Safety and Efficacy of CTAP101 to Treat Secondary Hyperparathyroidism in Stage 3 or 4 CKD and Vitamin D Insufficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of CTAP101 to Treat Secondary Hyperparathyroidism in Stage 3 or 4 CKD and Vitamin D Insufficiency (NCT01704079), a randomized phase 3 study. The primary outcome is Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline.

2. Clinical Question

The trial was designed to evaluate efficacy as well as safety and tolerability. Its primary outcome is a responder count: each participant is classified according to whether the stated iPTH reduction threshold was attained. The posted result therefore describes the frequency of this defined response in each randomized group; it does not, by itself, describe the size of each participant’s hormone change or the distribution of changes across participants.

The comparison is between CTAP101 and placebo within the trial population and follow-up period. The result should be read in that context. The registry record does not report further eligibility details, such as the precise laboratory thresholds used to define vitamin D insufficiency, so those details cannot be inferred from the population description alone.

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled study sponsored by OPKO IP Holdings II, Inc. The registry record lists 216 participants as enrolled and the study status as completed. The recorded study period began in 2012-11, with primary completion in 2014-08.

Participants were assigned to CTAP101 30 μg capsules or a sugar pill matched to CTAP101. The study was double-blind, meaning the design masked treatment assignment, although the registry record does not describe which study personnel or participants were masked or how masking was maintained. It identifies a parallel-group model, so the comparison is between groups followed during the study rather than a crossover between treatments.

The intervention description states that the CTAP101 group began with one capsule daily at bedtime for 12 weeks, with a possible increase to two capsules daily for the rest of the study if needed. The placebo group received one sugar pill daily at bedtime for 12 weeks and then two sugar pills for weeks 13–26. The intervention description for CTAP101 is truncated in the registry record, so further details about dose adjustment or matching procedures are not reported there. The trial’s overall duration is described as 26 weeks, while the primary outcome timeframe is approximately 6 months.

The posted primary analysis uses the intent-to-treat population. A per-protocol population is also reported for secondary outcomes. The registry record does not explain how participants were assigned to those populations, how deviations from the protocol were handled, or whether additional analysis populations were used. Details of the randomization procedure, allocation concealment, stratification, and trial-specific sample-size justification 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.

Before assignment: Subjects were stratified by CKD stage and were randomized in a 2:1 ratio to receive a daily 30 μg oral dose of CTAP101 capsules (or matching placebo) for 12 weeks at bedtime. Subjects presenting on a regimen of bone metabolism therapy were to discontinue their prior treatment for at least 28 days' washout (except for bisphosphonates).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat

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 Number of Participants in the Intent to Treat Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline, measured over Approximately 6 months.

The primary endpoint counts participants in the intent-to-treat population who achieved a decrease in plasma intact parathyroid hormone (iPTH) of at least 30% from pretreatment baseline. The registry gives the timeframe as approximately 6 months and describes participants attaining the threshold as responders. This is a binary endpoint: each participant either meets the specified response definition or does not.

A threshold endpoint can make a trial question concrete. Instead of asking whether the average laboratory value changed, it asks how many participants crossed a prespecified response boundary. Comparing the number meeting that definition between randomized groups can describe whether the response occurred more often in one group during the study. The posted counts and unadjusted comparisons offer one way to express that contrast.

As a general statistical point, categorizing a continuous measurement at a threshold can simplify interpretation, but it also discards information about the magnitude of change. A participant just meeting the cutoff and one with a much larger reduction are both counted as responders. The registry record does not report the rationale for selecting the 30% threshold, the exact calculation used to determine each participant’s change, or further details of the efficacy assessment phase. The result therefore answers the stated responder question, not every possible question about iPTH trajectories or the clinical meaning of different-sized changes.

7. Results Posted in the Registry

• CTAP101 30 μg Capsules: 34.0% (49/144) versus 6.9% (5/72) on control; risk difference 27.1 percentage points (95% CI 17.4 to 36.8), risk ratio 4.90 (2.04–11.76); unadjusted two-proportion z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CTAP101 30 μg Capsules: 39.5% (47/119) versus 8.3% (5/60) on control; risk difference 31.2 percentage points (95% CI 19.9 to 42.4), risk ratio 4.74 (1.99–11.29); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for CTAP101 30 μg Capsules than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CTAP101 30 μg Capsules: 83.3% (120/144) versus 6.9% (5/72) on control; risk difference 76.4 percentage points (95% CI 67.9 to 84.8), risk ratio 12.00 (5.14–28.04); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for CTAP101 30 μg Capsules than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • CTAP101 30 μg Capsules: 97.5% (116/119) versus 8.3% (5/60) on control; risk difference 89.1 percentage points (95% CI 81.6 to 96.7), risk ratio 11.70 (5.05–27.09); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for CTAP101 30 μg Capsules than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover the iPTH responder definition in the per-protocol population and normal serum total 25-hydroxyvitamin D in both the intent-to-treat and per-protocol populations. Across these outcomes, the observed results follow a pattern favoring the CTAP101 group. The secondary findings therefore point in a direction broadly consistent with the primary responder comparison, while addressing related but distinct outcomes and populations.

