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 Clinical Study to Evaluate the Effect of pH on Pain Upon Local Anesthetic Administration. (NCT01304082), a randomized na study. The primary outcome is Rank-transformed Pain Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01304082 |
| Phase | NA |
| Condition | Local Anesthetics |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Double |
| Enrollment | 29 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
The study planned to recruit patients who had a clinical indication for lumbar medial branch nerve blocks at Massachusetts General Hospital. The registry reports enrollment of 29. Eligibility details beyond the stated clinical indication, and characteristics of the enrolled patients, are not reported in the registry record. The study was single-center.
Intervention
The local anesthetic interventions were lidocaine and alkalinized lidocaine. The registry describes administering blocks at adjacent spinal levels and says the solutions were typically lidocaine or bicarbonate-buffered lidocaine. It also describes adding a saline control as part of the research procedure. The intervention details for each arm are not further specified in the registry record.
Comparator
The listed solutions were normal saline, lidocaine and alkalinized lidocaine. The planned procedure included a saline control and lidocaine at the control location before continuing with the nerve blocks. The exact sequence allocation, handling of treatment order and pairwise comparisons are not reported in the registry record. The crossover model indicates that participants received more than one study condition, but the registry does not give the full schedule.
Primary question
The primary outcome was rank-transformed pain score, recorded immediately upon injection of each solution. The underlying pain rating was described as an 11-point numeric rating scale from 0, no pain, to 10, worst pain imaginable. The trial sought to assess how solution pH related to injection pain. The registry summary also describes interest in onset of local anesthesia, with time until hypoesthesia and anesthesia listed as secondary outcomes. Numerical results for these outcomes are not reported in the registry record, so the direction and precision of any observed differences cannot be evaluated.
3. Trial Design
The registry identifies this as a single-center, randomized, double-blind clinical study with a crossover model. It lists enrollment of 29 and Massachusetts General Hospital as the sponsor. The registry start is 2011-01, primary completion is 2014-11, and status is terminated. These entries describe the record and do not by themselves explain why the study was terminated or whether all planned assessments were completed; that information is not reported in the registry record.
The study concerned pain during local anesthetic administration in patients receiving lumbar medial branch nerve blocks. The summary describes three blocks at adjacent spinal levels, typically using lidocaine or bicarbonate-buffered lidocaine, and adding a saline control. It further says lidocaine was provided at the control location before continuing with the nerve blocks. The registry does not report the randomized sequence, the number of injections each participant received under each condition, or any washout or order-management procedure. Those details matter for understanding how a crossover comparison was implemented.
Randomization is intended to reduce systematic differences in treatment assignment, while double masking is intended to limit the influence of treatment knowledge on care or outcome assessment. These are general explanations of the design terms; specific allocation procedures and masking arrangements are not reported in the registry record. Likewise, the record does not specify who was masked or how the solutions were made indistinguishable.
A crossover design can permit within-participant comparisons, because a participant may contribute observations under multiple conditions. That feature can help account for stable differences between participants, but only if the analysis and design address order and possible carryover effects. Whether and how this trial addressed those issues is not reported in the registry record. No interpretation of the outcome estimates is possible from the design description alone, and the primary outcome results 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.
Overall Study
| Stage | C, L, A | C, A, L | L, C, A | A, C, L | A, L, C |
|---|---|---|---|---|---|
| STARTED | 3 | 2 | 11 | 8 | 5 |
| First Intervention | 3 | 2 | 11 | 8 | 5 |
| Second Intervention | 3 | 2 | 11 | 8 | 5 |
| Third Intervention | 3 | 2 | 11 | 8 | 5 |
| COMPLETED | 3 | 2 | 11 | 8 | 5 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
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 | All Study Participants |
|---|---|---|
| Participants analysed | 29 | |
| Age, Continuous | years | 54.5 (44.5 to 62.5) |
| Sex: Female, Male: Female | Participants | 13 |
| Sex: Female, Male: Male | Participants | 16 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 17 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 11 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 29 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 29 |
| Baseline Pain Score | units on a scale | 6 (4 to 7) |
6. Primary Endpoint
The registry lists the primary outcome as Rank-transformed Pain Score, measured over immediate, upon injection of each solution.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | rank |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is listed as rank-transformed pain score, measured immediately upon injection of each solution. The underlying pain rating is described as a validated 11-point numeric rating scale, ranging from 0 for no pain to 10 for worst pain imaginable. The reported endpoint is therefore a transformation of the ratings into ranks, rather than the original pain score expressed directly in scale points.
