HEXT (Hypo EXTended): Effect of PTH on Skeleton in Hypoparathyroidism: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for HEXT (Hypo EXTended): Effect of PTH on Skeleton in Hypoparathyroidism (NCT01199614), a na phase 3 study. The primary outcome is Change in Dose of Calcium Supplementation.

2. Clinical Question

The study summary also states broader aims: assessing long-term control of serum and urinary calcium, quality of life, safety when PTH(1-84) is administered for up to 12 years, and changes in typical signs and symptoms of hypoparathyroidism. Those aims provide context, but they are not substitutes for the primary endpoint. The listed secondary outcome is percent change in bone mineral density by DXA. Numerical results for the primary outcome are not reported in the registry record, so the direction and size of the observed dose change cannot be described from this record.

3. Trial Design

HEXT is recorded as a Phase 3, completed, single-group study sponsored by Columbia University. The registry lists a start date of 2009-12 and a primary completion date of 2017-06-26. Enrollment was 62. Allocation is listed as NA, and masking is listed as none. The intervention is open-label PTH(1-84), with variable dosing rather than a fixed dose specified for all participants.

The study summary describes visits every six months at the principal investigator’s study offices. For new patients who had not previously used PTH(1-84), it also describes a screening visit four weeks before baseline and a local pre-baseline laboratory assessment to check stability before baseline. These details describe the planned visit structure in the summary; the record does not give participant-level attendance or follow-up information.

The primary outcome is change in calcium-supplementation dose, expressed as percent change, with a timeframe of baseline to up to 4 years. The outcome description says the analysis included 27 evaluable subjects treated with open-label PTH(1-84) for 4 years. This is a subset of the enrollment count, but the reasons that fewer subjects are included in that outcome description are not reported in the registry record.

Because there is no listed control group, changes over time are observed within the treated cohort rather than contrasted with outcomes under a concurrent alternative. The record describes long-term safety as an aim of treatment for up to 12 years; it does not establish from the information reported that every participant was followed for that duration. The study’s detailed protocol, statistical analysis plan, and reasons for the selected design 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

Analysis population for the primary outcome, as defined in the registry: Analyzed data from this cohort included 27 evaluable subjects treated with open-label PTH(1-84) for 4 years.

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 Change in Dose of Calcium Supplementation, measured over Baseline, up to 4 years.

The primary endpoint is change in the dose of calcium supplementation. It is expressed as percent change, with baseline as the reference period and follow-up extending up to 4 years. The registry identifies the measure as continuous and states that the reported summary is a mean with standard deviation. Its description links supplementation requirements to maintaining serum and urinary calcium levels.

This endpoint is useful for describing whether calcium supplementation requirements changed during treatment. In a condition where calcium levels are monitored and supplementation is part of care, dose change can represent an important aspect of treatment management. However, dose change alone does not establish why a dose changed, whether calcium levels were stable for each participant, or whether other outcomes changed. Interpreting it alongside serum and urinary calcium measurements would require those results, which are not reported in the registry record.

The registry describes the primary-outcome population as 27 evaluable subjects who received open-label PTH(1-84) for 4 years. It does not provide the numerical mean change, standard deviation, confidence interval, or a statistical test for this endpoint. Consequently, the magnitude and precision of the primary outcome cannot be assessed from the record. The endpoint’s definition and population are reported, but its numerical finding is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome summarized by a mean and standard deviation. A mean is a measure of the central level of observations, while a standard deviation describes how spread out observations are around that mean. For this endpoint, the observations concern percent change in calcium-supplementation dose. The registry does not provide the actual mean or standard deviation, so neither the central result nor its observed variability can be assessed.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with the observed data under a specified statistical procedure. It helps distinguish the estimated size of an effect from the uncertainty around that estimate. A narrow interval indicates greater precision than a wide interval, although precision alone does not establish clinical importance or eliminate bias. No confidence interval for the primary endpoint is reported in the registry record. Its width and the precision of the endpoint estimate therefore cannot be evaluated.

What does the single-group design allow?

In general, a single-group analysis describes outcomes among participants receiving the study intervention. It can show how measurements changed over time in that group, if the relevant estimates are reported. Without a concurrent comparator, it cannot directly estimate how those outcomes would have changed under a different treatment or without the intervention. Other changes over time may contribute to within-group changes. Here, the record lists a single-group model, open-label treatment, no masking, and allocation as NA; it does not list a control arm.

The primary endpoint’s timeframe is baseline to up to 4 years, and the outcome description identifies 27 evaluable subjects treated for 4 years. The record identifies mean and standard deviation as the summary measures, but it does not state the exact statistical test, model, covariates, or handling of repeated measurements. Those analysis details are not reported in the registry record. It is therefore not possible to determine whether the posted analysis, if any, adjusted for participant characteristics or used all available measurements over time.

