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 N-of-1 Trials In Children With Hypertension (NCT03461003), a randomized phase 4 study. The primary outcome is Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03461003 |
| Phase | Phase 4 |
| Condition | Pediatric Hypertension |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 49 |
| Arms in the primary outcome | n/a |
| Lead sponsor | The University of Texas Health Science Center, Houston |
| Results posted | Yes |
2. Clinical Question
Population
Children with pediatric hypertension, as described in the registry record. The record does not provide additional eligibility details or a more specific description of the enrolled population.
Intervention
The NICHE method: antihypertensive treatment is selected using an n-of-1 trial to identify a preferred therapy. The record defines preference in advance by the greatest reduction in ambulatory blood pressure without intolerable side effects. Listed interventions include the NICHE method and several antihypertensive drugs; the detailed drug description is incomplete in the registry record.
Comparator
Usual care, for which no protocol was introduced to standardize blood pressure management in the control arm. The registry record does not describe the specific treatment decisions made under usual care.
Primary question
Does assignment to the NICHE approach, compared with usual care, result in more participants having ambulatory blood pressure control at 6 months from enrollment? The registry record defines the outcome but does not report a single comparison of the groups for this endpoint.
3. Trial Design
The registry describes a randomized, single-masked, parallel trial of the n-of-1 approach in children with hypertension. The trial is listed as phase 4 and completed. Enrollment is reported as 49. The study dates are 2018-04-02 for the start and 2020-11-14 for primary completion.
The central design contrast is between the NICHE method and usual care. In the NICHE arm, treatment selection uses an n-of-1 trial to identify a preferred therapy for an individual patient. The registry defines the preferred therapy as the one producing the greatest reduction in ambulatory blood pressure without intolerable side effects. The control arm did not introduce a protocol to standardize blood pressure management. Listed interventions include amlodipine, lisinopril, hydrochlorothiazide, and losartan, as well as the NICHE method and usual care. The detailed description of tested drugs is incomplete in the registry record, so it does not establish how each drug was used or allocated.
Although the treatment-selection approach uses individual-patient data, the registered study model is parallel: the listed comparison is between trial arms. The registry calls the masking single but does not report which people were masked. Other operational details, including the randomization procedure and treatment duration, are not reported in the registry record.
The study’s stated aim is to assess whether the n-of-1 approach improves blood pressure control compared with usual care and to advance learning about the use of this trial approach in pediatric hypertension. That statement describes the research question, not a finding. The posted results do not provide a single reduced comparison for the primary outcome.
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 | NICHE Method | Usual Care |
|---|---|---|
| STARTED | 23 | 26 |
| Received Intervention | 21 | 22 |
| Completed 6-month Follow up | 18 | 23 |
| COMPLETED | 18 | 23 |
| NOT COMPLETED | 5 | 3 |
Reasons for not completing this period:
| Reason | NICHE Method | Usual Care |
|---|---|---|
| Lost to Follow-up | 2 | 2 |
| Withdrawal by Subject | 3 | 1 |
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 | NICHE Method | Usual Care | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 26 | 49 | |
| Age, Continuous | years | 15.9 (14.7 to 16.9) | 15.9 (14.4 to 16.8) | 15.9 (14.7 to 16.9) |
| Sex: Female, Male: Female | Participants | 9 | 7 | 16 |
| Sex: Female, Male: Male | Participants | 14 | 19 | 33 |
| Race/Ethnicity, Customized: Hispanic (black or white) | Participants | 17 | 18 | 35 |
| Race/Ethnicity, Customized: White (non-Hispanic) | Participants | 1 | 1 | 2 |
| Race/Ethnicity, Customized: Black (non-Hispanic) | Participants | 5 | 6 | 11 |
| Race/Ethnicity, Customized: Asian | Participants | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 1 | 1 |
| Region of Enrollment: United States | participants | 23 | 26 | 49 |
| Primary language of parent: English | Participants | 11 | 13 | 24 |
| Primary language of parent: Spanish | Participants | 12 | 13 | 25 |
| Clinic Site: Multidisciplinary HTN clinic | Participants | 12 | 14 | 26 |
| Clinic Site: County based clinic | Participants | 11 | 12 | 23 |
| Hypertension type: Primary | Participants | 17 | 22 | 39 |
| Hypertension type: Secondary | Participants | 6 | 4 | 10 |
| Mean 24-hour ambulatory blood pressure at baseline (without medication): Systolic blood pressure | mm Hg | 130 (126 to 133) | 130 (127 to 134) | 130 (127 to 134) |
| Mean 24-hour ambulatory blood pressure at baseline (without medication): Diastolic blood pressure | mm Hg | 76 (71 to 80) | 76 (74 to 81) | 76 (71 to 81) |
| BMI percentile for gender and age | percentile | 96.8 (10.5 to 99.8) | 95.8 (49.0 to 99.8) | 96 (10.5 to 99.8) |
| BMI categories: Underweight | Participants | 0 | 0 | 0 |
| BMI categories: Health weight | Participants | 4 | 6 | 10 |
| BMI categories: Overweight | Participants | 6 | 6 | 12 |
| BMI categories: Obese | Participants | 13 | 14 | 27 |
| Number of participants with Chronic Kidney Disease | Participants | 5 | 3 | 8 |
| Number of participants with Diabetes Mellitus | Participants | 2 | 2 | 4 |
| Number of participants with Proteinuria | Participants | 2 | 3 | 5 |
| Number of participants who avoid calcium channel blocker | Participants | 0 | 1 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Ambulatory Blood Pressure (BP) Control at 6 Months, measured over 6 months from enrollment.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the number of participants with ambulatory blood pressure control at 6 months from enrollment. It is a count endpoint: the outcome is whether a participant meets the registry’s definition of blood pressure control at the stated assessment time.
