Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC) (NCT01672853), a randomized phase 2 study. The primary outcome is Change From Baseline in MQC on Liver Biopsy at Week 96.

2. Clinical Question

3. Trial Design

This was a phase 2b, dose-ranging, randomized, double-blind, placebo-controlled trial with a parallel-group design. It evaluated simtuzumab, identified in the official title as GS-6624, against placebo in adults with primary sclerosing cholangitis. The registry lists the study status as completed and reports enrollment of 235. The recorded study start was 2013-03-04, and primary completion was 2016-08-08.

Participants were allocated to one of three arms: simtuzumab 75 mg, simtuzumab 125 mg, or placebo. Each assigned regimen was described as continuing for 96 weeks. The primary outcome was change from baseline in MQC on liver biopsy at Week 96. The listed primary analysis population comprised randomized participants who received at least one dose of study drug and had available data. The endpoint counts differ by arm and are stated with the outcome results; enrollment should not be treated as the number contributing data to every analysis.

The registry classifies the trial as randomized and triple-masked. Its official title describes it as double-blind, while the registry masking classification is triple. The identities of the parties masked are not reported in the registry record. Further details of the randomization procedure, allocation concealment, site structure, and the trial's original statistical design assumptions are not reported in the registry record. The two dose groups were compared with placebo in separate posted analyses, rather than as a pooled simtuzumab group.

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: 298 participants were screened.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants in the Full Analysis Set (participants who were randomized into the study and received at least 1 dose of study drug) with available data were analyzed.

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: The Safety Analysis Set included participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in MQC on Liver Biopsy at Week 96, measured over Baseline; Week 96.

The primary endpoint was change from baseline in MQC on liver biopsy at Week 96, expressed as a percentage of MQC. It was analyzed as a continuous outcome, with the registry identifying the summary measure as a mean and the measure of spread as a standard deviation. In practical terms, the endpoint represents a difference between a participant's baseline biopsy measurement and the Week 96 measurement, then summarizes those changes across participants with available data.

A continuous endpoint can retain information about the size and direction of measured change rather than reducing each participant's result to a yes-or-no category. A liver-biopsy measure is relevant to a trial concerned with liver fibrosis because it assesses tissue findings, although the registry record does not give the measurement procedure, scoring details, or a threshold for clinically important change. The endpoint is a measure of biopsy change over the stated period; it is not itself a direct summary of symptoms, function, or all consequences of PSC.

The primary analysis was limited to participants in the Full Analysis Set who were randomized, received at least one dose, and had available endpoint data. The registry record does not describe how missing Week 96 biopsy data were handled or provide a fuller operational definition of MQC.

7. Results Posted in the Registry

• SIM 75 mg: mean -0.50 versus 0.00 on control; difference -0.50 (95% CI -2.37 to 1.37), standardized effect d = -0.09; z-test p = 0.601.
• SIM 125 mg: mean 0.50 versus 0.00 on control; difference 0.50 (95% CI -1.61 to 2.61), standardized effect d = 0.08; z-test p = 0.642.

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.

Study Drug Exposure

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • SIM 75 mg: mean 92.00 versus 87.40 on control; difference 4.60 (95% CI -1.40 to 10.60), standardized effect d = 0.24; z-test p = 0.133.
  • SIM 125 mg: mean 83.80 versus 87.40 on control; difference -3.60 (95% CI -11.26 to 4.06), standardized effect d = -0.15; z-test p = 0.357.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SIM 75 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between SIM 125 mg and the control. The interval gives the range of effects that remain compatible with the data.

The secondary-outcome record is less complete than the primary-outcome record. Study drug exposure is posted as a continuous measure, while the registry also lists permanent discontinuation of study drug due to an adverse event and treatment-emergent laboratory abnormalities as secondary outcomes. Results for those latter outcomes are not reported in the registry record. This means the secondary evidence cannot be treated as a fully reported set of efficacy and safety comparisons.

Exposure describes how long participants were recorded as receiving study drug, not a clinical response. The posted means show that exposure varied across arms, and the recalculated contrasts have confidence intervals that include zero. These comparisons therefore do not establish a clear separation in exposure between either simtuzumab dose and placebo. They are also not direct evidence about the primary biopsy endpoint: differences in time on study drug could relate to adherence, discontinuation, or other factors, but the registry record does not provide enough information to identify explanations.

