Effect of Ondansetron for Withdrawal Symptoms: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Ondansetron for Withdrawal Symptoms (NCT00695864), a non-randomized na study. The primary outcome is Change in Withdrawal Symptoms With Placebo and With Ondansetron.

2. Clinical Question

The registry record frames the study around subjective opioid withdrawal symptoms during medication weaning. It describes a within-participant sequence involving placebo and ondansetron, but does not give the sequence, dosing details, washout arrangements, or the method used to assign participants or withdrawal episodes to treatment. Those details are important for understanding how the two post-dose measurements relate to one another and how any observed change should be interpreted.

The outcome is based on participants’ ratings of 15 symptoms. A score combines the reported symptom ratings into a total, with higher scores indicating more symptoms and/or greater severity. The central question is therefore about change in a participant-reported symptom score, not a clinician-rated diagnosis or a longer-term outcome. The registry record does not report numerical outcome estimates, uncertainty intervals, or statistical test results, so the direction, size, and precision of any observed change cannot be assessed from the posted results.

3. Trial Design

The study is listed as completed, with Stanford University as sponsor. Its recorded start was 2008-05 and primary completion was 2009-07. The condition is Substance Withdrawal Syndrome, and the registry lists the phase as NA. The listed enrollment is 31. These design and administrative details describe the registered study; they do not by themselves establish how many participants contributed to the primary analysis.

The registry records allocation as non-randomized, masking as double, and the model as single group. The intervention name is “Ondansetron and Placebo crossover,” and the arm descriptions list placebo and ondansetron. The primary outcome timeframe specifies baseline, 1 hour post dose placebo, and 1 hour post dose ondansetron. Together these entries indicate that both treatment conditions and a crossover label are part of the record, but the registry does not report the sequence or operational details needed to reconstruct the crossover procedure.

Non-randomized allocation matters when comparing treatment conditions. If treatment order or condition is related to participant characteristics, withdrawal episode, time, or other factors, a difference between measurements could reflect those factors as well as treatment. The registry itself cautions that the arms are not a like-for-like control comparison. Double masking is recorded, but the record does not specify who was masked or how masking was maintained. The rationale for enrollment, sample-size justification, and detailed analysis plan are not reported in the registry record.

The outcome population differs from the enrollment figure: the primary outcome description reports 9 participants and 13 independent trials, and notes that 3 participants contributed more than 1 distinct withdrawal episode. It also says that 5 of the 14 participants assigned to intervention were withdrawn from the study and/or analysis. The registry does not explain the relationship among those counts, the enrolled participants, and the analyzed observations. Accordingly, the repeated episodes should not be assumed to be independent participant-level observations.

4. Participant Flow and Accounting

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

Before assignment: Of 31 patients enrolled, 17 did not experience withdrawal symptoms and were therefore not assigned an intervention.

Placebo

Reasons for not completing this period:

Ondansetron

Analysis population for the primary outcome, as defined in the registry: 9 participants and 13 independent trials (3 patients had more than 1 distinct withdrawal episode) were analyzed. Of the 14 participants assigned to intervention, 5 were withdrawn from the study and/or analysis.

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 Change in Withdrawal Symptoms With Placebo and With Ondansetron, measured over Baseline, 1 hour post dose Placebo, 1 hour post dose Ondansetron.

The primary outcome is “Change in Withdrawal Symptoms With Placebo and With Ondansetron.” It is described as a continuous measure, reported as a mean with standard error, and its unit is percent change. Measurements are identified at baseline, 1 hour after placebo, and 1 hour after ondansetron. The registry does not report the actual mean changes, standard errors, or a comparison estimate.

The outcome is the Subjective Opioid Withdrawal Scale. Participants rated 15 withdrawal symptoms from 0 to 4. Their symptom ratings were summed into a score for each participant, with a minimum of 0 and a maximum of 60. Higher scores indicate more symptoms and/or symptoms experienced at greater severity. A change score is intended to describe whether the reported symptom burden differs from baseline or between the post-dose conditions.

