A Study Comparing the Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Oral Solution With PREPOPIK® for Colon Cleansing in Preparation for Colonoscopy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Comparing the Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Oral Solution With PREPOPIK® for Colon Cleansing in Preparation for Colonoscopy (NCT03017235), a randomized phase 3 study. The primary outcome is Percentage of Subjects Classified as a Responder Defined by "Excellent" or "Good".

2. Clinical Question

The comparison concerns the performance of two formulations of a bowel preparation, not a comparison with no preparation. The registry record describes the study purpose as comparing the oral solution with PREPOPIK® for colon cleansing in adults undergoing colonoscopy. Its primary endpoint reduces a four-category endoscopist rating to a binary outcome: excellent or good counts as a response; fair or inadequate does not. That makes the clinical question about the proportion meeting the prespecified responder definition, rather than about an average cleansing score or a change from baseline.

The registry record labels the sponsor analysis as a non-inferiority analysis. However, the non-inferiority margin and details of the decision rule are not reported in the registry record. The posted percentages therefore describe the observed responder proportions, while the sponsor’s formal non-inferiority result must be read in light of the reported analysis and the unreported margin.

3. Trial Design

This was a randomized, assessor-blinded, multicenter, parallel-group phase 3 study. The registry record lists single masking and random allocation. It describes two active treatment groups: sodium picosulfate, magnesium oxide and anhydrous citric acid oral solution, and sodium picosulfate, magnesium oxide and anhydrous citric acid powder for oral solution, branded PREPOPIK®. The study was completed. The registry record lists a start date of 2017-02-20 and primary completion date of 2017-09-15.

The overall enrollment was 917. For the primary endpoint, the reported group denominators were 448 for the oral solution and 453 for PREPOPIK®. Those are the denominators displayed for the primary outcome and need not be interpreted as the number of participants randomized unless the registry record says so. The primary efficacy population is described as the modified intention-to-treat set: all intention-to-treat participants who received at least 1 dose, analyzed according to randomized treatment. The registry record does not report the total number randomized by group or provide a detailed accounting of exclusions and missing primary outcome data.

The assessor-blinded feature is relevant because the primary outcome was based on an endoscopist’s rating of colon cleansing during colonoscopy. The registry record says a blinded endoscopist used the Modified Aronchick Scale. It does not report which parties other than the assessor were masked, how masking was maintained, or whether masking was evaluated. The allocation concealment procedure and randomization sequence methods are not reported in the registry record.

The reported primary analysis was a weighted percentage difference and was classified as non-inferiority. The registry record also gives arm-level responder percentages with 95% confidence intervals. Details of the weighting method, the non-inferiority margin, the original sample-size justification, and the full statistical analysis plan are not reported in the registry record. The posted sample-size illustrations are separate from the original trial design assumptions.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary efficacy analysis was conducted for the mITT analysis set and was defined as all ITT subjects who received at least 1 dose of treatment. The mITT analysis set was analyzed according to randomized treatment.

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.

Population: Modified intention-to-treat (mITT) was considered as the main analysis set. mITT was defined as all ITT subjects who received at least 1 dose of treatment. The mITT analysis set was analyzed according to randomized treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Subjects Classified as a Responder Defined by "Excellent" or "Good", measured over During colonoscopy procedure (5-9 hours after completed treatment).

The primary endpoint is the percentage of participants classified as responders, where a responder had overall colon cleansing rated excellent or good on the Modified Aronchick Scale. A blinded endoscopist assessed cleansing during the colonoscopy procedure, 5-9 hours after completed treatment. The scale has four categories. Excellent and good both indicate that more than 90% of the mucosa was seen, with the distinction involving the amount of suctioning needed for adequate visualization. Fair also requires more than 90% of the mucosa to be seen but describes a mixture of liquid and semisolid stool. Inadequate indicates that less than 90% was seen and that semisolid and solid stool could not be suctioned or washed.

Combining excellent and good into a responder outcome gives a direct proportion: the share of assessed participants meeting the study’s definition of successful overall cleansing. A binary endpoint is relatively straightforward to interpret across treatment groups, but it also discards distinctions among the four scale categories. It does not show whether a participant rated fair was close to good or whether an inadequate rating was substantially different from fair. The outcome is an endoscopic assessment at the colonoscopy, not a measure of longer-term health or a participant-reported symptom.

