Minimally Invasive Sensing of Beta-lactam Antibiotics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Minimally Invasive Sensing of Beta-lactam Antibiotics (NCT03847610), a na phase 1 study. The primary outcome is Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling.

2. Clinical Question

This is a measurement-feasibility question, not a randomized treatment comparison. The record describes a single-group study, with allocation listed as not applicable and no masking. Its focus is whether readings from a sensing device correspond with measurements made using a comparator method over a stated timeframe of up to 12 hours. Such correspondence concerns measurement performance; it is distinct from asking whether a drug changes a clinical outcome.

The registry record identifies the study as an in-house feasibility study of a microneedle biosensor developed within Imperial College London. It does not report numerical findings for the primary outcome, so the degree of agreement cannot be assessed from the registry record.

3. Trial Design

The registry record describes a completed Phase 1, single-group study involving healthy volunteers. Enrollment is listed as 11. The start date is 2018-04-12, and primary completion is listed as 2018-08-10. The sponsor is Imperial College London. The brief summary characterizes the study as an in-house feasibility study of a microneedle biosensor developed within the institution.

The listed interventions are phenoxymethyl penicillin and a microneedle array. No dose, administration schedule, device placement procedure, or detailed visit schedule is reported in the registry record. The primary outcome timeframe is up to 12 hours. The record lists masking as none and allocation as not applicable. It therefore does not describe random assignment or a masked control group.

The stated primary outcome assesses the biosensor’s ability to track phenoxymethylpenicillin concentrations, with microdialysis and blood sampling named in the outcome title. The outcome description specifies a Bland-Altman plot for agreement between interstitial phenoxymethylpenicillin concentrations and microneedle data, defining the mean difference between microneedle and microdialysis measurements. The record lists one outcome measure and no analyses.

This design is suited to an initial assessment of measurement feasibility, but it does not establish comparative performance against a randomized alternative. The registry record does not report a protocol, sample-size justification, detailed analysis plan, or description of how many participants contributed measurements at each timepoint. Those design details should not be inferred from the Phase 1 label, enrollment, or outcome wording.

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: One volunteer withdrew consent to undergo microdialysis on the study day and was withdrawn from the analysis. The participant did not cite a reason for declining microdialysis catheter insertion. Therefore, ten volunteers were included in the study.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Assessment of the Biosensors Ability to Track Phenoxymethylpenicillin Concentrations Compared to Observations Made by Microdialysis and Blood Sampling, measured over Up to 12 hours.

The primary endpoint concerns agreement between phenoxymethylpenicillin concentration readings from a microneedle biosensor and measurements made by microdialysis. The endpoint is continuous, expressed in mg/L, and specifies a mean with a 95% Confidence Interval. Its timeframe is up to 12 hours. The outcome description says agreement would be described using a Bland-Altman plot and identifies the mean difference between microneedle and microdialysis measurements as the quantity of interest.

In general, a mean difference describes average directional bias: whether one method tends, on average, to give higher or lower readings than another. A Bland-Altman approach is generally used to assess agreement between measurement methods, rather than simply whether they are correlated. Two methods can move together while still differing systematically in their readings. Assessment of agreement also usually considers how widely individual paired differences vary. The registry record does not report numerical differences or limits of agreement, so those properties cannot be evaluated for this study.

The endpoint is relevant to the stated feasibility aim because it focuses on whether microneedle readings track a comparator measurement. Blood sampling appears in the outcome title, but the endpoint description does not specify a blood-sampling statistic or a distinct blood comparison. No numerical endpoint result is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous measurement endpoint and names a Bland-Altman plot as the intended way to describe agreement. It also identifies a mean difference between microneedle and microdialysis measurements. The record does not report the numerical result, analysis details, or an analysis plan. The explanations below are general statistical context, not a claim that any particular procedure was used beyond what the registry states.

What does a mean difference tell us?

In general, when two methods measure the same quantity in paired observations, the difference for each pair can be examined. The average of those differences describes average bias, including its direction. If differences are calculated as microneedle minus microdialysis, a positive average would indicate higher readings from the microneedle method on average; a negative average would indicate lower readings. The registry record names the mean difference but does not report its value or specify the subtraction order. The direction of any observed bias is therefore not available.

