Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia (NCT01270828), a randomized phase 3 study. The primary outcome is Number of Participants With Loss of Therapeutic Response..

2. Clinical Question

This question focuses on maintaining response during the double-blind comparison, rather than only on a single pain measurement at the end of follow-up. The registry’s definition combines a pain-response criterion with specified reasons for discontinuation, so the event can reflect either inadequate response or treatment stopping for one of those reasons. The primary endpoint is recorded as a participant count, and the primary efficacy analysis set is defined as participants randomized to the double-blind phase who received at least 1 dose of study drug there. The registry reports 806 participants enrolled overall; that enrollment figure is distinct from the arm counts used for the posted primary endpoint results.

3. Trial Design

The registry describes a phase 3, randomized, double-blind, parallel-group, placebo-controlled study. Its stated purpose was to explore the safety and efficacy of a once-a-day pregabalin formulation versus placebo for patients with postherpetic neuralgia. The record lists 806 participants as enrolled and marks the study as completed. Start and primary-completion dates are recorded as 2011-03 and 2014-09.

The primary endpoint results are reported for the double-blind groups: Pregabalin CR DB and Placebo DB. The primary efficacy set was the full analysis set, defined as participants randomized to the double-blind phase who received at least 1 dose of study drug in that phase. The primary results list 208 participants in the pregabalin group and 205 in the placebo group. Those arm counts are not the same as the overall enrollment figure, because the registry gives them for the primary double-blind endpoint analysis.

The endpoint timeframe is 13 Weeks. The registry definition refers to a preceding single-blind treatment baseline and a double-blind phase, but details of the wider sequence and the trial’s original allocation procedures are not reported in the registry record. The record identifies the study as randomized and double-blind, but does not report further details of the randomization process or masking procedures. The dose range recorded for the pregabalin CR tablet is 82.5 to 660mg; further dose assignment or adjustment details are not reported in the registry record.

4. Participant Flow and Accounting

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

Before assignment: The study consisted of 4 phases: Baseline (1 week \[wk\]): to determine study entry criteria; Single Blind (SB) (6 wks): to determine optimized dose; Double Blind (DB) (13 wks): responders with at least 50% improvement in pain at SB were considered and randomized to pregabalin or matching placebo; and DB taper phase (1 wk).

Pregabalin CR SB

Reasons for not completing this period:

Double Blind Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set (FAS) was the primary efficacy analysis set and consisted of all participants randomized to the DB phase who received at least 1 dose of study drug in the DB phase.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Baseline analysis population description consisted of all participants randomized to the DB phase who received at least 1 dose of study medication in the DB phase (full analysis set).

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Loss of Therapeutic Response., measured over 13 Weeks.

The primary endpoint is the number of participants with loss of therapeutic response over 13 Weeks. The registry defines loss of therapeutic response as pain response below 30% relative to the single-blind phase baseline, or discontinuation in the double-blind phase due to lack of efficacy or adverse events. For the pain-response component, baseline is the mean of the last 7 observations before single-blind treatment; that baseline is compared with the 7 days rolling average of pain response during the double-blind phase. Discontinuation due to lack of efficacy could occur at the study physician’s discretion.

This composite event is intended to capture loss of response during follow-up, while also counting specified treatment discontinuations. It therefore summarizes more than a single observed pain score: a participant can meet the endpoint through the pain-response threshold or through one of the recorded discontinuation reasons. The registry identifies the full analysis set as the primary efficacy population. That set includes participants randomized to the double-blind phase who received at least 1 dose of study drug in that phase.

As a general statistical point, a participant-level binary endpoint makes a comparison of event occurrence between groups straightforward to describe. Its interpretation depends on the exact event definition and analysis population, both of which matter when considering what the count represents.

7. Results Posted in the Registry

• Pregabalin CR DB: 13.9% (29/208) versus 30.7% (63/205) on control; risk difference -16.8 percentage points (95% CI -24.7 to -8.9), risk ratio 0.45 (0.31–0.67); unadjusted two-proportion z-test p = <0.001.

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.

Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pregabalin CR DB: 23.6% (49/208) versus 42.4% (87/205) on control; risk difference -18.9 percentage points (95% CI -27.8 to -10.0), risk ratio 0.56 (0.41–0.74); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Pregabalin CR DB than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With 30% Reduction in the Mean Pain Score.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pregabalin CR DB: 95.6% (197/206) versus 83.8% (171/204) on control; risk difference 11.8 percentage points (95% CI 6.0 to 17.6), risk ratio 1.14 (1.07–1.22); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Pregabalin CR DB than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Participants With 50% Reduction in the Mean Pain Score.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pregabalin CR DB: 88.3% (182/206) versus 68.6% (140/204) on control; risk difference 19.7 percentage points (95% CI 12.0 to 27.5), risk ratio 1.29 (1.16–1.43); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Pregabalin CR DB than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary binary outcomes show a generally consistent direction across the outcomes with numerical results: fewer participants in the pregabalin group met the secondary loss-of-response definition, while more met the reported pain-reduction thresholds. This overall pattern is directionally compatible with the primary result, which also records fewer loss-of-response events in the pregabalin arm. The secondary outcomes provide related context, but they measure distinct definitions or thresholds and should not be treated as interchangeable with the primary endpoint.

The registry lists additional secondary outcomes concerning weekly mean pain, a one-week pain rating, and sleep measures. Numerical results for those outcomes are not reported in the registry record in the material described by these analyses, so their direction and precision cannot be characterized. The record reports 17 outcome measures and 16 posted secondary outcomes, underscoring that the displayed binary results are only part of the overall outcome set.

As a general statistical point, examining multiple outcomes creates multiplicity: even when there is no true difference for any outcome, the chance of at least one apparently notable result can increase as more tests are conducted. An adjustment strategy or prespecified hierarchy can address this issue, but such a plan is not reported in the registry record. Accordingly, unadjusted secondary p-values and intervals carry less confirmatory weight than a clearly prespecified primary analysis. They remain useful descriptive evidence, but should be interpreted in the context of all outcomes examined and the uncertainty about multiplicity handling.

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

• Participants With Secondary LTR Based on 5 Day Rolling Average Diary Results
• Percentage of Participants With 30% Reduction in the Mean Pain Score.
• Percentage of Participants With 50% Reduction in the Mean Pain Score.
• Change From Baseline to Endpoint in Weekly Mean Pain Score.
• Change in the Weekly NRS-Pain (1-Week Recall).
• Change in the Medical Outcomes Study-Sleep Scale (MOS-SS).
• Change in the MOS-SS-Quantity of Sleep.
• The MOS-SS-Optimal Sleep.

9. Statistical Interpretation

10. Statistical Methods Explained

What does the primary analysis test?

The registry reports a Log Rank analysis comparing the two double-blind groups for the primary endpoint, with p < 0.001. As a general statistical explanation, the Log Rank method compares the timing of events between groups across follow-up, rather than looking only at the final proportion with an event. Its interpretation depends on the event definition, follow-up, and how censoring or incomplete observation is handled. Those implementation details are not reported in the registry record.

The outcome is described as the number of participants with loss of therapeutic response, and the registry also gives a timeframe of 13 Weeks. The endpoint definition incorporates a rolling-average pain criterion and specified discontinuations. Because the registry’s reported test is time-to-event while the displayed endpoint is a participant count, it is important not to conflate the sponsor’s Log Rank result with a test calculated only from the final counts.

What does the recalculation represent?

The accompanying recalculated comparison is an unadjusted difference in event risk based on the posted group counts. In general, a risk difference expresses the contrast between the proportions experiencing an event in two groups. A negative value for this endpoint indicates fewer events in the pregabalin group than in the placebo group. The confidence interval for that recalculation excludes zero, and its unadjusted p-value is p < 0.001. This is a simple count-based re-analysis; it does not reproduce the timing information used by a Log Rank analysis.

As a general statistical point, an unadjusted analysis does not account for covariates or other adjustment procedures. The registry record does not report an adjusted effect estimate for this comparison. The sponsor’s reported Log Rank test remains the analysis explicitly recorded for the primary endpoint.

How should binary secondary outcomes be read?

Some secondary outcomes are recorded as participants meeting or not meeting a threshold, such as a pain reduction threshold or the secondary loss-of-response definition. For these outcomes, the posted counts and percentages describe the observed groups. The registry gives Chi-squared tests for the two pain-reduction outcomes and Log Rank tests for the loss-of-response outcomes. A Chi-squared test is a general method for assessing whether the distribution of a categorical outcome differs across groups; it does not, by itself, quantify the size of the difference or its clinical importance.