The primary efficacy population was the modified intention-to-treat set, defined in the registry record as intention-to-treat participants who received at least 1 dose, analyzed according to randomized treatment. This population definition matters when interpreting the denominators and the scope of the endpoint estimate.

7. Results Posted in the Registry

• PREPOPIK®: 81.5% (369/453) versus 87.7% (393/448) on control; risk difference -6.3 percentage points (95% CI -11.0 to -1.6), risk ratio 0.93 (0.88–0.98); unadjusted two-proportion z-test p = 0.009.

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.

Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Right Segment of the Colon

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PREPOPIK®: 89.6% (406/453) versus 94.2% (422/448) on control; risk difference -4.6 percentage points (95% CI -8.1 to -1.0), risk ratio 0.95 (0.92–0.99); unadjusted two-proportion z-test p = 0.012.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for PREPOPIK® than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Transverse Segment of the Colon

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PREPOPIK®: 94.0% (426/453) versus 96.0% (430/448) on control; risk difference -1.9 percentage points (95% CI -4.8 to 0.9), risk ratio 0.98 (0.95–1.01); unadjusted two-proportion z-test p = 0.181.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PREPOPIK® and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Left Segment of the Colon

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PREPOPIK®: 91.2% (413/453) versus 94.6% (424/448) on control; risk difference -3.5 percentage points (95% CI -6.8 to -0.1), risk ratio 0.96 (0.93–1.00); unadjusted two-proportion z-test p = 0.042.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for PREPOPIK® than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes include responder definitions for the right, transverse and left colon segments, along with tolerability questionnaire outcomes. Across the three segment-specific responder outcomes, the oral-solution group has higher reported percentages than PREPOPIK®. This broad direction is consistent with the primary overall responder result. The sponsor’s segment analyses do not all have the same degree of precision: the transverse comparison’s reported confidence interval includes zero, unlike the intervals for the right and left segment comparisons.

Regional ratings add context because an overall response can conceal differences in particular portions of the colon. They are nevertheless related assessments made during the same colonoscopy and should not be treated as wholly independent confirmations of the primary endpoint. The questionnaire outcomes address participant-reported tolerability and preparation experience, which are distinct from the blinded endoscopist’s assessment of cleansing. The registry record lists 22 secondary outcomes posted, while the trial record reports 23 outcome measures overall.

Secondary analyses are often less persuasive than the primary result when many outcomes are examined. Each additional comparison creates another opportunity for a chance finding, especially if the results are interpreted without adjustment for multiplicity. The registry record does not report a multiplicity adjustment or a complete hierarchy for secondary testing. Therefore, secondary p-values should be regarded as exploratory or supportive rather than as independent proof of a treatment difference. Their value lies in showing whether the overall pattern is broadly coherent and in identifying where uncertainty remains, not in replacing the primary endpoint.

The segment results generally point in the same direction as the overall outcome, but the registry record alone does not establish that every region has a distinct treatment effect. Nor can the questionnaire endpoints resolve the non-inferiority margin issue for the primary analysis. Their interpretation should remain tied to their own definitions, methods and uncertainty.

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

• Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Right Segment of the Colon
• Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Transverse Segment of the Colon
• Percentage of Subjects Classified as a Responder Defined by a Score ≥2 in the Left Segment of the Colon
• Frequency of Each Category on the Subject Tolerability Questionnaire (How Many Bowel Movements Did You Have in the Week Prior to Starting Colon Preparation?)
• Frequency of Each Category on the Subject Tolerability Questionnaire (How Much Bowel Preparation Was Left in Bottle After Drinking it?)
• Frequency of Each Category on the Subject Tolerability Questionnaire (Was the Bowel Preparation Tolerable?)
• Frequency of Each Category on the Subject Tolerability Questionnaire (How Willing Are You to Use This Preparation in the Future?)
• Frequency of Each Category on the Subject Tolerability Questionnaire (If Difficulties Existed, Were They Due to Your Current Health Status?)

9. Statistical Interpretation

10. Statistical Methods Explained

Binary outcomes and percentage differences

The primary outcome is binary at the participant level: each participant is classified as a responder or not a responder. The arm-level percentage is the number classified as responders divided by the number assessed in that group, expressed as a percentage. In this trial, the responder definition is an excellent or good overall cleansing rating. A percentage is useful because it communicates the frequency of the defined outcome in each treatment group, but it does not preserve the detailed four-category rating from which the outcome was derived.