The primary endpoint and exposure answer different questions. A biopsy-change comparison concerns the measured liver-tissue outcome at Week 96; exposure concerns duration of study drug use over the stated period. The exposure results do not resolve the uncertainty in the primary comparisons, and the primary results do not fill in the missing secondary discontinuation and laboratory results.

Secondary results generally carry less weight when many outcomes are considered without a reported plan for controlling multiplicity. Testing multiple outcomes increases the chance that at least one result appears notable by chance. The registry record does not report whether the secondary outcomes were prespecified in a formal testing hierarchy, how their analyses were adjusted, or how missing observations were handled. The secondary findings should therefore be viewed as contextual rather than as independent confirmation of the primary result. In particular, the unreported outcomes cannot support a conclusion about discontinuation or laboratory abnormalities.

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

• Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event
• Study Drug Exposure
• Percentage of Participants Experiencing Any Treatment-Emergent Laboratory Abnormality

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, so the record summarizes each arm with a mean and standard deviation. A mean describes the center of the observed changes, while a standard deviation describes how spread out individual measurements are around that center. Neither summary alone shows the uncertainty around a between-arm comparison. The comparisons and their confidence intervals address that separate question.

What does a mean difference represent?

A mean difference compares the average outcome in one arm with the average in another. The recalculated comparisons subtract the placebo mean from the relevant simtuzumab-arm mean. A negative estimate indicates a lower mean change in the simtuzumab arm than in placebo; a positive estimate indicates a higher mean change. The sign describes direction on the recorded scale, not whether that direction is beneficial. The registry does not provide enough information about MQC scoring to attach a clinical interpretation to a particular sign or magnitude.

The recalculated estimates are simple unadjusted comparisons based on posted summary statistics. They are not a reproduction of the sponsor's least-squares analysis. An unadjusted comparison uses the arm-level summaries without applying a model-based adjustment. The registry reports least-squares mean differences for its own analysis, but the method field is not specified. Consequently, the estimates can be compared as descriptions of the same broad contrast, but should not be treated as identical estimands or as a numerical audit of a fully documented model.

How should the confidence interval be understood?

A confidence interval gives a range of values compatible with the estimate under the statistical procedure and assumptions used to construct it. A narrower interval indicates greater statistical precision; a wider interval indicates greater uncertainty about the size of the contrast. When an interval includes zero for a difference, the results do not clearly separate a positive contrast from a negative one at the interval's stated confidence level. This does not prove that the groups are equivalent, and it does not mean that zero is the only plausible value. The primary comparisons' intervals include zero and extend in both directions.

A p-value is a measure of how unusual the observed data, or data more extreme, would be under a specified null hypothesis and analysis. It is not the probability that the null hypothesis is true, nor does it measure clinical importance. The recalculated p-values are explicitly unadjusted. The registry does not report p-values for its least-squares comparisons. Where multiple outcomes or dose comparisons are examined, unadjusted p-values do not account for the broader set of tests.

Why can variability matter?

Variation among participants affects how precisely a group mean and the between-group contrast can be estimated. Greater spread generally makes a mean contrast less precise when other features are held constant. The standard deviations reported for the primary outcome describe variation in observed biopsy changes; they do not explain its causes. The trial record does not report a model for the distribution of the outcome or an analysis addressing unusual values. General statistical practice may use transformations, robust methods, or other approaches where distributional features make a simple normal approximation unsuitable, but the registry does not state that such methods were used for this endpoint.

The posted recalculation uses the summary-statistic approach indicated by the continuous outcome and the available arm-level means, standard deviations, and sample sizes. Such a recalculation is useful for a transparent, unadjusted comparison, but it cannot recover participant-level adjustments, covariance structures, or missing-data procedures that may have been part of a fuller analysis. The registry's analysis method is not reported in enough detail to assess those elements.

What does the analysis population imply?

The primary outcome description says that participants randomized into the study and receiving at least one dose were analyzed if data were available. This defines the group contributing to the stated analysis, but it does not establish that every randomized participant was included in each endpoint calculation. The outcome counts are given by arm. The registry does not report how missing endpoint measurements were handled, whether any imputation was used, or whether sensitivity analyses assessed the effect of missing data. Those details matter because results based on available cases may be affected if the availability of a Week 96 biopsy is related to the outcome.

In general, over-dispersion means that observed variability is greater than a model's assumed variability. It can make standard errors too small and confidence intervals too narrow if not accommodated. That concept is relevant when a statistical model assumes a particular variance structure, but the registry does not report a model or evidence of over-dispersion for the primary endpoint. It would therefore be inappropriate to assert that over-dispersion occurred in this trial.