What do the sample-size illustrations mean?

The described sample-size calculations are planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider effects defined as stated fractions of the observed effect. Such calculations ask, in general, how many participants per arm might be needed under the assumptions for a future two-arm comparison. They are not the design used in this single-group trial and are not evidence of the trial’s achieved power. The record does not report the numerical planning outputs or the observed effect used to generate them, so no required sample size can be stated.

A planning calculation depends on its assumptions. In general, the effect size chosen determines how demanding the target comparison is: planning for a smaller effect requires more information than planning for a larger one, all else equal. The significance level, allocation, and statistical approximation also shape the result. These illustrations should therefore be read as conditional scenarios, not as guarantees that a study will detect an effect or as summaries of what the current cohort observed.

Why can over-dispersion matter?

In general, over-dispersion occurs when outcome variability is greater than a statistical model expects. If a model assumes less variability than the data contain, it can understate uncertainty and make results appear more precise than they are. Models designed to account for extra variation may be needed for outcomes whose variability exceeds their assumptions. The primary endpoint is identified as continuous and summarized with a mean and standard deviation; the registry does not report an over-dispersion assessment or a model addressing it. No claim about over-dispersion in this study can therefore be made.

The registry record lists zero analyses. It does not report a test statistic, p-value, confidence interval, adjusted estimate, or detailed analysis procedure for the primary outcome. Consequently, statistical significance and precision are not available for interpretation. The absence of these details is distinct from evidence that an analysis found no change: the record does not report a numerical estimate that would support either conclusion.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Open-label PTH(1-84)")
n   <- c(27)
m   <- c(37)
sp  <- c(43)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Open-label PTH(1-84)  27  37.000  43.000  19.990  54.010

11. Multiplicity, Missing Data and Analysis Populations

The registry record describes a primary outcome and lists percent change in BMD by DXA as a secondary outcome. The study summary also states aims concerning serum and urinary calcium, quality of life, safety, and typical signs and symptoms. It does not report how many formal hypotheses were tested, whether outcomes were ordered in a testing hierarchy, or whether any adjustment for multiple comparisons was planned. Multiplicity procedures and their rationale are not reported in the registry record.

When multiple outcomes or comparisons are examined, general statistical practice recognizes that the chance of at least one apparently notable finding can increase if each is assessed independently. Prespecified outcome priorities and multiplicity procedures can help clarify how results should be interpreted. Because the registry does not report such procedures or numerical outcome tests, the impact of multiplicity on this study’s conclusions cannot be evaluated.

The primary outcome description refers to 27 evaluable subjects treated for 4 years, compared with enrollment of 62. The reasons for this difference and the number or pattern of missing measurements are not reported in the registry record. No missing-data method, imputation approach, sensitivity analysis, or participant flow accounting is described. It is therefore not possible to determine whether the analyzed participants differ from those without evaluable endpoint data or how missing outcomes might affect the estimate.

The record does not describe an intention-to-treat population or other prespecified analysis populations. It identifies the 27 subjects as evaluable for the primary outcome, but the criteria for evaluability are not reported in the registry record. These gaps limit assessment of whether the analysis followed a prespecified plan and how robust the outcome might be to choices about inclusion or missing data.

12. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypocalcemia (21.0%), surgery elective (4.8%), swelling of face, tongue (4.8%), pneumonia (3.2%), infection in uterus (3.2%).

The registry reports 62 people at risk for serious adverse events, with 25 affected, in the open-label PTH(1-84) group. It also reports 62 at risk for other adverse events, with 27 affected. Deaths are reported as 0. The registry lists selected serious-event terms with percentages: Hypocalcemia, 21.0%; Surgery elective, 4.8%; Swelling of face, tongue, 4.8%; Pneumonia, 3.2%; Infection in uterus, 3.2%; and Hypercalcemia, 1.6%.

These figures describe safety reporting in the treated group. The listed percentages are reported as written; the record does not provide event counts for each listed term in this summary. The serious-event terms should not be read as proof that treatment caused those events. The registry does not report an attribution assessment, timing, event duration, exposure time for each participant, or a concurrent control group for comparison. It also does not provide enough information to determine whether a person could contribute more than one event term. The counts and terms therefore characterize reported events, but they do not provide a comparative rate or establish causation.

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

The record documents a study of open-label PTH(1-84) in hypoparathyroidism and identifies change in calcium-supplementation dose as the primary outcome. It reports that the endpoint analysis included 27 evaluable subjects treated for 4 years. It also records enrollment of 62 and describes safety events in the treatment group. These details establish the study context and what was recorded, but they are not enough to quantify the primary outcome.

