endpoint was intended to be summarized descriptively or evaluated using a formal hypothesis test. It also does not report model assumptions, handling of follow-up time, covariate adjustment, or a prespecified decision threshold. These details cannot be inferred from the endpoint name or the phase label.

General statistical context: for a binary participant outcome, a simple descriptive analysis may report the number with an event and the number assessed. A model-based analysis may incorporate additional assumptions. Over-dispersion is a concern when variability exceeds what a chosen count model expects; it can make standard errors too small if ignored. That general issue does not imply that an over-dispersed model applies to this endpoint. The registry does not report a model or enough results to assess model fit or dispersion.

Why separate endpoint and safety data?

The serious and other adverse-event fields are safety summaries. They should not be interpreted as the primary endpoint because the registry labels the endpoint specifically as participants with peripheral neurotoxic reactions. The record does not say that its adverse-event categories are identical to the endpoint definition or that their observation windows and assessment procedures match.

Overall, the registry gives the intervention, endpoint name, endpoint timeframe, and selected design information, but not the statistical results needed for quantitative inference. General methods can explain what such results would mean, but cannot supply the missing outcome estimate or analysis.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Vitamin D3 2000 IU/Day")
n      <- c(9)
events <- c(5)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Vitamin D3 2000 IU/Day  9  5  55.6  21.2  86.3  26.7  81.1  26.2  81.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, so it does not describe how many primary or secondary hypotheses were planned, whether any multiplicity adjustment was intended, or how the primary endpoint was distinguished from other analyses. The record lists one outcome measure and no analyses, but those registry fields do not establish the full prespecified analysis strategy.

Multiplicity refers generally to the increased chance of a false-positive finding when multiple hypotheses are tested. Whether it is a concern depends on the analyses and decision rules actually used. Since the record reports no analysis results or testing plan, there is no basis to assess whether multiplicity adjustment was needed or applied.

The record also does not report how missing endpoint data were handled, the number assessed for the primary outcome, or whether participants with incomplete follow-up were included in an analysis. It gives a primary endpoint timeframe of up to 12 months, but does not describe participant-level follow-up or missingness. General statistical context: missing data can affect an estimate when the probability of missing an outcome is related to the outcome or participant characteristics. The direction and size of any such effect depend on the missingness pattern and assumptions made in the analysis.

No analysis population is described. The registry does not state whether analyses were intended to include all enrolled participants, only those who started the intervention, or another defined group. These distinctions cannot be settled from the enrollment figure or the safety fields. The posted record therefore does not permit an assessment of the primary outcome’s completeness, analysis population, or multiplicity handling.

12. 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.

The registry lists the Vitamin D3 2000 IU/Day group with 9 at risk for serious adverse events and 0 participants affected. It also lists 9 at risk for other adverse events and 0 participants affected. These entries describe the safety figures recorded for this study group.

These safety counts are separate from the primary endpoint, which is the number of participants with peripheral neurotoxic reactions. The registry does not state that the safety categories correspond exactly to the primary endpoint definition. A zero in the safety fields should therefore not be read as a primary endpoint result or as proof that no peripheral neurotoxic reactions occurred.

The serious-event term list contains no listed terms. That means the registry record does not provide term-level detail for serious adverse events. The record also does not give further information about event timing, duration, severity, attribution, or completeness of safety follow-up. Zero recorded affected participants is a description of these posted fields; it does not establish that the intervention is free of risk or characterize safety beyond this study record.

General statistical context: adverse-event counts depend on how events are defined, collected, and reported, as well as on the participants observed. A count without additional detail is limited evidence about the range or likelihood of harms.

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

The registry record describes an investigation of Vitamin D3 given during oxaliplatin treatment, with prevention of peripheral neurotoxic reactions as the primary question. It establishes that the study was phase II, single group, and recorded as terminated, with enrollment of 9. It also identifies the endpoint framework and timeframe.

The primary outcome result is not reported. The registry therefore does not show how many participants experienced peripheral neurotoxic reactions, nor does it provide an estimate of uncertainty around that outcome. The recorded safety figures—0 participants affected by serious adverse events and 0 by other adverse events in the listed group—are not a substitute for the missing primary endpoint result.

The study design also limits what any observed outcome could establish. With no control group, an event count among participants receiving Vitamin D3 would not show what would have happened to comparable participants without it. A single-group observation cannot separate an intervention effect from other possible explanations for the observed outcomes.