Finally, the registry's primary analysis method, its original sample-size justification, interim-analysis plans, and multiplicity strategy are not reported in the registry record. The uncertainty intervals and recalculated p-values should be read with those reporting limits in mind, rather than as a complete account of the trial's prespecified statistical plan.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty remains around an estimated contrast. For the simple unadjusted comparison of simtuzumab 75 mg with placebo, the mean difference was -0.5 and the 95% confidence interval ran from -2.373 to 1.373. For 125 mg versus placebo, the mean difference was 0.5 and the interval ran from -1.606 to 2.606. Each interval includes zero and values on either side of zero. Thus, the estimated direction is not precise enough to rule out contrasts in the opposite direction under these analyses.

The sponsor's reported least-squares comparisons also have 95% confidence intervals that include zero: -0.4 with limits of -2.3 and 1.6 for the 75 mg comparison, and 1.0 with limits of -1.0 and 3.0 for the 125 mg comparison. These are sponsor-reported differences in least-squares means, not the same calculation as the simple unadjusted mean differences. The method details needed to explain any differences between the approaches are not reported in the registry record.

A 95% confidence interval is not a statement that there is a 95% probability that the true effect lies inside this particular interval. In general, it describes the long-run coverage property of the method under its assumptions. It also does not define which values would matter clinically. The registry does not report a threshold for meaningful change in MQC, so the intervals cannot be classified as excluding or including a clinically important effect on the basis of a stated threshold.

These intervals indicate uncertainty about the magnitude of the contrasts, not proof of equivalence. A finding that does not clearly separate the arms can reflect a small contrast, substantial variability, limited information, or some combination; the posted summaries alone do not identify which explanation applies. The available-data analysis population and unreported missing-data procedures are further considerations when judging how precisely the posted estimates represent the randomized groups.

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 illustrations based on the observed effect sizes in the posted comparisons, not the trial's original design calculations. For these continuous-outcome comparisons, the figures are participants per arm, not total events. The assumptions stated for the illustration are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The assumed effect to detect is the stated fraction of the observed effect.

The 80% power column represents the number of participants per arm that the calculation estimates would be needed for an 80% chance of detecting the specified effect under those assumptions, if that effect and the other assumptions were correct. The 90% power column uses a higher target probability of detection and therefore generally requires more participants per arm. For example, the planning illustration for the full observed effect in the 75 mg comparison gives 1,758 participants per arm for 80% power and 2,353 participants per arm for 90% power. The figures are tied to the observed contrast used in each comparison, not to a guaranteed effect in a future study.

The rows that plan for 75% or 50% of the observed effect use smaller target effects than the row based on 100% of the observed effect. Smaller effects are harder to distinguish from random variation, so the calculations require more participants per arm to reach the same power target. The displayed curve reflects this same relationship across assumed effects; it is a planning aid rather than a record of trial enrollment or an estimate of a treatment effect.

These calculations are not observed power. They are prospective planning illustrations computed from the observed effect and the stated assumptions, and should not be interpreted as evidence that the completed trial had a particular probability of detecting its true effect. The trial's own original sample-size assumptions and justification 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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.500; pooled standard deviation σ = 5.290.
2. n = 2 × (1.96 + 0.842)² × 5.290² / -0.500² = 1,757.4, rounded up to 1,758 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
delta <- -0.5                      # observed difference in means
sigma <- 5.29042297048275                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1672853)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,758 (80% power), 2,353 (90% power)
 75% of observed effect: n per arm = 3,125 (80% power), 4,183 (90% power)
 50% of observed effect: n per arm = 7,030 (80% power), 9,411 (90% power)
power.t.test: 1758.4 
Simulated power at n = 1,758 per arm: 0.800 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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's own primary analyses are reported as differences in least-squares means, with 95% confidence intervals. The simple recalculations instead compare the posted arm means using unadjusted summary-statistic methods. Both approaches address the broad question of how each simtuzumab dose compares with placebo, but the estimates are not identical statistical quantities: least-squares means arise from a model, while the recalculation is unadjusted.

For both doses, the sponsor-reported confidence interval includes zero, as do the recalculated confidence intervals. The sponsor's reported values are -0.4 for the 75 mg comparison and 1.0 for the 125 mg comparison; the registry does not include p-values for these analyses. The recalculated mean differences are -0.5 and 0.5, with unadjusted p-values of 0.601 and 0.642, respectively. These p-values belong to the recalculated comparisons and should not be attributed to the sponsor's analyses.