In general, ranking converts observed values into their relative ordering. Rank-based methods can be useful when an analysis is intended to rely less on assumptions about the original measurement distribution. They do not preserve the original scale units: a difference in rank is not directly interpretable as a particular number of pain-rating points. The registry lists the endpoint parameter as a least-squares mean and its dispersion as a 95% confidence interval. The exact ranking procedure, statistical model, and interpretation of the estimated least-squares means are not reported in the registry record.
Immediate recording is pertinent to the stated question because the outcome concerns pain upon administration, rather than pain at a later follow-up. The endpoint does not, by itself, measure the later onset of reduced or absent sensation; those topics appear separately among the secondary outcomes. Numerical estimates, confidence limits and other inferential results for the primary endpoint are not reported in the registry record. Thus the endpoint definition establishes what was intended to be measured, but not what the study found.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a primary outcome and its measurement scale, but it does not report the primary outcome estimates. There is no reported least-squares mean, 95% confidence interval, p-value, or treatment comparison for rank-transformed pain score. Consequently, the posted record does not establish which solution had a higher or lower pain score, how large any observed difference was, or how precisely a difference was estimated. The stated hypothesis that less acidic solutions produce less burning is a study rationale, not a result.
The endpoint is a rank-transformed version of ratings on a scale from 0 to 10. If results were available, their interpretation would depend on the reported contrast, its uncertainty, and the analysis model. Rank-based estimates would describe relative ordering on the transformed scale rather than a direct change in original pain-score points. A confidence interval generally describes a range of values compatible with the estimate under the model and assumptions used; it is not a guarantee about the true effect. Here, no interval endpoints are reported, so the uncertainty cannot be assessed.
The crossover model is relevant to interpretation because comparisons may be made within participants. In general, that can reduce the impact of stable differences between people, but treatment order and possible carryover can also matter. The record does not report the sequence, a carryover assessment, or the statistical approach used for repeated observations. These methodological details are not reported in the registry record, and their absence prevents a reader from determining how the design was reflected in the analysis.
The registry lists secondary outcomes for time until hypoesthesia, time until anesthesia, and rank-transformed pain score upon needle stick. It does not report numerical results for those outcomes either. The primary question cannot be answered from the available outcome descriptions alone, and secondary outcomes cannot substitute for missing primary-outcome estimates. No conclusion about the magnitude, direction, or statistical uncertainty of an effect should be inferred from the trial hypothesis, the design, or the safety counts.
The status is recorded as terminated, but the reason for termination and the relationship between termination and outcome reporting are not reported in the registry record. Enrollment is recorded as 29, but that figure does not reveal how many observations were available for each endpoint or how missing assessments were handled. The registry also does not report participant characteristics or analysis populations. These omissions limit assessment of precision, completeness, and applicability. The statistical interpretation is therefore limited to the study question, design and outcome definitions; efficacy results are not reported in the registry record.
9. Statistical Methods Explained
The registry describes a randomized, double-blind crossover design and identifies rank-transformed pain score as the primary outcome. It lists least-squares mean as the outcome parameter and a 95% confidence interval as the measure of dispersion. The model formula, included covariates, handling of repeated observations and exact contrast are not reported in the registry record. The descriptions below explain the general statistical concepts, not methods confirmed to have been used in this study.
What does randomization contribute?
In general, randomization assigns study conditions using a chance-based process. It can reduce systematic differences in the factors that influence assignment, including factors that are measured and factors that are not measured. It does not ensure that groups or treatment periods are identical, and it does not correct problems caused by missing observations, departures from the planned procedure, or an unsuitable analysis. The registry reports randomization but does not report how the sequence was generated, concealed, or implemented.
What is distinctive about a crossover comparison?
In general, a crossover study exposes a participant to more than one condition, allowing comparisons that may use observations from the same person. A participant can serve as a partial reference for their own response, which can help account for stable personal differences. This benefit depends on the design and analysis. The order of conditions may matter, and a prior condition may influence a later observation. Adequate spacing, sequence balance and explicit statistical handling can be important, depending on the intervention and outcome. The registry does not report the full treatment schedule, washout arrangements, sequence balance, or methods for assessing carryover. It is therefore not possible to say how these considerations were addressed.
What does a rank transformation mean?
In general, ranking places observations in order rather than analyzing their original values directly. This approach can be useful when an analysis relies on relative ordering or when the original measurement scale does not fit a particular model assumption. The transformation changes the interpretation: a result on a rank scale is not a pain-score difference in the original 0-to-10 units. Ties and the specific ranking procedure can also affect analysis, but their handling is not reported in the registry record. The record names a rank-transformed endpoint without explaining the detailed calculation.