Control is defined using American Heart Association criteria. Systolic and diastolic blood pressure throughout wake and sleep must be less than the 95th percentile based on the patient’s gender and height. Ambulatory measurement uses a 24-hour blood pressure monitor that records blood pressure at regular intervals across the 24-hour period. This captures readings during both waking and sleeping periods, rather than relying on a single clinic measurement.
This endpoint is relevant to the trial’s question because the intervention aims to select therapy using ambulatory blood pressure information, and the stated primary outcome concerns control measured in that way. However, the registry record does not report the primary endpoint as a single comparison between the NICHE method and usual care. It therefore provides the outcome definition but not a comparative estimate or the precision of such an estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies ambulatory blood pressure control at 6 months from enrollment as the primary outcome and gives a clinical definition for control. It does not provide a single arm-to-arm result for that outcome. The record explicitly indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Accordingly, the posted results do not establish how the groups compared on the primary endpoint, nor do they provide a confidence interval or significance test for a single primary contrast.
This missing comparison limits what can be concluded from the registered results. The study’s aim was to assess whether the NICHE n-of-1 approach improves blood pressure control relative to usual care, but an aim is not an observed result. Without the group-specific primary outcome counts, an effect estimate, and its uncertainty, the direction and precision of a primary-outcome difference cannot be described from this record. No claim about benefit or lack of benefit follows from the absence of a reported comparison.
The registry lists six outcome measures and identifies several secondary outcomes, including changes in mean 24-hour and wake ambulatory systolic blood pressure, self-reported adherence, medication discontinuation due to side effects, and satisfaction. The record does not provide analyses for these outcomes in the information available for this assessment. It lists 0 analyses. That listing should be read as a reporting limitation, not as evidence that no analyses were conducted outside the registry.
The adverse-event information is distinct from the missing primary efficacy comparison. The registry reports group-specific counts for serious and other adverse events and deaths. Those counts describe events recorded in the safety information; they do not fill the gap in the primary blood pressure outcome. In particular, event counts alone do not establish whether an event was caused by an intervention, and the record does not report that attribution.
Overall, the posted information describes the trial question, design, and outcome definitions, and gives limited adverse-event counts. It does not report the comparative primary result needed to quantify the observed difference between the randomized groups. Interpretation should remain bounded by that reporting gap.
9. Statistical Methods Explained
Several statistical ideas help distinguish the trial’s design from the results that are actually reported. The registry describes random assignment to a parallel comparison, but the results record does not present a single reduced comparison for the primary endpoint. These are separate issues: a randomized design can support a comparative estimate, while the registry record still needs to report the outcome data and analysis for that estimate to be interpreted.
What does the primary count represent?
The primary endpoint is a count of participants meeting a binary clinical definition: ambulatory blood pressure is either classified as controlled or it is not, at the specified assessment. The registry defines control using systolic and diastolic readings during wake and sleep, with values required to be less than the 95th percentile based on gender and height. The count is therefore a summary of how many participants meet that definition in an arm; it is not itself a continuous blood pressure measurement.
For a binary endpoint, a comparative analysis may describe the difference between the proportions meeting the definition, a ratio of those proportions, or another suitable contrast. Those are general examples of possible summaries, not results reported for this trial. The record does not provide a single primary-outcome comparison, so no such estimate should be inferred. Group counts and denominators are necessary context for interpreting an estimate, and the primary group-specific counts are not reported in the registry record.
Why does uncertainty matter?
