This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Neuropathic Pain Syndrome Patient Study (MK-0000-072) (NCT00570310), a randomized phase 1 study. The primary outcome is Daily Evening Patient Reported Pain Intensity Scores.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00570310 |
| Phase | Phase 1 |
| Condition | Neuralgia, Postherpetic, Diabetic Neuropathy, Painful Small-Fiber Neuropathy |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 104 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Merck Sharp & Dohme LLC |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with chronic neuropathic pain syndromes, including postherpetic neuralgia, diabetic neuropathy, painful small-fiber neuropathy, and idiopathic distal sensory polyneuropathy. The primary outcome population was narrower: participants who had at least a 30% decrease in mean average daily pain intensity during the last 3 days of maintenance relative to baseline. This is an enriched population selected for response during the maintenance phase, rather than an unrestricted group of all people with these conditions.
Intervention
Group A remained on pregabalin during the entire double-blind period, at a dose of up to 600 mg/day by mouth. The registry summary describes the study as examining generic pregabalin, while the intervention and arm descriptions identify the treatment as pregabalin. The record does not report further details about the formulation.
Comparator
Group B received placebo. The study is described as randomized, double-blind, and parallel-group, with placebo as the comparator. The posted primary outcome includes 30.0 participants in the pregabalin arm and 32.0 in the placebo arm.
Primary question
The primary question was how daily evening patient-reported pain intensity changed from the mean of the last 3 days of the maintenance period to the last 3 days of the double-blind period, at the 6-week timeframe. Pain was rated on a 0-10 numeric rating scale, where 0 means no pain and 10 means the worst pain imaginable. The posted comparison concerns change in this score among the maintenance-phase responders.
3. Trial Design
The registry classifies this as a Phase 1, randomized, double-blind, parallel-group study. Its title describes an enriched-enrollment, randomized-withdrawal design, and its stated purpose is to investigate methodology for proof-of-concept trials in chronic neuropathic pain, using pregabalin as a test drug. The record lists an enrollment of 104 and a completed status. The study start is recorded as 2007-12 and primary completion as 2008-09.
Enrichment is important to the question being answered. The primary outcome population consisted of participants who had at least a 30% decrease in average daily pain intensity during the maintenance phase relative to baseline. Thus, the primary result is not an estimate for every participant initially considered for the study. It pertains to the specified responder population during the subsequent double-blind comparison. The posted primary outcome lists 30.0 participants in the pregabalin group and 32.0 in the placebo group; the registry record does not provide a participant-flow account that explains how those outcome counts relate to the enrolled total.
The arm descriptions say that Group A remained on pregabalin throughout the double-blind period and Group B received placebo. The intervention entries likewise identify pregabalin and placebo. Although the study title emphasizes randomized withdrawal, details such as the maintenance-phase treatment sequence, allocation procedures, and timing of randomization are not reported in the registry record. The description supports the broad characterization of a withdrawal comparison, but it does not supply enough operational detail to reconstruct every stage of the protocol.
The listed secondary outcome is time to efficacy failure during the randomized-withdrawal portion. The record also reports two outcome measures and two analyses, but does not provide enough information to determine the full prespecified outcome hierarchy or which analyses were intended as primary for decision-making. The total enrollment and the primary-outcome arm counts are different quantities: the former describes enrollment, while the latter gives the reported counts for this outcome. The safety denominators are reported separately and should not be treated as interchangeable with either figure.
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: All patients were titrated up to the maximum tolerated dose of active treatment (pregabalin) over approximately 12 days. Patient were treated at the maximum tolerated dose until randomization at which time patient were either continued on active treatment or withdrawn from active treatment (i.e. placebo) in a double-blind fashion.
Overall Study
| Stage | Pregabalin | Placebo |
|---|---|---|
| STARTED | 53 | 51 |
| COMPLETED | 51 | 45 |
| NOT COMPLETED | 2 | 6 |
Reasons for not completing this period:
| Reason | Pregabalin | Placebo |
|---|---|---|
| Adverse Event | 1 | 2 |
| Lack of Efficacy | 1 | 4 |
Analysis population for the primary outcome, as defined in the registry: Patients who had a ≥30% decrease in mean of average daily pain intensity during the last 3 days of the maintenance phase relative to baseline.