These limitations do not make the registry information meaningless. The record documents the intervention strategy, clinical question, endpoint, and selected safety information. Those details can help readers understand what the study set out to examine. But the record does not provide enough outcome and analysis information to determine whether the primary endpoint was met or to quantify any treatment effect.

General statistical context: a study’s purpose, design, outcome definition, and analysis results each answer different questions. An endpoint specifies what is measured; a design determines what comparisons are supported; and an estimate with uncertainty describes observed data under an analysis. Here, the design is described, but the primary endpoint estimate and its analysis are not reported. No conclusion about prevention can be drawn from the available primary outcome information.

14. Why This Trial Matters Statistically

This study illustrates why the endpoint result and the design must be considered together. The registry specifies a clinically focused participant outcome—peripheral neurotoxic reactions during oxaliplatin treatment—and identifies NCI CTCAE Version 4.0 as its assessment framework. But the primary result is not reported, so the intended outcome cannot be evaluated quantitatively from the record.

The single-group design is also central. Even if a primary event count were available, it would describe outcomes among participants receiving Vitamin D3 rather than establish a comparative effect. A control group is important when the goal is to distinguish outcomes associated with an intervention from outcomes that might occur without it. The registry explicitly identifies the study as single group and does not describe a like-for-like comparator.

The record is useful for teaching the distinction between safety reporting and efficacy-related endpoints. The adverse-event fields report zero affected participants in the listed categories, while the named primary endpoint concerns peripheral neurotoxic reactions. These data fields answer different questions and should not be merged or treated as interchangeable.

It also demonstrates the importance of reporting analysis details. The registry does not report the primary outcome estimate, uncertainty, analysis population, missing-data handling, or statistical analysis plan. Without these, readers cannot assess precision, completeness, or whether the analysis followed a prespecified approach.

General statistical context: transparent reporting allows readers to separate what was planned, what was observed, and what can be inferred. For this record, the study objective and design are documented more clearly than the primary outcome findings. That distinction is important when interpreting registry evidence, especially when a study lacks a concurrent comparison group.

15. 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 primary limitation for interpretation is that the registry record does not report the primary endpoint result. It names the outcome as the number of participants with peripheral neurotoxic reactions and specifies a timeframe of up to 12 months, but provides no endpoint count, denominator assessed, or estimate of uncertainty. The posted safety figures do not resolve this absence.

The single-group design provides no control comparison. As a result, the study cannot separate outcomes observed during Vitamin D3 use from outcomes that might have occurred during oxaliplatin treatment without Vitamin D3. Allocation is listed as NA and masking as none; no additional comparator or blinding information is reported.

The record does not explain why the study was terminated. It also does not report whether termination changed follow-up, affected endpoint ascertainment, or resulted in incomplete data. Enrollment is reported, but the number assessed for the primary outcome and the handling of missing observations are not reported in the registry record.

Further design and analysis details are absent, including a statistical analysis plan, sample-size justification, analysis population, and any reported analyses. The endpoint description identifies NCI CTCAE Version 4.0 but does not provide more detail about the assessment process or the endpoint-specific data.

Finally, the safety entries provide limited context: the record lists zero affected participants in the serious and other adverse-event categories, but does not provide term-level serious-event details or broader information on event timing, attribution, and follow-up. These limitations restrict both interpretation of the primary question and evaluation of safety from the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess Prevention of Oxaliplatin-induced Neurotoxicity Through Vitamin D Pathway — NCT01499940.
• Registry record last updated 2021-11-10; status last verified 2021-11.
• Results first posted 2021-09-05.
• 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.

19. Record Summary

The registry describes NCT01499940, a phase II study of Vitamin D3 during oxaliplatin treatment, with enrollment of 9 and single-group design. The listed regimen was Vitamin D3 2000 IU/day, starting on the day of the first oxaliplatin cycle and continuing while participants received oxaliplatin and remained on study. The record lists no masking, status as terminated, start in 2012-01, and primary completion in 2012-12.

The primary endpoint was the number of participants with peripheral neurotoxic reactions, assessed using NCI CTCAE Version 4.0 over up to 12 months. The primary endpoint result and its analysis are not reported in the registry record. The safety fields list 0 participants affected by serious adverse events and 0 affected by other adverse events in the Vitamin D3 2000 IU/Day group.

With no control group and no reported primary endpoint estimate, the registry record does not support a comparative conclusion about prevention. It also does not report a statistical analysis plan, missing-data approach, or reason for termination.