The per-protocol iPTH outcome is related most directly to the primary endpoint because it uses the same reduction threshold but a different analysis population. The vitamin D outcomes assess whether serum total 25-hydroxyvitamin D was normal, rather than whether iPTH crossed the primary response threshold. They provide additional information about a different laboratory measure. This relationship does not make the secondary outcomes substitutes for the primary endpoint, nor does it establish that one outcome caused another.

Each secondary outcome has a reported Cochran-Mantel-Haenszel p-value of < 0.001, and the posted unadjusted comparisons also report p-values of <0.001. These results should be interpreted cautiously as secondary evidence. General statistical explanation: when several outcomes are tested, the chance of obtaining at least one apparently unusual result can increase unless the analysis accounts for multiple testing. The registry record does not report whether a multiplicity adjustment was planned or used, so the secondary p-values should not be treated as if they necessarily control an overall error rate.

The registry lists three secondary outcomes, but it does not provide a complete hierarchy of hypotheses, indicate which secondary analyses were confirmatory, or report a multiplicity strategy. The pattern can be noted without assigning the same evidential weight to each result as to the primary endpoint. The secondary analyses add context to the trial’s outcome profile, but their populations, outcome definitions, and multiplicity status limit how strongly they can support broader conclusions.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants in the Per Protocol Population With Decrease in Plasma Intact Parathyroid Hormone (iPTH) of ≥30% From Pre-treatment Baseline
• Subjects in the Intent to Treat Population With Normal Serum Total 25-hydroxyvitamin D
• Subjects in the Per Protocol Population With Normal Serum Total 25-hydroxyvitamin D

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary because each participant is counted as a responder or non-responder according to whether iPTH decreased by at least 30% from pretreatment baseline. The posted results give the number of participants in each group and the number counted as responders. An unadjusted comparison can be calculated from those group counts, treating the two groups as independent. The recalculated result is a simple comparison and does not represent a model adjusted for other variables or trial strata.

What does the risk difference express?

The risk difference is the difference between the response proportions in the two groups. Its posted estimate is 0.271, with an interval from 0.174 to 0.368. This is an absolute contrast on the proportion scale. General explanation: absolute contrasts can be useful because they describe how far apart the observed response proportions are, rather than expressing one proportion relative to another. The registry record does not report an adjusted risk-difference estimate from the sponsor’s analysis.

How do relative measures differ?

The posted unadjusted risk ratio is 4.9, with an interval from 2.041 to 11.76. It compares the response proportion in the CTAP101 group with the response proportion in the placebo group as a ratio. The posted odds ratio is 6.912, with an interval from 2.615 to 18.27. An odds ratio compares odds rather than proportions. General explanation: risk ratios and odds ratios are relative measures, while the risk difference is an absolute measure. They are not interchangeable, and a large relative measure does not by itself convey the absolute frequency of the outcome. The group counts and proportions are needed to understand the setting for these comparisons.

What does the sponsor-reported test add?

The registry reports a Cochran-Mantel-Haenszel analysis for the primary comparison and a p-value of < 0.001. General explanation: a Cochran-Mantel-Haenszel procedure can assess an association between treatment group and a categorical outcome across strata. The registry record does not state the strata used, whether the analysis was adjusted for particular factors, or the detailed test specification. It reports no corresponding effect estimate or interval for this analysis, so the p-value alone does not quantify the magnitude or precision of the sponsor’s estimated treatment contrast.

The recalculated unadjusted test is reported separately with p <0.001. The two p-values arise from different reported analyses and should not be treated as identical tests. Both are below the displayed thresholds, but the sponsor’s analysis remains the trial-reported analysis. The record does not provide the full analysis plan needed to establish whether additional adjustments or testing procedures were prespecified.

Why use an interval as well as a p-value?