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.
| Characteristic | Unit | Pregabalin | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 30 | 32 | 62 | |
| Age, Continuous | years | 61.7 (SD 10.8) | 59.3 (SD 11.0) | 60.5 (SD 10.9) |
| Sex: Female, Male: Female | Participants | 8 | 14 | 22 |
| Sex: Female, Male: Male | Participants | 22 | 18 | 40 |
| Body Mass Index | kilograms/meter^2 | 32.6 (20.9 to 49.3) | 31.3 (18.5 to 49.5) | 31.9 (18.5 to 49.5) |
6. Primary Endpoint
The registry lists the primary outcome as Daily Evening Patient Reported Pain Intensity Scores, measured over Baseline and 6 Weeks.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | Full Range |
| Unit | Units on a Scale |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in daily evening patient-reported pain intensity. Participants rated pain on a 0-10 numeric rating scale, anchored at no pain and the worst pain imaginable. The endpoint compares the mean of the last 3 days of the maintenance period with the last 3 days of the double-blind period, with the registry giving a 6-week timeframe. The reported measure is a least-squares mean.
A repeated short period of daily ratings can describe pain near the end of each study phase rather than relying on a single recalled assessment. Comparing the end-of-maintenance ratings with the end-of-double-blind ratings also makes the outcome directly relevant to the withdrawal question: whether pain scores change after participants enter the blinded comparison. That is a general reason such an endpoint can be useful; the registry record does not state the investigators’ specific rationale for choosing these exact assessment windows.
Interpretation depends on the selected population. The endpoint applies to participants whose pain intensity had already decreased by at least 30% during the maintenance phase relative to baseline. It therefore addresses change among those qualifying responders, not the initial response of an unselected population. The reported arm values are 0.14 for pregabalin and 1.57 for placebo. The registry labels arm dispersion as full range, with bounds of -2.0 to 4.33 for pregabalin and -1.83 to 8.0 for placebo. Those bounds describe the posted arm summaries and should not be confused with the confidence interval for the between-group analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted ANOVA comparison reports a mean difference in final values of -1.42 for pregabalin versus placebo. Its 90% confidence interval runs from -2.25 to -0.60, and the reported p-value is 0.003. The arm-level least-squares mean values are 0.14 for pregabalin and 1.57 for placebo. These summaries describe change on the pain-intensity scale for the responder population defined in the registry.
Read in the listed pregabalin-versus-placebo order, the negative contrast indicates a lower change value in the pregabalin arm than in the placebo arm. The registry’s endpoint is change from the maintenance period to the double-blind period, so the contrast describes a difference in change values over those periods. The numbers alone do not establish the clinical importance of that contrast. The registry record does not report a threshold for a clinically important between-group difference.
A confidence interval expresses uncertainty around an estimated contrast under the analysis assumptions. The posted 90% interval does not include zero, while the p-value of 0.003 is the reported test result for the analysis. These are related but distinct summaries: the interval conveys a range of estimates compatible with the analysis, while the p-value measures how unusual the data would be under the tested null hypothesis and assumptions. Neither is the probability that the treatment effect is true, and neither resolves whether the effect matters to patients.
The posted arm ranges are wide relative to the central arm values: the pregabalin range is -2.0 to 4.33 and the placebo range is -1.83 to 8.0. A full range records the endpoints of the observed values, not the precision of the estimated mean difference. It can be strongly affected by extreme observations. The 90% confidence interval for the contrast is the relevant posted interval for uncertainty about that comparison; it should not be substituted with either arm’s full range.
The responder-based design narrows the scope of the result. It focuses on participants who met the maintenance-phase response criterion, so the observed contrast should not automatically be generalized to people who did not meet that criterion or to all people with neuropathic pain. The record lists several neuropathic pain conditions, but does not report condition-specific effect estimates. It therefore does not establish whether the contrast is similar across those diagnoses.
The total enrollment is 104, whereas the primary-outcome counts are 30.0 and 32.0. Safety denominators are 51 and 53. The registry record does not explain the relation among these sets of counts, the extent of missing outcome data, or the reasons for participants not appearing in a particular result. The outcome estimate must therefore be read with its posted analysis population in mind, without treating the enrolled total as the denominator for every result.
9. Statistical Methods Explained
What does the reported mean difference describe?
The registry reports an ANOVA analysis with the parameter described as mean difference in final values. The compared groups are pregabalin and placebo, and the estimate is -1.42. The endpoint itself is described as change from the mean of the last 3 days of maintenance to the last 3 days of the double-blind period. The reported arm values are least-squares means, which are model-based group means rather than necessarily simple arithmetic averages. The record does not provide the full model specification, so details about covariates, repeated-measures structure, or other adjustments are not reported in the registry record.