The secondary recalculations are unadjusted comparisons of the posted summaries. Their estimates and intervals can describe the direction and precision of those particular comparisons, but multiple testing matters when many outcomes are examined. Whether a secondary result should be treated as confirmatory depends on the prespecified analysis plan and multiplicity approach. Those details are not reported in the registry record.

What does a confidence interval add?

In general, a confidence interval gives a range of effect values compatible with the data and the method’s assumptions at the stated confidence level. For a risk difference, an interval that includes zero is compatible with no difference under that calculation; an interval that excludes zero indicates that zero is outside the interval. The interval is not a probability statement about the true effect, and it does not account for every possible source of bias or uncertainty. The posted recalculated primary interval excludes zero.

Precision depends on both the estimate and the amount of information in the data. A relatively narrow interval indicates more precise estimation under the model, while a wider interval indicates less precision. These general ideas do not establish that the analysis assumptions are met; the registry does not report all details needed to assess those assumptions.

What is not described?

The registry record does not report the original sample-size justification, a full statistical analysis plan, details of missing-data handling, or an interim-analysis plan. It also does not report enough information to reconstruct all aspects of the Log Rank procedure, including how incomplete follow-up was treated. These absences limit independent assessment of whether the analyses followed a prespecified plan and how robust the findings are to alternative analytic choices.

11. Confidence Intervals and Precision

The registry reports the primary group counts and a Log Rank p-value, but does not provide a numerical confidence interval for the sponsor’s Log Rank analysis. The p-value indicates evidence under that test; it does not show the range of effect sizes compatible with the data. The simple recalculation based on the posted counts does include a confidence interval for the risk difference, and that interval excludes zero. Its numerical limits are not restated.

As a general explanation, a confidence interval describes uncertainty in an estimate under the calculation’s assumptions. It is not a guarantee that the true value lies within the interval, nor does it measure uncertainty from unreported aspects of design, endpoint assessment, or missing data. A narrow interval typically indicates greater statistical precision than a wide interval, but precision is not the same as freedom from bias.

The sponsor-reported Log Rank analysis and the recalculated interval refer to related but not identical quantities. The Log Rank method uses event timing, while the recalculated risk-difference interval uses group event counts. The latter should therefore be interpreted as an unadjusted summary of the posted counts, not as the confidence interval for the sponsor’s time-to-event analysis. The registry record does not report a numerical interval for that sponsor analysis, so its precision cannot be described numerically from the registry’s reported analysis.

The secondary comparisons also have uncertainty, and their intervals should be considered alongside the number of outcomes examined. Because a multiplicity procedure is not reported in the registry record, individual secondary intervals and p-values should not be read as though they necessarily account for the full set of analyses.

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 comparisons, not total event counts. They are illustrations based on the observed effect, rather than a statement of the trial’s original recruitment target or design justification. The registry’s own sample-size assumptions are not reported in the registry record.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses the stated fraction of the observed effect as the effect to detect. The 80% power column gives the illustrative participants per arm under those assumptions for an 80% chance of detecting that specified effect if it were the true effect. The 90% power column gives the corresponding per-arm planning figure for a 90% chance. These are planning interpretations, not guarantees about a future study.

For example, the primary comparison’s planning figures are 96 participants per arm for 80% power and 128 participants per arm for 90% power when planning for 100% of the observed effect. Planning for 75% of the observed effect gives 182 participants per arm for 80% power and 243 for 90% power. Planning for 50% of the observed effect gives 434 participants per arm for 80% power and 580 for 90% power. The pattern illustrates a general statistical principle: smaller effects are harder to detect and require more participants under otherwise unchanged assumptions.

These figures are not observed power. They do not tell whether the completed trial had a particular probability of success after its results were known. They are hypothetical planning calculations tied to the observed effect and the stated assumptions; different assumptions or a different true effect would lead to different requirements.

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 = 0.307; treatment proportion p₁ = 0.139; average p̄ = 0.223.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5890 = 1.1545.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5769 = 0.4856.
4. n = (1.1545 + 0.4856)² / (-0.1679)² = 95.4, rounded up to 96 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 <- 0.307317073170732                          # control proportion
p1 <- 0.139423076923077                          # 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(1270828)
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 = 96 (80% power), 128 (90% power)
 75% of observed effect: n per arm = 182 (80% power), 243 (90% power)
 50% of observed effect: n per arm = 434 (80% power), 580 (90% power)
power.prop.test: 95.4 
Simulated power at n = 96 per arm: 0.809 (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. Analyses Reported by the Sponsor

The registry’s reported primary analysis is a Log Rank comparison, with p < 0.001. That is the sponsor-reported inferential result for the primary endpoint. The recalculation based on the posted event counts is an unadjusted risk-difference analysis and gives p < 0.001. The two p-values come from different methods and should not be treated as duplicate outputs from the same test.