An average difference is not a complete description of agreement. In general, differences can cluster closely around the average or vary substantially from one pair to another. A method could have little average bias while individual paired readings still differ considerably. A Bland-Altman display is commonly used to examine the pattern of paired differences and their spread across the measurement range. No plotted values or numerical agreement limits are reported in the registry record.

What does the confidence interval contribute?

In general, a confidence interval gives a range of values compatible with the data and the method used to estimate the quantity. For a mean difference, it conveys uncertainty about the average bias. It is not a guarantee that an individual measurement falls within the interval, and it is not a substitute for describing the spread of individual paired differences. The primary outcome specifies a 95% Confidence Interval, but the interval and its associated mean are not reported in the registry record.

Precision depends on features such as the number and distribution of paired observations and the variability of their differences. The enrollment entry alone does not establish how many paired measurements were available or used. The record does not report the primary outcome analysis population, missing paired observations, or a precision calculation.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model assumes. If an analysis assumes less variability than the data contain, uncertainty may be understated and confidence intervals may be too narrow. This concept is relevant when measurements are repeated or clustered, because readings from the same person may be related rather than independent. The registry record does not report whether the analysis treated repeated measurements as independent, modeled within-person correlation, or assessed over-dispersion. It would be inappropriate to infer that any of these methods was used.

What is the role of comparison methods?

In general, comparing measurement methods is different from comparing treatment groups. The goal is to understand whether readings correspond sufficiently for the intended measurement purpose, including any systematic bias and the variability of differences. Correlation alone is not proof of agreement: values may rise and fall together while maintaining a consistent offset or wide individual differences. Here, microdialysis is named in the endpoint description, while blood sampling appears in the outcome title. The record does not give a separate statistical definition for blood-sampling comparisons.

The record lists one outcome measure and no analyses. It does not report model specifications, confidence-interval construction, rules for repeated measurements, outlier handling, or criteria for judging acceptable agreement. Accordingly, statistical explanations of these methods should be understood as general background rather than descriptions of undocumented procedures in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists one outcome measure and no analyses. A single listed outcome does not establish that the protocol had no additional planned comparisons, timepoints, or exploratory measurements; those details are not reported in the registry record. The record also does not describe a multiplicity strategy, such as adjustment of significance thresholds or a hierarchy among outcomes. Since no analysis results are reported, there is no basis for evaluating how multiplicity may have affected a reported finding.

Missing-data handling is not reported in the registry record. It does not state how incomplete measurement pairs, missed timepoints, unusable sensor readings, or withdrawals would be handled. For agreement analysis, missing one of the two measurements in a pair can prevent that pair from contributing to a direct difference calculation. In general, the amount and pattern of missingness can affect both the estimate and its uncertainty; no missingness information is available.

The primary outcome population field is blank, and the record does not define an analysis population. It does not say which enrolled participants contributed to the primary outcome or how the number of usable measurements was determined. Enrollment is listed as 11, while the safety group lists 10 participants at risk; the record does not explain how those entries relate to the endpoint population.

These gaps limit assessment of selective reporting, analysis choices, and the representativeness of the analyzed measurements. They should be treated as unreported details, not as evidence that particular procedures were or were not followed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists a Healthy Volunteer safety group with 10 participants at risk. It reports 0 participants affected by serious adverse events, 0 affected by other adverse events, and 0 deaths. No serious adverse event terms are listed. These figures describe the safety entries in the registry record; they do not describe the primary measurement-agreement endpoint.

A zero in an adverse-event field means that no affected participants are recorded for that category in the listed safety group. It should not be interpreted as proof that an event is impossible or that the study establishes safety in a broader population. In general, safety observations are interpreted in light of the number of participants observed, the observation period, event definitions, and completeness of reporting. The registry record does not provide detailed event definitions or further safety follow-up information.

The overall enrollment entry is 11, whereas the safety group’s at-risk count is 10. The record does not explain the difference, so these counts should not be treated as interchangeable. The listed zero counts do not resolve that discrepancy or establish how many participants contributed to the primary endpoint.

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

This study is described as an in-house feasibility assessment of a microneedle biosensor for tracking phenoxymethylpenicillin concentrations. Its primary endpoint is framed around agreement between microneedle readings and microdialysis measurements, with blood sampling also named in the outcome title. This framing identifies the measurement question, but it does not itself answer it.