What is a least-squares mean?
In general, a least-squares mean is a model-based estimate of an average, often calculated for specified treatment conditions while accounting for terms included in the model. Its meaning depends on the model, the data and the estimand being targeted. The registry lists this parameter for the primary outcome but does not report the model specification or the contrast between conditions. Without those details and the estimates themselves, the least-squares means cannot be reconstructed or interpreted as an adjusted treatment effect.
How should a confidence interval be read?
In general, a confidence interval communicates the uncertainty around an estimate under the analysis assumptions. A narrower interval indicates greater precision than a wider interval, but interval width does not establish clinical importance. Whether an interval includes a null value is relevant to some inferential questions, but interpretation also depends on the chosen contrast and analysis plan. The record specifies a 95% confidence interval for the primary outcome, but does not report its endpoints. Its precision and compatibility with possible effects therefore cannot be assessed.
Why can over-dispersion matter?
In general, over-dispersion occurs when variability in observed data exceeds what a model assumes. If not accounted for, standard errors and confidence intervals may be too optimistic. The relevance depends on the outcome type and model. The primary endpoint is rank-transformed pain score, and no model details or dispersion diagnostics are reported in the registry record. It would be inappropriate to claim that over-dispersion was present or that any particular correction was used.
What do the planning assumptions mean?
The registry includes a description of sample-size planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. Such calculations are planning illustrations, not evidence of the study's observed power and not a substitute for the trial's design rationale. The record does not report the trial's own sample-size justification. Because the study is described as a crossover trial with three listed solutions, assumptions for equal allocation between two arms should not be read as a full description of its actual design or analysis. Numerical planning results and the observed effect are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies rank-transformed pain score as the primary outcome and lists secondary outcomes for time until hypoesthesia, time until anesthesia, and rank-transformed pain score upon needle stick. It also records four outcome measures and four analyses. The relationship between every listed measure and each analysis is not explained in the registry record. No numerical outcome results are reported.
When a study examines multiple outcomes or contrasts, the chance of at least one apparently notable result can increase if each is assessed separately. Statistical plans may address this through a prespecified primary comparison, adjustment for multiple testing, or a clear distinction between confirmatory and exploratory analyses. These are general considerations. The registry record does not report whether a multiplicity adjustment was planned or used, which contrasts were prespecified, or how secondary outcomes were to be interpreted.
The record does not report the number of participants with evaluable primary outcome data, the amount or pattern of missing data, or how missing observations were handled. It also does not report whether analyses followed an intention-to-treat, per-protocol, complete-case, or other population definition. In a crossover design, incomplete observations across conditions can affect which within-participant comparisons are available; the handling of such cases is not reported in the registry record.
These gaps matter because outcome selection, missingness and analysis population can influence both the estimate and its uncertainty. Enrollment alone cannot establish endpoint completeness. Without the analysis plan, population definitions and results, it is not possible to judge the extent of multiplicity control or the sensitivity of findings to missing data.
11. 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 |
|---|---|---|---|
| Normal Saline | 0 | 29 | 0.0% |
| Lidocaine | 0 | 29 | 0.0% |
| Alkalinized Lidocaine | 0 | 29 | 0.0% |
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 |
|---|---|
| Normal Saline | 0 of 29 |
| Lidocaine | 0 of 29 |
| Alkalinized Lidocaine | 0 of 29 |
The registry lists serious adverse events and other adverse events for normal saline, lidocaine and alkalinized lidocaine. For each listed condition, 29 participants are recorded as at risk, with 0 serious events and 0 other events. These are the recorded counts in the registry, not estimates of comparative risk. They should be read as event counts for the listed groups, not as proof that an event could not occur or that the conditions have identical safety profiles.
The deaths fields are null for each group. A null entry does not provide a count of zero; deaths are not reported in the registry record. No serious adverse event terms are listed. The record does not provide event definitions beyond the serious and other categories, follow-up duration, severity details, relatedness assessments, or information about how adverse events were collected. It also does not explain how safety observation was handled within the crossover design.
Zero recorded events in a registry entry are limited evidence about safety, especially when event numbers and follow-up details are unavailable. The counts do not establish that no unrecorded events occurred, and they do not support a numerical comparison among conditions. They describe only what is reported in the registry record.
12. What the Result Does, and Does Not, Mean
The record describes a clinical question about whether local anesthetic solution pH is related to pain during injection and whether pH is related to onset of local anesthesia. It identifies a randomized, double-blind crossover design, three listed solutions, a primary pain endpoint and several secondary outcomes. These details explain the study's purpose and intended measurements.