The recalculated comparison is useful as a transparent count-based description of the observed groups: it uses the posted event counts and compares event proportions without adjustment. It does not reproduce the event-time analysis, and it does not replace the registry’s reported Log Rank result. The sponsor’s reported analysis is therefore the relevant reference for what the registry says was the primary analysis; the recalculation offers a supplementary view of the posted summaries.

The registry also gives no numerical confidence interval for its Log Rank estimate, while the count-based recalculation has an interval for the risk difference. That interval describes the recalculated quantity only. Details of the sponsor’s full analysis plan, adjustment procedures, and missing-data handling are not reported in the registry record, so those features cannot be compared directly with the simple recalculation.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary endpoint and lists multiple secondary outcomes, but a multiplicity strategy is not reported in the registry record. It is therefore not possible to determine from the record whether the secondary tests were adjusted, arranged in a prespecified hierarchy, or treated as exploratory. When many statistical tests are conducted, some may appear notable by chance alone; this general concern is why unadjusted secondary results warrant cautious interpretation.

The primary efficacy population is defined as the full analysis set: participants randomized to the double-blind phase who received at least 1 dose of study drug in that phase. That definition clarifies who was included in the primary efficacy analysis, but the registry does not report a detailed accounting of exclusions, missing endpoint observations, or the handling of incomplete follow-up. Missing-data methods, imputation procedures, and sensitivity analyses are not reported in the registry record.

The primary endpoint includes a rolling-average pain-response criterion and discontinuations due to lack of efficacy or adverse events. The registry does not report how event timing or censoring was handled in the Log Rank analysis, nor does it give a breakdown of the primary events by endpoint component. These omissions limit assessment of how the reported result would change under alternative missing-data or endpoint-handling choices.

The registry reports a Log Rank analysis for the primary endpoint and Chi-squared analyses for two listed pain-reduction outcomes. It does not report a complete statistical analysis plan or an interim-analysis plan. Thus, the available record supports describing the reported methods and outcomes, but not confirming all prespecification, multiplicity, or missing-data decisions.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombocytopenia (0.5%), bronchopneumonia (0.5%), cerebrovascular disorder (0.5%), anaemia of chronic disease (0.5%), cardiac failure (0.5%).

For the double-blind groups, the registry records serious adverse events affecting 7 of 208 participants in the Pregabalin CR DB group and 3 of 205 in the Placebo DB group. Other adverse events are recorded for 7 of 208 and 1 of 205 participants, respectively. These are counts of affected participants in the registry’s safety summary; they do not by themselves establish that an event was caused by study treatment.

The registry also lists a Pregabalin CR SB group with 801 participants at risk, 17 affected by serious adverse events, and 202 affected by other adverse events. That group is distinct from the double-blind comparison and should not be combined with either double-blind arm when interpreting the randomized comparison. The listed serious-event terms include thrombocytopenia, bronchopneumonia, cerebrovascular disorder, anaemia of chronic disease, cardiac failure, and acute sinusitis, each recorded at 0.5%. The record does not provide an arm attribution for those listed terms in the registry record.

Adverse-event counts are descriptive safety information. The registry summary does not supply details about event duration, severity beyond the serious classification, relatedness assessments, or comparative statistical testing. Those details are not reported in the registry record.

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

The posted primary results show fewer participants with loss of therapeutic response in the Pregabalin CR DB group than in the Placebo DB group: 29 of 208 compared with 63 of 205. The registry reports a Log Rank p-value of p < 0.001. The unadjusted count-based recalculation also gives evidence of a group difference, with p < 0.001, but it is not the same analysis as the registry’s time-to-event result.

This finding describes the recorded endpoint under the registry’s definition and analysis population. Loss of therapeutic response combines a pain-response threshold with discontinuation for lack of efficacy or adverse events. The result does not reveal how many events came from each part of that composite, and the component breakdown is not reported in the registry record.