A confidence interval is a statistical range expressing the uncertainty around an estimated effect under the assumptions of the analysis. It helps readers assess which effect sizes are compatible with the observed data; it is not a guarantee that the true effect lies within the interval. A point estimate without an interval gives less information about precision, while an interval without a clearly defined estimate and analysis can also be difficult to interpret. No confidence interval for a single primary comparison is reported in the registry record.
A significance test addresses compatibility between the observed data and a specified null hypothesis under a statistical model. A p-value does not measure the probability that the null hypothesis is true, and it does not convey the size or clinical importance of an effect. No p-value for a reduced primary comparison is reported in the registry record. In the absence of a defined comparison and its uncertainty, a significance claim cannot be made from the posted primary outcome information.
How should the n-of-1 approach be understood?
In general, an n-of-1 trial uses repeated observations within an individual to inform which treatment may be preferable for that individual. The registry says the NICHE method uses this approach to select preferred antihypertensive therapy, with preference defined in advance by greatest ambulatory blood pressure reduction without intolerable side effects. This individual-level treatment-selection concept is not the same as the registered trial’s overall comparison. The registry lists a parallel model, with NICHE and usual care as the arms. The record does not describe the details needed to reconstruct individual treatment sequences or how patient-level decisions were aggregated for analysis.
What do the planning calculations mean?
Sample-size calculations are planning illustrations, not observed trial findings. The registry’s stated assumptions describe illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations ask what sample size might be needed under those assumptions. They do not represent the study’s observed power, and they are not evidence that the original design used those assumptions. The registry record does not report the trial’s own sample-size justification or statistical plan. Since no reduced primary comparison is reported, the planning illustrations should not be treated as an independent substitute for the missing outcome estimate.
Why can outcome definitions and analyses differ?
The primary outcome is described as having several categories or time points and is not reduced to one comparison in the record. A study may collect measurements at multiple times or classify outcomes in several ways; an analysis must specify which observations contribute to the comparison and how repeated measurements are handled. Those decisions affect the estimand, meaning the precise treatment effect the analysis is intended to describe. The registry record does not report enough detail to identify a single estimand or analysis for the primary outcome. General explanations of statistical methods cannot resolve that reporting gap.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists six outcome measures, including the primary ambulatory blood pressure control outcome and secondary measures relating to ambulatory systolic pressure, medication discontinuation due to side effects, self-reported adherence, and satisfaction. When a study examines multiple outcomes, time points, or alternative comparisons, the chance of finding at least one apparently notable result can increase. This is the general issue of multiplicity. Prespecified testing strategies can help control or contextualize that issue, but the registry record does not report a multiplicity strategy or identify which outcomes were formally tested.
The record states that the primary outcome has several categories or time points and was not reduced to one comparison. It lists 0 analyses. This means the posted registry information does not give the analysis details needed to understand how outcome categories or time points were handled. It does not establish that no analysis occurred elsewhere. The statistical analysis plan, including any interim analyses, is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The record does not describe how unavailable ambulatory measurements, missing follow-up, or incomplete survey responses were handled, or whether any sensitivity analyses were used. It also does not report analysis populations, such as the exact set of randomized participants included in each outcome analysis.
These omissions matter because the interpretation of a treatment comparison depends on which participants and observations were included and how multiple outcomes were considered. They do not justify assuming a particular method or treating unreported analyses as negative findings. The available registry information supports describing the planned outcome domains, but not reconstructing the multiplicity, missing-data, or analysis-population decisions.
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 |
|---|---|---|---|
| NICHE Method | 0 | 23 | 0.0% |
| Usual Care | 0 | 26 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| NICHE Method | 0 of 23 |
| Usual Care | 0 of 26 |
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 |
|---|---|
| NICHE Method | 0 of 23 |
| Usual Care | 3 of 26 |
Most frequent non-serious adverse event terms
| Event term | Organ system | NICHE Method | Usual Care |
|---|---|---|---|
| Dizziness | Gastrointestinal disorders | 0 of 23 | 1 of 26 |
| Tiredness | General disorders | 0 of 23 | 1 of 26 |
| Sleeping Poorly | General disorders | 0 of 23 | 1 of 26 |
The registry reports no serious adverse events for the NICHE Method group, with 23 participants at risk, and no serious adverse events for the Usual Care group, with 26 participants at risk. It reports no deaths in either group. For other adverse events, the registry records 0 in the NICHE Method group, with 23 participants at risk, and 3 in the Usual Care group, with 26 participants at risk.
These are the posted counts, not a comparative safety analysis. The registry does not report event descriptions for the other adverse events, their severity, timing, or whether investigators considered them related to an intervention. The counts therefore should not be interpreted as evidence about causation or as a complete characterization of risk. The record also does not provide an uncertainty estimate for a between-group safety contrast. The event figures are best read as descriptive reporting within the registry, alongside the limitations in event detail and analysis.