General explanation: a confidence interval represents a range of values compatible with the data under a particular statistical method and its assumptions. It helps describe the uncertainty and scale of an estimate, while a p-value addresses evidence against a null hypothesis. An interval is not a guarantee that the true effect lies within its limits, and its interpretation depends on the method and confidence level. The confidence level is not reported in the registry record for the posted intervals, so it should not be assumed from the displayed values alone.

The reported intervals for the recalculated risk difference, risk ratio, and odds ratio are based on the posted summary counts. They are unadjusted. They do not account for possible missing outcomes, clustering, stratification, or other features unless those are part of the calculation; the posted recalculations are explicitly unadjusted. The registry does not report enough detail to assess whether other analysis methods were used in the sponsor’s full statistical plan.

What do the population labels mean?

The primary endpoint is reported for the intent-to-treat population, while one secondary iPTH endpoint is reported for the per-protocol population. General explanation: intent-to-treat analyses are commonly intended to preserve the comparison based on randomized assignment, whereas per-protocol analyses focus on participants meeting specified protocol conditions. The exact definitions and exclusions for these populations are not reported in the registry record. Differences between populations can affect which participants contribute to an estimate, so the per-protocol result should not be read as identical to the primary intent-to-treat analysis.

For the secondary outcomes, the registry also reports Cochran-Mantel-Haenszel p-values. Those analyses concern distinct outcomes and, in one case, a distinct analysis population. Their p-values do not establish that a formal adjustment for multiple comparisons was made. The multiplicity plan and missing-data methods are not reported in the registry record.

11. Confidence Intervals and Precision

The primary unadjusted risk-difference estimate is 0.271, with an interval from 0.174 to 0.368. This interval gives a range for the absolute contrast in response proportions under the unadjusted calculation. Both limits are above zero, so the interval does not include no difference on the risk-difference scale. The registry record does not report the confidence level associated with the interval, which limits how specifically its coverage can be described.

The relative estimates are less tightly bounded in proportional terms: the posted risk ratio is 4.9, with an interval from 2.041 to 11.76, and the odds ratio is 6.912, with an interval from 2.615 to 18.27. These intervals reflect uncertainty in relative measures calculated from the same group results. Their breadth indicates that the exact relative contrast is not pinned down to a single value, even though the estimates favor a higher responder proportion in the CTAP101 group.

General explanation: precision concerns the range of plausible effect values, not merely whether a test crosses a significance threshold. A narrower interval generally indicates greater precision for the particular estimate and method; a wider interval leaves more uncertainty about its size. Precision depends on the data and analysis assumptions. Here, the intervals are unadjusted recalculations from posted summary statistics, and they do not represent an adjusted sponsor estimate. The registry does not provide the interval level, a sponsor effect interval, or details sufficient to assess all sources of uncertainty. Accordingly, the point estimate and interval should be read together with the analysis population, endpoint definition, and follow-up timeframe.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total events. This trial’s outcomes are participant counts, so the listed figures are per-arm participant requirements for planning illustrations. The assumptions stated for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each illustration uses a stated fraction of the observed effect as the effect to detect.

The 80% power column means the number of participants per arm in the planning calculation for an 80% chance of detecting the stated effect under those assumptions, if that effect were the true one and the assumptions held. The 90% power column uses the same interpretation with a 90% chance. These are planning quantities, not observed features of the trial. They do not show the trial’s probability of success after the results were observed and are not observed power.

The rows that plan for 100%, 75%, and 50% of the observed effect represent progressively smaller target effects. Smaller effects are harder to distinguish from random variation, so the planning illustrations require more participants per arm as the target effect gets smaller. These figures are derived from the observed result and are not the trial’s original design calculation. The original design assumptions and sample-size justification are not reported in the registry record.

Any curve associated with these planning results should be read as illustrating the same assumptions and relationship between target effect and required sample size, rather than as a record of the trial’s actual recruitment or a guarantee that a future study will achieve its target. The calculations use equal allocation even though the posted primary analysis groups do not have equal participant counts. That distinction is another reason to treat them as illustrations rather than as a reconstruction of the study design.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.069; treatment proportion p₁ = 0.340; average p̄ = 0.205.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5708 = 1.1187.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5377 = 0.4525.
4. n = (1.1187 + 0.4525)² / (0.2708)² = 33.7, rounded up to 34 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.0694444444444444                          # control proportion
p1 <- 0.340277777777778                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1704079)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 34 (80% power), 45 (90% power)
 75% of observed effect: n per arm = 53 (80% power), 71 (90% power)
 50% of observed effect: n per arm = 101 (80% power), 134 (90% power)
power.prop.test: 33.7 
Simulated power at n = 34 per arm: 0.835 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as a Cochran-Mantel-Haenszel comparison with p < 0.001. It does not report the effect estimate, confidence interval, stratum details, or full test specification for that analysis. The sponsor-reported result therefore provides evidence from the stated categorical analysis but does not quantify the sponsor analysis’s effect size in the registry record.