A risk difference, also called a difference in proportions, compares the responder percentage in one group with the responder percentage in the other. Its sign depends on the order of subtraction, so it is essential to identify which group is first. The sponsor reports the weighted percentage difference in the oral-solution-minus-PREPOPIK® direction. The separate unadjusted recalculation uses the posted summary counts and proportions without the sponsor’s weighting. Those approaches answer related but not identical analytical questions. When the posted sponsor analysis and a simple recalculation differ in method, the sponsor’s own reported analysis is the formal trial analysis; the recalculation is a descriptive check, not a replacement for it.

Confidence intervals

A confidence interval gives a range of values that are reasonably compatible with the data and the assumptions of the method. A 95% confidence interval is not a guarantee that a particular interval contains the true value, nor does it mean that 95% of participants fall within the interval. For an arm-level percentage, the interval expresses uncertainty in the estimated group proportion. For a difference, the interval expresses uncertainty in the estimated contrast between groups. If a confidence interval for a difference includes zero, the data are compatible with no difference under that interval method; if it excludes zero, that is evidence of a difference under the corresponding assumptions. This interpretation is not interchangeable with a non-inferiority decision, which depends on a prespecified margin.

Non-inferiority analysis

A non-inferiority analysis asks whether the outcome with one intervention is not unacceptably worse than the comparator by more than a prespecified margin. The margin is central: it defines the largest difference that would still meet the study’s criterion. The registry record labels the sponsor’s primary and some secondary analyses as non-inferiority and reports weighted percentage differences, confidence intervals and p-values. The non-inferiority margin and the exact decision rule are not reported in the registry record. Consequently, the reported analysis can be described, but the margin-based conclusion cannot be independently checked from the registry entry alone. A p-value below a conventional threshold does not substitute for knowing the margin.

Weighted and unadjusted estimates

The sponsor’s method is described as a weighted percentage difference. Weighting can account for features of the design or analysis, but the particular weights and their rationale are not reported in the registry record. The unadjusted recalculation uses the posted group-level counts and denominators. It does not include covariate adjustment or reproduce details of the sponsor’s analysis that are unavailable in the registry record. Agreement in direction is reassuring about the basic descriptive pattern, but it does not make the methods identical. The sponsor’s posted result should be used when describing the trial’s own formal analysis.

p-values

A p-value measures how unusual data at least as inconsistent with a specified null hypothesis would be if that hypothesis and the statistical model were correct. It does not quantify effect size, the chance that the null is true, or clinical importance. An unadjusted p-value also does not account for the fact that multiple outcomes may have been examined. The registry record gives the sponsor’s p-value for the primary and secondary analyses and an unadjusted p-value for the recalculated comparison. They should be identified by their analysis source and not treated as interchangeable.

General statistical considerations

For a binary outcome, precision depends on the number of participants and the frequency of the outcome in each group. A larger sample can narrow uncertainty, but it does not remove bias from outcome assessment, missing data, or analysis choices. Randomization helps balance prognostic factors on average, while assessor blinding can reduce the influence of knowledge of treatment assignment on the rating. Neither feature guarantees that all sources of bias are absent. The registry record does not report enough detail to assess the randomization procedures, missing-data methods, analysis adjustments, or full non-inferiority plan.

The posted planning illustrations use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect specified as a fraction of the observed effect. These are illustration assumptions, not a statement of the trial’s original design. The registry record’s original sample-size assumptions are not reported. Such calculations describe prospective planning scenarios; they do not estimate the probability that this completed trial has detected an effect.

11. Confidence Intervals and Precision

The primary arm-level estimates are 87.7% for the oral solution and 81.5% for PREPOPIK®. Their respective 95% confidence intervals are 84.3% to 90.6% and 77.6% to 84.9%. The intervals communicate uncertainty in each group’s responder percentage, not the range of individual participant outcomes. Their overlap should not be used as a substitute for a confidence interval or test of the between-group contrast.

