Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients (NCT00420771), a randomized phase 2 study. The primary outcome is Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group phase 2 pilot trial of gabapentin versus placebo. The registry lists quadruple masking. The study summary describes the protocol as randomized, double-blind, and placebo-controlled, so the record uses different masking descriptions in its trial-design field and summary. It does not explain the masking roles or how masking was implemented.

The registry lists enrollment of 19 and a completed status. The start and primary completion dates are recorded as 2007-01 and 2011-01. Arm-level endpoint data are reported for 6 participants in the active medication arm and 10 in the placebo arm; the primary endpoint description states that 16 participants had post-randomization data available. The record does not explain why these endpoint counts are smaller than total enrollment or provide a participant flow account.

The study summary describes weekly manual-guided psychotherapy for all subjects, directed at abstinence and improving current functioning. It also describes weekly assessment of benzodiazepine use using self-report and urine toxicology, with psychological symptoms assessed through clinician and self-rated instruments. These are descriptions of the proposed protocol; the registry record does not report adherence to psychotherapy or detailed implementation results.

The primary endpoint was a continuous measure of mean reduction change in benzodiazepine use per day, comparing the baseline week before study entry with the last week of participation. The endpoint timeframe is described as data collected during 8 weeks of trial or length of participation. The registry does not report a detailed statistical analysis plan, the allocation procedure, or the rationale for the planned enrollment.

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

Analysis population for the primary outcome, as defined in the registry: a total of 16 participants had data available post randomization

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 Mean Reduction Change in Benzodiazepine Use Per Day Based on Time Line Follow Back, measured over data collected during 8 weeks of trial or length of participation.

The primary endpoint measures change in benzodiazepine use per day, in milligrams per day. The registry describes it as the mean reduction change between the baseline week before study entry and the last week of study participation, based on the Time Line Follow Back. The endpoint is continuous: each participant’s use is represented on a numeric scale rather than as a yes-or-no outcome.

Repeatedly assessing use is relevant to the stated trial aim of reducing benzodiazepine abuse. The study summary describes weekly assessment using a combination of self-report and urine toxicology. The primary endpoint specifically names the Time Line Follow Back, a self-report method that organizes reports of use over time. The registry record does not explain how self-report and urine toxicology were combined for the posted endpoint, or how missing weekly assessments were handled.

The endpoint description sets the comparison window as baseline week to the last week of study participation, with the timeframe described as data collected during 8 weeks of trial or length of participation. This means the endpoint is tied to each participant’s study duration, rather than being described as a single common assessment date for everyone. The record does not give individual participation lengths.

Arm summaries are reported as means and standard deviations. A mean describes the average recorded endpoint value within an arm, while the standard deviation describes how spread out participant values were around that average. These summaries do not by themselves establish how precisely the difference between arms is estimated. No confidence interval or inferential comparison for the primary endpoint is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous, and the registry reports an arm mean and standard deviation for each treatment group. These statistics describe the endpoint distribution within each arm. The mean gives the average reduction change among participants with available endpoint data. The standard deviation describes how dispersed participants’ values were around that arm’s mean. Neither statistic alone estimates the uncertainty in a comparison between arms.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical procedure. For a treatment comparison, it can show both the estimated direction and the precision of the between-arm contrast. A narrow interval suggests greater precision than a wide interval; an interval that spans values on both sides of no difference can reflect substantial uncertainty. No confidence interval for this endpoint is reported in the registry record, so the precision of the arm contrast cannot be assessed from an interval.

What does the absence of a comparative test mean?

The posted results include descriptive arm summaries, but no p-value or other inferential result for the two-arm comparison. In general, a test evaluates how compatible the observed data are with a specified null hypothesis under model assumptions. It does not measure the probability that a treatment is effective, and it does not replace consideration of the estimated effect and its uncertainty. Here, the registry record does not report a test result or detail the model that would have been used. The record’s note that values are missing or not estimable for a two-arm comparison means that no such comparison should be inferred from the arm summaries alone.

Why does the standard deviation matter?

In general, an outcome with greater participant-to-participant variability is harder to estimate precisely for a fixed amount of data. The standard deviations reported for the endpoint are 4.0 in the active medication arm and 6.7 in the placebo arm, with endpoint counts of 6 and 10. These summaries indicate that observed values were not identical across participants. The registry does not report a distribution plot, individual values, or a model assessing whether the data met any particular distributional assumptions.

Over-dispersion is a general concern when count outcomes vary more than a simple count model would predict, and it can affect standard errors and confidence intervals if the model does not account for it. This endpoint, however, is reported as a continuous measure, not as a count. The registry does not identify a fitted model or report an over-dispersion assessment. It would therefore be inappropriate to claim that over-dispersion was present or that it was addressed in the analysis.

What can the planning illustrations say?