They do not establish the outcome. Numerical primary and secondary results, estimates of contrasts, confidence intervals and p-values are not reported in the registry record. The hypothesis that less acidic solutions produce less burning is not evidence that the hypothesis was supported. The available material does not show the direction, size or precision of any treatment difference, so it cannot support a conclusion that one solution produced more or less pain than another.
The primary measure was rank-transformed, so even a reported result would need interpretation on that transformed scale. It would not automatically translate into a change in the original pain rating. A full interpretation would also require the analysis model, contrast definition, handling of the crossover sequence, missing-data approach and outcome data. Those details are not reported in the registry record.
Enrollment of 29 and the recorded safety counts are descriptive registry entries. They do not show that the outcome data were complete or that the study was able to estimate a particular effect with adequate precision. The terminated status is recorded, but the reason for termination is not reported in the registry record. The record therefore supports a description of the intended comparison and reported safety counts, but not a judgment about the primary research question or the strength of evidence for a treatment difference.
13. Why This Trial Matters Statistically
This trial is statistically notable because it applies a crossover design to an immediate, subjective outcome recorded during a clinical procedure. In general, within-participant comparisons can reduce the influence of stable differences among participants. At the same time, order effects and dependence between repeated observations become important. The registry identifies the crossover structure, but does not report the sequence, period handling or analysis model needed to assess how these issues were addressed.
The primary endpoint is also presented on a rank-transformed scale rather than as the original rating. That choice changes what an estimate means and limits direct interpretation in pain-score units. The registry provides the underlying 0-to-10 scale description and names a least-squares mean with a 95% confidence interval, but does not report numerical estimates. This makes the distinction between a well-defined measurement and an interpretable result especially important.
The record lists multiple outcomes, including pain and timing measures. A reader assessing a study with several outcomes would ordinarily want to know which comparisons were primary, how multiplicity was handled, and how missing observations were treated. Those details are not reported in the registry record. The presence of a primary endpoint is useful, but it does not answer these analytic questions by itself.
Finally, the status is terminated and no outcome estimates are reported. This highlights why registry design information and result reporting serve different purposes: the former explains what was intended, while the latter is needed to assess observed effects and uncertainty. The available record is informative about the study question and structure, but it does not permit an outcome-based statistical conclusion.
14. 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 leaves important details of the design and analysis unspecified. Although it names randomization, double masking and a crossover model, it does not report the allocation sequence method, concealment, who was masked, the order of solutions, or how the sequence was implemented. It also does not describe washout or carryover procedures. These omissions limit assessment of whether the design controlled order-related influences.
The primary outcome is defined as rank-transformed pain score, but the ranking procedure, model specification, covariates and planned contrasts are not reported in the registry record. Least-squares mean and 95% confidence interval are named, but no estimates or interval endpoints are reported. The registry summary is truncated, so it does not provide a complete account of all procedural details or outcome definitions.
Participant characteristics, endpoint-specific sample sizes, completeness of follow-up and missing-data handling are not reported in the registry record. Enrollment cannot establish how many observations contributed to each analysis. The record also does not explain the relationship between the four outcome measures and four analyses, or state whether multiplicity was addressed.
The status is terminated, but the reason for termination and any implications for completion of planned assessments are not reported in the registry record. Although safety counts are listed, follow-up duration, collection methods and event relatedness are not described. These limitations prevent a reader from evaluating the robustness, completeness and precision of the study findings, apart from the more fundamental absence of numerical outcome results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clinical Study to Evaluate the Effect of pH on Pain Upon Local Anesthetic Administration. — NCT01304082.
- Registry record last updated 2017-04-11; status last verified 2017-02.
- Results first posted 2017-04-11.
- 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.
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18. Record Summary
The registry describes a single-center, randomized, double-blind crossover study of pain upon local anesthetic administration during lumbar medial branch nerve blocks. It lists lidocaine, alkalinized lidocaine and normal saline, enrollment of 29, and rank-transformed pain score as the primary outcome. Secondary outcomes concern time until hypoesthesia, time until anesthesia, and rank-transformed pain score upon needle stick.
The record lists status as terminated, with start in 2011-01 and primary completion in 2014-11. For each listed solution, it records 0 serious adverse events and 0 other adverse events among 29 at risk; deaths are not reported. Numerical results for the primary and secondary outcomes, the reason for termination, and key analysis details are not reported in the registry record.