In general, an analysis of variance compares group means while representing outcome variability in a statistical model. It can estimate a contrast and test a null hypothesis of no group difference. The label ANOVA alone does not reveal all modeling choices. For example, the registry record does not say which terms were included, how assumptions were assessed, or how any departures from those assumptions were handled. Those details matter for assessing whether the model reflects the design and data.
How should the interval and p-value be read?
The reported 90% confidence interval for the contrast is -2.25 to -0.60. In general, a confidence interval gives a range of effect estimates compatible with the observed data under the specified model and its assumptions, at the stated confidence level. It is not a range containing a specified proportion of individual participants’ scores, and it is not a probability statement about the particular estimate. The interval’s width reflects statistical uncertainty as represented by the analysis. The registry record does not explain why a 90% interval was selected.
The reported p-value is 0.003. In general, a p-value assesses how incompatible the observed data are with a specified null hypothesis, assuming the model and test conditions hold. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of the effect. The registry record gives the p-value but does not report whether it was adjusted for multiple analyses.
What do the arm summaries add?
The arm-level values are 0.14 for pregabalin and 1.57 for placebo. The record labels the dispersion as full range and gives bounds of -2.0 to 4.33 and -1.83 to 8.0, respectively. In general, a full range describes the lowest and highest observed values; it is not a standard error or confidence interval. It can help convey the spread of observed values, but it does not by itself quantify the uncertainty in the estimated between-group contrast.
The arm counts for the primary outcome are 30.0 and 32.0. They are distinct from the safety denominators and the overall enrollment. In general, the number of observations contributing to a result affects its precision, but the counts alone do not explain why they differ from the enrollment or safety counts. The record does not provide the missing-data method or a participant disposition that would clarify those differences.
What can be concluded about re-calculation?
A simple unadjusted re-calculation from posted summary statistics, when available, is not the same analysis as a sponsor’s model-based analysis. It may omit covariate adjustment, use different assumptions, or rely on less information than the original analysis. In this record, no separate recalculated contrast or interval is reported. The posted ANOVA result is the available analyzed comparison, and the registry record does not give enough model detail to independently reproduce it from the arm summaries alone.
More generally, agreement between an unadjusted calculation and a model-based result would not establish that the analyses answer precisely the same question. A difference could arise from adjustment or analysis choices rather than an arithmetic error. Conversely, a matching estimate would not reveal whether the model assumptions are appropriate. The registry record does not provide sufficient detail to assess those issues fully.
What about planning calculations?
Planning illustrations use assumptions to estimate the number of participants needed for a future study under a chosen effect, significance level, allocation, and statistical approximation. They are not observed trial outcomes and are not observed power. The stated assumptions for this study’s planning illustration are a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. The registry record does not report the resulting participant counts in the material described by these registry entries, nor does it report that these assumptions were used to design the trial. The study’s own sample-size justification is not reported in the registry record.
In general, a planning calculation depends on the effect chosen as relevant, outcome variability, allocation, significance threshold, and model assumptions. Using the observed effect as a planning reference does not mean that the observed effect is a stable estimate of the effect expected in a future study. Planning outputs should be read as conditional illustrations, not as proof that a study had adequate power or as evidence about what the study observed.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| ANOVA | Mean Difference (Final Values) -1.42 | -2.25 to -0.60 | 0.003 |
The posted analysis is an ANOVA comparison, with a mean difference in final values of -1.42, a 90% confidence interval from -2.25 to -0.60, and p = 0.003. This is the sponsor’s reported analysis in the registry record. The record does not include a separate unadjusted recalculated contrast, so there is no reported recalculation to compare numerically with the sponsor’s estimate.
The registry record does not flag a discrepancy between the posted analysis and a recalculation. That does not establish that an independent calculation would reproduce every detail of the sponsor’s model: the model specification and calculation inputs needed to do so are not reported in the registry record. The arm-level values and ranges provide descriptive information, but they do not reconstruct all modeling choices. The sponsor analysis should therefore be read as the posted inferential result, with its estimate, interval, and p-value, while recognizing that the underlying model details are not fully documented in the registry record.
In general, an unadjusted calculation from summary statistics and a sponsor’s model-based analysis can differ because they may use different assumptions or information. A numerical comparison is useful only when both estimates and their methods are available. No claim about such a difference can be made from this record.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists Daily Evening Patient Reported Pain Intensity Scores as the primary outcome and time to efficacy failure during the randomized-withdrawal portion as a secondary outcome. It reports two outcome measures and two analyses. The record does not describe a statistical testing hierarchy, a multiplicity adjustment, or which comparisons were designated as confirmatory. The number of outcomes and analyses alone does not establish how the investigators controlled the chance of false-positive findings across tests.