As a participant-reported measure, the scale captures subjective symptom experience, which is relevant to the question posed by this study. Its interpretation depends on complete and comparable ratings at the specified time points. The registry does not state how percent change was calculated, how missing symptom items were handled, or whether the primary contrast was between each post-dose measurement and baseline or between the two post-dose conditions. Those details are not reported in the registry record, so the precise estimand—the treatment effect the analysis was intended to estimate—cannot be reconstructed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary measure summarized as a mean with standard error. General statistical context helps explain what those summaries would mean, but the registry does not report the numerical summaries or identify the analysis used to produce them.

What does a mean describe?

General: a mean is an average across the observations included in an analysis. For this outcome, the underlying score combines participant ratings across 15 symptoms, each rated from 0 to 4, into a total from 0 to 60. The registry says higher scores indicate more symptoms and/or greater severity. A mean change can describe the average change in the analyzed group, but it does not show whether every participant changed in the same direction. Individual responses can vary around a group average.

The outcome unit is percent change, but the registry does not specify the formula used to calculate it. In general, percentage change depends on the reference value and calculation convention, and can behave differently when baseline values are low or zero. Without the exact formula and the reported values, the scale’s numerical interpretation cannot be independently assessed from the record.

What does a standard error describe?

General: a standard error expresses the estimated sampling variability of a statistic such as a mean. It is not the standard deviation of individual scores and does not by itself show the full range of participant experiences. A smaller standard error generally indicates a more precise estimate under the model used, while a larger one indicates less precision. The record names standard error as the dispersion measure, but no actual standard errors or confidence intervals are reported.

General: a confidence interval combines an estimate with an uncertainty range under specified statistical assumptions. Its width reflects both the variability in the data and the amount of information contributing to the estimate. It can help readers assess which effect sizes remain compatible with the data; it does not assign a probability to a fixed treatment effect. No confidence interval is reported for this primary outcome, so the precision of any observed change is unavailable.

Why does the study structure matter?

Repeated observations from the same participant are often statistically related. In this study description, 3 participants had more than 1 distinct withdrawal episode, and 13 independent trials were analyzed among 9 participants. General: observations that share a participant may be more similar than observations from different participants. An analysis that accounts for this correlation can produce different uncertainty estimates from one that treats every observation as independent. The registry does not describe the analysis model or how repeated episodes were handled, so it is not possible to determine whether or how within-participant dependence was considered.

The record names the intervention as a placebo-and-ondansetron crossover and gives measurements at baseline and 1 hour after each condition. In a crossover study, general: the same participant may experience more than one treatment condition, allowing comparisons within participants. Such comparisons can reduce the influence of stable differences between people, but interpretation still depends on treatment sequence, timing, possible carryover, and other time-related changes. The registry does not report the sequence, washout, or carryover procedures, nor does it explain how these design features were incorporated in analysis. The allocation entry is non-randomized, and the record cautions that the arms are not a like-for-like control comparison; the crossover label alone does not establish that treatment order was randomized or that all relevant biases were controlled.

How should planning calculations be read?

The registry’s planning description states that an illustration is based on the observed effect rather than the trial’s own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial was designed or conducted with those characteristics. No resulting sample-size values are reported in the registry record, and the record does not provide the observed effect needed to evaluate such an illustration.

General: a sample-size calculation estimates the number of participants per arm required under stated assumptions to attain a chosen probability of detecting a specified effect if that effect is real. Such a calculation is conditional on assumptions about variability, the target effect, significance level, allocation, and analysis. It is not an observed result and does not establish the probability that this completed study detected an effect. When an assumed effect is taken from observed data, the planning estimate can be unstable, particularly when the underlying analysis is small or uncertain. The registry does not report its own sample-size justification or the detailed inputs needed to reproduce a calculation.

In general, over-dispersion means that the observed variability exceeds what a chosen statistical model assumes. If a model fails to account for extra variability—such as correlation among repeated episodes—its standard errors may be too small and its intervals too narrow. Whether over-dispersion was assessed or relevant in this analysis is not reported in the registry record.