12. What the Result Does, and Does Not, Mean
The record establishes that the study was designed to compare an n-of-1 treatment-selection approach with usual care in children with hypertension. It specifies ambulatory blood pressure control at 6 months from enrollment as the primary endpoint and gives the definition used to classify control. It also reports selected safety counts. These details clarify the question the trial was intended to address.
The record does not provide a single comparative primary-outcome result. Consequently, it does not show the magnitude or direction of a difference in control between the arms, how precisely such a difference was estimated, or whether a statistical test supported a particular interpretation. The study’s stated objective must not be mistaken for evidence that the approach improved control, and the absence of a reported result must not be mistaken for evidence that it did not.
The n-of-1 concept is intended to use an individual patient’s data to guide treatment selection. This trial’s registered design, however, is a randomized parallel comparison of the NICHE method with usual care. A reader can understand the intended contrast from the record, but cannot evaluate its primary comparative outcome without the missing group results and analysis.
The listed adverse-event counts offer limited descriptive safety information, not proof of safety or harm. Important analysis details—including how missing outcomes were handled, which participants entered each analysis, and how multiple outcomes or time points were addressed—are not reported in the registry record. Overall, the record documents a clinically focused randomized research question, while the posted outcome information is insufficient to determine the comparative result.
13. Why This Trial Matters Statistically
This trial is statistically notable because it brings together two levels of evidence. An n-of-1 approach aims to use repeated data from an individual to inform treatment choice, while the registered study evaluates the approach through a parallel randomized comparison with usual care. The distinction matters: an individualized treatment process and an arm-level trial comparison answer related but different questions.
The primary endpoint also depends on a defined ambulatory measurement and classification rule. Blood pressure is assessed over a 24-hour period, with control determined from systolic and diastolic values during wake and sleep against a percentile threshold based on gender and height. This makes the outcome more specific than a general label of improved blood pressure, while also making complete measurement and clear analysis decisions important for interpretation.
The registry illustrates why outcome definitions alone are not enough to assess a trial. A stated primary endpoint does not tell readers the observed group counts, the estimated contrast, or the uncertainty around it. Since the registry does not report a single primary comparison, the central statistical question remains unanswered in the posted results. Reporting that limitation clearly is important: it separates the rationale and design of a trial from evidence about its observed comparative outcome.
The record also highlights the need to describe how individual-level decisions are translated into a trial-level analysis. The registry does not provide the detailed analysis plan needed to evaluate that connection. Thus, the trial’s design is relevant to researchers studying both individualized treatment selection and randomized evaluation, but the available results do not support a statistical conclusion about comparative effectiveness.
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 main limitation of the registry record is that it does not report the primary outcome as a single comparison between the randomized groups. The record notes that the outcome has several categories or time points and was not reduced to one comparison. It therefore lacks the primary group-specific counts, an effect estimate, and an uncertainty interval needed to assess the central trial question.
Further analysis details are not reported in the registry record. These include the statistical plan, the handling of missing outcome data, the analysis populations, and the approach to multiple outcomes or time points. The record also lists 0 analyses, which limits the available detail but does not show whether analyses were conducted outside the registry.
The description of the NICHE approach and tested drugs is incomplete. While the registry lists several antihypertensive drugs and defines preferred therapy in terms of ambulatory blood pressure reduction without intolerable side effects, it does not fully describe treatment sequences, individual-level decision rules, or how those decisions were represented in the comparative analysis. The record also does not identify which people were masked despite listing single masking.
Safety reporting is limited to counts. Event descriptions, attribution, timing, and comparative uncertainty are not reported in the registry record. These limitations restrict interpretation of both efficacy and safety; they should not be filled by assumptions about the protocol or analyses.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: N-of-1 Trials In Children With Hypertension — NCT03461003.
- Registry record last updated 2022-09-09; status last verified 2022-08.
- Results first posted 2022-09-09.
- 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 completed, randomized, single-masked, parallel phase 4 trial comparing the NICHE n-of-1 method with usual care in children with hypertension. Enrollment is reported as 49. The primary endpoint is the number of participants with ambulatory blood pressure control at 6 months from enrollment, defined using American Heart Association criteria for systolic and diastolic blood pressure across wake and sleep.
The registry does not report a single comparative result for the primary endpoint and lists 0 analyses. It reports no serious adverse events or deaths in either arm, and other adverse-event counts of 0 for NICHE Method and 3 for Usual Care. These safety figures are descriptive; event details and attribution are not reported. Key information about analysis methods, missing data, and analysis populations is also not reported in the registry record.