The method field for the sponsor analyses is not specified, and the registry does not give enough detail to reproduce the least-squares estimates or explain their model assumptions. The sponsor's analysis therefore remains the registry's reported analysis, while the recalculation serves as a transparent unadjusted comparison from the posted summaries. The registry does not flag a discrepancy between the analyses. Neither set of estimates should be presented as proof that the doses are equivalent; both leave uncertainty around the magnitude and direction of the contrast.

15. Multiplicity, Missing Data and Analysis Populations

The primary endpoint was evaluated in two separate dose-versus-placebo comparisons. The registry also lists secondary outcomes, including study drug exposure, permanent discontinuation due to an adverse event, and treatment-emergent laboratory abnormalities. When multiple comparisons are made, the chance of at least one apparently unusual result can increase. Statistical methods can account for this multiplicity, for example by controlling a family-wise error rate or by specifying a hierarchical testing sequence. The registry record does not report whether either approach, or another multiplicity strategy, was used.

The recalculated p-values are unadjusted, so they do not account for testing both doses or for other outcomes. The sponsor's reported primary analyses include confidence intervals but no p-values, and the registry does not provide enough analysis detail to determine how those intervals relate to a broader testing plan. This limits any interpretation that depends on treating a particular nominal threshold as confirmatory. The registry's original statistical analysis plan is not reported in the registry record.

The primary population is described as randomized participants who received at least one dose and had available data. The record does not state how many randomized participants lacked primary endpoint data in each arm or why data were unavailable. It does not describe imputation, other missing-data methods, or sensitivity analyses. If participants with missing Week 96 measurements differ systematically from those with observed measurements, an available-data comparison may not represent the full randomized groups. That is a general concern about missing outcomes, not evidence that such a bias occurred in this trial.

The method for the sponsor's least-squares analyses is not specified. Further details that would help assess the result—including model covariates, assumptions, handling of missing data, and any interim analyses—are not reported in the registry record. The original sample-size justification and planning assumptions are also not reported. The planning illustration based on observed effects is not a substitute for that original design information. These omissions do not invalidate the posted estimates, but they limit how completely readers can evaluate the prespecified analysis strategy and the robustness of the conclusions.

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: cholangitis (7.6%), abdominal pain (3.9%), pneumonia (2.6%), cholangiocarcinoma (2.6%), oesophageal varices haemorrhage (2.5%).

The registry reports serious adverse-event counts by arm, including the number at risk and the number affected. For simtuzumab 75 mg, 16 of 79 participants were affected; for simtuzumab 125 mg, 23 of 77 were affected; and for placebo, 21 of 78 were affected. The record reports zero deaths in each arm. These are descriptive counts and should be read in the context of the arm-specific numbers at risk, rather than as a formal adjusted comparison.

The listed serious-event terms include cholangitis at 7.6%, abdominal pain at 3.9%, pneumonia at 2.6%, cholangiocarcinoma at 2.6%, oesophageal varices haemorrhage at 2.5%, and abdominal pain upper at 1.3%. These percentages describe listed terms; they do not constitute a complete account of every adverse event or establish that an event was caused by study drug. The registry record does not report a statistical comparison of serious adverse events between arms or provide enough context to infer differences in risk.

Counts of affected participants, event terms, and deaths are distinct descriptions and should not be added together. The record also lists permanent discontinuation due to an adverse event as a secondary outcome, but its result is not reported in the registry record. These safety data are descriptive and do not by themselves establish comparative safety.

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

The primary results show small observed mean changes in MQC in all three arms, with the posted arm means near zero. The simple unadjusted dose-versus-placebo estimates have confidence intervals that include zero, and the sponsor-reported least-squares comparisons do as well. The registry record therefore does not show a clearly separated primary endpoint contrast for either simtuzumab dose. At the same time, the intervals extend to values on both sides of zero, so the estimates do not establish that the true contrasts are zero or that the treatments are equivalent.

The endpoint is specifically change from baseline in a liver-biopsy measure at Week 96. It is not a direct measure of every feature of PSC, and the registry does not report a threshold that would define a clinically meaningful change in MQC. The findings should not be stretched into claims about symptoms, long-term outcomes, or all aspects of fibrosis progression. They describe this measured endpoint in the analysis population stated in the record.