For the sponsor’s weighted primary difference, the reported estimate is 6.3 percentage points and its 95% confidence interval runs from 1.8 to 10.9. This interval is above zero, indicating that the sponsor’s estimated difference favors the oral-solution group in the stated direction. However, a non-inferiority interpretation requires the margin, which is not reported in the registry record. The interval’s relation to zero alone does not answer whether the prespecified non-inferiority criterion was met.

The unadjusted recalculation also indicates a difference in the same direction, with p = 0.009. The estimates are not identical in method: the recalculation is based on summary counts, whereas the registry’s sponsor analysis is weighted. The amount of precision in either estimate should therefore be judged within its own analysis method, and the formal sponsor analysis remains the primary reference for the trial’s reported inference.

Confidence intervals remain compatible with a range of underlying effects. They do not account for every possible source of uncertainty, such as missing outcome data or analysis choices that are not described. The registry record does not report the missing-data handling, non-inferiority margin, or full statistical plan, limiting how completely the precision and robustness of the primary conclusion can be evaluated.

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 sample-size illustrations are planning scenarios based on the observed effect, not the original trial design. For this binary outcome, the entries are participants per arm, not total events. The calculations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set at the stated fraction of the observed effect. The original trial’s own sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm in a hypothetical future study that would have an 80% chance of detecting the specified effect under those assumptions, if the assumed effect and model were correct. The 90% power column describes a higher target chance of detection for the same specified effect. These are planning probabilities tied to a hypothetical repeated-study framework; they are not a probability that the observed result is true or clinically important.

At 100% of the observed effect, the illustration lists 520 participants per arm for 80% power and 696 participants per arm for 90% power. Planning for 75% of the observed effect gives 887 and 1,187 participants per arm, respectively. Planning for 50% of the observed effect gives 1,907 and 2,552 participants per arm, respectively. The pattern reflects a general feature of study planning: smaller effects are harder to distinguish from random variation and therefore require more participants for the same power target.

These figures are not observed power. They do not retrospectively measure whether this completed trial was adequately powered, and they should not be read as proof that a result is reliable or unreliable. They are illustrations conditional on the stated assumptions, especially the use of the observed effect as the planning reference. The trial’s own design assumptions are not reported in the registry record.

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 = 0.877; treatment proportion p₁ = 0.815; average p̄ = 0.846.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5106 = 1.0007.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5087 = 0.4281.
4. n = (1.0007 + 0.4281)² / (-0.0627)² = 519.9, rounded up to 520 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 <- 0.877232142857143                          # control proportion
p1 <- 0.814569536423841                          # 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(3017235)
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 = 520 (80% power), 696 (90% power)
 75% of observed effect: n per arm = 887 (80% power), 1,187 (90% power)
 50% of observed effect: n per arm = 1,907 (80% power), 2,552 (90% power)
power.prop.test: 519.9 
Simulated power at n = 520 per arm: 0.799 (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 record reports the sponsor’s primary analysis as a weighted percentage difference of 6.3 percentage points, with a 95% confidence interval from 1.8 to 10.9 and p = 0.007. The comparison is in the oral-solution-minus-PREPOPIK® direction, and the analysis is labeled non-inferiority. The sponsor’s result is the trial’s reported formal analysis and takes precedence over the unadjusted recalculation.

The recalculation uses the posted responder counts and denominators to compare the groups without the sponsor’s weighting. It yields a direction consistent with the arm-level percentages, with a higher observed responder percentage in the oral-solution group, and an unadjusted p-value of 0.009. These estimates are not competing versions of the same calculation: the sponsor’s weighted method may incorporate analysis features not reproduced by a simple calculation from aggregate counts. The registry record does not report the details of the weighting method.

The sponsor’s analysis is identified as non-inferiority, but the non-inferiority margin and complete decision rule are not reported in the registry record. The reported estimate and interval can be stated as posted; the margin-based criterion cannot be independently verified from the record alone. Neither the sponsor p-value nor the recalculated p-value establishes equivalence. The sponsor analysis should be treated as the formal reported result, while the recalculation serves as a simple, unadjusted comparison of the posted summaries.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, time points, subgroups or statistical comparisons. Even if each individual test uses a conventional threshold, examining many tests increases the chance that at least one result will appear notable by chance. This matters for the secondary outcomes in this trial, which include regional responder measures and several tolerability questionnaire measures in addition to the primary outcome.