A statistically notable result does not alone establish the clinical importance of an effect, explain why the groups differed, or guarantee a similar result in another study. The record does not provide all information needed to assess missing-data handling, multiplicity, or the original design assumptions. The recalculated risk difference is a simple summary of the posted counts, not an adjusted causal estimate or a substitute for the sponsor’s Log Rank analysis.

The secondary results with numerical data broadly point in the same direction for the reported pain-response and loss-of-response outcomes. However, multiple outcomes were examined, and a multiplicity plan is not reported in the registry record. Other listed pain and sleep outcomes cannot be characterized numerically from the stated results. Safety counts are also descriptive and do not establish whether an event was caused by treatment.

Overall, the registry documents a difference in recorded primary endpoint experience between the randomized double-blind groups. The limits of the available record mean that the result should be interpreted as evidence about this endpoint, population, and analysis—not as a complete account of every outcome or source of uncertainty.

18. Why This Trial Matters Statistically

This trial illustrates why the analysis method should be read alongside the endpoint definition. The primary outcome is presented as a number of participants with loss of therapeutic response, but the registry reports a Log Rank test. The former conveys event counts; the latter compares event timing across follow-up. A count-based recalculation can help describe the observed groups, but it answers a different statistical question from a time-to-event analysis.

The endpoint is also composite. It includes both a pain-response rule based on rolling averages and specified reasons for discontinuation. Composite endpoints can summarize several ways an outcome may occur, but the total count can obscure which component contributes most. The registry does not report a component breakdown, so the overall endpoint cannot be decomposed from the available record.

The record provides an opportunity to distinguish statistical evidence from precision and planning. The sponsor’s Log Rank p-value is reported separately from the unadjusted recalculated comparison, and the latter has a confidence interval. The planning figures illustrate how assumed effect size and desired power affect participant requirements, but they are not observed power and do not document the study’s original design rationale.

Finally, the registry lists many outcomes and analyses, while multiplicity, missing-data procedures, and the full analysis plan are not reported in the registry record. That distinction matters for interpreting secondary findings and judging how completely the posted results describe the intended statistical approach.

19. 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 trial-specific limitations follow from what is and is not described in the registry record. The primary endpoint combines a pain-response threshold with discontinuation for lack of efficacy or adverse events, but the record does not break down how many participants met each component. The endpoint therefore cannot be interpreted as a pain-only measure from the overall count.

The sponsor’s primary result is reported as a Log Rank p-value, but a numerical effect estimate and confidence interval for that analysis are not reported in the registry record. The count-based recalculation has a different estimand and does not reproduce the timing-based analysis. Details of censoring, incomplete follow-up, and missing-data handling are also not reported, limiting independent assessment of the time-to-event result.

The primary efficacy set is defined, but detailed participant flow and reasons for exclusion from the analysis are not reported in the registry record. Nor are the original sample-size justification, interim-analysis plan, or full statistical analysis plan. The sample-size illustrations use the observed effect and stated planning assumptions, so they cannot fill the gap about the trial’s original design assumptions.

The record lists numerous secondary outcomes and analyses, but a multiplicity strategy is not reported. The numerical secondary findings should therefore be interpreted cautiously, and the additional pain and sleep outcomes cannot be described where numerical results are absent. Finally, the safety summary provides affected-participant counts and selected event terms, but detailed relatedness, severity, and duration information is not reported in the registry record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety And Efficacy Study Of Once Daily Controlled Release Pregabalin In The Treatment Of Patients With Postherpetic Neuralgia — NCT01270828.
• Registry record last updated 2021-01-28; status last verified 2015-12.
• Results first posted 2016-01-13.
• 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.

23. Record Summary

The registry describes a completed phase 3 randomized, double-blind, parallel-group, placebo-controlled study of once-daily controlled-release pregabalin for postherpetic neuralgia. Overall enrollment was 806. The primary endpoint was participants with loss of therapeutic response over 13 Weeks, analyzed in a full analysis set defined by randomization to the double-blind phase and receipt of at least 1 dose.

The primary endpoint count was 29 of 208 in the Pregabalin CR DB group and 63 of 205 in the Placebo DB group. The registry reports a Log Rank result of p < 0.001; a separate unadjusted recalculation from the counts gives p < 0.001. The numerical secondary results show a broadly consistent direction for the reported binary pain-response and loss-of-response outcomes.

The registry does not report the original sample-size justification, multiplicity plan, detailed missing-data methods, or full statistical analysis plan. These gaps limit assessment beyond the posted endpoints and analyses.