In general, a sample-size calculation estimates how many participants a future study might need under stated assumptions about the effect to detect, variability, significance level, allocation, and statistical method. Such calculations are planning illustrations, not results from participants and not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. The registry does not report that these assumptions were used to design the original trial, nor does it report the trial’s own sample-size justification.

Observed power is not an additional measure of the strength of a result. In general, calculations based on the observed effect and observed sample size largely restate the information in the test result and can be misleading when used to explain a non-significant result. The planning illustrations are more appropriately understood as hypothetical planning scenarios, not as evidence about the probability that the trial detected a true effect. No planning counts are repeated in this explanation.

The primary endpoint compares a baseline week with the last week of participation. In general, analysis of change can be affected by the way baseline values are handled, the completeness of repeated measurements, and the choice of statistical model. The registry record does not report whether a baseline-adjusted model, an analysis of change scores, or another approach was used, and it does not provide details of any covariate adjustment. No specific inferential method should be attributed to this trial on the basis of the posted arm summaries.

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("Active Medication", "Placebo")
n   <- c(6, 10)
m   <- c(4, 2.3)
sp  <- c(4, 6.7)
sd  <- sp      # posted standard deviations
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  Active Medication  6  4.000  4.000  -0.198  8.198
CARM  Placebo  10  2.300  6.700  -2.493  7.093

11. Multiplicity, Missing Data and Analysis Populations

The study summary describes aims beyond the primary endpoint, including craving, mood, anxiety, and sleep disturbance. The registry reports no secondary outcome results. It therefore does not show whether these measures were analyzed, what estimates were obtained, or whether any findings were considered exploratory. The number of secondary outcomes with posted results is 0.

Multiplicity arises in general when several outcomes, time points, or comparisons are tested: as the number of statistical tests grows, the chance of at least one apparently unusual result can increase. Researchers may address this through a prespecified hierarchy, adjustment procedures, or a clear distinction between primary and exploratory analyses. The registry record does not report a multiplicity strategy, nor does it provide enough analysis detail to determine how multiple outcomes or time points were handled. No correction method should be assumed.

The primary endpoint description states that 16 participants had data available after randomization, compared with overall enrollment of 19. The arm summaries report endpoint counts of 6 for active medication and 10 for placebo. The record does not give reasons for missing endpoint data, the timing of withdrawals, or whether missingness differed by arm. It also does not describe imputation, a sensitivity analysis, or another missing-data method. These details matter because the interpretation of a complete-case summary can depend on why outcome data are unavailable.

The registry does not state whether participants were analyzed according to randomized assignment, whether all randomized participants were included in any analysis, or how treatment discontinuation was handled. The analysis population and missing-data approach are therefore not reported in the registry record. The endpoint counts should be read as the numbers contributing to the posted arm summaries, not as evidence of a particular analysis-population rule.

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.

Most frequent non-serious adverse event terms

The posted serious adverse event figures show 0 participants affected in the gabapentin group, among 6 at risk, and 0 participants affected in the placebo group, among 10 at risk. These counts describe participants recorded as affected by a serious adverse event in the registry’s safety results. They do not establish that serious events are impossible, or that none occurred outside the registry’s recorded reporting period or definitions.

The record lists no serious adverse event terms. It separately reports other adverse events for 6 participants in the gabapentin group, among 6 at risk, and 5 participants in the placebo group, among 10 at risk. These are participant counts for the category labeled other adverse events; they should not be conflated with the serious adverse event figures. The record does not supply event-level descriptions for these other events in the posted safety information.

Death counts are not reported in the registry record. The safety counts are based on small groups, so they provide limited information about uncommon events. In general, an absence of recorded serious events in a small trial is not the same as evidence that a treatment has no serious risks. The registry’s figures describe what was posted for this trial; they do not support a broader safety conclusion.

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

The result establishes that the registry contains mean endpoint summaries for the two randomized arms among participants with data available after randomization. The active medication arm’s reported mean reduction change was 4.0 milligrams per day, with a standard deviation of 4.0 and 6 participants. The placebo arm’s reported mean was 2.3 milligrams per day, with a standard deviation of 6.7 and 10 participants. These figures are descriptive, and the registry does not report a confidence interval or inferential comparison.

Those arm summaries do not establish whether the groups differed beyond what could plausibly arise from sampling variation. They do not say how much uncertainty surrounds the between-arm contrast, and they do not provide a basis for a conclusion about statistical significance. The registry notes that values are missing or not estimable for a two-arm comparison of this continuous endpoint. A direction suggested by the means alone should not be treated as a confirmed comparative effect.

The trial’s small enrollment and the endpoint counts limit how precisely the posted results can describe a broader population. The standard deviations indicate variation in outcomes among participants, while the registry provides no individual values or inferential interval. The results cannot identify how consistently participants changed, or whether the group averages reflect a similar pattern across participants.