In general, when several hypotheses are tested, the chance of at least one nominally small p-value can increase if the tests are treated as a family. Prespecifying a hierarchy or applying an adjustment can address that concern, but the registry record does not say whether either approach was used. The reported p-value of 0.003 should therefore be interpreted as the result attached to the posted ANOVA comparison, without assuming that it is adjusted for other analyses.
The outcome population is defined by a maintenance-phase response criterion: at least a 30% decrease in mean average daily pain intensity during the last 3 days of maintenance relative to baseline. That definition is reported, but the exact analysis-set designation, any departures from the randomized assignment, and the rules for including participants with incomplete observations are not reported in the registry record.
Missing-data handling is also not reported in the registry record. The primary outcome counts are 30.0 for pregabalin and 32.0 for placebo, while the safety denominators are 51 and 53, and overall enrollment is 104. These counts should not be treated as interchangeable. Without a participant-flow account and missing-data methods, the reasons for the differing counts and their possible implications for interpretation remain unclear.
The record does not report interim analyses, stopping rules, or procedures for handling missing outcome measurements. Those details should not be inferred from the randomized, double-blind, parallel-group description. The registry record also does not provide condition-specific analysis populations or explain whether subgroup analyses were planned.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pregabalin | 0 | 51 | 0.0% |
| Placebo | 1 | 53 | 1.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pregabalin | 37 of 51 |
| Placebo | 36 of 53 |
Most frequent serious adverse event terms
| Event term | Organ system | Pregabalin | Placebo |
|---|---|---|---|
| Arrhythmia | Cardiac disorders | 0 of 51 | 1 of 53 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pregabalin | Placebo |
|---|---|---|---|
| Dizziness | Nervous system disorders | 10 of 51 | 11 of 53 |
| Somnolence | Nervous system disorders | 8 of 51 | 7 of 53 |
| Constipation | Gastrointestinal disorders | 6 of 51 | 2 of 53 |
| Dry Mouth | Gastrointestinal disorders | 6 of 51 | 2 of 53 |
| Fatigue | General disorders | 4 of 51 | 4 of 53 |
| Oedema Peripheral | General disorders | 5 of 51 | 3 of 53 |
| Vision Blurred | Eye disorders | 3 of 51 | 4 of 53 |
| Weight Increased | Investigations | 3 of 51 | 2 of 53 |
| Nausea | Gastrointestinal disorders | 3 of 51 | 1 of 53 |
| Disturbance In Attention | Nervous system disorders | 2 of 51 | 2 of 53 |
Serious events with the highest arm-level rate: arrhythmia (1.9%).
The posted safety figures list 51 participants at risk in the pregabalin group and 53 in the placebo group. Serious adverse events affected 0 participants in the pregabalin group and 1 participant in the placebo group. Other adverse events affected 37 and 36 participants, respectively. These are counts paired with the stated at-risk denominators; no comparative safety test or uncertainty interval is reported in the registry record.
Arrhythmia is listed among the top serious adverse event terms at 1.9%. The record does not specify the denominator underlying that percentage or provide enough detail to connect it to a particular participant count. Deaths are not reported in the registry record; the absence of a reported death count should not be interpreted as a count of zero.
In general, adverse-event counts describe events recorded during the study, not necessarily events caused by treatment. The registry figures alone do not establish causality, severity beyond the serious-event classification, timing, recurrence, or the clinical context of individual events. Small counts can also be imprecise indicators of comparative safety. These numbers should be read as descriptive results for the listed groups, not as a complete safety assessment.
13. What the Result Does, and Does Not, Mean
The posted results describe a randomized, double-blind comparison of pregabalin with placebo among participants who had met a maintenance-phase pain-response criterion. For the primary pain-intensity change outcome, the registry reports a mean difference in final values of -1.42, a 90% confidence interval from -2.25 to -0.60, and p = 0.003. The arm values are 0.14 for pregabalin and 1.57 for placebo. These figures summarize the reported analysis and its uncertainty under the model used.
They do not establish how the result would apply to people who did not meet the responder criterion, to every condition listed in the record, or to a broader clinical population. The study is enriched, and the registry does not report condition-specific estimates. The result also does not establish the clinical importance of the observed contrast: no threshold for a clinically important difference is reported. Statistical evidence against a null hypothesis and clinical relevance are different questions.