The numerical mean change, standard deviation, confidence interval, and statistical test for the primary endpoint are not reported in the registry record. Thus, the record does not show how much the calcium-supplementation dose changed or how precisely that change was estimated. No conclusion that the dose increased, decreased, or stayed the same can be drawn from the endpoint information reported.

The study’s single-group, open-label design does not provide a randomized, concurrent comparison. Even if a within-group change were reported, it would not by itself show what would have happened under a different treatment or in the absence of the study intervention. The record also does not report results for the listed secondary BMD outcome or numerical findings for the other aims in the study summary.

The safety counts and listed serious-event terms indicate that events were recorded among participants at risk, and the registry reports 0 deaths. Without a comparator, exposure details, or attribution information, these figures cannot establish whether events were caused by treatment or whether event occurrence differed from another treatment condition.

The findings that can be stated from this record are therefore limited: the study was completed, used an open-label single-group design, and specified a primary dose-change outcome. The clinical size, statistical precision, and comparative meaning of that outcome are not reported in the registry record. These limitations do not demonstrate that there was no effect; they mean the numerical evidence needed to characterize an effect is absent from the record.

14. Why This Trial Matters Statistically

This study is statistically instructive because the registry identifies a continuous endpoint that is tied to treatment management rather than a direct comparison between randomized groups. The primary outcome concerns percent change in calcium-supplementation dose, and the summary connects that measure with serum and urinary calcium levels. Interpreting such an endpoint requires attention to the measurement definition, follow-up period, and participant set, not simply the direction of a reported mean.

The record also highlights the distinction between enrollment and an endpoint analysis population. Enrollment is 62, while the primary-outcome description identifies 27 evaluable subjects treated for 4 years. A statistical reader needs the reasons for the difference, the rules used to define evaluability, and the handling of missing observations to judge whether the analysis represents the enrolled cohort. Those details are not reported in the registry record.

Its single-group design is another important interpretive feature. Within-group changes can describe the course of observed measurements, but causal or comparative claims require more than a before-and-after description. Without a control group, changes over time cannot be directly contrasted with an alternative condition. Open-label conduct also means masking is not part of the design, although the record does not describe whether or how that affected measurement or analysis.

Finally, a clearly named endpoint does not guarantee that its statistical result is available for scrutiny. The record states the summary measure and timeframe but does not report the numerical estimate or uncertainty. That distinction matters: endpoint definition, study completion, and safety listings are not replacements for a reported outcome estimate. The record is useful for understanding the design and intended questions, while leaving the primary result’s magnitude and precision unresolved.

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 most direct limitation for interpreting this trial record is that the primary endpoint’s numerical result is not reported. Although the outcome is defined as percent change in calcium-supplementation dose and the record identifies a mean and standard deviation as summaries, neither value is stated. There is also no reported confidence interval or test result. Consequently, the primary finding cannot be quantified or assessed for precision.

The outcome population is reported as 27 evaluable subjects treated for 4 years, while enrollment was 62. The registry does not explain why these counts differ, define evaluability, describe participant flow, or report missing-data methods. This prevents assessment of whether the endpoint analysis may be affected by incomplete follow-up or selection into the evaluable group.

The single-group, open-label design has no concurrent comparison in the record. It can describe outcomes observed during treatment, but cannot provide a randomized estimate contrasting PTH(1-84) with another condition. The registry does not report the detailed protocol, statistical analysis plan, or adjustments that might clarify the analysis choices.

The study summary states aims beyond the primary endpoint, including long-term calcium control, quality of life, safety, and symptoms. Numerical results for these aims are not reported in the registry record. The listed secondary outcome is BMD change by DXA, but its numerical result is also not reported. The safety information gives affected counts and selected serious-event percentages without timing, exposure duration, attribution, or a concurrent comparison. These limitations constrain interpretation of both efficacy-related outcomes and safety findings.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: HEXT (Hypo EXTended): Effect of PTH on Skeleton in Hypoparathyroidism — NCT01199614.
• Registry record last updated 2024-07-05; status last verified 2024-07.
• Results first posted 2024-07-05.
• 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.

19. Record Summary

HEXT is a completed Phase 3, open-label, single-group study of PTH(1-84) in hypoparathyroidism, sponsored by Columbia University. The registry reports enrollment of 62, a start date of 2009-12, and a primary completion date of 2017-06-26. The primary outcome is change in calcium-supplementation dose, expressed as percent change from baseline up to 4 years. Its description identifies 27 evaluable subjects treated for 4 years.

The registry does not report the numerical primary-outcome estimate, its variability, or a statistical test. It lists percent change in BMD by DXA as a secondary outcome and reports selected safety information, including 0 deaths. The reasons for the difference between enrollment and the evaluable endpoint population, the missing-data approach, and the detailed statistical plan are not reported in the registry record. The single-group design does not provide a concurrent randomized comparison.