The record has important limitations for interpreting the results: the sponsor's statistical method is not fully described, missing-data handling is not reported, and the approach to multiplicity is not reported. The recalculated p-values are unadjusted, and the sponsor did not post p-values for its least-squares comparisons. Secondary results are incomplete, with exposure reported but results for other listed secondary outcomes not reported in the registry record.

The appropriate statistical reading is therefore limited and descriptive: the observed primary comparisons do not clearly distinguish either dose from placebo, while the uncertainty intervals leave a range of possible contrasts. This is not proof of no effect, a demonstration of equivalence, or a complete assessment of benefits and harms. It is an interpretation of the posted registry results, in light of the outcomes and analysis details the record documents.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares two doses of the same intervention with a placebo group and reports a continuous biopsy outcome. That design allows the posted results to show both the direction and estimated size of each dose contrast, while the confidence intervals communicate uncertainty. Reporting separate dose comparisons also avoids hiding potentially different patterns behind a pooled active-treatment average.

The trial illustrates why an estimated difference and its precision should be read together. The arm means alone might suggest that one dose moved in a different direction from the other, but both sponsor-reported intervals and the simple recalculated intervals include zero. The observed estimates therefore need to be distinguished from a precise, confirmatory separation between arms. Conversely, intervals spanning both directions should not be converted into a claim that the doses and placebo are equivalent.

It also demonstrates the value and limits of registry reporting. The posted sponsor comparisons and arm-level summaries allow an independent, unadjusted recalculation, but the method details for the least-squares analysis are absent. The record defines the analysis population in broad terms, yet does not explain missing-data procedures or multiplicity control. Those details are central to judging how robust and confirmatory the reported comparisons are.

Finally, the planning illustrations show how sample-size requirements depend on the assumed effect: smaller effects require more participants per arm to attain a stated power target under the stated assumptions. Because these illustrations use observed effects and are not the trial's original design calculations, they should not be confused with a prespecified sample-size justification or with observed power. Together, the trial's results and reporting gaps offer a practical example of why effect estimates, uncertainty, analysis choices, and registry completeness all matter in clinical-trial interpretation.

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 primary endpoint is reported as change in MQC on liver biopsy, but the registry does not give a fuller definition of MQC, the scoring procedure, or a threshold for clinically meaningful change. This limits interpretation of the scale and of whether a given numerical contrast would matter clinically. The outcome is specific to the biopsy measure and Week 96 assessment; the record does not establish how it relates to other dimensions of PSC.

The primary analysis population includes randomized participants who received at least one dose and had available data. This is not described as an analysis of every randomized participant regardless of treatment received or endpoint availability. Arm-specific endpoint counts are reported, but the registry does not explain missing measurements, reasons for missingness, or methods used to address it. The degree to which available-case findings may represent all randomized participants therefore cannot be assessed from the record.

The sponsor reports least-squares mean differences, but the statistical method is not specified. The record does not describe covariate adjustment, model assumptions, or how the confidence intervals were obtained. The recalculated comparisons are unadjusted and cannot reproduce a model-based analysis without those details. The multiplicity strategy for the two dose comparisons and other outcomes is not reported; accordingly, the recalculated p-values should not be treated as multiplicity-adjusted confirmatory tests.

The registry lists secondary outcomes for discontinuation and laboratory abnormalities but does not report their results. The trial's original sample-size justification, interim analyses, and full statistical analysis plan are also not reported in the registry record. These trial-specific reporting limitations constrain assessment of the planned analysis, completeness of secondary evidence, and robustness of the posted primary estimates. They do not establish that the trial was conducted improperly; they define what cannot be evaluated from this record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults With Primary Sclerosing Cholangitis (PSC) — NCT01672853.
• Registry record last updated 2019-10-22; status last verified 2019-10.
• Results first posted 2019-10-22.
• 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

NCT01672853 is a completed phase 2b randomized, parallel-group, placebo-controlled trial of simtuzumab (GS-6624) in adults with primary sclerosing cholangitis. The three regimens were simtuzumab 75 mg, simtuzumab 125 mg, and placebo, each described for 96 weeks. The registry reports enrollment of 235 and identifies Gilead Sciences as sponsor.

The primary outcome was change from baseline in MQC on liver biopsy at Week 96. The sponsor's two least-squares mean comparisons with placebo had 95% confidence intervals that included zero. Simple unadjusted recalculations also had intervals including zero. The registry does not report the sponsor analysis method, missing-data procedures, or multiplicity strategy. Results for listed secondary outcomes of permanent discontinuation and treatment-emergent laboratory abnormalities are not reported in the registry record.