The unadjusted recalculation uses the posted group counts to estimate a risk difference of 0.271, with an interval from 0.174 to 0.368, and reports p <0.001. This is not the same analysis as the Cochran-Mantel-Haenszel test. It is a direct, unadjusted comparison of the group response proportions, while the registry names a method that can accommodate stratification. The record does not state which strata, if any, were used in the sponsor analysis.

The registry results do not flag a discrepancy between the reported and recalculated analyses. The numerical p-values differ in their displayed thresholds, but both indicate evidence against the corresponding null under their respective methods. They should not be combined or treated as interchangeable. The sponsor’s analysis is the trial-reported analysis; the recalculation adds an unadjusted estimate and interval derived from the posted counts. Neither should be used to infer unreported analysis-plan details.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and three secondary outcomes, but it does not report a complete testing hierarchy or a method for controlling multiplicity across outcomes. The posted secondary p-values should therefore be read as outcome-specific results, not as proof that a family-wise error rate or another overall error measure was controlled. The record also does not state whether any secondary outcomes were prespecified as confirmatory or exploratory.

Missing-data handling is not reported in the registry record. The posted primary analysis population is intent to treat, but that label does not reveal how missing endpoint measurements, withdrawal, or incomplete follow-up were handled. The record does not state whether participants with unavailable outcome data were counted as non-responders, excluded, imputed, or addressed through another method. The number of participants with missing primary outcomes is also not reported in the registry record.

The primary analysis is described for the intent-to-treat population, and secondary results include both intent-to-treat and per-protocol populations. The exact population definitions, protocol-deviation rules, and exclusions used for the per-protocol analysis are not reported. General statistical explanation: results can differ across analysis populations because the participants included may differ, and exclusions after randomization can affect comparability. The population labels alone are not enough to establish how these issues were addressed.

The full statistical analysis plan, the original sample-size justification, any interim analyses, and the handling of multiplicity and missing data are not reported in the registry record. Those omissions limit the ability to determine whether the posted analyses match a prespecified plan or how robust the estimates are to alternative assumptions. They do not change the reported counts, but they constrain the conclusions that can be drawn about the analysis process.

16. Safety Results

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

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: sepsis (2.8%), dehydration (2.8%), cardiac failure congestive (2.1%), pneumonia (2.1%), blood creatinine increased (2.1%).

The registry reports serious adverse events in 11 of 72 participants in the sugar-pill group and 22 of 144 participants in the CTAP101 group. Other adverse events are reported for 18 of 72 participants in the sugar-pill group and 32 of 144 participants in the CTAP101 group. These are counts among the stated groups; the record does not provide an adjusted safety comparison or uncertainty intervals for these figures.

The registry lists sepsis and dehydration at 2.8% each, cardiac failure congestive, pneumonia, and blood creatinine increased at 2.1% each, and anaemia at 1.4% among the top serious adverse event terms. The record does not specify the group attribution for these listed terms in the summary information, so the percentages should not be assigned to a particular treatment group on that basis. Death counts are not reported in the registry record.

These safety figures describe reported events during the trial and do not establish that an event was caused by a study treatment. The registry record does not provide event-level narratives or a complete assessment of seriousness, timing, relatedness, or exposure-adjusted rates. The counts should be read as descriptive safety information rather than as a standalone comparison of treatment risk.

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

The posted primary result shows that more participants in the CTAP101 group than in the placebo group met the trial’s defined iPTH responder threshold in the intent-to-treat analysis. The unadjusted risk difference and its interval quantify that observed contrast, while the sponsor-reported Cochran-Mantel-Haenszel test supplies a separate analysis result. Together, these findings describe the trial’s primary comparison; they do not answer every question about hormone change, safety, or longer-term outcomes.

The endpoint is a threshold-based laboratory response measured over approximately 6 months. It does not show the amount by which each participant’s iPTH changed, whether changes were sustained after the study, or whether participants experienced other outcomes as a result. The registry does not report the rationale for choosing the response threshold or the confidence level for the recalculated intervals. Those details matter when moving from a statistical result to a broader interpretation.

The result also does not establish that CTAP101 is appropriate for any particular person or replace clinical judgment. It applies to the enrolled trial population and the recorded study conditions. The registry description identifies stage 3 or 4 chronic kidney disease and vitamin D insufficiency, but does not report all eligibility criteria or detailed participant characteristics in the information.