The study summary describes psychological measures as additional aims, but no secondary results are posted. The available endpoint figures do not answer questions about craving, mood, anxiety, or sleep disturbance. Similarly, the posted safety figures describe recorded adverse events in this study but do not establish a general safety profile.

In general, randomized comparisons are designed to assess differences between groups, but interpretation depends on the analysis, data completeness, and precision of estimates. The registry record does not report the detailed statistical plan, sample-size justification, missing-data methods, or comparative inferential result. The proper conclusion is limited to the reported arm-level summaries and the information absent from the registry record. The findings should not be described as proving that gabapentin does or does not reduce benzodiazepine use.

14. Why This Trial Matters Statistically

This trial is statistically informative as a small randomized pilot with a continuous primary outcome and incomplete endpoint availability relative to enrollment. It illustrates why arm means alone are not enough to assess a randomized comparison. Means describe the observed groups, while uncertainty measures are needed to judge how precisely the contrast is estimated. The registry reports the means and standard deviations, but not a confidence interval or inferential test for the comparison.

The endpoint also highlights the importance of defining the measurement window. Benzodiazepine use was summarized by comparing the baseline week with the last week of study participation, while the timeframe is described as data collected during 8 weeks of trial or length of participation. Such timing choices affect what a change score represents. The record does not explain whether all participants had the same length of follow-up or how variable participation length was addressed.

The difference between overall enrollment and participants with endpoint data makes missing-data reporting central to interpretation. Without reasons for unavailable observations and an account of the analysis population, readers cannot assess whether endpoint summaries might reflect a selected subset of randomized participants. This limitation is distinct from the small sample size: even a clearly reported arm summary may be difficult to interpret when the pathway from enrollment to analysis is not described.

The registry’s lack of posted secondary findings also matters. The study summary names several psychological aims, yet the record contains no secondary outcome results. Clear separation of prespecified primary analyses from secondary or exploratory work is important when multiple outcomes are considered. The registry does not report that distinction or a multiplicity approach.

Finally, the stated sample-size illustrations are planning scenarios based on an observed effect and explicit assumptions, rather than a record of the original design rationale. Keeping that distinction clear prevents planning calculations from being mistaken for observed evidence or for the trial’s own justification. The registry does not report its original sample-size rationale or detailed statistical plan.

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 registry record offers limited detail for evaluating the primary endpoint. It reports arm means, standard deviations, and participant counts, but not a confidence interval, p-value, or other inferential comparison. It also notes that values are missing or not estimable for a two-arm comparison. The reason for this limitation is not reported in the registry record.

Endpoint data were available after randomization for 16 participants, while enrollment was 19. The posted endpoint counts are 6 and 10. The record does not explain the participant flow, reasons for unavailable data, or whether missing observations were related to participant characteristics or outcomes. Without those details, the possibility of bias from incomplete follow-up cannot be assessed.

The endpoint uses the baseline week and the last week of participation. The record does not report how the endpoint was calculated for participants with different participation lengths, how self-report was combined with urine toxicology, or whether the weekly measurements were used in any additional analysis. Individual-level data and measurement-completeness information are not reported.

The registry does not provide the detailed statistical analysis plan, model specifications, handling of baseline values, covariate adjustments, or missing-data procedures. It also does not report a sample-size justification, an interim analysis plan, or a multiplicity strategy. These methods should not be inferred from the randomized design or from the posted arm summaries.

Although the study summary describes craving, mood, anxiety, and sleep disturbance as additional aims, no secondary outcome results are posted. The safety information reports no participants affected by a serious adverse event in either group, but the groups are small, and death counts are not reported. These limitations constrain what can be concluded about both efficacy-related outcomes and safety from the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gabapentin Treatment of Benzodiazepine Abuse in Methadone Maintenance Patients — NCT00420771.
• Registry record last updated 2019-04-24; status last verified 2019-04.
• Results first posted 2018-07-12.
• 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 identifies a completed, randomized, parallel-group phase 2 pilot trial of gabapentin versus placebo in methadone maintenance patients abusing benzodiazepines. Overall enrollment was 19. The active medication arm received gabapentin 1200 mg three times daily; the placebo pills were described as identical in appearance to those in the experimental arm. The registry lists quadruple masking.

The primary endpoint was mean reduction change in benzodiazepine use per day, in milligrams per day, comparing the baseline week with the last week of participation. The registry reports endpoint data for 16 participants after randomization: 6 in the active medication arm and 10 in the placebo arm. Arm means and standard deviations are posted, but no inferential two-arm comparison, confidence interval, or secondary outcome results are reported.

The safety record lists no participants affected by serious adverse events in either group, while other adverse events were recorded in both groups. The registry does not report death counts. Important details—including the sample-size rationale, statistical analysis plan, missing-data methods, and reasons for the difference between enrollment and endpoint data availability—are not reported in the registry record.