The registry record reports no numerical primary outcome result and no analyses. It therefore does not show the estimated mean difference, the 95% Confidence Interval, or the spread of paired differences. Without those results, the direction, size, and precision of any observed disagreement cannot be assessed. Completion of the study and listing of the endpoint do not establish that the device tracked concentrations well or poorly.

In general, a measurement-feasibility study can inform whether a device warrants further evaluation, but interpretation depends on observed agreement, the variability of differences, the measurement range, and the intended use. A mean difference addresses average bias but does not alone establish how closely each individual reading matches a comparator. The registry record does not report numerical limits of agreement or acceptance criteria.

The record also does not provide a randomized control comparison or a clinical outcome question. Consequently, it should not be read as evidence comparing treatment effects. The appropriate statistical reading is narrower: the record documents a planned measurement-agreement assessment in healthy volunteers, but the reported information is insufficient to quantify its findings or their uncertainty.

13. Why This Trial Matters Statistically

The trial is statistically notable for posing a method-comparison question rather than a conventional treatment-effect question. The primary endpoint concerns whether a microneedle biosensor’s concentration readings agree with microdialysis measurements. This distinction matters because agreement and association are not interchangeable. In general, methods can show similar trends but still differ enough in individual readings to be poorly aligned.

The endpoint wording points toward an informative framework: a mean difference can describe average bias, while a Bland-Altman assessment can examine paired differences. A confidence interval can communicate uncertainty around the average difference. Those elements are useful only when accompanied by the actual numerical estimates and an account of the variation across pairs. The registry record names the approach but reports no analysis results, making this an example of why endpoint definitions and observed findings must be kept distinct.

The single-group feasibility context is also important. With no randomized allocation and no masking listed, the record does not describe a blinded, controlled trial of comparative clinical effects. The study’s listed interventions and comparator measurements instead situate the question around a sensing device. Its enrollment and Phase 1 designation do not substitute for evidence about agreement or precision.

For biostatistical interpretation, the record highlights key questions that remain open: how paired readings were formed, how repeated measurements were handled, how many pairs were analyzed, and what level of disagreement would be considered acceptable. These are not reported in the registry record. The statistical importance lies in recognizing both the relevance of the stated method-comparison objective and the limits imposed by absent numerical results and analysis details.

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 principal limitation for interpreting the registry record is that no primary outcome estimate or analysis is reported. Although the endpoint specifies a mean, a 95% Confidence Interval, and a Bland-Altman plot, there are no numerical results with which to assess average bias or variability in paired differences.

The outcome description refers to microneedle and microdialysis measurements, while blood sampling appears in the title. The registry record does not clarify the role of blood sampling in the primary analysis or define a separate statistic for that comparison. Nor does it specify the subtraction order for the mean difference, the number of paired readings, or the measurement schedule within the timeframe of up to 12 hours.

Details about the device procedure, drug dose, data handling, analysis population, missing measurements, repeated-measure methods, and criteria for acceptable agreement are not reported in the registry record. The absence of those details limits reproducibility and makes it difficult to judge whether the stated summary would fully characterize performance across participants and measurements.

The record lists enrollment as 11 but gives a safety at-risk count of 10, without explaining the distinction. The primary outcome population is not reported. This prevents a clear account of how many participants contributed to endpoint analyses. These limitations concern what can be established from the registry record; they do not demonstrate that the study lacked procedures or analyses that were not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Minimally Invasive Sensing of Beta-lactam Antibiotics — NCT03847610.
• Registry record last updated 2024-03-27; status last verified 2024-03.
• Results first posted 2020-12-29.
• 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.

18. Record Summary

NCT03847610 is listed as a completed Phase 1, single-group study sponsored by Imperial College London. It enrolled 11 healthy volunteers, with a start date of 2018-04-12 and primary completion on 2018-08-10. The interventions listed are phenoxymethyl penicillin and a microneedle array. The study summary describes an in-house feasibility assessment of a microneedle biosensor.

The primary outcome assesses tracking of phenoxymethylpenicillin concentrations, specifying a mean with a 95% Confidence Interval in mg/L over up to 12 hours. Its description names a Bland-Altman plot and the mean difference between microneedle and microdialysis measurements. The registry lists one outcome measure and no analyses; numerical endpoint results are not reported in the registry record.

The safety group lists 10 participants at risk, with 0 serious adverse events, 0 other adverse events, and 0 deaths. The record does not explain the difference between this at-risk count and the enrollment entry.