The registry record lists 22 secondary outcomes posted and four analyses. It reports p-values for the primary analysis and the three segment responder analyses, but a multiplicity adjustment, testing hierarchy, or rule for controlling the overall error rate is not reported in the registry record. Without those details, the secondary p-values should not be interpreted as if each were the sole prespecified test. The record also does not provide enough information to determine whether all listed outcomes were analyzed according to a single prespecified plan.

Missing-data handling is also not reported in the registry record. The primary efficacy population is described as all intention-to-treat participants who received at least 1 dose, analyzed according to randomized treatment. The record gives primary endpoint denominators of 448 and 453, but does not explain how participants without an assessable colonoscopy rating were handled, whether any outcome data were imputed, or how the analysis accounted for missingness. Missingness can affect estimates if the likelihood of an unavailable result is related to treatment or the outcome.

The registry record does not report interim analyses, the original sample-size justification, or a complete statistical analysis plan. It also does not report the non-inferiority margin. These absences limit assessment of prespecification, error control and robustness. They do not demonstrate that the trial omitted such procedures; they mean that the registry record does not document them. Interpretation should distinguish reported analysis results from details that cannot be verified from the record.

16. 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: adenocarcinoma of colon (0.9%), rectal adenocarcinoma (0.4%), atrial fibrillation (0.2%), ascites (0.2%), post procedural haemorrhage (0.2%).

The registry record reports serious adverse events for 9 of 448 participants in the oral-solution group and 6 of 453 participants in the PREPOPIK® group. It reports zero deaths in each group. The record also gives counts of 378 and 384 participants, respectively, in the other adverse-event category, among the same at-risk group sizes. These counts are descriptive; they do not by themselves establish that one preparation has a higher or lower safety risk.

The listed serious adverse-event terms include adenocarcinoma of colon, rectal adenocarcinoma, atrial fibrillation, ascites, post procedural haemorrhage and breast cancer metastatic, each with the percentages recorded in the registry. Those terms should not be taken to indicate that every listed event was caused by study treatment. The record does not establish causality through the event list alone, and the event categories may include conditions with different clinical contexts.

Safety comparisons based on these counts are limited by the number of events, the follow-up captured in the record, and the absence of detailed timing and attribution information. The registry record does not provide a full narrative account of seriousness, relatedness, exposure time, or how events were collected. These results describe reported adverse-event counts in the trial groups; they do not support medical advice or a definitive comparative safety conclusion.

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

The primary outcome shows that a larger proportion of participants in the oral-solution group met the study’s excellent-or-good responder definition than in the PREPOPIK® group. The arm-level percentages were 87.7% and 81.5%, respectively. The sponsor’s weighted analysis reports a 6.3 percentage-point difference with a 95% confidence interval from 1.8 to 10.9 and labels the analysis non-inferiority. The unadjusted recalculation has the same direction, but it is not the sponsor’s weighted method.

These results describe the trial’s measured endpoint in the analyzed population. They do not establish that the treatments are identical, that every participant will have the same experience, or that the observed difference has a particular clinical importance. A confidence interval gives a range of plausible values under the statistical method, not a guarantee about the true effect. A p-value is not the probability that the treatment works or that the finding arose by chance.

The non-inferiority label requires particular care. Non-inferiority depends on a prespecified margin and a defined decision rule. Since the margin is not reported in the registry record, the formal threshold cannot be checked from the posted registry entries alone. The sponsor’s analysis remains the formal reported analysis, but its margin-based interpretation cannot be fully reconstructed from the record.

The findings also concern colon cleansing assessed during colonoscopy, 5-9 hours after completed treatment. They do not answer questions about outcomes outside the studied setting or time frame. The record describes a population of adults undergoing colonoscopy and an analysis set that included intention-to-treat participants who received at least 1 dose; generalization beyond this context requires evidence beyond these results.

Finally, posted secondary and safety information adds context but does not remove uncertainty. Multiple secondary comparisons, missing-data handling, the original sample-size rationale and other statistical-plan details are not reported in the registry record. The appropriate reading is therefore specific: the observed responder percentage was higher with oral solution in this trial, and the sponsor reported a positive weighted difference under a non-inferiority analysis whose margin is not available in the registry entry.