The registry does not report a test statistic, p-value, effect estimate, confidence interval, model specification, covariate adjustment, or diagnostic assessment. Consequently, general descriptions of these methods should not be mistaken for a description of methods actually used in the study. The posted information supports a description of the intended outcome and its timing, but not a reconstruction of the statistical analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Placebo - Sugar Pill", "Ondansetron")
n   <- c(9, 9)
m   <- c(-22.08, -42.71)
sp  <- c(8.61, 7.47)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Placebo - Sugar Pill  9  -22.080  25.830  -41.935  -2.225
CARM  Ondansetron  9  -42.710  22.410  -59.936  -25.484

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or methods for handling multiple comparisons. The three stated measurement occasions—baseline, 1 hour after placebo, and 1 hour after ondansetron—could support more than one possible contrast, but the registry does not identify which contrast was designated for inference or whether any additional comparisons were conducted. It is therefore not possible to assess whether multiplicity was considered or whether reported tests, if any, were adjusted.

Missing-data information is also limited. The outcome description states that 5 of the 14 participants assigned to intervention were withdrawn from the study and/or analysis. It does not distinguish withdrawal from analysis exclusion, give reasons, identify which time points or treatment conditions were missing, or explain how missing values were handled. The record does not report an intention-to-treat analysis, a per-protocol analysis, imputation, or a sensitivity analysis. Those procedures are not reported in the registry record.

The analysis population is described as 9 participants and 13 independent trials, with 3 participants contributing more than 1 distinct withdrawal episode. The record does not define the analysis unit or explain how participant-level and episode-level observations were combined. This matters because participants who contribute multiple episodes may contribute more information than those with one episode, and their observations may be correlated. No method for accounting for that dependence is reported.

These omissions limit assessment of both bias and precision. Excluding participants or episodes can affect the estimated change if the reasons for missingness are related to symptoms or treatment. Multiple testing can also affect interpretation when several contrasts are examined. The registry does not provide enough information to determine whether either issue changed the results, and numerical analysis results are not reported.

12. 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.

The registry lists 14 participants at risk for serious adverse events in the placebo group and 0 serious adverse events. For ondansetron, it also lists 14 participants at risk and 0 serious adverse events. The listed counts for other adverse events are 14 at risk and 0 affected in each group. These are the figures recorded for the named groups; they do not provide a detailed account of event definitions, monitoring duration, or how the event counts relate to the outcome analysis population.

Deaths are recorded as null for both groups. A null entry is not a reported death count of zero; deaths are not reported in the registry record. The registry also lists no serious-event terms, but does not provide a narrative describing surveillance or reporting procedures.

General: an observed count of zero means no events were recorded in the specified category and population during the recorded observation. It does not establish that the underlying risk is zero, and it does not rule out events that were not captured, reported, or included in that category. With the limited safety detail available, the listed counts should be read as registry entries rather than as a comprehensive assessment of safety.

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

The record establishes that the study examined changes in a participant-reported opioid withdrawal symptom score at baseline and 1 hour after placebo and ondansetron. It also documents the scale’s structure, the registered design labels, and the population description for the primary outcome. These details help readers understand the clinical question and the kind of measurement used.

The posted results do not establish the size or direction of any change. Numerical mean changes, standard errors, confidence intervals, and p-values are not reported in the registry record. It is therefore not possible to say from this record whether the score increased or decreased after either condition, whether the conditions differed, or how precise any comparison was. The absence of numerical results is not evidence that no change occurred; it means the result cannot be evaluated from the information recorded.

The design details also constrain interpretation. Allocation is recorded as non-randomized, and the registry cautions that the arms are not a like-for-like control comparison. The crossover label and timing entries do not specify treatment order, assignment, or analysis procedures. The analysis description includes repeated withdrawal episodes from some participants, but does not explain how their dependence was handled. These features leave uncertainty about the comparability of conditions and the precision of any potential estimate.

The listed adverse-event counts show no serious or other adverse events recorded in the named groups, while death counts are not reported in the registry record. Those entries should not be taken as proof that no harms occurred. They also do not resolve the unanswered efficacy question.