General explanation: statistical evidence about a group comparison is not a prediction that every participant will have the same response, and it does not establish causation for individual adverse events. The trial’s randomization supports a group-level comparison, but the available registry record leaves details of conduct, missing data, analysis planning, and follow-up beyond the study period unreported. Accordingly, the results should be understood as evidence about the measured outcomes within this trial, not as a universal claim or a recommendation.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and analysis population are central to statistical interpretation. The primary outcome is not an average laboratory change; it is the number of participants meeting a specified reduction threshold. That choice makes the result readily interpretable as a responder comparison, while leaving out information about how far individual values changed and how close non-responders came to the threshold.

It also illustrates why absolute and relative measures answer different questions. The risk difference expresses the contrast in response proportions, while the risk ratio and odds ratio express relative contrasts. Reading the effect estimate alongside the group counts and interval helps avoid treating a p-value as a measure of effect size or precision. The sponsor-reported test and unadjusted recalculation offer complementary but distinct statistical views, with different reported details.

The registry lists outcomes in more than one analysis population and includes several secondary endpoints. This makes attention to population definitions, missing outcomes, and multiplicity important. Those analysis details are not reported in the registry record, so readers cannot fully assess the planned handling of these issues. The planning illustrations also demonstrate a general design principle: targeting a smaller effect calls for more participants under the stated assumptions. They are not a reconstruction of the trial’s original sample-size rationale.

More broadly, the record shows both the value and limits of registry results. Posted counts and analyses allow a reader to inspect the direction and precision of the primary comparison, while unreported methodological details limit deeper assessment. Distinguishing observed outcomes, recalculated estimates, sponsor analyses, and planning illustrations is essential to keeping the statistical conclusions proportional to the information available.

19. 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 does not report the complete eligibility criteria, baseline characteristics, randomization procedure, allocation concealment, or details of masking. The intervention description for CTAP101 is truncated, and the record does not provide further details about dose changes or matching procedures. These omissions limit assessment of how the trial was conducted and to whom the results may apply.

The primary endpoint is binary and threshold-based. The posted responder counts do not describe the distribution or magnitude of iPTH changes. The rationale for the 30% threshold and the detailed definition of the efficacy assessment phase are not reported. The outcome timeframe is approximately 6 months, so the registry results do not establish whether responses persisted beyond the recorded study period.

The sponsor-reported analysis is identified as Cochran-Mantel-Haenszel, but the registry does not report an effect estimate, interval, test details, or strata. The recalculated comparisons are unadjusted and use the posted summary counts. The confidence level for the displayed intervals is not reported. The trial’s original sample-size justification and assumptions are also not reported; the planning illustrations are based on the observed effects and stated assumptions instead.

The registry does not report how missing outcomes were handled, the definitions of the per-protocol population, or whether multiplicity adjustments were made. It does not report interim analyses or the full statistical analysis plan. Safety information is summarized as event counts and selected serious-event terms, without a full account of timing, relatedness, or group attribution for the listed terms. Death counts are not reported in the registry record. These limitations restrict assessment of robustness, safety comparisons, and generalizability beyond the posted outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Safety and Efficacy of CTAP101 to Treat Secondary Hyperparathyroidism in Stage 3 or 4 CKD and Vitamin D Insufficiency — NCT01704079.
• Registry record last updated 2025-01-13; status last verified 2025-01.
• Results first posted 2016-08-17.
• 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.

23. Record Summary

The record describes a completed phase 3 randomized, double-blind, parallel-group, placebo-controlled study sponsored by OPKO IP Holdings II, Inc. It enrolled 216 participants with stage 3 or 4 chronic kidney disease and vitamin D insufficiency. The primary outcome counted intent-to-treat participants whose iPTH decreased by at least 30% from pretreatment baseline over approximately 6 months.

The posted primary results show 49 of 144 participants meeting that definition in the CTAP101 group and 5 of 72 in the sugar-pill group. The sponsor-reported Cochran-Mantel-Haenszel result is p < 0.001; the unadjusted recalculation reports a risk difference of 0.271, with an interval from 0.174 to 0.368 and p <0.001. Three secondary outcomes are also reported, along with descriptive adverse-event counts.

The registry record does not report key details including the full statistical analysis plan, missing-data handling, multiplicity strategy, or confidence level for the recalculated intervals. The posted results describe the trial outcomes and analyses recorded, with those omissions limiting further assessment.