18. Why This Trial Matters Statistically

This trial illustrates why the choice of endpoint and analysis framework matters in clinical research. The primary outcome is a binary responder measure derived from a four-category endoscopic rating. It is easy to communicate as a percentage, but the binary definition compresses distinctions between excellent, good, fair and inadequate cleansing. Interpretation depends on understanding exactly which categories count as a response.

It also demonstrates the difference between an arm-level comparison and a non-inferiority claim. The group percentages and their confidence intervals describe observed outcomes. A weighted difference is the sponsor’s reported comparative analysis. A non-inferiority conclusion additionally depends on a margin that defines how much worse would still be acceptable under the study’s rule. Without that margin in the registry record, readers can report the posted analysis but cannot independently verify the threshold-based decision.

The contrast between the sponsor analysis and the unadjusted recalculation is a useful reminder that summary-data calculations may not reproduce a formal analysis that uses weighting or other methods. A simple recalculation can check the direction and provide context, but it cannot replace a prespecified analysis or recover unreported methods. The registry’s distinction between the formal result and a summary-based recalculation is therefore important to transparent interpretation.

Finally, the secondary outcomes show why multiplicity and precision matter. Related regional outcomes can offer useful context, but multiple unadjusted comparisons do not provide the same evidential weight as a primary endpoint governed by a clearly documented analysis plan. Reading effect estimates alongside confidence intervals, population definitions, missing-data information and the limits of the registry record helps keep conclusions proportionate to what was measured.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific details needed for a full statistical appraisal are not reported in the registry record. The non-inferiority margin and complete decision rule are absent, so the threshold underlying the sponsor’s non-inferiority analysis cannot be independently assessed. The weighting method for the sponsor’s percentage difference is also not described in detail. The reported weighted result and the unadjusted summary-based recalculation therefore cannot be treated as identical analyses.

The record does not report the original sample-size justification, the assumptions used to plan the completed trial, or the full statistical analysis plan. The planning illustrations based on the observed effect are not substitutes for those original design details. Interim analyses and any adjustment for multiple outcomes are not reported. This leaves uncertainty about how the primary and secondary tests were prespecified and how error rates were managed.

Missing outcome data and their handling are not described. Although the primary efficacy population definition and group denominators are reported, the registry record does not explain whether any participants lacked an assessable cleansing rating or what methods were used for incomplete data. The randomization sequence, allocation concealment and masking procedures beyond the assessor-blinded description are also not reported.

The primary outcome is a dichotomized endoscopic rating at a specific assessment occasion. It does not retain all information in the four-point scale and does not describe outcomes beyond the colonoscopy assessment. The registry record gives secondary regional and tolerability outcomes, but many secondary comparisons raise multiplicity concerns when adjustment is not documented. Safety counts are available, but detailed timing, attribution and follow-up information are not provided in the registry record. These limitations constrain the completeness of interpretation; they do not, by themselves, show that the trial methods were inadequate.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study Comparing the Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Oral Solution With PREPOPIK® for Colon Cleansing in Preparation for Colonoscopy — NCT03017235.
• Registry record last updated 2018-11-14; status last verified 2018-10.
• Results first posted 2018-11-14.
• 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

NCT03017235 is a completed randomized, assessor-blinded, multicenter, parallel-group phase 3 study sponsored by Ferring Pharmaceuticals. It compared sodium picosulfate, magnesium oxide and anhydrous citric acid oral solution with the PREPOPIK® powder for oral solution in adults undergoing colonoscopy. The registry record lists 917 participants enrolled.

The primary endpoint was the percentage classified as a responder, defined as an excellent or good overall cleansing rating by a blinded endoscopist during colonoscopy, 5-9 hours after completed treatment. The reported percentages were 87.7% for oral solution and 81.5% for PREPOPIK®. The sponsor reported a weighted difference of 6.3 percentage points, with a 95% confidence interval from 1.8 to 10.9 and p = 0.007, labeled as a non-inferiority analysis. The non-inferiority margin is not reported in the registry record.

The posted secondary results include regional responder outcomes and tolerability measures. Serious adverse events were reported for 9 participants in the oral-solution group and 6 in the PREPOPIK® group; zero deaths were reported in each group. These registry results should be interpreted alongside the unreported details of missing-data handling, multiplicity, the original design assumptions and the full analysis plan.