General: statistical evidence about an average change is not identical to evidence about every participant’s experience, and statistical significance is not the same as clinical importance. Assessing either requires an effect estimate and uncertainty information, as well as a clear account of the comparison and analysis. The registry does not provide those results. The appropriate conclusion is limited to what the record documents: a completed study with a defined symptom measure and a reported analysis population, but no posted numerical primary outcome analysis from which to judge the treatment comparison.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of how registry design labels, outcome descriptions, and analyzed populations need to be read together. The record labels allocation non-randomized and the model single group, while naming the intervention as a placebo-and-ondansetron crossover and listing separate placebo and ondansetron arm descriptions. These details are not interchangeable. The explicit registry caution that the arms are not a like-for-like control comparison is important when considering any apparent contrast between conditions.

The population description also illustrates why participant counts and observation counts should be distinguished. The primary outcome description reports 9 participants and 13 independent trials, with 3 participants contributing more than 1 withdrawal episode. A larger count of episodes does not automatically mean the same amount of independent information as observations from different participants. Statistical methods may need to account for clustering or repeated measures; the record does not say how that was handled.

Attrition is another key issue for interpreting an analysis. The record states that 5 of the 14 participants assigned to intervention were withdrawn from the study and/or analysis, but does not explain the reasons or missing-data procedures. Without that context, readers cannot assess how well the analyzed population represents those assigned or enrolled.

Finally, the entry demonstrates the difference between a recorded study question and a reported result. It defines the symptom score and assessment timing, yet gives no numerical primary outcome analysis. Statistical interpretation depends not only on the design and endpoint but also on the effect estimate, uncertainty, and analysis details. When these are absent, the study’s question can be described, but its observed treatment comparison cannot be quantified from the registry record.

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.

Several limitations specific to this registry entry restrict interpretation. The most consequential is that no numerical primary outcome results are reported. The record identifies a mean percent-change outcome with standard error but provides no change estimates, uncertainty intervals, or test results. The direction and size of the observed changes therefore cannot be described.

The design information leaves important questions unresolved. Allocation is listed as non-randomized, while the intervention name includes crossover and the model is listed as single group. The record does not explain the treatment sequence, how conditions were assigned, whether a washout was used, or how potential carryover and time effects were addressed. Double masking is recorded, but who was masked and how masking was maintained are not reported.

The participant flow is not fully explained. The entry reports enrollment of 31, says 14 participants were assigned to intervention, notes that 5 of those were withdrawn from the study and/or analysis, and describes an outcome population of 9 participants and 13 independent trials. The registry does not reconcile these counts or explain why participants or episodes were excluded. It also does not specify whether repeated episodes were analyzed as correlated observations.

The outcome definition is incomplete for reproducing the analysis. Although the scale and assessment times are described, the formula for percent change, the primary contrast, handling of missing symptom items, and statistical model are not reported. The analysis plan, sample-size justification, and multiplicity procedures are also not reported in the registry record. Consequently, the posted entry is insufficient to reproduce or fully audit an outcome analysis, even apart from the absence of numerical results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of Ondansetron for Withdrawal Symptoms — NCT00695864.
• Registry record last updated 2017-05-15; status last verified 2017-05.
• Results first posted 2017-05-15.
• 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

NCT00695864, “Effect of Ondansetron for Withdrawal Symptoms,” is recorded as completed and sponsored by Stanford University. The registry lists Substance Withdrawal Syndrome as the condition, enrollment of 31, non-randomized allocation, double masking, and a single-group model. The intervention is named as an ondansetron-and-placebo crossover.

The primary outcome concerns change in Subjective Opioid Withdrawal Scale scores at baseline and 1 hour after placebo and ondansetron. Participants rated 15 symptoms from 0 to 4, with summed scores from 0 to 60 and higher scores indicating more or more severe symptoms. The outcome description reports 9 participants and 13 independent trials, including repeated episodes for 3 participants; it also notes 5 withdrawals from among 14 participants assigned to intervention.

Numerical primary outcome estimates and statistical analysis results are not reported in the registry record. The entry lists zero serious and other adverse events in each named group, while deaths are not reported.