The result does not by itself establish long-term effects, effects beyond the recorded study period, or comparative outcomes outside the specific treatment and placebo groups described. It also does not resolve the efficacy-failure outcome, for which no result is included in the registry record for this analysis. The registry lists that outcome as secondary, but a result for it is not reported in the registry record.
The safety counts are descriptive and do not establish that an event was caused by treatment or that one group had a definitively different safety profile. The differing denominators across enrollment, primary outcome, and safety results also limit direct comparisons unless their relationship is clarified. Taken together, the record supports a narrow reading of the posted pain-intensity comparison in the selected responder population, while leaving important questions about generalizability, missing data, and clinical importance unresolved.
14. Why This Trial Matters Statistically
This study is statistically notable because its title and stated purpose focus on trial methodology as well as the use of pregabalin as a test drug. An enriched, randomized-withdrawal design asks a different question from a trial that begins with an unselected group and compares initial treatment responses. By restricting the primary outcome population to participants who had achieved at least a 30% reduction during maintenance, the comparison centers on what happens among those meeting that response criterion during the double-blind period.
That design feature affects interpretation of both the estimate and its scope. The reported contrast is tied to the selected population and the transition from maintenance to double-blind treatment. It should not be treated as an estimate of response across all people with chronic neuropathic pain. This distinction is important in clinical research because the target population and treatment stage are part of the estimand: the statistical quantity being estimated is meaningful only in relation to who was analyzed and when outcomes were assessed.
The posted estimate is accompanied by a confidence interval and a p-value, allowing readers to distinguish an effect estimate from its uncertainty and test result. The record also presents arm-level values and ranges, which have a different statistical role from the interval for the contrast. Understanding these distinctions helps prevent a descriptive range from being read as inferential precision, or a p-value from being taken as a measure of clinical importance.
The record’s gaps also illustrate why outcome definitions, participant flow, missing-data rules, and multiplicity plans matter. The primary-outcome counts differ from the safety denominators and enrolled total, while the reasons for those differences are not reported. A precise numerical estimate can still have limitations in scope and reproducibility when key analysis details are unavailable.
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 outcome is restricted to participants who had at least a 30% decrease in mean average daily pain intensity during the last 3 days of maintenance relative to baseline. This enrichment makes the findings specific to people meeting that criterion. The registry record does not report the number of participants who did not meet it or provide comparative outcome estimates for them.
The primary analysis counts, 30.0 for pregabalin and 32.0 for placebo, are not reconciled with the overall enrollment of 104 or the safety denominators of 51 and 53. The record does not give participant flow, reasons for exclusion from the primary outcome analysis, or details of missing observations. It is therefore not possible from the registry record to assess the extent to which incomplete data or analysis-population choices may affect the reported result.
The ANOVA estimate is posted, but the model specification is not. Covariates, diagnostic checks, and the handling of model assumptions are not reported in the registry record. The arm summaries are labeled as least-squares means with full-range dispersion, but the registry does not supply the full analysis details needed to reproduce the sponsor’s inference. No separate recalculated contrast is reported.
The record names multiple neuropathic pain conditions but does not provide condition-specific results. It also does not report a clinically important difference threshold, the multiplicity strategy, or the missing-data method. Details of allocation implementation, maintenance-phase procedures, interim analyses, and the study’s sample-size justification are not reported in the registry record. These limitations constrain assessment of generalizability, precision, and reproducibility.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Neuropathic Pain Syndrome Patient Study (MK-0000-072) — NCT00570310.
- Registry record last updated 2015-05-07; status last verified 2015-04.
- Results first posted 2010-02-05.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
NCT00570310 is a completed Phase 1, randomized, double-blind, parallel-group study of pregabalin and placebo in chronic neuropathic pain syndromes. The registry title describes an enriched-enrollment, randomized-withdrawal study focused on trial methodology. Enrollment was 104, with the study start recorded as 2007-12 and primary completion as 2008-09.
The primary outcome was change in daily evening pain intensity, rated on a 0-10 scale, from the last 3 days of maintenance to the last 3 days of the double-blind period. The analyzed population met a maintenance-phase response criterion of at least a 30% decrease relative to baseline. The posted ANOVA comparison reports a mean difference of -1.42, a 90% confidence interval from -2.25 to -0.60, and p = 0.003.
The registry also lists time to efficacy failure as a secondary outcome and reports descriptive adverse-event counts. Details on missing-data handling, multiplicity, participant flow, and the full analysis model are not reported in the registry record.